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Osteogenesis of a Bioactive Ceramic‐Calcium Phosphosilicate Composite System in Goat Femur Defect
International Journal of Applied Ceramic Technology
Abstract
In spite of the array of synthetic bone grafts available, the pursuit for an ideal graft continues. In view of this, a synthetic bioactive calcium phosphosilicate composite (HABGS) has been developed combining the properties of hydroxyapatite and silicate system. The in vivo performance of HABGS granules in goat femur defect stimulated a favorable environment for de novo bone formation with faster resorption. The ceramic composite is attractive for its low Si content together with its negligible levels at implanted sites and vital organs postimplantation. Herein, we propose the safety and efficacy of this composite as a promising bone substitute.
... The material has an attractively low Si content with negligible levels at implanted sites and vital organs postimplantation. [24] Furthermore, a HASi scaffold loaded with culture-expanded autologous bone marrow-derived mesenchymal stem cells primed into osteogenic lineage was implanted in a 12-year-old child presenting with a post-septic gap non-union of 4 cm in the proximal humerus successfully. [25] a HASi scaffold loaded with culture-expanded autologous bone marrow-derived mesenchymal stem cells primed into osteogenic lineage was implanted in a 12-year-old child presenting with a postseptic gap nonunion of 4 cm in the proximal humerus successfully. ...
Background: Cystic defects that are critical sized or larger require bone replacement strategies. However, due to inherent disadvantages of the various types of grafts, none of the available materials are best suited for these defects. Among the alloplastic materials, hydroxyapatite (HA)-based grafts are the most popular, due to their osteoconductive nature and resemblance to mineral bone. The aim of the study was to assess the utility of the novel material "Chitra-HASi" as a bone substitute in the maxillofacial region. Materials and Methods: In a single-arm, prospective study, patients with radicular and dentigerous cysts were included and the minimum defect size was standardized at 20 × 20 mm or above. The Chitra-HASi material was developed by a wet precipitation technique and adopted for use following multiple in vitro and in vivo studies, confirming its safety and biocompatibility profile. All cysts underwent enucleation, followed by peripheral ostectomy and apicectomy of the teeth involved. The HASi graft was packed inside the cystic defect in a granular form and covered with a mucoperiosteal flap. Panoramic radiographs were taken preoperatively and at 3, 6, and 12 months postoperatively. Results: Twenty-three patients were included in the study, of which only 10 patients could be followed up for 12 months after graft placement. The mean preoperative bone density was found to be 14.9% ± 4.97 (standard deviation), whereas the postoperative 3-month, 6-month, and 12-month densities had a mean difference of −11.3%, −22.9%, and −37.3%, respectively, and the differences were statistically significant. Minor complications such as sinus formation (n = 7) and extrusion of granules (n = 4) were noted, which were managed conservatively. Only two patients required graft removal secondary to infection, leading to a persistent sinus tract. Conclusion: The results of the study suggest that Chitra-HASi granules show potential as an alternative to other bone substitutes. The addition of silica to the porous HA material offers superior strength characteristics and needs long-term evaluation to assess its stability in large cystic defects.
... The material has an attractively low Si content with negligible levels at implanted sites and vital organs postimplantation. [24] Furthermore, a HASi scaffold loaded with culture-expanded autologous bone marrow-derived mesenchymal stem cells primed into osteogenic lineage was implanted in a 12-year-old child presenting with a post-septic gap non-union of 4 cm in the proximal humerus successfully. [25] a HASi scaffold loaded with culture-expanded autologous bone marrow-derived mesenchymal stem cells primed into osteogenic lineage was implanted in a 12-year-old child presenting with a postseptic gap nonunion of 4 cm in the proximal humerus successfully. ...
Background:
Cystic defects that are critical sized or larger require bone replacement strategies. However, due to inherent disadvantages of the various types of grafts, none of the available materials are best suited for these defects. Among the alloplastic materials, hydroxyapatite (HA)-based grafts are the most popular, due to their osteoconductive nature and resemblance to mineral bone. The aim of the study was to assess the utility of the novel material "Chitra-HASi" as a bone substitute in the maxillofacial region.
