Article

Current trends and future perspectives of bone substitute materials - From space holders to innovative biomaterials

Authors:
  • Johanniter Evangelical Hospital Bethesda
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Abstract

An autologous bone graft is still the ideal material for the repair of craniofacial defects, but its availability is limited and harvesting can be associated with complications. Bone replacement materials as an alternative have a long history of success. With increasing technological advances the spectrum of grafting materials has broadened to allografts, xenografts, and synthetic materials, providing material specific advantages. A large number of bone-graft substitutes are available including allograft bone preparations such as demineralized bone matrix and calcium-based materials. More and more replacement materials consist of one or more components: an osteoconductive matrix, which supports the ingrowth of new bone; and osteoinductive proteins, which sustain mitogenesis of undifferentiated cells; and osteogenic cells (osteoblasts or osteoblast precursors), which are capable of forming bone in the proper environment. All substitutes can either replace autologous bone or expand an existing amount of autologous bone graft. Because an understanding of the properties of each material enables individual treatment concepts this review presents an overview of the principles of bone replacement, the types of graft materials available, and considers future perspectives. Bone substitutes are undergoing a change from a simple replacement material to an individually created composite biomaterial with osteoinductive properties to enable enhanced defect bridging.

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... Osseous regeneration approaches and grafting procedures were already conducted in early 1900s by Vittorio Putti and contemporaries, who established a significant foundation for further research in this field (3,4). Today, the specialties of oral and maxillofacial surgery and periodontology have a great demand for autogenous bone grafts, allografts, and in particular bone substitute materials (BSM) (5). In contrast to extensive bony defect situations after trauma or ablative tumor surgery, defects that are limited to the dentoalveolar field have great relevance as implantological cases. ...
... Looking into the question of which grafting material is suitable for a particular indication, it is crucial to decide not only based on the patient's individual case but also with the different material properties in mind. Many clinical studies have examined autologous bones as the preferred gold standard material followed by allogenous grafts (5,7,8). However, there are reports of donor site morbidity associated with autografts and concerns regarding the transmission of diseases from allografts. ...
... In this context, bone substitute materials serve as a promising alternative. BSMs are usually classified in three main groups: natural, synthetic, and composite materials (Table I) (5,7,8). ...
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Background/aim: With the demographic change and associated chronic bone loss, the need for cytocompatible bone replacement materials arise in modern medicine. The aim of this in vitro study was to investigate the cytocompatibility of eleven different bone substitute materials and membranes. Materials and methods: Seven bone substitute materials and four membranes were assessed in vitro. The specimens were tested based on their interaction with MC3T3 pre-osteoblasts, through the utilization of viability, proliferation, and cytotoxicity assays. Cell vitality was evaluated using live-dead staining. Results: Although we found minor differences in cytocompatibility among the assessed materials, all tested materials can be considered as cytocompatible with a viability of more than 70% of the negative control, which indicates the non-toxic range as defined in current, international standards (DIN EN ISO 10993-5:2009, German Institute for Standardization, Berlin, Germany). Direct live-dead staining assays confirmed satisfactory cytocompatibility of all tested membranes. Conclusion: All examined bone substitute materials and membranes were found to be cytocompatible. In order to assess whether the observed minor differences can impact regenerative processes, further in vivo studies need to be conducted.
... Multiple growth factors influence this process, including platelet-derived growth factors (PDGFs), fibroblast growth factors (FGFs) and transforming growth factors-β (TGFs-β). These four fundamental properties enable new bone formation which occurs in parallel to direct osseous interconnection [17,18]. Additionally, various other properties will influence the success rate of a bone graft. ...
... Additionally, various other properties will influence the success rate of a bone graft. These include, but are not limited to, biocompatibility, bioresorbability, sterility, structural integrity, adequate porosity for vascular ingrowth, plasticity, ease of handling, cost, and compressive strength [17]. A combination of these factors forms the basis for their use, adequate long-term tolerance by host tissues, and increased chances of successful osteo-regenerative processes occurring [17]. ...
... These include, but are not limited to, biocompatibility, bioresorbability, sterility, structural integrity, adequate porosity for vascular ingrowth, plasticity, ease of handling, cost, and compressive strength [17]. A combination of these factors forms the basis for their use, adequate long-term tolerance by host tissues, and increased chances of successful osteo-regenerative processes occurring [17]. ...
Article
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After tooth loss, bone resorption is irreversible, leaving the area without adequate bone volume for successful implant treatment. Bone grafting is the only solution to reverse dental bone loss and is a well-accepted procedure required in one in every four dental implants. Research and development in materials, design and fabrication technologies have expanded over the years to achieve successful and long-lasting dental implants for tooth substitution. This review will critically present the various dental bone graft and substitute materials that have been used to achieve a successful dental implant. The article also reviews the properties of dental bone grafts and various dental bone substitutes that have been studied or are currently available commercially. The various classifications of bone grafts and substitutes, including natural and synthetic materials, are critically presented, and available commercial products in each category are discussed. Different bone substitute materials, including metals, ceramics, polymers, or their combinations, and their chemical, physical, and biocompatibility properties are explored. Limitations of the available materials are presented, and areas which require further research and development are highlighted. Tissue engineering hybrid constructions with enhanced bone regeneration ability, such as cell-based or growth factor-based bone substitutes, are discussed as an emerging area of development.
... Calciumphosphat-Zemente sind Zwei-bis Dreikomponenten Systeme, bestehend aus ein bis zwei pulverförmigen Stoffen und einer wässrigen Lösung. Durch Mischung entsteht eine formbare Paste, die durch Fällung von Calciumphosphat in situ aushärtet (Kolk et al., 2012). ...
... Nachteilig äußert sich, dass Calciumphosphat-Zemente eine sehr geringe lasttragende Kapazität besitzen. Deshalb müssen bei Einsatz in lasttragenden Gebieten zusätzlich stabilisierende Osteosynthesen eingebracht werden (Kolk et al., 2012). ...
... Dadurch können insbesondere die körpereigenen Proteine die Nanoporen des Scaffolds besiedeln (Gerike et al., 2006). Trotz der hohen Porosität besitzt NanoBone ® eine relativ hohe Bruchfestigkeit von 40 MPa (Kolk et al., 2012). Der Scaffold verfügt über eine gute Osteokonduktivität, Biokompatibilität und Bioresorptionsfähigkeit (Abshagen et al., 2009). ...
Thesis
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Hintergrund und Ziele: Goldstandard in der Therapie von großen Knochendefekten ist derzeit die autologe Transplantation von Knochengewebe. Allerdings generiert dieses Therapieverfahren an der Entnahmestelle einen weiteren Hebedefekt und liefert häufig nicht ausreichend Material für umfangreiche Läsionen. Deshalb wurden in den letzten Jahren enorme Fortschritte im Tissue Engineering (TE) von vaskularisiertem Knochenersatz erzielt. Das TE kann als alternative Therapieoption eingesetzt werden. Doch ab einer gewissen Größe des Knochendefekts ist die Vaskularisation unabdingbar, damit der Knochenersatz ausreichend mit Sauerstoff und Nährstoffen versorgt wird und in den Defekt einheilen kann. Somit scheint die initiale Vaskularisation der Konstrukte der Schlüsselschritt für die erfolgreiche Überbrückung der Defektstelle zu sein. Ziel dieser in vitro Studie war es, zwei verschiedene Knochenersatzstoffe hinsichtlich ihrer Biokompatibilität, ihrer Förderung der Matrixbildung und der Vaskularisation zu vergleichen. Die Ergebnisse können wichtige Informationen für die spätere Anwendung im Großtiermodell des Schafes liefern, um die in vivo Therapie von großen Knochendefekten voranzutreiben. Methoden: Von drei Merinolandschafen wurden durch Knochenmarkpunktion am Hüftkamm MSC (mesenchymale Stammzellen) und durch eine venöse Blutentnahme EPC (endotheliale Progenitorzellen) gewonnen. Für diese Studie wurden die Knochenersatzstoffe NanoBone® und easy-graft® CRYSTAL, die sich in klinischer Anwendung befinden, verwendet. Die kultivierten und expandierten Zellen wurden in Kokultur auf den Scaffolds unter verschiedenen Modalitäten in einem 3D-Bioreaktorsystem über drei Wochen kultiviert. Die Kultur erfolgte entweder unter dynamischen oder gepulsten Bedingungen. Dynamisch bedeutet in dieser Studie, dass die Scaffolds mit 10 ml/h konstantem Medienfluss versorgt wurden, gepulst bedeutet, dass über 12 Stunden ein Medienfluss von 10 ml/h gewährleistet wurde, es folgten 12 Stunden Pause ohne Fluss. Die Wirkung der Wachstumsfaktoren BMP-2 (bone morphogenetic protein-2, Knochen-Morphogeneseprotein-2) und VEGF-A (vascular endothelial growth factor A, vaskulärer endothelialer Wachstumsfaktor) auf die Matrixbildung und Vaskularisation wurde evaluiert. Die Daten wurden mittels histologischer und molekularbiologischer Auswertung erhoben. Die Quantifizierung der eingewachsenen Matrixfläche erfolgte an histologischen Schnitten, die Daten wurden statistisch ausgewertet. Die real-time PCR Daten wurden aufgrund der geringen Gruppengröße nicht statistisch ausgewertet. Ergebnisse: Die beiden getesteten Knochenersatzstoffe zeigten sich als biokompatibel und osteoinduktiv. Die dreidimensionale Kokultur ließ sich in allen Gruppen über einen Zeitraum von drei Wochen erhalten. Die Quantifizierung der eingewachsenen Matrixfläche lieferte keine statistisch signifikanten Unterschiede zwischen den Gruppen, es zeigten sich aber Tendenzen. Insbesondere konnte die Matrixbildung vor allem in der Peripherie der Konstrukte und weniger im Zentrum beobachtet werden. In der histologischen Auswertung fanden sich in den gepulsten NanoBone® Gruppen gefäßähnliche Strukturen. Diese Strukturen konnten ausschließlich in den NanoBone® Gruppen bemerkt werden. Mit der Perjodsäure Schiff-Färbung (periodic acid Schiff, PAS) konnte an ausgewählten Stellen in allen NanoBone® Gruppen der für NanoBone® typische Matrixwechsel detektiert werden. Die Handhabung der Knochenersatzstoffe, insbesondere die Besiedelung und Kultivierung im Bioreaktor war bei NanoBone® deutlich einfacher durchzuführen, als bei easy-graft® CRYSTAL. Die gepulste Kultivierung im 3D-Bioreaktor gestaltete sich vorteilhaft gegenüber der dynamischen, was sich in der gesteigerten Matrixbildung und Hochregulation der Knochenmarker in der PCR zeigte. In dieser Studie hatte der Einsatz der Wachstumsfaktoren keinen Effekt. Schlussfolgerungen: Die Bildung gefäßähnlicher Strukturen in den gepulsten NanoBone® Gruppen zeigt, dass eine in vitro Prävaskularisation von Konstrukten gelingen kann. Die Ergebnisse legen nahe, dass NanoBone® für die in vitro Verwendung besser geeignet ist als easy-graft® CRYSTAL. Da die Matrixbildung hauptsächlich in der Peripherie der Konstrukte stattfand und weniger im Zentrum, bedarf es diesbezüglich weiterer Forschung, um Optimierungskonzepte zu erarbeiten, damit in Zukunft ex vivo besiedelte Konstrukte zur Therapie großer Knochendefekte eingesetzt werden können. Der nächste Schritt wäre die in vitro Erkenntnisse dieser Studie in einem Tibiadefektmodell des Schafes umzusetzen, um damit zu einer klinischen Anwendung zu gelangen.
... Biological repair of bone defects has been a major challenge for orthopedics [1,2]. Autologous bone, allogenic bone, or osteoconductive biomaterials have been successfully used for the repair of bone defects in certain practices [3][4][5]. However, these methods have some limitations, such as donor site morbidity, limited sources, and immune rejection [3][4][5]. ...
... Autologous bone, allogenic bone, or osteoconductive biomaterials have been successfully used for the repair of bone defects in certain practices [3][4][5]. However, these methods have some limitations, such as donor site morbidity, limited sources, and immune rejection [3][4][5]. Tissue-engineered bone could be an effective substitute, with excellent bone regeneration potential and feasibility for commercialization [6,7]. ...
Article
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In situ cell recruitment is a promising regenerative medicine strategy with the purpose of tissue regeneration without stem cell transplantation. This chemotaxis-based strategy is aimed at ensuring a restorative environment through the release of chemokines that promote site-specific migration of healing cell populations. Stromal cell-derived factor-1α (SDF-1α) is a critical chemokine that can regulate the migration of mesenchymal stem cells (MSCs). Accordingly, here, SDF-1α-loaded microporous oligo[poly(ethylene glycol) fumarate]/bis[2-(methacryloyloxy)ethyl] phosphate composites (SDF-1α/OPF/BP) were engineered and probed. SDF-1α/OPF/BP composites were loaded with escalating SDF-1α concentrations, namely, 0 ng/ml, 50 ng/ml, 100 ng/ml, and 200 ng/ml, and were cocultured with MSC. Scratching assay, Transwell assay, and three-dimensional migration model were utilized to assess the migration response of MSCs. Immunofluorescence staining of Runx2 and osteopontin (OPN), ELISA assay of osteocalcin (OCN) and alkaline phosphatase (ALP), and Alizarin Red S staining were conducted to assess the osteogenesis of MSCs. All SDF-1α/OPF/BP composites engendered a release of SDF-1α (>80%) during the first four days. SDF-1α released from the composites significantly promoted migration and osteogenic differentiation of MSCs documented by upregulated expression of osteogenic-related proteins, ALP, Runx2, OCN, and OPN. SDF-1α at 100 ng/ml was optimal for enhanced migration and osteogenic proficiency. Thus, designed SDF-1α/OPF/BP composites were competent in promoting the homing and osteogenesis of MSCs and thus offer a promising bioactive scaffold candidate for on-demand bone tissue regeneration.
... Obwohl mehrere Untersuchungen zur Einheilung von dentalen Implantaten durch Optimierung von Oberflächenstrukturen bei diabetischen oder anderen ungünstigen Stoffwechselbedingungen vorliegen [33,111,142] Außerdem ist BioOss ® sehr volumenstabil [143]. Bei der Herstellung werden anorganische Anteile entfernt, und es bleibt nur eine harte, hochmineralisierte Knochenstruktur bestehen [70]. Es wurde bereits in einigen Studien bestätigt, dass BioOss ® durch seine osseokonduktiven Eigenschaften zu einer effektiven Knochenregeneration führt [70,76]. ...