Materials and methods:
In a single-arm, prospective study, patients with radicular and dentigerous cysts were included and the minimum defect size was standardized at 20 × 20 mm or above. The Chitra-HASi material was developed by a wet precipitation technique and adopted for use following multiple in vitro and in vivo studies, confirming its safety and biocompatibility profile. All cysts underwent enucleation, followed by peripheral ostectomy and apicectomy of the teeth involved. The HASi graft was packed inside the cystic defect in a granular form and covered with a mucoperiosteal flap. Panoramic radiographs were taken preoperatively and at 3, 6, and 12 months postoperatively.
Results:
Twenty-three patients were included in the study, of which only 10 patients could be followed up for 12 months after graft placement. The mean preoperative bone density was found to be 14.9% ± 4.97 (standard deviation), whereas the postoperative 3-month, 6-month, and 12-month densities had a mean difference of -11.3%, -22.9%, and -37.3%, respectively, and the differences were statistically significant. Minor complications such as sinus formation (n = 7) and extrusion of granules (n = 4) were noted, which were managed conservatively. Only two patients required graft removal secondary to infection, leading to a persistent sinus tract.
Conclusion:
The results of the study suggest that Chitra-HASi granules show potential as an alternative to other bone substitutes. The addition of silica to the porous HA material offers superior strength characteristics and needs long-term evaluation to assess its stability in large cystic defects.
Osteoproductive materials that induce quick bone regeneration are needed for the developing area of scaffold-based bone engineering. Bioactive silica-based glasses, ceramics, and hybrids are called to play an important role in this field. Organic-inorganic hybrid materials based on SiO2-modified PDMS-P2O5-CaO are studied in this work. These materials are synthesized by the sol-gel method, and the influence of the composition on the reaction kinetic, obtained porosities, degradation and bioactive behavior, and cytotoxicity is studied. Materials with greater contents in CaO yield faster reaction kinetics and produce porous materials that favor a quicker degradation, whereas with greater P2O5 contents produce denser and more stable materials. The incorporation of CaO and P2O5 up to 5 and 25 % in weight into the SiO2 network, respectively, resulted in an increase of the apatite-forming ability in PBS. None of the studied compositions are cytotoxic, showing cellular viability over 70 % at all times.
This study demonstrates the feasibility of creating stable, preconsolidated, yet permeable preforms
for liquid resin infusion (RIFT) manufacture of composite materials. While being one of the cheapest and simplest methods of composites manufacture, RIFT with flexible tooling is known for high risk of dimensional and internal defects due to insufficient consolidation of textile preforms. Achieving the quality of a rigid mold solution, at the cost and simplicity of a flexible mold process, is the principal challenge of the RIFT.
The approach presented suggests stabilizing a compliant preform through pointwise and highly controlled integration of a binder, and its consolidation prior to liquid molding. The printed resin creates a stiff skeleton, securing material for resin infusion and curing. This study explores the feasibility and efficiency of novel binding techniques, and the effects it may have on preform properties. Successful implementation of the concept for a multiply woven preform is demonstrated and the concept potential is discussed.
A quantitative and qualitative investigation of the sol-gel derived bioactive glass-ceramic system (BGS)-apatite-wollastonite (AW) type granules in the size range of 0.5-1 mm was performed. Scanning electron micrographs (SEM) of the sintered granules revealed the rough material surface with micropores in the range 10-30 μm. X-ray diffraction (XRD) pattern of the granules revealed the presence of crystalline phases of the hydroxyapatite and wollastonite, and the functional groups of the silicate and phosphates were identified by Fourier transform infrared spectroscopy (FT-IR).
Phase pure hydroxyapatite (HA) and a 0.8 wt % silicon substituted hydroxyapatite (SiHA) were prepared by aqueous precipitation methods. Both HA and SiHA were processed into granules 0.5-1.0 mm in diameter and sintered at 1200 degrees C for 2 h. The sintered granules underwent full structural characterization, prior to implantation into the femoral condyle of New Zealand White rabbits for a period of 23 days. The results show that both the HA and SiHA granules were well accepted by the host tissue, with no presence of any inflammatory cells. New bone formation was observed directly on the surfaces and in the spaces between both HA and SiHA granular implants. The quantitative histomorphometry results indicate that the percentage of bone ingrowth for SiHA (37.5%+/-5.9) was significantly greater than that for phase pure HA (22.0%+/-6.5), in addition the percentage of bone/implant coverage was significantly greater for SiHA (59.8%+/-7.3) compared to HA (47.1%+/-3.6). These findings indicate that the early in vivo bioactivity of hydroxyapatite was significantly improved with the incorporation of silicate ions into the HA structure, making SiHA an attractive alternative to conventional HA materials for use as bone substitute ceramics.