... Bei der Herstellung werden anorganische Anteile entfernt, und es bleibt nur eine harte, hochmineralisierte Knochenstruktur bestehen [70]. Es wurde bereits in einigen Studien bestätigt, dass BioOss ® durch seine osseokonduktiven Eigenschaften zu einer effektiven Knochenregeneration führt [70,76]. ...
Thesis
ZUSAMMENFASSUNG HINTERGRUND UND ZIELE Die Zahl der Menschen, die an Diabetes Mellitus erkranken, steigt in vielen Teilen der Weltbevölkerung permanent an. In der Mund-, Kiefer- und Gesichtschirurgie stellt Diabetes Mellitus deshalb eine große Herausforderung dar, wenn es um die Verwendung eines geeigneten Knochenersatzmaterials (KEM) geht. Nach einem Trauma, einer Zahnextraktion, einer Resektion, durch angeborene Erkrankungen oder Tumorerkran-kungen kann es zu Knochenverlust oder Knochendefekten kommen. Für die Regenera-tion dieser Defekte sind häufig Knochentransplantate notwendig. Das erste Ziel der vorliegenden Studie ist die Evaluation des Einflusses einer diabeti-schen Stoffwechsellage die Knochenregeneration und Osseointegration von KEM. Als zweites Ziel gilt die Evaluation der Expression der Knochenmatrixproteine Kollagen Typ 1 und Osteocalcin bei jeweils gesundem und diabetischem Stoffwechsel so-wie deren Einfluss auf die Osseointegration. Zudem wurde untersucht, ob KEMs sowohl in gesundem als auch in diabetischem Stoffwechsel einen positiven Einfluss auf die Heilung eines Knochendefektes, gegenüber Knochendefekten ohne KEM haben. METHODEN Die Studie wurde an insgesamt 16 Hausschweinen (lat. Sus scrofa domesticus) durchge-führt. Die Tiere sind in zwei Gruppen aufgeteilt worden, wobei die erste Gruppe aus sieben Schweinen mit diabetischer Stoffwechsellage bestand. Der Diabetes wurde hier vorab mit Streptozotocin induziert. Die gesunde Kontrollgruppe bestand aus neun Schweinen. Sechs Monate nach der Behandlung mit Streptozotocin wurden jedem Versuchstier jeweils neun Knochendefekte (Critical Size Defects) in die Schädelkalotte ge-setzt und mit unterschiedlichen KEMs gefüllt. In dieser Arbeit sind dafür die KEMs autogener Knochen, xenogener Knochen (BioOss®) und der ungefüllte Knochendefekt relevant. Die Knochenbiopsien wurden jeweils nach zwei Wochen (1. Opferung) und acht Wo-chen (2. Opferung) untersucht. Anschließend erfolgte die quantitative Evaluation der Knochenneubildung und der Knochendichte der Knochenprobe aus der Schädelkalotte mittels Lichtmikroskopie und Mikroradiographie. Zur Evaluation der Osseointegration des KEM wurde der Anteil von Osteoid am Gesamtknochen anhand einer Masson-Goldner-Trichrom-Färbung ausgewertet. Zudem wurde die Expression von Kollagen-Typ 1 und Osteocalcin durch immunhistochemische Nachweisverfahren bestimmt. ERGEBNISSE UND BEOBACHTUNGEN Die vorliegende Studie liefert Belege für den negativen Einfluss von Diabetes Mellitus auf die Osseointegration von KEM und dessen Einfluss auf die Knochenneubildung. Unsere Daten zeigen, dass gegenüber der gesunden Versuchsgruppe die Knochenneubildung und -mineralisationsdichte in der Kalotte der diabetischen Gruppe sowohl nach zwei als auch nach acht Wochen reduziert war. Lediglich die Anteile des Osteoids waren nach acht Wochen im diabetischen Tiermodell (KEM autogener Knochen: 8,85 % +/- 2,11 %) höher als im gesunden (KEM autogener Knochen: 5,13 % +/- 3,63 %), je-doch ohne Signifikanz (p = 0,272). Die Expression der Knochenmatrixproteine war ebenfalls verändert. Die Expression von Kollagen-Typ 1 war in der vorliegenden Studie in der Kalotte der diabetischen Versuchstiergruppe (KEM Autogener Knochen: 37,55 % +/- 12,20 %) höher als im gesunden Tiermodell (KEM Autogener Knochen: 33,19 % +/- 16,79 %), ebenfalls ohne Signifikanz (p = 0,598). Die Osteocalcin-Expression hingegen war in der diabetischen Versuchstiergruppe (KEM BioOss®: 12,09 % +/- 10,56 %) gegenüber der gesunden Gruppe (KEM BioOss®: 20,45 % +/- 11,20 %) signifikant reduziert (p = 0,003). In dem neugebildete Knochen der Leerdefekte ließ sich nach 8 Wochen sowohl im gesunden (p = 0,044), als auch im diabetischen Stoffwechsel (p = 0,0001) eine signifikant niedrigere Osteocalcinkonzentration nachweisen, als in den Defekten, die mit autogenem Knochen gefüllt wurden. SCHLUSSFOLGERUNGEN Die vorliegende Studie zeigt, dass sich die Stoffwechselerkrankung Diabetes Mellitus negativ auf die Osseointegration von KEM, die Knochenregeneration und die Mineralisation des neugebildeten Knochens auswirkt. Die Expression von Osteocalcin und Kol-lagen-Typ 1 ist im diabetischen Tiermodell gegenüber dem gesunden Tiermodell verän-dert. Dies gilt unabhängig vom verwendeten KEM. Im Allgemeinen wird die Knochenregeneration durch den Einsatz von beiden KEMs unterstützt. Die Knochenregeneration im Leerdefekt verläuft verlangsamt und die Mine-ralisation im neugebildeten Knochen ist geringer gegenüber den Defekten mit KEM.
... Calcium phosphate ceramics are commonly used in clinical practice as synthetic bone substitutes, and are contained in different alloplastic forms, such as calcium sulfate, tricalcium phosphate (TCP), or biphasic TCP (BTCP) 34,35 . For achieving sufficient β-TCP resorption properties, the ideal balanced ratio of HA and β-TCP ranges between 65:35 and 55:45 36,37 . ...
... However, the corresponding histomorphometric analysis of the healing process of the human bone allograft in animal research is limited because the human-derived bone substitute must be assessed as xenogeneic transplant in animals, and here the collagen structures still contained can cause immunological reactions 31 . A sufficient evaluation of calcified tissue and a quantitative analysis of bone formation can be done in human and animal research via μCT to evaluate bone graft healing 34,[42][43][44][45] . Due to the isotropic voxel sizes and standardized voxel units, the use of volumetric μCT data is appropriate for quantitative analysis, such as the analysis of the bone structural morphology using high-resolution 3D imaging at in vivo and ex vivo laboratory settings 29,[46][47][48] . ...
Article
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To minimize the postoperative risks posed by grafting autologous transplants for cleft repair, efforts are being made to improve grafting materials for use as potential alternatives. The aim of this study was to compare the bone graft quality of different bone substitutes including the gold standard autografts during the healing processes after cleft repair in the context of orthodontic treatment. In 21 Wistar rats, a complete, continuity‐interrupting cleft was created. After 4 weeks, cleft repair was performed using autografts from the hips’ ischial tuberosity, human xenografts, or synthetic bone substitutes [beta‐tricalcium phosphate (β‐TCP)/hydroxyapatite (HA)]. After another 4 weeks, the first molar movement was initiated in the reconstructed jaw for 8 weeks. The bone remodeling was analyzed in vivo using micro‐computed tomography (bone mineral density and bone volume fraction) and histology (new bone formation). All the grafting materials were statistically different in bone morphology, which changed during the treatment period. The β‐TCP/HA substitute demonstrated less resorption compared to the autologous and xenogeneic/human bone, and the autografts led to a stronger reaction in the surrounding bone. Histologically, the highest level of new bone formation was found in the human xenografts, and the lowest was found in the β‐TCP/HA substitute. The differences between the two bone groups and the synthetic materials were statistically significant. Autografts were confirmed to be the gold standard in cleft repair with regard to graft integration. However, parts of the human xenograft seemed comparable to the autografts. Thus, this substitute could perhaps be used as an alternative after additional tissue‐engineered modification.
... Although collagen is widely used as a carrier of rhBMP-2, the watersoluble protein can be rapidly released from collagen by compression, diffusion, and degradation of the collagen in physiological conditions due to its poor mechanical stability [14]. To overcome these problems, many biomaterials have been researched as rhBMP-2 carriers to achieve stable localized rhBMP-2 concentrations for a sufficient period of time [15][16][17]. Incorporating the rhBMP-2 to the 3D-printed PCL scaffold has been difficult due to hydrophobic property of PCL. ...
... rhBMP-2 is a potent growth factor that enhances the osteoblastic differentiation of stem cells, angiogenesis, and new bone formation. Maintaining an adequate concentration of rhBMP-2 at the graft site for a required period of time is essential for graft success because of its short biological half-life, watersoluble property, and rapid clearance [14][15][16]. Therefore, a proper carrier of rhBMP-2 may be critical for its successful use. ...
Article
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The onlay-graft, one of the most difficult graft conditions, is used for diverse clinical conditions, including plastic and dental surgery. The graft should withstand continuous pressure from overlying tissues and have excellent bone formation capability in a limited bone contact situation. We recently developed a 3D printed Kagome-structured PCL scaffold that has a stronger mechanical property. This study evaluated the clinical feasibility of this scaffold for onlay-graft use. The value of the scaffold containing recombinant human bone morphogenetic protein-2 in a hyaluronate-based hydrogel (rhBMP-2/HA) to enhance bone regeneration was also assessed. 3D-printed Kagome-PCL scaffolds alone (n=12, group I) or loaded with rhBMP-2/HA (n=12, group II) were grafted using a rat calvarial onlay-graft model. Following sacrifice at 2, 4, and 8 weeks, all 3D-printed Kagome-PCL scaffolds were accurately positioned and firmly integrated to the recipient bone. Micro-computed tomography and histology analyses revealed a constant height of the scaffolds over time in all animals. New bone grew into the scaffolds in both groups, but with greater volume in group II. These results suggest the promising clinical feasibility of the 3D-printed Kagome-PCL scaffold for onlay-graft useand it could substitute the conventional onlay-graft in the plastic and dental reconstructive surgery in the near future.
... Therefore, the development of long-lasting materials for bone substitutes is of essential clinical importance. The critical requirements for bone implants including biocompatibility, mechanical strength, and stability [4,5]. Metal alloys are commonly used for artificial bone substitutes to support healing processes for bone fractures and joint replacements. ...
... O 2 plasma pretreatment showed no impact on the chemical functionality (Fig. 3 (c)). The characteristic Ca-P peaks were found at 950-1150 cm − 1 for PO 4 3− functionalities, implying the successful incorporation of Ca-P layer by alternative immersions (Fig. 3 (d, e, f, g) and Table S1). In addition, the appearance of peaks at 875 cm − 1 and 1420 cm − 1 (ν 2 vibrations of C -O) indicated that Ca-P was carbonated. ...
Article
A facile and effective plasma polymerized hexamethyldisilazane (ppHMDSZ) combining with calcium phosphate (Ca-P) coating to promote osteoconduction meanwhile provide resistance to corrosion is developed in this study. The composites of Ca-P and ppHMDSZ thin films were deposited on bone substitutes to investigate the osteoblast compatibility. The amount of the Ca-P coatings was modulated with a linear deposition rate of 7.37 μg/(cm²∙cycle) by alternative immersion cycles (1, 2, 5, and 10) in solutions containing calcium and phosphate, measured by quartz crystal microbalance (QCM). Importantly, cell behaviors including cell adhesion, proliferation, and functional activity responded positively toward the surface wettability and roughness of the CaP layers. Moreover, the human osteoblast cells (hFOB1.19) revealed excellent compatibility on the stainless steel coated with Ca-P/ppHMDSZ composite films. The combination of bioceramics and corrosion resistance plasma polymerized HMDSZ films showed a synergistic effect on the biocompatibility and osteoconductive for bone tissue engineering applications.
... It also belongs to the limits of the study that bone substitutes of two different particle sizes were compared: 0.5-1 mm versus 1-2 mm. However, the difference was not significant and may not have affected the results [73][74][75]. The critical difference was studied to be between the particles of less than 0.4 mm and more than 1 mm [73]. ...
... Another study suggested that the granularity was not of a significant relevance but was rather dependent on the clinical defect size. It seems that the microstructure characteristics of the material rather than its granularity plays an important role [75]. ...
Article
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Bovine bone substitute materials (BSMs) are used for oral bone regeneration. The objective was to analyze the influence of BSM biofunctionalization via hyaluronic acid (HA) on human osteoblasts (HOBs). BSMs with ± HA were incubated with HOBs including HOBs alone as a negative control. On days 3, 7 and 10, cell viability, migration and proliferation were analyzed by fluorescence staining, scratch wound assay and MTT assay. On days 3, 7 and 10, an increased cell viability was demonstrated for BSM+ compared with BSM− and the control (each p ≤ 0.05). The cell migration was enhanced for BSM+ compared with BSM− and the control after day 3 and day 7 (each p ≤ 0.05). At day 10, an accelerated wound closure was found for the control compared with BSM+/− (each p < 0.05). The highest proliferation rate was observed for BSM+ on day 3 (p ≤ 0.05) followed by BSM− and the control (each p ≤ 0.05). At day 7, a non-significantly increased proliferation was shown for BSM+ while the control was higher than BSM− (each p < 0.05). The least proliferation activity was observed for BSM− (p < 0.05) at day 10. HA biofunctionalization of the BSMs caused an increased HOB activity and might represent a promising alternative to BSM− in oral bone regeneration.
... The biological activity of Ti-based alloys and their ability to induce bone growth are inadequate, and the rate of osseointegration after implantation in the human body is slow [7]. In this regard, Figure 1 shows the physiological structure of human bones [8,9]. The inorganic substance of bone is mainly phosphate. ...