Silicon (Si) substitution in the crystal structures of calcium phosphate (CaP) ceramics such as hydroxyapatite (HA) and tricalcium phosphate (TCP) generates materials with superior biological performance to stoichiometric counterparts. Si, an essential trace element required for healthy bone and connective tissues, influences the biological activity of CaP materials by modifying material properties and by direct effects on the physiological processes in skeletal tissue. The synthesis of Si substituted HA (Si-HA), Si substituted alpha-TCP (Si-alpha-TCP), and multiphase systems are reviewed. The biological performance of these Si substituted CaP materials in comparison to stoichiometric counterparts is discussed. Si substitution promotes biological activity by the transformation of the material surface to a biologically equivalent apatite by increasing the solubility of the material, by generating a more electronegative surface and by creating a finer microstructure. When Si is included in the TCP structure, recrystallization to a carbonated HA is mediated by serum proteins and osteoblast-like cells. Release of Si complexes to the extracellular media and the presence of Si at the material surface may induce additional dose-dependent stimulatory effects on cells of the bone and cartilage tissue systems.
Twenty five years of development of bioactive ceramics are reviewed with emphasis on: 1) the sequence of interfacial reactions between implant and tissue, 2) relation of clinical applications to the composition, structure and physical form of the implant (bulk, powders, coatings, composites). Two classes of bioactivity are proposed: Class A bioactive implants are osteoproductive due to both intracellular and extracellular factors and Class B bioactive implants that are osteoconductive due to extracellular factors. Future directions of the field are proposed including: 1) use of biomolecular design of bioactive surfaces to achieve regeneration of tissues, and 2) biomechanical design of bioactive composites to create optimized interfacial gradients in strength, toughness and elastic properties.
-INTRODUCTION TO BIOMATERIALS. -THE STRUCTURE OF SOLIDS. -CHARACTERIZATION OF MATERIALS-I. -CHARACTERIZATION OF MATERIALS-II: ELECTRICAL, OPTICAL, X-RAY ABSORPTION, ACOUSTIC, ULTRASONIC, ETC.-METALLIC IMPLANT MATERIALS. -CERAMIC IMPLANT MATERIALS. -POLYMERIC IMPLANT MATERIALS. -COMPOSITES AS BIOMATERIALS. -STRUCTURE-PROPERTY RELATIONSHIPS OF BIOLOGICAL MATERIALS. -TISSUE RESPONSE TO IMPLANTS. -SOFT TISSUE REPLACEMENT I: SUTURES, SKIN, AND MAXILLOFACIAL IMPLANTS. -SOFT TISSUE REPLACEMENT II: BLOOD INTERFACING IMPLANTS. -HARD TISSUE REPLACEMENT I: LONG BONE REPAIR. -HARD TISSUE REPLACEMENT-II: JOINTS AND TEETH. -TRANSPLANTS. -BIODEGRADABLE MATERIALS FOR TISSUE ENGINEERING. -APPENDICES.
The present authors previously showed that titanium metal, which was exposed to 5.OMNaOH solution at 60°C for 24 h and heat-treated at 600°C for 1 h, spontaneously forms a bonelike apatite layer on its surface in the living body, and tightly bonds to the bone through the apatite layer. In the present study, mechanism of the apatite formation on the bioactive titanium metal was investigated in an acellular simulated body fluid (SBF). A thin sodium titanate layer was formed on the surface of the titanium metal by the NaOH and heat treatments. The sodium titanate layer released Na+ ions via exchange with H3O+ ions in SBF, to form a lot of Ti-OH groups on its surface. The Ti-OH groups first combined with Ca2+ ions in SBF, and then later with PO43- ions to form the apatite. Titania and Na2O-TiO2 gels prepared by a sol-gel method as model substances of the sodium titanate layer on the surface of the titanium metal showed that Ti-OH groups of anatase structure are effective for the apatite nucleation, whereas those of amorphous structure and Na2Ti5O11 crystal are not effective.
Biomaterials is a field that continues to attract a significant amount
of attention from researchers, industry, educationalists and regulators.
This book is the first to provide readers with an understanding of
fundamental theory relating to the use of metals in biomedical
applications in addition to comprehensively covering applied aspects
encompassing practical and technical advantages and disadvantages.
Topics highlighted in the book include guidelines for selecting
materials; shape memory alloys; degradation and surface modification;
adhesion to ceramics and polymers; biocompartibility and tissue-implant
interactions; and European and North American regulatory issues.
Ceramics used for the repair and reconstruction of diseased or damaged parts of the musculo-skeletal system, termed bioceramics, may be bioinert (e.g., alumina and zirconia), resorbable (e.g., tricalcium phosphate), bioactive (e.g., hydroxyapatite, bioactive glasses, and glass-ceramics), or porous for tissue ingrowth (e.g., hydroxyapatite-coated metals). Applications include replacements for hips, knees, teeth, tendons, and ligaments and repair for periodontal disease, maxillofacial reconstruction, augmentation and stabilization of the jaw bone, spinal fusion, and bone repair after tumor surgery. Pyrolytic carbon coatings are thromboresistant and are used for prosthetic heart valves. The mechanisms of tissue bonding to bioactive ceramics have resulted in the molecular design of bioceramics for interfacial bonding with hard and soft tissue. Bioactive composites are being developed with high toughness and elastic modulus that match with bone. Therapeutic treatment of cancer has been achieved by localized delivery of radioactive isotopes via glass beads. Clinical success of bioceramics has led to a remarkable advance in the quality of life for millions of people.
A simple gel casting process is described for the preparation of uniform green HAP (hydroxy apatite) ceramic bodies. Such green compacts were observed to sinter more uniformly compared to the compacts derived by the dry pressing technique. The samples were sintered at temperatures ranging between 1100 and 1250 °C for 2 h. The sintering characteristics of the compacts were assessed by density measurements, microhardness variations and scanning electron microscopy. The highest density was obtained for gel cast samples, i.e. > 99%, when they were sintered at 1200 °C for 2 h. The microstructure of the above sample was highly uniform. The improved uniformity in structure and properties of the sintered gel cast samples would make them suitable for better dental and orthopaedic implants.
Bioactive glass (BAG)-S53P4 is an osteoconductive bone substitute with proven antibacterial and bone bonding properties. In a multicentre study 11 patients with verified chronic osteomyelitis in the lower extremity and the spine were treated with BAG-S53P4 as a bone substitute. The cavitary bone defect and the surrounding of a spinal implant were filled with BAG-S53P4. The most common pathogen causing the infection was Staphylococcus aureus. The mean follow-up was 24 months (range 10-38). BAG-S53P4 was well tolerated. Nine patients healed without complications. One patient who achieved good bone formation sustained a superficial wound infection due to vascular problems in the muscle flap, and one patient had an infection due to a deep haematoma. This study shows that BAG-S53P4 is a good and well-tolerated bone substitute, and can be used in treatment of osteomyelitis with good primary results.
Samples from intraosseous dental implants, removed from patients for mechanical failures, were examined to analyse the interaction between hydroxyapatite as plasma sprayed coating on titanium supports and human bone. The implantation time varied up to 8 years. No failures had arisen from problems at the interface between the hydroxyapatite coating and bone. The number of samples examined and the implantation times give good statistical conclusions. Histological and microchemical studies showed the good performance and compatibility of this sprayed hydroxyapatite. We present evidence from the best samples which show close bonding with the surrounding bone tissue. New bone is seen all around the coated implant. The composition of the calcium phosphate deposited on the hydroxyapatite and cellular approach were determined, and demonstrate the efficiency of the interaction between this plasma sprayed hydroxyapatite and the bone.
The synthesis of model porous metal-CPC materials, and their use in one-parametric studies of bone tissue ingrowth enhancement were considered. By using the same starting calcium-deficient hydroxyapatite powder, three different coatings, CAP1, CAP2 and CAP3, were obtained of thicknesses 50 +/- 5, 75 +/- 5 and 75 +/- 5 microns, respectively. CAP1 and 2 were either the starting powder mixed in a 3:1 ratio CPC: poly(lactic acid) or the powder by itself. The CAP3 coating was the result of a thermal treatment producing a mixture of oxyhydroxyapatite, alpha- and beta-tricalcium phosphate. Orderly oriented wire mesh porous coated specimens were implanted, along with the same specimens lined with CAP 1, 2 or 3. Subsequently, the total of 156 specimens was retrieved at 2, 4 or 6 wk, and tested mechanically and processed for histomorphometry. The data produced considerable evidence for the CPC-dependent enhancement of bone tissue ingrowth in porous metals immediately after implantation. They prove that the materials processing of CPC coatings influences the resulting biological behaviour substantially. Furthermore, they support the hypothesis that ceramic dissolution is a causative factor on the bone tissue growth enhancement mechanisms.