... Among the advanced manufacturing technologies, three-dimensional (3D) printing and additive manufacturing (AM) can be used for substrate alloy preparation [14,15], surface modification, or coating manufacture. [8,9,16]. Figure 2 further summarizes the research papers on surface modification of Ti alloys published in the Web of Science Core Collection over the past three years. Among the >2000 papers, over 1700 are concerned with wear and corrosion properties, and more than 600 and nearly 500 papers are dedicated to improving bioactivity and antibacterial properties, respectively, suggesting that these are the three most important aspects for enhancing the biomedical performances of Ti and Ti alloys. ...
Article
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Ti is widely used as a material for orthopedic implants. As rapid and effective osseointegration is a key factor for the successful application of implants, biologically inert Ti materials start to show inherent limitations, such as poor surface cell adhesion, bioactivity, and bone-growth-inducing capabilities. Surface modification can be an efficient and effective approach to addressing the biocompatibility, mechanical, and functionality issues of the various Ti implant materials. In this study, we have overviewed more than 140 papers to summarize the recent progress in the surface modification of Ti implants by physical and/or chemical modification approaches, aiming at optimizing their wear resistance, biocompatibility, and antimicrobial properties. As an advanced manufacturing technology for Ti and Ti alloys, additive manufacturing was particularly addressed in this review. We also provide an outlook for future research directions in this field as a contribution to the development of advanced Ti implants for biomedical applications.
... Due to the different indications in oral surgery, a broad variety of xenogeneic BSM is available in various delivery forms, ranging from bone blocks over granules to bone pastes [16]. Moldable BSMs have already been shown to be advantageous in indications such as socket preservation, sinus augmentation, and treatment of bone cysts [17,18]. Their viscous properties allow for an optimal filling of irregularly shaped bone defects up to the defect borders [19]. ...
... All of them are based on synthetic CaP granules composed of pure CaP phases such as hydroxyapatite (HA) or β-tricalcium phosphate (β-TCP) or mixtures of both compounds called biphasic BSM [38]. In this context, it has been shown that these BSM have their own indication area in which their application leads to the desired regenerative outcome [18,40]. Thereby, its regenerative properties are mainly depending on the integrated CaP granules. ...
Article
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The present in vivo study analyses both the inflammatory tissue reactions and the bone healing capacity of a newly developed bone substitute material (BSM) based on xenogeneic bone substitute granules combined with hyaluronate (HY) as a water-binding molecule. The results of the hyaluronate containing bone substitute material (BSM) were compared to a control xenogeneic BSM of the same chemical composition and a sham operation group up to 16 weeks post implantationem. A major focus of the study was to analyze the residual hyaluronate and its effects on the material-dependent healing behavior and the inflammatory tissue responses. The study included 63 male Wistar rats using the calvaria implantation model for 2, 8, and 16 weeks post implantationem. Established and Good Laboratory Practice (GLP)-conforming histological, histopathological, and histomorphometrical analysis methods were conducted. The results showed that the new hyaluronate containing BSM was gradually integrated within newly formed bone up to the end of the study that ended in a condition of complete bone defect healing. Thereby, no differences to the healing capacity of the control BSM were found. However, the bone formation in both groups was continuously significantly higher compared to the sham operation group. Additionally, no differences in the (inflammatory) tissue response that was analyzed via qualitative and (semi-) quantitative methods were found. Interestingly, no differences were found between the numbers of pro- and anti-inflammatory macrophages between the three study groups over the entire course of the study. No signs of the HY as a water-binding part of the BSM were histologically detectable at any of the study time points, altogether the results of the present study show that HY allows for an optimal material-associated bone tissue healing comparable to the control xenogeneic BSM. The added HY seems to be degraded within a very short time period of less than 2 weeks so that the remaining BSM granules allow for a gradual osteoconductive bone regeneration. Additionally, no differences between the inflammatory tissue reactions in both material groups and the sham operation group were found. Thus, the new hyaluronate containing xenogeneic BSM and also the control BSM have been shown to be fully biocompatible without any differences regarding bone regeneration.
... 48,84 The demand for bone graft substitutes is extremely high, with over two million bone grafting procedures performed annually worldwide. 85 The requirements for an ideal bone graft material are clearly defined. Hence, the substitute material should combine the properties of osteogenesis, osteoinduction, osteoconduction and osteointegration. ...
... These interconnecting pores are intended to enable cell infiltration, interaction with adjacent tissues and vascularization, which is indispensable for the successful implantation. 85 The formation and ingrowth of newly formed bone into the implant is enhanced by the use of highly porous scaffolds. The pore size considered ideal depends on the clinical application but should be at least 100 µm. ...
Thesis
A multitude of human tissues, such as bones, tendons, or muscles, are characterized by a hierarchical and highly ordered structure. In many cases, the loss of these tissues requires reconstruction using biocompatible replacement materials. In the field of bone replacement, the pore structure of the material has a crucial influence. Anisotropic porosity would have the advantage of facilitating the ingrowth of cells and newly formed blood vessels as well as the transport of nutrients. In this thesis, scaffolds with a highly ordered and anisotropic pore structure were fabricated using unidirectional freezing. Systematic investigations were carried out on biopolymer solutions (alginate and chitosan) to gain a deeper understanding of the freeze-structuring process. The knowledge gained was then applied to the development of anisotropically structured bone substitute materials. Here, the previously existing material platform for anisotropically structured calcium phosphates was extended to low-temperature phases such as calcium deficient hydroxyapatite (CDHA) or the secondary phosphates monetite and brushite. After the implantation of a biomaterial, the inevitably triggered initial immune response plays a key role in the success of a graft, with immune cells such as neutrophils or macrophages being of particular importance. In this thesis, the influence of anisotropically structured alpha-TCP and CDHA scaffolds as well as their unstructured references on human monocytes/macrophages was investigated. Macrophages produced extracellular traps (ETs) due to mineral nanoparticles formed by the binding of phosphate and calcium ions to human platelet lysate. In particular, incubation of alpha-TCP samples in lysate containing cell culture medium resulted in pronounced particle formation and enhanced release of ETs.
... It has some weaknesses, however, including limited bone supply, demand for an additional donor site, related postoperative morbidity (pain, haematoma and delayed ambulation) and inherent susceptibility to resorption in the long term [6][7][8][9][10]. For this reason, different tissue-engineered bone substitutes have been investigated, which should improve bone fusion and eliminate donor site morbidity [8,[35][36][37]. ...
... Calcium phosphate ceramics are among the candidate bone substitute grafting materials contained in various types of alloplastic biomaterials, such as calcium sulphate, TCP or β-TCP [37,38]. To ensure the ideal resorption of the material, the preferred ratio of HA and β-TCP ranges from 65:35 to 55:45 [39,40]. ...
Article
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Objective The aim of the present study was to investigate the influence of three grafting materials for cleft repair on ortho- dontic tooth movement in rats. Materials and methods Artificial alveolar clefts were created in 21 Wistar rats and were repaired 4 weeks later using auto- grafts, human xenografts and synthetic bone substitute (beta-tricalcium phosphate/hydroxyapatite [β-TCP/HA]). A further 4 weeks later, the first molar was moved into the reconstructed maxilla. Microfocus computed tomography (μCT) was per- formed six times (T0–T5) to assess the tooth movement and root resorption. After 8 weeks, the affected reconstructed jaw was resected for histopathological investigation. Results Total distances reached ranged from 0.82 ± 0.72 mm (β-TCP/HA) to 0.67 ± 0.27 mm (autograft). The resorption was particularly determined at the mesiobuccal root. Descriptive tooth movement slowed and root resorption increased slightly. However, neither the radiological changes during tooth movement (μCT T1 vs. μCT T5: autograft 1.85 ± 0.39 mm3 vs. 2.38 ± 0.35 mm3, p = 0.30; human xenograft 1.75 ± 0.45 mm3 vs. 2.17 ± 0.26 mm3, p = 0.54; β-TCP/HA: 1.52 ± 0.42 mm3 vs. 1.88 ± 0.41 mm3, p = 0.60) nor the histological differences after tooth movement (human xenograft: 0.078 ± 0.05 mm2; β-TCP/HA: 0.067 ± 0.049 mm2; autograft: 0.048 ± 0.015 mm2) were statistically significant. Conclusion The autografts, human xenografts or synthetic bone substitute used for cleft repair seem to have a similar effect on the subsequent orthodontic tooth movement and the associated root resorptions. Clinical relevance Development of root resorptions seems to have a secondary role in choosing a suitable grafting material for cleft repair.
... Accordingly, we were able to show the potential of a defined nanotopography of about 30 nm pores present on the surface of collagen to induce osteogenic differentiation of human inferior turbinate as well as human mesenchymal stem cells in our previous work [12,14]. This property can be called osteogenicity or osteopromotive [4]. Interestingly, the here applied bone substitute material NanoBone ® is likewise known to have a porous surface in the nanoscale, although pore diameters (10-20 nm, [29]) are smaller than those present on Spongostan™ (30 nm, [14]). ...
Article
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Bone substitute materials are becoming increasingly important in oral and maxillofacial surgery. Reconstruction of critical size bone defects is still challenging for surgeons. Here, we compared the clinically applied organic bone substitute materials NanoBone® (nanocrystalline hydroxyapatite and nanostructured silica gel; n = 5) and Actifuse (calcium phosphate with silicate substitution; n = 5) with natural collagen-based Spongostan™ (hardened pork gelatin containing formalin and lauryl alcohol; n = 5) in bilateral rat critical-size defects (5 mm diameter). On topological level, NanoBone is known to harbour nanopores of about 20 nm diameter, while Actifuse comprises micropores of 200-500 µm. Spongostan™, which is clinically applied as a haemostatic agent, combines in its wet form both nano- and microporous topological features by comprising 60.66 ± 24.48 μm micropores accompanied by nanopores of 32.97 ± 1.41 nm diameter. Micro-computed tomography (µCT) used for evaluation 30 days after surgery revealed a significant increase in bone volume by all three bone substitute materials in comparison to the untreated controls. Clearly visual was the closure of trepanation in all treated groups, but granular appearance of NanoBone® and Actifuse with less closure at the margins of the burr holes. In contrast, transplantion of Spongostan™ lead to complete filling of the burr hole with the highest bone volume of 7.98 ccm and the highest bone mineral density compared to all other groups. In summary, transplantation of Spongostan™ resulted in increased regeneration of a rat calvarial critical size defect compared to NanoBone and Actifuse, suggesting the distinct nano- and microtopography of wet Spongostan™ to account for this superior regenerative capacity. Since Spongostan™ is a clinically approved product used primarily for haemostasis, it may represent an interesting alternative in the reconstruction of defects in the maxillary region.
... In the last decade, synthetic bone substitutes (SBS) have become a reliable alternative to autografts, allografts and xenografts [1,2]. Most of the synthetic bone substitute materials are based on calcium phosphates (CaP) due to the chemical similarity of these compounds to the extracellular calcified bone matrix [3]. ...
Article
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In addition to their chemical composition various physical properties of synthetic bone substitute materials have been shown to influence their regenerative potential and to influence the expression of cytokines produced by monocytes, the key cell-type responsible for tissue reaction to biomaterials in vivo. In the present study both the regenerative potential and the inflammatory response to five bone substitute materials all based on β-tricalcium phosphate (β-TCP), but which differed in their physical characteristics (i.e., granule size, granule shape and porosity) were analyzed for their effects on monocyte cytokine expression. To determine the effects of the physical characteristics of the different materials, the proliferation of primary human osteoblasts growing on the materials was analyzed. To determine the immunogenic effects of the different materials on human peripheral blood monocytes, cells cultured on the materials were evaluated for the expression of 14 pro- and anti-inflammatory cytokines, i.e., IL-6, IL-10, IL-1β, VEGF, RANTES, IL-12p40, I-CAM, IL-4, V-CAM, TNF-α, GM-CSF, MIP-1α, Il-8 and MCP-1 using a Bio-Plex® Multiplex System. The granular shape of bone substitutes showed a significant influence on the osteoblast proliferation. Moreover, smaller pore sizes, round granular shape and larger granule size increased the expression of GM-CSF, RANTES, IL-10 and IL-12 by monocytes, while polygonal shape and the larger pore sizes increased the expression of V-CAM. The physical characteristics of a bone biomaterial can influence the proliferation rate of osteoblasts and has an influence on the cytokine gene expression of monocytes in vitro. These results indicate that the physical structure of a biomaterial has a significant effect of how cells interact with the material. Thus, specific characteristics of a material may strongly affect the regenerative potential in vivo.
... Despite the fact that a wide range of osteoplastic materials (metallic materials, silicates, calcium phosphate ceramics, biopolymers) are used in existing medical methods, a significant number of studies have been carried out that are aimed both at developing novel materials and at studying the methods for modification and functionalization of implants for the recovery of damaged bone tissues [1,2]. ...
Article
Data obtained by the authors upon creating composite materials based on biopolymers and calcium phosphates adapted to the prototyping technology are presented. Results concerning the creation and investigation of the properties of three-dimensional structures for the replacement of bone defects, as well as novel studies of the functionalization of three-dimensional prototypes based on calcium phosphates and a biopolymer, namely, modification of the surface of mineral-polymer materials by the biomimetic application of active calcium phosphates, are shown.
... Seven of the review papers studied in this article [54][55][56][57][58][59][60] focused on the analysis of the properties, advantages and disadvantages of the different materials that have been and are currently used for bone regeneration. On the other hand, five of them [61][62][63][64][65] were dedicated to classifying and studying the different methods for manufacturing customized structures for bone regeneration and how these techniques have evolved over the years. ...
Article
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Clinicians should be aware of the main methods and materials to face the challenge of bone shortage by manufacturing customized grafts, in order to repair defects. This study aims to carry out a bibliographic review of the existing methods to manufacture customized bone scaffolds through 3D technology and to identify their current situation based on the published papers. A literature search was carried out using “3D scaffold”, “bone regeneration”, “robocasting” and “3D printing” as descriptors. This search strategy was performed on PubMed (MEDLINE), Scopus and Cochrane Library, but also by hand search in relevant journals and throughout the selected papers. All the papers focusing on techniques for manufacturing customized bone scaffolds were reviewed. The 62 articles identified described 14 techniques (4 subtraction + 10 addition techniques). Scaffold fabrication techniques can be also be classified according to the time at which they are developed, into Conventional techniques and Solid Freeform Fabrication techniques. The conventional techniques are unable to control the architecture of the pore and the pore interconnection. However, current Solid Freeform Fabrication techniques allow individualizing and generating complex geometries of porosity. To conclude, currently SLA (Stereolithography), Robocasting and FDM (Fused deposition modeling) are promising options in customized bone regeneration.