Silicon was found to be a constituent of certain glycosaminoglycans and polyuronides, where it occurs firmly bound to the polysaccharide matrix. 330-554 ppm of bound Si were detected in purified hyaluronic acid from umbilical cord, chondroitin 4-sulfate, dermatan sulfate, and heparan sulfate. These amounts correspond to 1 atom of Si per 50,000-85,000 molecular weight or 130-280 repeating units. 57-191 ppm occur in chondroitin 6-sulfate, heparin, and keratan sulfate-2 from cartilage, while hyaluronic acids from vitreous humor and keratan sulfate-1 from cornea were Si-free. Large amounts of bound Si are also present in pectin (2580 ppm) and alginic acid (451 ppm). The bound Si is not dialyzable, does not react with ammonium molybdate, is not liberated by autoclaving or 8 M urea, and is stable against weak alkali and acid. Strong alkali and acid hydrolyze the Si-polysaccharide bond. Free, direct-reacting, dialyzable silicate is obtained. Enzymatic hydrolysis of hyaluronic acid or pectin does not liberate silicic acid, but leads to products of low molecular weight still containing Si in bound form. It is concluded that Si is present as a silanolate, i.e., an ether (or esterlike) derivative of silicic acid, and that R(1)-O-Si-O-R(2) or R(1)-O-Si-O-Si-O-R(2) bridges play a role in the structural organization of glycosaminoglycans and polyuronides. Thus, Si may function as a biological crosslinking agent and contribute to architecture and resilience of connective tissue.
Rat bone cells were cultured in the presence of bioactive glass-ceramic containing crystalline apatite and wollastonite. Scanning electron microscopy observations of the surface of the seeded ceramic disks revealed that cells attached, spread, and proliferated on the material surface. Soaking in cell-free culture medium showed that no change occurred in the surface structure. However, when cultured with bone cells and observed under a transmission electron microscope, an electron-dense layer was noted initially at the surface of the material, before bone formation occurred. In addition, energy-dispersive X-ray microanalysis demonstrated the presence of calcium and phosphorus in this layer. Progressively, during the following days of culture, active osteoblasts synthetized and laid down an osteoid matrix composed of numerous collagen fibrils arranged either parallel or perpendicularly to the first-formed electron-dense layer. Mineralization initiated on the ceramic surface dispersed then along the collagenous fibrils, leading to a mineralized matrix which surrounded the ceramic particles. These results demonstrate the capacity of apatite-wollastonite glass ceramic to initiate biomineralization in osteoblast cultures and to achieve a direct bond between the surface apatite layer of the bioactive glass-ceramic and the mineralized bone matrix.
The effects of physiological biomolecules, particularly proteins, on the reactivity of bioactive glasses is being heavily researched. However, the effects of bioactive glasses on the activity of proteins have received little attention. Activity of horseradish peroxidase (HRP) adsorbed to the silica gel and hydroxycarbonate apatite layers of 45S5 bioactive glass was investigated. Surface reactions were terminated after development of a silica gel layer by the addition of edta to the reaction solution, which completely inhibited calcium phosphate formation. Complete loss of HRP activity on the silica gel layer was found to occur within 21 h while a minimal amount of activity from HCA-adsorbed HRP persisted indefinitely. These results show that bioactive glasses may serve as "friendly hosts" for adsorbed proteins, such as biologically active growth factors. These active peptides then, in turn, may generate an increased cellular response in the surrounding tissue, thereby enhancing the biogenic response.
This paper describes a method for the sensitive detection of aluminium in biological tissues by real time confocal laser scanning microscopy after staining with lumogallion. The method enabled detection of aluminium > or = 9 micrograms g-1 in bone and is more sensitive than the conventional histochemical methods with aluminium and solochrome azurine, etc. Lumogallion reacts specifically with aluminium to form a fluorescent complex so that the proposed method is useful for detection and identification of aluminium in tissues.