... Calcium sulfate is a widely used biomaterial, e.g. as bone void filler in orthopedic and dental applications (Kolk et al., 2012). There are also several pharmaceutical products based on calcium sulfate, for example implantable beads containing antibiotics (Agarwal and Healey, 2014) and the NanoZolid® technology based Liproca® Depot formulation for local antiandrogen prostate cancer treatment (Grudén et al., 2018;Tammela et al., 2017). ...
Article
Aim: The study was designed to evaluate the ability of the calcium sulfate based NanoZolid® drug delivery technology to locally release the epidermal growth factor (EGF) protein while maintaining its biological activity. Methods: NanoZolid-formulated EGF protein labelled with a near infrared dye (EGF-NIR) depots or EGF-NIR dissolved in PBS were injected subcutaneously into mice bearing EGF receptor (EGFR) positive human A549 lung cancer tumors inoculated subcutaneously. The release and biodistribution of the EGF-NIR were investigated in vivo longitudinally up to 96 hours post administration, utilizing whole body fluorescence imaging. In order to confirm the in vivo findings, histological analysis of tumor cryosections was performed to investigate EGF-NIR fluorescent signal and EGFR expression level by immunofluorescence labelling. Results: The in vivo fluorescence imaging showed a controlled release profile of the EGF-NIR loaded in the NanoZolid depots compared to free EGF-NIR. Histological analysis of the tumors further demonstrated a prevailing distribution of EGF-NIR in regions with high levels of EGFR expression. Conclusion: Calcium sulfate based depots can be used to formulate EGF while maintaining its biological activity, e.g. receptor binding capability. This may have a good clinical potential for local delivery of biomolecules to enhance treatment efficacy and minimize systemic adverse effects.
... Recapitulating natural fracture healing in vivo remains a limitation in biomaterial-based bone regeneration strategies. Current approaches to bone regeneration typically promote intramembranous ossification through the use of osteoconductive and osteoinductive biomaterials [23,24] and are not designed for the specific anatomic conditions or site at which they are being used, which can lead to unsatisfactory healing. Therefore, there has been increasing interest in biomaterials-based strategies that promote endochondral ossification, including chondrogenic priming of scaffolds [25,26], mechanical loading [27], and aligned pore architectures [28]. ...
Article
Most fractures heal by a combination of endochondral and intramembranous ossification dependent upon strain and vascularity at the fracture site. Many biomaterials-based bone regeneration strategies rely on the use of calcium phosphates such as nano-crystalline hydroxyapatite (nHA) to create bone-like scaffolds. In this study, nHA was dispersed in reactive polymers to form composite scaffolds that were evaluated both in vitro and in vivo. Matrix assays, immunofluorescent staining, and Western blots demonstrated that nHA influenced mineralization and subsequent osteogenesis in a dose-dependent manner in vitro. Furthermore, nHA dispersed in polymeric composites promoted osteogenesis by a similar mechanism as particulated nHA. Scaffolds were implanted into a 2-mm defect in the femoral diaphysis or metaphysis of Sprague-Dawley rats to evaluate new bone formation at 4 and 8 weeks. Two formulations were tested: a poly(thioketal urethane) scaffold without nHA (PTKUR) and a PTKUR scaffold augmented with 22 wt% nHA (22nHA). The scaffolds supported new bone formation in both anatomic sites. In the metaphysis, augmentation of scaffolds with nHA promoted an intramembranous healing response. Within the diaphysis, nHA inhibited endochondral ossification. Immunohistochemistry was performed on cryo-sections of the bone/scaffold interface in which CD146, CD31, Endomucin, CD68, and Myeloperoxidase were evaluated. No significant differences in the infiltrating cell populations were observed. These findings suggest that nHA dispersed in polymeric composites induces osteogenic differentiation of adherent endogenous cells, which has skeletal site-specific effects on fracture healing. Significance Statement Understanding the mechanism by which synthetic scaffolds promote new bone formation in preclinical models is crucial for bone regeneration applications in the clinic where complex fracture cases are seen. In this study, we found that dispersion of nHA in polymeric scaffolds promoted in vitro osteogenesis in a dose-dependent manner through activation of the PiT1 receptor and subsequent downstream Erk1/2 signaling. While augmentation of polymeric scaffolds with nHA enhanced intramembranous ossification in metaphyseal defects, it inhibited endochondral ossification in diaphyseal defects. Thus, our findings provide new insights into designing synthetic bone grafts that complement the skeletal site-specific fracture healing response.
... Bone tissue has innate regenerative potential after injury, provided that the impairment is mild and the defect size is small [1]. However, large bony defects that cannot be repaired require bone grafting with autologous, allogeneic, or artificial grafts [2]. Autologous bone grafts are the 'gold standard' treatment of large bony defects; however, a limited supply of bone and donor site morbidity restrict their application in practice. ...
Article
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Magnesium phosphate cement (MPC) has been evaluated as an inorganic bone filler due to its favorable biocompatibility, biodegradability, rapid setting, high initial strength, and osteogenic potential. However, the setting time of MPC is so rapid that it makes it difficult to use in practice, and the clinical properties of MPC could be further be improved by adding bioactive materials. Here we developed novel bioactive chondroitin sulfate (CS)-MPC composites (CS-MPCs) by incorporating different amounts of CS into MPC. The compositions, microstructures, and physiochemical properties of CS-MPCs and their induced in vitro cellular responses and in vivo bone regeneration properties were evaluated. CS-MPCs had a longer setting time, lower hydration temperature, higher compressive strength, and more neural pH than MPC. CS-MPCs demonstrated similar degradation ratios relative to MPC in Tris-HCl solution. CS-MPCs promoted pre-osteoblast cell proliferation, attachment, and differentiation in vitro and enhanced bone formation surrounding implants in vivo. In conclusion, through CS modification, our novel CS-MPCs have improved physiochemical properties that enhance compatibility in vitro and bone regeneration in vivo, making them attractive materials for bone regeneration.
... Regenerative therapies may take two different approaches, cell seeded scaffolds [49], which require a prior ex vivo step where stem or differentiated cells are grown on the scaffold to prepare implantable constructs or cell homing where an "in situ" cell recruitment and colonization is required [50]. The second one relies more in the body ability to heal and it may have a shorter period for translation to the clinic [51] but both approaches depend on the capacity of the material [52] and manufactured device to induce or facilitate tissue ingrowth [53]. We are proposing the use of DPSCs in combination with 3D printed PCL scaffolds as the baseline for developing preclinical large animal models but also for the manufacturing of 3D models for in vitro studies that can substitute or reduce the need for animal models in the development and testing of new treatments in agreement with international animal care guidelines. ...
Article
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The search of suitable combinations of stem cells, biomaterials and scaffolds manufacturing methods have become a major focus of research for bone engineering. The aim of this study was to test the potential of dental pulp stem cells to attach, proliferate, mineralize and differentiate on 3D printed polycaprolactone (PCL) scaffolds. A 100% pure Mw: 84,500 ± 1000 PCL was selected. 5 × 10 × 5 mm3 parallelepiped scaffolds were designed as a wood-pilled structure composed of 20 layers of 250 μm in height, in a non-alternate order ([0,0,0,90,90,90°]). 3D printing was made at 170 °C. Swine dental pulp stem cells (DPSCs) were extracted from lower lateral incisors of swine and cultivated until the cells reached 80% confluence. The third passage was used for seeding on the scaffolds. Phenotype of cells was determined by flow Cytometry. Live and dead, Alamar blue™, von Kossa and alizarin red staining assays were performed. Scaffolds with 290 + 30 μm strand diameter, 938 ± 80 μm pores in the axial direction and 689 ± 13 μm pores in the lateral direction were manufactured. Together, cell viability tests, von Kossa and Alizarin red staining indicate the ability of the printed scaffolds to support DPSCs attachment, proliferation and enable differentiation followed by mineralization. The selected material-processing technique-cell line (PCL-3D printing-DPSCs) triplet can be though to be used for further modelling and preclinical experiments in bone engineering studies.
... Osteoconductive structural guidance is essential to constructing functionalized bone substitutes and should be employed in combination with osteoinductive factors and multiple cell compounds that are important in bone healing. Scaffolds are 3D frameworks made of biomaterials that can induce and regulate cellular attachment, proliferation, migration, and differentiation (Figure 4) [29,64,65]. The primary task of scaffolds in BTE is to construct a structural and mechanical support for 3D cell-cell interactions, providing a microenvironment that is responsive for osteoinducible cells to attach, function, and produce bone ECM on the surface [66]. ...
Article
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Over the past decades, a number of bone tissue engineering (BTE) approaches have been developed to address substantial challenges in the management of critical size bone defects. Although the majority of BTE strategies developed in the laboratory have been limited due to lack of clinical relevance in translation, primary prerequisites for the construction of vascularized functional bone grafts have gained confidence owing to the accumulated knowledge of the osteogenic, osteoinductive, and osteoconductive properties of mesenchymal stem cells and bone-relevant biomaterials that reflect bone-healing mechanisms. In this review, we summarize the current knowledge of bone-healing mechanisms focusing on the details that should be embodied in the development of vascularized BTE, and discuss promising strategies based on 3D-bioprinting technologies that efficiently coalesce the abovementioned main features in bone-healing systems, which comprehensively interact during the bone regeneration processes.
... Mineralized bone retains more structural integrity, while the decalcification of demineralized bone is thought to expose bone morphogenetic protein and increase osteoinduction. 38 ...
Technical Report
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Tooth extraction is a common procedure in the field of dentistry. Although atraumatic extraction is always preferred, it is not always accomplished. In this course, we will cover topics such as how normal healing occurs and why atraumatic tooth extraction is desired, as well as how best to achieve this result. We will also discuss various techniques for socket augmentation and preservation, as well as when a particular technique is indicated. After taking this course, participants will be versed in the various grafting options available to practitioners and be able to discern what option may be most suitable for their clinical needs. The authors will also discuss the role of immediate implants in dentistry and how they can effect extraction sites.
... The marine sponge, which contains calcareous or siliceous spicules or collagen/spongin, creates a porous biomimetic environment that promotes osteogenesis in vitro by replicating the cancellous architecture of bone tissue and the complicated canal system [61]. Marine seashell is the best biogenic material consisting of carbonate with richly interspersed micro-structures in a densely compact structure [62]. Marine seashells can improve the osteogenic response to human tissue due to strong mechanical, Osteoinductive properties and orthopedic application [63]. ...
Article
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Hard tissue reconstruction of bone has attracted the interest of clinical researchers to overcome the anomalous effect on general well-being. Bone is a supporting skeleton structure that also plays a pivotal role in the normal physiological functioning body. The introduction of bone tissue engineering has been instrumental in overcoming fragmental defined bone to diseases, accidents, or debilitating conditions. For this, various bone grafting materials are used to restore the patency. These various bone grafting options have shown promising results. But the search for ideal grating material continues. However, the available grafting resources may not ensure regeneration. And the grafts like autogenous grafts that provide the capacity, are often, acquired in limited quantity. Its incapacity to fill the defect has led to the requirement of alternative material. Marine sources have shown acceptable clinical outcomes and are rendered safe for use also have a rich calcium phosphate-containing scaffold, over which the new cells are formed owing to its porous and 3D grains. The wide range of available marine sources has been put into clinical trials. The collagen found in the Marine sources has shown comparatively better results than that of the available synthetic alternatives.
... Various off-the-shelf synthetic bone substitutes, such as biodegradable ceramics and polymers, are readily available in the clinic for use in orthopedic interventions [1][2][3]. Although the performance of certain synthetic replacements are even reported to be noninferior to autograft in applications such as spinal fusion, the success rate is not optimal [4,5]. ...
Article
Full-text available
Therapeutic pathogen recognition receptor (PRR) ligands are reaching clinical practice following their ability to skew the immune response in a specific direction. We investigated the effects of various therapeutic PRR ligands on bone cell differentiation and inflammation. Following stimulation, alkaline phosphatase (ALP) activity (Day 10), osteocalcin, osteonectin expression (Day 14), and calcium deposition (Day 21) were quantified in bone marrow-derived human mesenchymal stem cells (hMSCs). The osteoclastogenic response was determined by measuring tartrate-resistant acid phosphate (TRAP) activity in human monocytes. TNF-α, IL-6, IL-8, and IL-10 expressions were measured by enzyme-linked immunosorbent assay as an indicator of the ligands' inflammatory properties. We found that nucleic acid-based ligands Poly(I:C) and CpG ODN C increased early ALP activity in hMSCs by 4-fold without affecting osteoclast formation. These ligands did not enhance expression of the other, late osteogenic markers. MPLA, Curdlan, and Pam3CSK4 did not affect osteogenic differentiation, but inhibited TRAP activity in monocytes, which was associated with increased expression of all measured cytokines. Nucleic acid-based ligands are identified as the most promising osteo-immunomodulators, as they favor early osteogenic differentiation without inducing an exaggerated immune-cell mediated response or interfering in osteoclastogenesis and thus can be potentially harnessed for multifunctional coatings for bone biomaterials.
... Although synthetic porous scaffolds of various materials have been well studied, such as bioceramics and polymers showing good biocompatibility [5,6], the clinical translation of these scaffolds has been hampered by their poor capabilities. In addition to biocompatibility, the ideal bone substitute should have mechanical properties close to those of bone and present a fully interconnected porous structure to allow bone growth and degrade in the human body as bone regenerates [7,8]. ...
Article
Full-text available
To evaluate the bone regeneration capacity of Zn–2Ag–0.04Mg alloy scaffold in vivo. Zn, Zn–2Ag and Zn–2Ag–0.04Mg scaffolds were implanted in the femur of New Zealand rabbits, and the degradation of the scaffolds and the regeneration of the bone were observed at 6th week and 6th month. Two-dimensional and three-dimensional micro-CT results showed the new bone in Zn–2Ag–0.04Mg alloy scaffold group was significant more than Zn scaffold group, the bone volume in Zn–2Ag–0.04Mg was higher. Moreover, the osteogenic index in the Zn–2Ag–0.04Mg alloy scaffold group was also higher than Zn scaffold group. At 6th month, the scaffold of Zn–2Ag–0.04Mg was smaller than Zn group or Zn–2Ag group. HE staining of the liver, kidney, and heart did not detect any abnormalities, confirmed the biosafety of the Zn–2Ag–0.04Mg alloy scaffold. The Zn–Ag–0.04Mg alloy scaffold exhibits good biocompatibility and bone regeneration ability in vivo.
... 15,16 To overcome these limitations, allogeneic bone, xenogeneic bone, and synthetic bone are used in clinical scenario with constant efforts to harvest an perfect grafting material. 17,18 The traditional classification of bone graft materials includes autogenous bone, allografts, xenografts, and alloplasts. 19 Allografts consist primarily of freeze-dried human bone with or without demineralization (demineralized freezedried bone allograft; freeze-dried bone allograft). ...
Article
Full-text available
A pilot study was conducted to analyze and compare the stability of dental implants using 2 different graft materials (autologous dentin graft and an alloplastic hydroxyapatite [HA] crystal) in the same patient. As far as we know, this study is first of its kind where socket preservation has been done using 2 different grafts in the same patient. Ten patients undergoing extraction of at least 2 teeth were selected. Atraumatic extractions were performed. Out of the 2 extraction sockets, 1 was grafted with autogenous tooth graft and other with HA crystals. Computed tomography scan was performed 3 months after grafting to evaluate bone mineral density. Primary implant stability was measured using resonance frequency analysis. It was observed that among both sites, autogenous tooth grafted sites showed better results.
... Zahnverluste, Nichtanlagen von Zähnen, dentale oder maxillofaziale Traumata, sowie Tumore oder Parodontalerkrankungen können zu alveolären Knochenverlusten führen (Axelsson et al., 2004). Um den Patienten entsprechend rekonstruieren zu können, ist häufig eine Knochenaugmentation vor der implantat-prothetischen Versorgung notwendig (Triplett und Schow et al., 1996, Oikarinen et al., 2003, Kolk et al., 2012. ...
Thesis
Ziel dieser Arbeit war es, Unterschiede in der Proteinexpression von Alveolar- und Beckenknochen aufzuzeigen, um Gründe für die unterschiedliche Transplantatkompetenz der beiden Knochenentitäten zu ermitteln. Darunter sollten Kandidatenproteine ermittelt werden, welche zur Verbesserung von Knochenersatzmaterialien verwendet werden können. Nach aktuellen Kenntnissen ist dies die erste experimentelle Arbeit, die das Proteom von Beckenknochen und Alveolarknochen aus derselben Spenderin untersucht und miteinander vergleicht. Mit der Methodik der LC-MS/MS Analyse konnten viele Proteine identifiziert werden, dessen vorkommen im Knochen bisher unbekannt waren. Diese Proteine gilt es weiter zu erforschen und deren Funktion im Knochen zu ermitteln. Zudem konnten auch Proteine identifiziert werden, worüber bereits in anderen Arbeiten bei der Analyse von Alveolar- oder Beckenknochen berichtet wurde. Sowohl bei der Analyse der einzelnen Knochenentitäten, als auch beim Vergleich zeigte sich, dass im Alveolarknochen vermehrt strukturgebende Proteine und Proteine der extrazellulären Matrix exprimiert wurden. Im Beckenknochen wurden dagegen Proteine, welche an Energiemetabolismen beteiligt und immunologisch aktiv sind vermehrt identifiziert. Diese Erkenntnis kann eine Ursache dafür sein, weshalb Beckenknochen anderen autologen Knochenersatzmaterialien überlegen ist. Ein gesteigerter Energiemetabolismus ist für das Bone-remodelling wichtig. Um dies jedoch zu verifizieren, sollte in weiteren Studien der direkte Einfluss, der in BK identifizierten Proteine auf den Knochenstoffwechsel und der Knochenregeneration erforscht werden. Erst dann kann entschieden werden, ob die identifizierten Proteine Potential zur Verbesserung von Knochenersatzmaterialien haben.
... Synthetic bone grafts are made of various materials, i.e. metals, polymers and ceramics [13,14], but calcium phosphates (CaP) have received particular attention because of their chemical similarity to the mineral part of natural bone and their attractive physico-chemical and biological properties. Among these, beta-tricalcium phosphate (β-TCP; Ca 3 (PO 4 ) 2 ; Ca/P = 1.500) is one of the most used CaP due to its cell-mediated resorption [15,16]. ...
Article
Full-text available
β-Tricalcium Phosphate (β-TCP), one of the most used bone graft substitutes, may contain up to 5 wt% foreign phase according to standards. Typical foreign phases include β-calcium pyrophosphate (β-CPP) and hydroxyapatite (HA). Currently, the effect of small amounts of impurities on β-TCP resorption is unknown. This is surprising since pyrophosphate is a very potent osteoclast inhibitor. The main aim of this study was to assess the effect of small β-CPP fractions (<1 wt%) on the in vitro osteoclastic resorption of β-TCP. A minor aim was to examine the effect of β-CPP and HA impurities on the physico-chemical properties of β-TCP powders and sintered cylinders. Twenty-six batches of β-TCP powder were produced with a Ca/P molar ratio varying between 1.440 and 1.550. Fifteen were further processed to obtain dense and polished β-TCP cylinders. Finally, six of them, with a Ca/P molar ratio varying between 1.496 (1 wt% β-CPP) and 1.502 (1 wt% HA), were incubated in the presence of osteoclasts. Resorption was quantified by white-light interferometry. Osteoclastic resorption was significantly inhibited by β-CPP fraction in a linear manner. The presence of 1% β-CPP reduced β-TCP resorption by 40%, which underlines the importance of controlling β-CPP content when assessing β-TCP biological performance.
... There are various biomaterials, such as inorganic ceramics or glass, that are used in the manufacture of skeletons for bone tissue engineering. Tissue engineering technologies that include bone reconstruction or regeneration to replace defects in the oral cavity and maxillofacial area require a temporary porous frame [14]. ...
Article
The present paper considers the role of orthodontic treatment and prosthetics in the recovery period after surgical treatment of an injury to the maxillofacial area. Analyzing the sources within the framework of the research topic, the author cconcludes tthat surgical treatment of maxillofacial trauma and postoperative rehabilitation often requires an interdisciplinary approach, which makes it a difficult task. This is due to the fact that these injuries usually affect several structures of the oral cavity and face, including hard and soft tissues, often causing malocclusion. Thus, the clinical picture and the appropriate treatment strategy may vary greatly from one person to another. Therefore, before drawing up a final treatment plan, a thorough and thoughtful multidisciplinary assessment of each patient is necessary.
... The bone defects are likely to form a dead cavity that carries risks, including infection, soft tissue depression and even pathological fracture [5]. Many reports have shown that bone substitutes are a promising solution Ivyspring International Publisher by promoting ossification and preventing tissue depression [11,12]. However, further studies and clinical trials have shown that there is an increased risk of infection for the patients treated with bone substitute [13,14]. ...
Article
Background: To evaluate hyperbaric oxygen therapy (HBOT) on infection rates and repair rates during the treatment of large jaw cysts. Methods: A prospective randomized, non-blinded, controlled clinical trial included 90 patients with jaw cysts, randomly divided into three groups. Patients were treated with enucleations and bone substitute was used in the experimental and control groups. The experimental group received HBOT. The primary predictor variable was HBOT. The infection rate, repair rate, preoperative volume of the jaw cysts, age, and sex were statistically analyzed. The Fisher exact test was used to compare the infection rate and postoperative complications. The repair rate of the bone defects was analyzed using the repeated-measures analysis of variance and the least significant difference tests. The Kendall's coefficient of concordance and Kappa statistics were calculated to evaluate the consistency between the two investigators. Results: The infection rate was 3.4% in the experimental group, 14.3% in the blank group, and 32.1% in the control group (P<0.05). The repair rate in the experimental group was significantly higher than in the control and blank groups at 1, 3 and 6 months after surgery (P<0.05). Conclusion: The results showed that HBOT reduced the postoperative infection rate following the enucleation of large jaw cysts with bone substitute filling, and it also improved the bone repair rate.
... Different intraoral donor sites are widely used as bone blocks or particulate bone. The most common intraoral sites are the symphysis and ramus/retromolar area [18][19][20][21][22], they have different degrees of morbidities and complications [23][24][25][26][27]. Non-autogenous bone grafts such as allografts, xenografts, and synthetic bone substitutes are widely used either alone or in combinations [28][29][30][31][32][33][34]. They eliminate the potential complications associated with autogenous donor sites and their availability is unlimited, however, they have osteoconductive characteristics and lack of osteoprogenitor cells. ...
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Autogenous bone is still considered the gold standard in bone augmentation for implant insertion in atrophic ridges. However, augmentation of multiple edentulous atrophic segments usually necessitates the use of extraoral donor sites. This chapter introduces the Wedge Technique, as a new bone augmentation method that can augment multiple edentulous ridges with intraoral cortical bone grafts. Patients with moderate to severe ridge atrophy in different regions of the jaws were treated with the wedge technique (WT). Patients received a panoramic radiograph immediately after the surgery, and they were examined clinically and radiographically (periapical radiograph) every 2 weeks. At four months, CBCT was performed to evaluate the bone gain. Reentry was performed after 4 to 5 months to evaluate the new bone volume and quality and to insert implants. The follow-up period ranged from 30 to 120 months. The healing process was uneventful, with minimal morbidity. The success rate was 95%, the bone gain average was 3–6 mm vertically and 3–9 mm horizontally. The wedge technique can augment multiple segments of atrophic ridges with a small amount of autogenous graft. The achieved bone volume was satisfying, especially that the majority of the augmented areas were at posterior mandibular defects.
... The use of synthetic bone materials eliminates the need to resect bone tissue from a secondary location in the body. Additionally, it does not carry the same risk of disease transmission as allogeneic graft materials [2]. In addition, artificial synthetic bone materials do not suffer from the risks of low supply or high cost associated with autologous bone and allografts. ...
Article
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Magnesium potassium phosphate cement (MKPC) has attracted considerable attention as a bone regeneration material. However, there are only a few reports on its biomechanical properties. To evaluate the biomechanical properties of MKPC, we compared the mechanical parameters of pedicle screws enhanced with either MKPC or polymethyl methacrylate (PMMA) bone cement. The results show that the maximum pull-out force of the pedicle screws was 417.86 ± 55.57 and 444.43 ± 19.89 N after MKPC cement setting for 30 min and 12 h, respectively, which was better than that of the PMMA cement. In fatigue tests, the maximum pull-out force of the MKPC cement group was 435.20 ± 7.96 N, whereas that of the PMMA cement in the control group was 346.80 ± 7.66 N. Furthermore, the structural characterization analysis of the MKPC cement revealed that its microstructure after solidification was an irregular tightly packed crystal, which improved the mechanical strength of the cement. The maximum exothermic temperature of the MKPC reaction was 45.55 ± 1.35 °C, the coagulation time was 7.89 ± 0.37 min, and the compressive strength was 48.29 ± 4.76 MPa, all of which meet the requirements of clinical application. In addition, the MKPC cement did not significantly inhibit cell proliferation or increase apoptosis, thus indicating good biocompatibility. In summary, MKPC exhibited good biomechanical properties, high initial strength, good biocompatibility, and low exothermic reaction temperature, demonstrating an excellent application potential in the field of orthopedics.
... Generally, the three key elements in tissue engineering fields are stem cells, biomaterials and growth factors. [4] The incorporation of growth factors is a very promising option in bone healing and/or stems cells that capable of reconstructing bone and marrow structures. [5] However, there are controversial results in the supportive role of bone morghogenic proteins in alveolar bone regeneration and the quantity of the mesenchymal stem cells required for optimum bone tissue regeneration. ...
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Objective: This trial preformed to evaluate clinically and radiographically, the efficacy of growth factors producing/inducing materials; Advanced-Platelet-Rich Fibrin (A-PRF) and Metformin (MF) respectively, in the surgical treatment of intrabony periodontal defects. Methods: Forty-eight systemically healthy chronic periodontitis patients with intrabony defect were divided equally into 4 groups. First Group, patients treated by open flap debridement (OFD). Second Group, patients treated by OFD + 1% MF gel. Third Group, patients treated by A-PRF, which inserted into the intra bony defect (IBD). Fourth Group treated by (1% MF + A-PRF). Parameters were gathered at baseline 6 and 9 months. Results: The reduction in probing depth (PD) and clinical attachment level (CAL) was greater in the A-PRF + 1% MF patients group than other groups. Combination of A-PRF + 1% MF showed statistically significant reduction of IBD greater than all other groups. Conclusions: Usage of combination of A-PRF + 1% MF seems to be superior in gaining bone than surgical treatment by OFD, OFD + A-PRF or OFD + MF only.
... Some of the most commonly used ceramics apart from bio-glass include hydroxyapatite (Hap), Calcium Phosphate (CaPs) and tricalcium phosphate (TCP) [65]. These materials have excellent porosity and a heavily interconnected structure which engenders bone and vasculature ingrowth and aids-in the transport of nutrients to the cells [66,67] in addition to exhibiting no toxic side effects [68]. In HA/β-TCP ceramic scaffolds mechanical strength was found to be inversely proportional to diameter [69] and these scaffolds promoted cell viability and differentiation both in-vitro and in-vivo [70]. ...
Article
Every year, millions of people around the world undergo bone graft and artificial prosthesis transplants which engenders the repair and/or replacement of native bone for treating bone defects and injury. As a result, bone has become the second most transplanted tissue globally and there is a growing need for advances in bone tissue engineering (BTE) to ensure improved quality of life. The advent of 3D bone scaffolds has led to a paradigm shift in this field. These scaffolds act as an extra cellular matrix (ECM) providing a 3D environment for cell adhesion, proliferation, and differentiation. The scaffolds so fabricated, must meet the mechanical and biological criteria for successful clinical translation. Initial iterations of these scaffolds were not constructed with precise geometries. This review looks at the various advances in scaffold designs, materials and 3D printing techniques employed, which enable us to fabricate scaffolds with tailored architecture and control its functionality. These advances allow us to optimize the parameters in the fabrication of these scaffolds, such that we can create structures with desired characteristics like controllable biodegradability using the least amount of material possible along with a precise pore size and high permeability for purposes of osteo-induction and osseointegration. This is followed by the computational analysis carried out on the samples to ensure they are suitable for a given application. Finally, this paper talks about regulatory hurdles (ethical, legal and social) faced by researchers, in addition to the various technical challenges, when it comes to the real-life implementation of this technology.
... However, the factors critical for success of grafting are the optimal size, shape, biomaterial and the anatomical structure of the bone defects. Thus, 3D printed scaffolds or synthetic bone grafts are considered more feasible due to their tuneable mechanical properties identical to the original bone tissue, and ease of rapid re-vascularization [7]. ...
Chapter
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Tissue grafting is mostly used for repair and replacement of severely damaged tissues, the key challenges are compatibility, availability of the grafts, complex surgical process and post-operative complications. Hence, additive technologies such as three-dimensional (3D) bioprinting have emerged as promising alternative for tissue engineering in order to ensure safety, compatibility, and rapid healing. The aim of this chapter is to give an elaborate account of 3D printed scaffolds for bone, cartilage, cardio-vascular and nerve tissue engineering. Various components such as polycap-rolactone, poly (lactic-co-glycolic acid), and β-tricalcium phosphate, bioglass 45S5, and nano-hydroxyapatite are combined with collagen and its derivatives to achieve specific pore size in the scaffolds for effective restoration of the defects of soft or hard tissues. Likewise, proanthocyanidin, oxidized hyaluronic acid, methacrylated gelatin, are used in collagen based 3D printed scaffolds for cartilage tissue engineering. Bioink with collagen as active component is also used for developing cardio-vascular implants with recellularizing properties. Collagen in combination with silk fibroin, chitosan, heparin sulphate and others are ideal for fabrication of elastic nerve guidance conduits. In view of the background, collagen-supplemented hydrogels can revolutionize future biomedical approaches for the development of complex scaffolds for tissue engineering.
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Osteoporosis is a public health problem, with bone loss being the main consequence. Hydroxyapatite (HA) has been largely used as a bioceramic to stimulate bone growth. In our work, a cerium-containing HA (Ce-HA) has been proposed and its effects on the antimicrobial and bone-inducing properties were investigated. The synthesis of the materials occurred by the suspension–precipitation method (SPM). The XRD (X-ray Diffraction) confirmed the crystalline phase, and the Rietveld refinement confirmed the crystallization of HA and Ce-HA in a hexagonal crystal structure in agreement with ICSD n° 26205. Characterizations by FT-IR (Fourier Transform Infrared Spectroscopy), XPS (X-ray Photoemission Spectroscopy), and FESEM-EDS (Field Emission Scanning Electron Microscope-Energy Dispersive X-ray Spectroscopy) confirmed the presence of cerium (Ce3+ and Ce4+). The antibacterial activity of Has was evaluated against Staphylococcus aureus 25,923 and Escherichia coli 25,922 strains, which revealed that the material has antimicrobial properties and the cytotoxicity assay indicated that Ce-containing HA was classified as non-toxic. The effects of Ce-HA on bone repair, after application in bone defects in the tibia of female rats with osteoporosis induced by ovariectomy (OVX), were evaluated. After 15 and 30 days of implantation, the samples were analyzed by Raman, histology and X-ray microtomography. The results showed that the animals that had the induced bone defects filled with the Ce-HA materials had more expressive bone neoformation than the control group.
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Regeneration of large bones remains a challenge in surgery. Recent developmental engineering efforts aim to recapitulate endochondral ossification (EO), a critical step in bone formation. However, this process entails the condensation of mesenchymal stem cells (MSCs) into cartilaginous templates, which requires long-term cultures and is challenging to scale up. Here, a biomimetic scaffold is developed that allows rapid and self-sustained EO without initial hypertrophic chondrogenesis. The design comprises a porous chondroitin sulfate cryogel decorated with whitlockite calcium phosphate nanoparticles, and a soft hydrogel occupying the porous space. This composite scaffold enables human endothelial colony-forming cells (ECFCs) and MSCs to rapidly assemble into osteovascular niches in immunodeficient mice. These niches contain ECFC-lined blood vessels and perivascular MSCs that differentiate into RUNX2+ OSX+ pre-osteoblasts after one week in vivo. Subsequently, multiple ossification centers are formed, leading to de novo bone tissue formation by eight weeks, including mature human OCN+ OPN+ osteoblasts, collagen-rich mineralized extracellular matrix, hydroxyapatite, osteoclast activity, and gradual mechanical competence. The early establishment of blood vessels is essential, and grafts that do not contain ECFCs fail to produce osteovascular niches and ossification centers. The findings suggest a novel bioengineering approach to recapitulate EO in the context of human bone regeneration.
Article
Bone graft materials have mixed effects of bone repair in the field of oral maxillofacial surgery. The qualitative analyses performed by previous studies imply that autogenous odontogenic materials and autogenous bone have similar effects on bone repair in clinical jaw bone transplantation. This retrospective systematic assessment and network meta-analysis aimed to analyze the best effect of clinical application of autogenous odontogenic materials and autogenous, allogeneic, and xenogeneic bone grafts in bone defect repair. A systematic review was performed by searching the PubMed, Cochrane Library, and other journal databases using selected keywords and Medical Subject Headings search terms. 10 Papers (n = 466) that met the inclusion criteria were selected. The assessment of heterogeneity did not reveal any overall statistical difference or heterogeneity (P = 0.051 > 0.05), whereas the comparison between autogenous and allogeneic bone grafts revealed local heterogeneity (P = 0.071 < 0.1). Risk of bias revealed nine unclear studies and one high-risk study. The overall consistency was good (P = 0.065 > 0.05), and the local inconsistency test did not reveal any inconsistency. The publication bias was good. The confidence regarding the ranking of bone graft materials after GRADE classification was moderate. The effects on bone repair in the descending order were as follows: autogenous odontogenic materials, xenogeneic bone, autogenous bone, and allogeneic bone. This result indicates that the autogenous odontogenic materials displayed stronger effects on bone repair compared to other bone graft materials. Autogenous odontogenic materials have broad development prospects in oral maxillofacial surgery.
Article
In this study, the osteo‐inductive potential of Prunus amygdalus dulcis (SA) extract that loaded with different concentrations in poly‐ε‐Caprolactone/gelatin (PCL/GEL) nanofibrous scaffolds was investigated. The morphology and composition of nanofibers were evaluated using field emission scanning electron microscope and FT‐IR spectroscopy. Mechanical properties, hydrophilicity and pore structures were determined by tensile test, contact angle, and N2 adsorption–desorption isotherm, respectively. By incorporation of SA extract into PCL/GEL nanofibers, mechanical capabilities as well as their physical qualities were improved. The response of human dental pulp stem cells on prepared scaffolds were studied using MTT assay, alkaline phosphatase activity, alizarin red assay, and quantitave real‐time PCR analysis. The SA loaded nanofibers presented excellent cell attachment and enhanced osteoblast proliferation and mineralization compared to the pristine PCL/GEL nanofibers. The analysis revealed the addition SA extract to PCL/GEL nanofibers increased the expression of osteogenic genes significantly. According to our findings, PCL/GEL/SA nanofibers show a lot of potential for bone tissue engineering. Prunus amygdalus dulics extract loaded PCL‐Gel nanofibrous scaffold induced osteogenic diferentioation of human dental pulp stem cells.
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Background and Objectives: Guided bone regeneration (GBR) surgeries are used for dental implant placements with insufficient bone volume. Biomaterials used in GBR are expected to produce sufficient volume and quality of bone swiftly. This study aims to histologically evaluate the effectiveness of the use of Hyalonect membranes alone or with autogenous grafts in intraosseous defects. Materials and Methods: This study is an experimental study on sheep. Surgeries were performed under general anesthesia in accordance with ethical rules. Five 10 mm defects were surgically created in each ilium of six sheep. One defect was left empty in each ilium (group ED). The defects in the experimental group were covered with Hyalonect membrane while unfilled (group HY) or after being filled with autogenous bone grafts (ABG) (group G+HY). In the control group, the defects were either covered with collagen membrane while unfilled (group CM) or after being filled with the ABG group (G+CM). The sheep were histologically and histomorphometrically evaluated after being postoperatively sacrificed in the third and sixth week (three animals in each interval). Results: All animals completed the study without any complications. No difference was found between groups in the third and sixth weeks regarding the inflammation, necrosis, and fibrosis scores. The G+CM (52.83 ± 3.06) group was observed to have a significantly higher new bone formation rate than all the other groups in the third week, followed by the G+HY group (46.33 ± 2.25). Similar values were found for HY and CM groups (35.67 ± 4.55 ve 40.00 ± 3.41, respectively, p = 0.185), while the lowest values were observed to be in group ED (19.67 ± 2.73). The highest new bone formation was observed in group G+CM (82.33 ± 4.08) in the sixth week. There was no difference in new bone formation rates between groups G+CM, G+HY (77.17 ± 3.49, p = 0.206), and CM (76.50 ± 2.43, p = 0.118). The insignificant difference was found ED group and group HY (55.83 ± 4.92, 73.50 ± 3.27, respectively, p = 0.09). The residual graft amount in the G+CM group was found to be statistically significant at 3 weeks (p = 0.0001), compared to the G+HY group, and insignificantly higher at the 6th week (p = 0.4). Conclusions: In this study, close values were observed between G+HY and G+CM groups. Further experimental and clinical studies with different graft materials are required to evaluate the effectiveness of HY in GBR.
Article
Surface modification of various materials using ultraviolet (UV) irradiation improves their wettability. The purpose of this study was to investigate the wettability of a β-tricalcium phosphate (TCP) surface and the composition changes and bioactivity of β-TCP after UV irradiation. We applied 172 nm UV treatment to a β-TCP surface and measured the contact angle before and after UV irradiation. Energy-dispersive X-ray and Fourier transform infrared spectroscopy examinations were performed on the β-TCP disk with or without UV treatment. In an adhesion test of bone marrow cells using β-TCP disks with and without UV irradiation, cell attachment was measured 10, 30, 50, and 70 h after β-TCP insertion. UV-irradiated β-TCP osteogenesis and absorption of bone substitutes were evaluated using hematoxylin and eosin and tartrate-resistant acid phosphatase (TRAP) staining in a rabbit sinus model. The contact angle on the TCP surface decreased from 70° to 10° owing to UV irradiation. Conversely, UV irradiation did not change the composition of carbon, oxygen, and phosphorus. In the cell adhesion test, UV-irradiated β-TCP significantly increased cell adhesion compared with UV-unirradiated β-TCP after 10 to 30 h of culture. In the rabbit sinus model, TRAP staining showed that UV-irradiated β-TCP significantly increased the number of TRAP-positive cells compared with unirradiated β-TCP granules in the central part of β-TCP. Our results indicate that the UV irradiation of β-TCP improves its clinical utility for surgical bone augmentation in the oral and maxillofacial region.
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An excellent combination of biomaterials permits prompt features and high-throughput investigations in various fields, particularly in the biomedical applications. This article investigates the bone regeneration ability and compatibility of the Gold (Au) Nanoparticles (NPs) medicated carbon nanotube reinforced hydroxyapatite (HAP) composite. The morphologies of the synthesized Au NPs, HAP and HAP/CNT, and HAP/CNT-Au composites vary suggestively with modifying the components and the final composite showing as bone mimic extracellular matrix morphology. The structure, phase, and composition of the as-synthesized HAP were studied by FTIR, XRD, EDAX, and TEM techniques. The materials' biocompatibility was investigated in the Stimulated Body Fluid (SBF) solution, which resulted in the composite having good biocompatibility, bioactivity nature and hydroxyapatite layer formed on the composite surface. The composite shows good viability with Adipose Tissue-derived Stem Cells (ADSC) to cell growth and cell proliferation in the biological evaluation. It represented the composites having a good ability for cell formation development. Since the HAP/CNT-Au composite are useful in medicinal applications such as orthopedic and orthodontic repair/regenerations after the evaluations of animal and clinical investigations.
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Background: Bone deficiency and soft tissue atrophy in the absence of maxillary lateral incisors are among the most challenging problems for implant clinicians. Autologous bone grafting is the gold standard for bone augmentation, but not without limitations. Platelet-rich fibrin (PRF), a biodegradable autologous biomaterial, has been widely used for bone and soft tissue management. Moreover, titanium plate is an advantageous barrier due to its good space-maintaining ability. However, there is a lack of literature on implant site development using titanium plate and PRF for congenitally missing maxillary lateral incisors. Case summary: The patient was a 19-year-old girl with a congenitally missing tooth (#12). She underwent implant placement and simultaneous autologous bone grafting with titanium plate and PRF. At the follow-up visit 15 d post-procedure, the vascularization of soft tissue was visible. There was no swelling or pain after the surgery. Six months postoperatively, bone regeneration was evident. Subsequently, the definitive restoration was placed, and the patient was satisfied with the esthetic outcomes. Conclusion: Implant site development using titanium plate and PRF for congenitally missing maxillary lateral incisors is a feasible procedure. In this case, the labial bone plate was displaced but remained connected to the base bone, ensuring blood supply. The titanium plate fixed the labial bone plate and maintained the osteogenic space, while the PRF provided growth factors and leukocytes for bone and soft tissue regeneration. Furthermore, the procedure reduced the surgical complexity and adverse reactions, displaying outstanding esthetic outcomes.
Article
In this research, sodium alginate-pectin composite (ALG-PEC CS) and nanocomposites (NCs) films with 0.5, 1, and 2 wt% TiO2 nanoparticles (NPs) were prepared using CaCl2 and glutaraldehyde (Glu) as cross-linkers. The cross-linking produces rigid scaffolds for sedimentation of hydroxyapatite (HA), it can also decrease solubility in water and simulated body fluid (SBF) solution to 10% or less. The increase of the adsorbed water and SBF extends the pores and consequently the surface area for HA growth. Bioactive ability was confirmed via HA's presence on the all films. It was revealed that the film containing 2 wt% TiO2 NPs had the best bioactivity without any in vitro cytotoxicity on MG-63 cell line and the best antibacterial performance against Staphylococcus aureus, and after 1 h all the bacteria were killed.
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Objectives: This study evaluated the cellular response of primary osteoblasts exposed to two different presentations of a low-temperature non-sintered deproteinized bovine bone matrix (DBBM). Materials and methods: Six different baths of a commercially available DBBM block (Bonefill® Porous Block) and one of DBBM granule (Bonefill® Porous) were evaluated to identify the mineral structure and organic or cellular remnants. Samples of the same baths were processed in TRIZOL for RNA extraction and quantification. For the immunologic cell reaction assay, primary human osteoblasts (pOB) were exposed to DBMM block (pOB + B) or granules (pOB + G), or none (control) for 1, 3, or 7 days of cell cultivation. Expression of proinflammatory cytokines by pOB was evaluated by crosslinked ELISA assay. In addition, total DNA amount, as well as cell viability via LDH evaluation, was assessed. Results: Organic remnants were present in DBBM blocks; 45.55% (±7.12) of osteocytes lacunae presented cellular remnants in blocks compared to 17.31% (±1.31) in granules. In three of five batches of blocks, it was possible to isolate bovine RNA. The highest concentration of TGF-β1 was found in supernatants of pOB + G on day 7 (218.85 ± 234.62 pg/mL) (p < 0.05), whereas pOB + B presented the lowest amount of TGF-β1 secretion at the end of evaluation (30.22 ± 14.94 pg/mL, p < 0.05). For IL-6 and OPG, there was no statistical difference between groups, while pOB + G induced more IL-8 secretion than the control (3.03 ± 3.38 ng/mL, p < 0.05). Considering the kinetics of cytokine release during the study period, all groups presented a similar pattern of cytokines, estimated as an increasing concentration for IL-6, IL-8, and OPG during cultivation. Adherent cells were observed on both material surfaces on day 7, according to H&E and OPN staining. Conclusion: Neither tested material induced a pronounced inflammatory response upon osteoblast cultivation. However, further studies are needed to elucidate the potential influence of organic remnants in bone substitute materials on the regeneration process.
Chapter
Biocomposites for medical applications manufactured from natural or man-made fibers are used to replace living tissues of the human body directly or indirectly. Health care expectations in terms of efficiency and sustainability are greater than ever before due to the rise in the life expectancy of the world’s population. Biocomposites in the form of devices such as biosensors, pacemakers, and artificial hearts are widely used to restore the function of and/or replace organs or regenerate tissues, to assist in healing, to correct abnormalities, and to improve the quality of life of the patients. Scientists have also focused on the production of medical equipment, the development of modern biomaterials, and new manufacturing methods and techniques. The choice of the proper material to be used is of paramount importance in the development of a medical device, as its properties and ability to fulfill the expected function will determine the success of the medical device itself. This chapter details the applications of biocomposites for biomedical devices.
Article
Aims: The aim of this study was to evaluate the cultural, psychological, and religious influences on the choice of autografts, allografts, xenografts, and synthetic bone products for the grafting procedure and with implant placement. Materials and methods: A qualitative methodology was employed, using the principles of the constant comparative method of the grounded theory; to investigate how people perceive and understand their experiences regarding the graft materials in implant dentistry. The data were collected using detailed qualitative interviews, till saturation was achieved, from 10 patients. Results: The three main themes that emerged in the analysis were: (a) grafting material preference, (b) religious and psychological influences, and (c) trust the doctor and cost influences. The three themes that emerged seemed to be interrelated. There were many statements of preference or rejection of choice based on religious, cultural, and psychological influences. Conclusions: Within the limitations of this study, three themes emerged and they indicated that the influence on the grafting material's choice is unique to every individual; it also shares similarities, based on common religious and cultural values.
Chapter
The need for bone replacement is not new and traverses many surgical specialties. Historically, autogenous reconstructive bone grafts obtained from the patient being treated were the preferred regenerative material, and their reconstructive properties remain the standard by which other materials are measured. The availability of autogenous grafts can be limited though, and harvesting bone carries with it varying degrees of morbidity and risk of complication. However, technological advances in the processing of biomaterials have significantly improved the properties of alternative osseous reconstructive options. This chapter focuses on available bone substitute materials and their intrinsic properties to aid the practitioner in selective clinical use.
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Surgery often leads to massive destruction of the skeleton. Cell-based bone reconstruction therapies promise new therapeutic opportunities for the repair of bone. Embryonic stem cells (ESCs) can be differentiated into osteogenic cells and are a potential cell source for bone tissue engineering. The purpose of this in vivo study was to investigate the bone formation in various constructs containing ESCs (with and without micromass technology) and insoluble collagenous bone matrix (ICBM). Murine ESCs were cultured as monolayer cultures as well as micromasses and seeded on ICBM. These constructs were implanted in immunodeficient rats. After one week, one, two and three months CT-scans were performed to detect any calcifications and the rats were sacrificed. The radiological examination shows a steep increase of the mineralized tissue in group 1 (ICBM+seeded ESC). This increase can be considered as statistical significant. In contrast, the volume of the mineralization in group 2 (ICBM+ESC-spheres) and group 3 (ESC-spheres) does not increase significantly during the study. ESCs in combination with ICBM do promote ectopic bone formation in vivo. Thus, this cell population as well as the biomaterial ICBM might be promising components for bone tissue engineering.
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By targeting dendritic cells, polymeric carriers in the nano to lower micron range constitute very interesting tools for antigen delivery. In this critical review, we review how new immunological insights can be exploited to design new carriers allowing one to tune immune responses and to further increase vaccine potency (137 references).
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A chitosan/marine-originated collagen composite has been developed. This composite gel was characterized and its biocompatibility, as well as an inflammatory reaction, was observed. The chitosan gel including N-3-carboxypropanoil-6-O-(carboxymethyl) chitosan of 3 mol%, 6-O-(carboxymethyl) chitosan of 62 mol% and 6-O-(carboxymethyl) chitin of 35 mol% was prepared and compounded with the salmon atelocollagen (SA) gel at different mixture ratios. The composite gels were injected subcutaneously in to the back of rats. The specimens were harvested for a histological survey as well as a tumor necrosis factor-alpha (TNF-α) assay by ELISA. The inflammatory cell infiltration and release of TNF-α were successively controlled low with the ratio of SA to chitosan at 10:90 or 20:80. The SA gel first, within 2 weeks, and then chitosan in the composite gel were slowly absorbed after implantation, followed by soft tissue formation. It is expected that this composite gel will be available as a carrier for tissue filler and drug delivery systems.
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Cell-based reconstruction therapies promise new therapeutic opportunities for bone regeneration. Unrestricted somatic stem cells (USSC) from cord blood and embryonic stem cells (ESCs) can be differentiated into osteogenic cells. The purpose of this in vivo study was to compare their ability to induce ectopic bone formation in vivo. Human USSCs and murine ESCs were cultured as both monolayer cultures and micromasses and seeded on insoluble collagenous bone matrix (ICBM). One week and 1, 2, and 3 months after implanting the constructs in immune-deficient rats, computed tomography scans were performed to detect any calcification. Subsequently, the implanted constructs were examined histologically. The radiological examination showed a steep increase in the mineralized bone-like tissue in the USSC groups. This increase can be considered as statistically significant compared to the basic value. Moreover, the volume and the calcium portion measured by computed tomography scans were about 10 times higher than in the ESC group. The volume of mineralization in the ESC group increased to a much smaller extent over the course of time, and the control group (ICBM without cells) showed almost no alterations during the study. The histological examinations parallel the radiological findings. Cord blood stem cells in combination with ICBM-induced ectopic bone formation in vivo are stronger than ESCs.
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Modern cell-based bone reconstruction therapies offer new therapeutic opportunities and tissue engineering represents a more biological-oriented approach to heal bone defects of the skeleton. Human unrestricted somatic stem cells (USSCs) derived form umbilical cord blood offer new promising aspects e.g., can differentiate into osteogenetic cells. Furthermore these cells have fewer ethical and legal restrictions compared to embryonic stem cells (ESCs). The purpose of this study was to evaluate the compatibility of osteogenic pre-differentiated USSCs with various biomaterials and to address the question, whether biomaterials influence the process of differentiation of the USSCs. After osteogenic differentiation with DAG USSCs were cultivated with various biomaterials. To asses the biocompatibility of USSCs the attachment and the proliferation of the cells on the biomaterial were measured by a CyQUANT(®) assay, the morphology was analyzed by scanning electron microscopy and the influence of the gene expression was analyzed by real time PCR. Our results provide evidence that insoluble collagenous bone matrix followed by β-tricalciumphosphate is highly suitable for bone tissue engineering regarding cell attachment and proliferation. The gene expression analysis indicates that biomaterials influence the gene expression of USSCs. These results are in concordance with our previous study with ESCs.
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The aim of the present study was to analyze the osteogenic potential of a biphasic calcium composite material (BCC) with a negative surface charge for maxillary sinus floor augmentation. In a 61 year old patient, the BCC material was used in a bilateral sinus floor augmentation procedure. Six months postoperative, a bone sample was taken from the augmented regions before two titanium implants were inserted at each side. We analyzed bone neoformation by histology, bone density by computed tomography, and measured the activity of voltage-activated calcium currents of osteoblasts and surface charge effects. Control orthopantomograms were carried out five months after implant insertion. The BCC was biocompatible and replaced by new mineralized bone after being resorbed completely. The material demonstrated a negative surface charge (negative Zeta potential) which was found to be favorable for bone regeneration and osseointegration of dental implants.
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Several grafting materials have been used in sinus augmentation procedures including autogenous bone, demineralized freeze-dried bone (DFDBA), hydroxyapatite, beta-tricalcium phosphate (beta-TCP), anorganic deproteinized bovine bone and combination of these and others. Up to now a subject of controversy in maxillofacial surgery and dentistry is, what is the most appropriate graft material for sinus floor augmentation. The aim of this study is to provide a body of evidence-based data regarding grafting materials in external sinus floor elevation concerning the fate of the augmented material at the histomorphological level, through a meta-analysis of the available literature. The literature searches were performed using the National Library of Medicine. The search covered all English and German literature from 1995 until 2006. For analyzing the amount of bone the parameter "Total Bone Volume" (TBV) was assessed. TBV is determined as the percentage of the section consisting of bone tissue. In a relatively early phase after implantation the autogenous bone shows the highest TBV values. Interestingly, the different TBV levels approximate during the time. After 9 months no statistically significant differences can be detected between the various grafting materials. From a clinical point of view, the use of autogenous bone is advantageous if a prosthetic rehabilitation (with functional loading) is expected within 9 months. In other cases the use of anorganic deproteinized bovine bone in combination with autogenous bone seems to be preferable. Donor side morbidity is ignored in this conclusion.
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We have evaluated the use of a synthetic porous ceramic (Triosite) as a substitute for bone graft in posterior spinal fusion for idiopathic scoliosis. In a prospective, randomised study 341 patients at five hospitals in the UK and France were randomly allocated either to autograft from the iliac crest or rib segments (171) or to receive Triosite blocks (170). All patients were assessed after operation and at 3, 6, 12 and 18 months. The two groups were similar with regard to all demographic and baseline variables, but the 184 treated in France (54%) had Cotrel-Dubouset instrumentation and the 157 treated in the UK usually had Harrington-Luque implants. In the Triosite group the average Cobb angle of the upper curve was 56°, corrected to 24°(57%). At 18 months, the average was 26°(3% loss). In the autograft group the average preoperative upper curve of 53°was corrected to 21°(60%). At 18 months the mean curve was 25°(8% loss). Pain levels after operation were similar in the two groups, being mild in most cases. In the Triosite group only three patients had problems of wound healing, but in the autograft group, 14 patients had delayed healing, infection or haematoma in the spinal wound. In addition, 15 autograft patients had pain at the donor site at three months. Seven had infections, two had haematoma and four had delayed healing. The haematological and serum biochemistry results showed no abnormal trends and no significant differences between the groups. There were no adverse events related to the graft material and no evidence of allergenicity, Our results suggest that Triosite synthetic porous ceramic is a safe and effective substitute for autograft in these patients. Histological findings on biopsy indicate that Triosite provides a favourable scaffolding for the formation of new bone and is gradually incorporated into the fusion mass.
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In seven Goettingen minipigs 3.5–4.7-ml cancellous bone defects were created in the area of the tibial head on both sides. The defects were filled with α-TCP or β-TCP (tricalciumphosphate). ITI implants (Straumann, Freiburg, Germany) of 3.2 × 12-mm length were inserted into the underlying ceramic substitutes. Two additional pigs were used as control. Within the periods of observation (4, 16, 20, 28, 46, 68, and 86 weeks) fluorescent dyes were applied. Nondecalcified thin-sliced sections were examined by means of light and fluorescence microscopy. In addition microangiography and microradiography were performed. Bony regeneration occurred basally and on the sides of the defect according the angiogenetic reossification pattern. Resorption was due to a hydrolytic and cellular degradation process. After 46 weeks histomorphological evaluation showed an incomplete osseointegration of the simultaneously implanted dental implants. The bone contact surface ratio was lower than 25%. After 86 weeks 95–97% of both α- and β-TCP were resorbed. Ceramic residuals stayed within the newly formed trabeculae thus resisting further degradation until remodeling occurred. Both α- and β-TCP show a comparable degradation process. At the 86-week postoperative point only small residuals of the ceramic can be found. These residuals stay within the newly formed trabeculae, which show a functional orientation. In comparison control defects showed only sparse reossification. The β-TCP material shows an accelerated degradation mode and has an optimal reactivity with the surrounding tissues. According to the results of this animal experiment both materials can be classified as bone-rebuilding materials. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 115–121, 2002; DOI 10.1002/jbm.10084
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In different animal investigations Pyrost demonstrated osteoconductive and osteostimulative effects. In ectopic tissues and especially in conditions of low osteogenetic potency, the combination of Pyrost and autogenic bone marrow effects bone formation. In a clinical prospective study, Pyrost was implanted in 1117 cases in the following indications: Donor site defects after bone transplantation, bone defects after tumor resection, revision of THA, acetabuloplasty, fracture treatment, pseudarthrosis and lengthening osteotomy, spondylodesis. In 87.3% the regeneration of the bone defects was complete, in 8% a partial regeneration was found. Excessive bone formation took place in 2.7%, insufficient regeneration in 2.0% in cases of instability or infection. According to the clinical results Pyrost is a suitable bone substitute in small bone defects and it is a valuable completion to the autogenic bone graft in large defects. In disadvantageous bone bed Pyrost has to be augmented with bone marrow and in large segmental defects the combination with autogenic bone grafts is recommendable. Presupposition for the application of bone substitutes like Pyrost in large defects is a sufficiant primary stability of the bone bed. The application in infected tissue is not favorable.
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Zur Behandlung angeborener oder erworbener Knochendefekte stehen als Alternativen zur Knochentransplantation eine Vielzahl verschiedener Knochenersatzmaterialien zur Verfügung.Komplikationen bei der Gewinnung autogenen Knochens, die begrenzte Verfügbarkeit und die Gefahr der Übertragung von Krankheitserregern förderten die Entwicklung einer Vielzahl von Knochenersatzmaterialien zur Minimierung dieser Probleme. Der vorliegende Artikel soll einen Überblick über die auf dem Markt erhältlichen Produkte geben.Neben anorganischen Materialien wie Keramiken aus Hydroxylapatit und/oder Tricalciumphosphat,“Calciumphosphatzemente”, Calciumsulfate und Biogläser werden organische Materialien (Polymere) und Komposite,Xenografts und Glas-Ionomer-Zemente vorgestellt.
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Bioactive implants are promising tools in regenerative medicine. Here we describe a versatile procedure for preparing a gene-activated matrix on titanium. Lyophilized copolymer-protected gene vectors (COPROGs) suspended in poly(d,l-lactide) (PDLLA) solutions in ethyl acetate were used to varnish solid surfaces. The gene-activated PDLLA surfaces were first established on polypropylene 96-well plates. Vector release from these surfaces in aqueous buffer, cell viability and gene transfer efficiency to NIH 3T3 fibroblasts was strongly dependent on the vector dose and its ratio to PDLLA film thickness. A detailed analysis of these relationships allowed establishing correlations which can be used to calculate suitable combinations of COPROGs and PDLLA yielding optimal gene transfer efficiency. This was verified with COPROG-activated PDLLA coatings on titanium foils. HEK 293 and mesenchymal stem cells expressed the BMP-2 gene comprised in the gene-activated surface in a manner that was consistent with the predicted dose-response and toxicity profiles found in NIH 3T3 cells. The systematic procedure presented here for identifying optimal coating compositions can be applied to any combination of vector type and coating material.
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In different animal investigations Pyrost demonstrated osteoconductive and osteostimulative effects. In ectopic tissues and especially in conditions of low osteogenetic potency, the combination of Pyrost and autogenic bone marrow effects bone formation. In a clinical prospective study, Pyrost was implanted in 1117 cases in the following indications: Donor site defects after bone transplantation, bone defects after tumor resection, revision of THA, acetabuloplasty, fracture treatment, pseudarthrosis and lengthening osteotomy, spondylodesis. In 87.3% the regeneration of the bone defects was complete, in 8% a partial regeneration was found. Excessive bone formation took place in 2.7%, insufficient regeneration in 2.0% in cases of instability or infection. According to the clinical results Pyrost is a suitable bone substitute in small bone defects and it is a valuable completion to the autogenic bone graft in large defects. In disadvantageous bone bed Pyrost has to be augmented with bone marrow and in large segmental defects the combination with autogenic bone grafts is recommendable. Presupposition for the application of bone substitutes like Pyrost in large defects is a sufficient primary stability of the bone bed. The application in infected tissue is not favorable.
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A focused library of methacrylate terpolymers was synthesized to explore the effects of varying surface chemistry and adhesive peptide ligands on cell function. The chemical diversity of methacrylate monomers enabled construction of a library of polymers in which one can systematically vary the chemical composition to achieve a wide range of contact angle, Young's modulus, and T(g) values. Furthermore, the materials were designed to allow surface immobilization of bioactive peptides. We then examined the effects of these material compositions on protein adsorption and cell attachment, proliferation, and differentiation. We observed that chemical composition of the polymers was an important determinant for NIH 3T3 cell attachment and proliferation, as well as human mesenchymal stem cell differentiation, and correlated directly with the ability of the polymers to adsorb proteins that mediate cell adhesion. Importantly, functionalization of the methacrylate terpolymer library with an adhesive GRGDS peptide normalized cellular responses. RGD-functionalized polymers uniformly exhibited robust attachment, proliferation, and differentiation irrespective of the underlying substrate chemistry. These studies provide a library-based approach to rapidly explore the biological functionality of biomaterials with a wide range of compositions and highlight the importance of cell and protein cell adhesion in predicting their performance.
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We report a simple and novel top-down method based on a drop-casting process for the controlled synthesis of all-bone-minerals biomimetic multicomponent bionanocomposites. Integration of micro- and nanoscale binary features into nanofibrous biocompatible polymer scaffold structures is successfully demonstrated. Compositional control of the constituents of the bionanocomposites resulted in uniform dispersion of hydroxyapatite nanospheres (~100-500 nm) among collagen nanofibers (~100 nm). The composites also present high calcium and oxygen contents and adequate phosphorus compositions comparable to the levels of bone tissues. Our preliminary results open up further possibilities to develop advanced tissue-engineered bionanocomposites for bone grafting.
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A review of the various coral bone graft substitutes currently available for experimental and biomedical applications and ongoing investigations of coral derived bone replacement materials is presented here. Natural and synthetic graft materials that have been studied in vitro and in vivo and used in different medical procedures in osseous tissue have focused mainly on freeze-dried bone, hydroxyapatite (HA), tricalcium phosphate (TCP) and coral. Coralline hydroxyapatite (CHA) is manufactured from marine coral, which has a natural trabecular structure similar to that of bone, by the hydrothermal conversion of the calcium carbonate skeleton of coral to hydroxyapatite, a calcium phosphate. While many studies have demonstrated promising biocompatible properties and osteogenic results, as a bone graft substitute and bone void filler, the use of CHA may be limited owing to its inherent mechanical weakness and reduced biodegradation. The benefits of CHA as bone graft are predominantly its safety, biocompatibility and osteoconductivity so that it can be used as a substitution biomaterial for bone in many indications clinically. CHA can also be used as an efficient carrier system for the local delivery of growth factors to enhance osteointegration and implant fixation into peri-implant osseous tissue.
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Preventing ridge collapse with the extraction of maxillary anterior teeth is vital to an esthetic restorative result. Several regenerative techniques are available and are used for socket preservation. The aim of this study is to analyze by clinical parameters the use of acellular dermal matrix (ADM) and anorganic bovine bone matrix (ABM) with synthetic cell-binding peptide P-15 to preserve alveolar bone after tooth extraction. Eighteen patients in need of extraction of maxillary anterior teeth were selected and randomly assigned to the test group (ADM plus ABM/P-15) or the control group (ADM only). Clinical measurements were recorded initially and at 6 months after ridge-preservation procedures. In the clinical measurements (external vertical palatal measurement [EVPM], external vertical buccal measurement [EVBM], and alveolar horizontal measurement [AHM]) the statistical analysis showed no difference between test and control groups initially and at 6 months. The intragroup analysis, after 6 months, showed a statistically significant reduction in the measurements for both groups. In the comparison between the two groups, the differences in the test group were as follows: EVPM = 0.83 ± 1.53 mm; EVBM = 1.20 ± 2.02 mm; and AHM = 2.53 ± 1.81 mm. The differences in the control group were as follows: EVPM = 0.87 ± 1.13 mm; EVBM = 1.50 ± 1.15 mm; and AHM = 3.40 ± 1.39 mm. The differences in EVPM and EVBM were not statistically significant; however, in horizontal measurement (AHM), there was a statistically significant difference (P<0.05). The results of this study show that ADM used as membrane associated with ABM/P-15 can be used to reduce buccal-palatal dimensions compared to ADM alone for preservation of the alveolar ridge after extraction of anterior maxillary teeth.
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The aim of this randomized, controlled clinical trial was to compare the potential of a synthetic bone substitute or a bovine-derived xenograft combined with a collagen membrane to preserve the alveolar ridge dimensions following tooth extraction. Twenty-seven patients were randomized into two treatment groups following single tooth extraction in the incisor, canine and premolar area. In the test group, the alveolar socket was grafted with Straumann Bone Ceramic (SBC), while in the control group, Bio-Oss deproteinized bovine bone mineral (DBBM) was applied. In both groups, a collagen barrier was used to cover the grafting material. Complete soft tissue coverage of the barriers was not achieved. After 8 months, during re-entry procedures and before implant placement, the horizontal and vertical dimensions of the residual ridge were re-evaluated and trephine biopsies were performed for histological analysis in all patients. Twenty-six patients completed the study. The bucco-lingual dimension of the alveolar ridge decreased by 1.1+/-1 mm in the SBC group and by 2.1+/-1 in the DBBM group (P<0.05). Both materials preserved the mesio-distal bone height of the ridge. No differences in the width of buccal and palatal bone plate were observed between the two groups. The histological analysis showed new bone formation in the apical part of the biopsies, which, in some instances, was in direct contact with both SBC and DBBM particles. The coronal part of the biopsies was occupied by a dense fibrous connective tissue surrounding the SBC and DBBM particles. Both biomaterials partially preserved the width and the interproximal bone height of the alveolar ridge.
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The most promising attempts to achieve bone regeneration artificially are based on the application of mediators such as bone morphogenetic proteins (BMPs) directly to the deficient tissue site. BMPs, as promoters of the regenerative process, have the ability to induce de novo bone formation in various tissues, and many animal models have demonstrated their high potential for ectopic and orthotopic bone formation. However, the biological activity of the soluble factors that promote bone formation in vivo is limited by diffusion and degradation, leading to a short half-life. Local delivery remains a problem in clinical applications. Several materials, including hydroxyapatite, tricalcium phosphate, demineralised bone matrices, poly-lactic acid homo- and heterodimers, and collagen have been tested as carriers and delivery systems for these factors in a sustained and appropriate manner. Unfortunately these delivery vehicles often have limitations in terms of biodegradability, inflammatory and immunological rejection, disease transmission, and most importantly, an inability to provide a sustained, continuous release of these factors at the region of interest. In coping with these problems, new approaches have been established: genes encoding these growth factor proteins can be delivered to the target cells. In this way the transfected cells serve as local "bioreactors", as they express the exogenous genes and secrete the synthesised proteins into their vicinity. The purpose of this review is to present the different methods of gene versus growth factor delivery in tissue engineering. Our review focuses on these promising and innovative methods that are defined as regional gene therapy and provide an alternative to the direct application of growth factors. Various advantages and disadvantages of non-viral and viral vectors are discussed. This review identifies potential candidate genes and target cells, and in vivo as well as ex vivo approaches for cell transduction and transfection. In explaining the biological basis, this paper also refers to current experimental and clinical applications.
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We developed a composite biphasic calcium phosphate (BCP) scaffold by coating a nanocomposite layer, consisting of hydroxyapatite (HA) nanoparticles and polycaprolactone (PCL), over the surface of BCP. The effects of HA particle size and shape in the coating layer on the mechanical and biological properties of the BCP scaffold were examined. Micro-computerized tomography studies showed that the prepared scaffolds were highly porous (approximately 91%) with large pore size (400-700 microm) and an interconnected porous network of approximately 100%. The HA nanoparticle (needle shape)-composite coated scaffolds displayed the highest compressive strength (2.1 +/- 0.17 MPa), compared to pure HA/beta-TCP (0.1 +/- 0.05 MPa) and to the micron HA - composite coated scaffolds (0.29 +/- 0.07 MPa). These needle shaped scaffolds also showed enhanced elasticity and similar stress-strain profile to natural bone. Needle shaped coated HA/PCL particles induced the differentiation of primary human bone derived cells, with significant upregulation of osteogenic gene expression (Runx2, collagen type I, osteocalcin and bone sialoprotein) and alkaline phosphatase activity compared to other groups. These properties are essential for enhancing bone ingrowth in load-bearing applications. The developed composite scaffolds possessed superior physical, mechanical, elastic and biological properties rendering them potentially useful for bone tissue regeneration.
Article
New approaches to enhance vertical bone regeneration in clinically relevant implant models are needed. Therefore, we analyzed the impact of recombinant human bone morphogenic protein 2 (rhBMP-2) on the healing of large buccal alveolar defects during osseointegration of transgingivally inserted implants. Twenty-four dental implants were inserted transgingivally in the mandibles of 6 labrador/golden retriever cross-bred dogs. Before implantation, a standardized buccal bone defect was created and refilled with either calcium phosphate as a carrier containing rhBMP-2 or calcium phosphate alone. Either ceramic abutments that enabled immediate implant loading or healing distance collars to prevent loading were mounted. Sixteen weeks after intervention, bone implant units were analyzed by radiofrequency analysis and histomorphometry. In total, 14 implants (58.3%) were available for further analysis. The mean depth of the bone defects, the gain of regenerated bone, the vertical osseointegration of the implants, and the bone-to-implant contact in the newly formed bone were slightly greater in the rhBMP-2-containing samples. In contrast, the osseointegration in the preexisting bone was even superior within the non-rhBMP-2-treated specimen. However no differences were statistically significant. When rhBMP-2-conducted bone regeneration was compared with control samples, no significant differences of newly formed bone were found at the bone-implant interface. The amounts of rhBMP-2 applied do not seem suitable to enhance implant osseointegration in large buccal defects.
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A combination of molecular dynamics (MD) simulations and docking calculations was employed to model and predict polymer-drug interactions in self-assembled nanoparticles consisting of ABA-type triblock copolymers, where A-blocks are poly(ethylene glycol) units and B-blocks are low molecular weight tyrosine-derived polyarylates. This new computational approach was tested on three representative model compounds: nutraceutical curcumin, anticancer drug paclitaxel and prehormone vitamin D3. Based on this methodology, the calculated binding energies of polymer-drug complexes can be correlated with maximum drug loading determined experimentally. Furthermore, the modeling results provide an enhanced understanding of polymer-drug interactions, revealing subtle structural features that can significantly affect the effectiveness of drug loading (as demonstrated for a fourth tested compound, anticancer drug camptothecin). The present study suggests that computational calculations of polymer-drug pairs hold the potential of becoming a powerful prescreening tool in the process of discovery, development and optimization of new drug delivery systems, reducing both the time and the cost of the process.
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A novel protocol for the synthesis of biocompatible and degradation controlled poly(lactic-co-glycolic acid) grafted hyaluronic acid (HA-PLGA) was successfully developed for periodontal barrier applications. HA was chemically modified with adipic acid dihydrazide (ADH) in the mixed solvent of water and ethanol, which resulted in a high degree of HA modification up to 85 mol.%. The stability of HA-ADH to enzymatic degradation by hyaluronidase increased with ADH content in HA-ADH. When the ADH content in HA-ADH was higher than 80 mol.%, HA-ADH became soluble in dimethyl sulfoxide and could be grafted to the activated PLGA with N,N'-dicyclohexyl carbodiimide and N-hydroxysuccinimide. The resulting HA-PLGA was used for the preparation of biphasi