This paper reviews the techniques and materials (bone graft and bone graft substitutes) that currently are used to treat nonunions and bone defects. The techniques reviewed are intramedullary nailing, plating, distraction osteogenesis, and electric stimulation. Bone graft and bone graft substitutes reviewed are as follows: vascularized bone transfers; autogenous bone graft; autogenous bone marrow; dimineralized bone matrix; growth factors; calcium sulphate; calcium phosphates; and allograft. The goal of management of fractures, nonunions, and segmental bony defects, is the return of function as quickly and completely as possible. Techniques and management strategies constantly are evolving to accomplish this goal. This paper reviews the history, indications, and limitations of bone repair techniques, methods of bone grafting, and materials available as bone graft substitutes.
The clinical outcome of bone grafting procedures depends on many factors, including type and fixation of the bone graft as well as the site and status of the host bed. Bone grafts serve one or both of two main functions, as a source of osteogenesis and as a mechanical support. Autografts, both cancellous and cortical, are implanted fresh, provide a source of osteoprogenitor cells, and are osteoinductive. The latter is a process whereby the transplanted tissue induces mesenchymal cells of the recipient to differentiate into osteoblastic cells. Cortical grafts, whether autogeneic or allogeneic, at least initially act as weight-bearing space fillers. All bone grafts are initially resorbed; cancellous grafts are completely replaced in time by creeping substitution, whereas cortical grafts remain an admixture of necrotic and viable bone for a prolonged period of time. The three-dimensional framework that supports invasion of the bone grafts by capillaries and osteoprogenitor cells, termed "osteoconduction", is another important function of both autografts and allografts. Because fresh allographs evoke both local and systemic immune responses that diminish or destroy the osteoinductive and conductive processes, freezing or freeze-drying of allografts is used clinically to improve incorporation. Graft incorporation is also influenced by the vascularity and composition of the host bed. Thus, the interaction of the host and the bone graft determines the success of these procedures, which ultimately is to provide a mechanically efficient support structure.
Large, cylindrical implants of a porous calcium phosphate ceramic ("hydroxyapatite" starting material, HAC) were used to replace far greater than critical-sized sections of the midshaft of sheep tibiae and retrieved at 2 and 9 months; external fixation was used in the first 5 months. Excellent clinical function of these implants was reported in a previous study. The material retrieved was embedded in PMMA, and blocks were sectioned and surfaces were polished and carbon coated prior to study using digital backscattered electron (BSE) imaging. Detailed scanning electron microscopy study of the pattern of osseointegration of the implanted material at early (2 months) and late (9 months) timepoints revealed a previously unrecognized pattern of integration/disintegration of this implant material in tandem with bone growth. We conclude that bone adaptation to the HAC leads to its fracture and that the newly generated surfaces are equally osteoconductive. This leads to a self-propagating, self-annealing system in which defects in the HAC are mended by intercalation of bone.
Bone grafting is frequently used to augment bone healing with the numerous approaches to reconstructing or replacing skeletal defects. Autologous cancellous bone graft remains the most effective grafting material because it provides the three elements required for bone regeneration: osteoconduction, osteoinduction, and osteogenic cells. Autologous cortical bone graft provides these three components to a limited extent as well and also provides the structural integrity important in reconstruction of larger defects. However, because autogenous grafting is associated with several shortcomings and complications, including limited quantities of bone for harvest and donor-site morbidity, alternatives have been used in a wide range of orthopaedic pathologic conditions. Grafting substitutes currently available include cancellous and cortical allograft bone, ceramics, demineralized bone matrix, bone marrow, and composite grafts. No single alternative graft material provides all three components for bone regeneration. The clinical applications for each type of material are dictated by its particular structural and biochemical properties. Composite grafts consisting of several materials are often used to maximize bone healing, especially where the grafting site is compromised.
In the last decade, indications for bone allografting in orthopedic surgery have progressively increased, related to, on the one part, treatment of benign or malignant tumors, but, on another (major) part, to treatment of major bone defects due to loosening of hip or knee total prostheses. In France, legislation and control concerning donated human tissues, safety precautions, and the uses for human tissues have been greatly modified over the last few years. The authors describe the various obligations implicated by these activities and the consequences for tissue banks and surgeons; They describe different processes for bone inactivation and their action on allograft mechanical properties, or the biological capability for integration to the host bone. The authors then discuss different current techniques for bone stock reconstruction and the results in prosthetic or tumoral surgery, as well as their consequences on current surgical indications. In conclusion, they emphasize the optimal conditions for the success of allografts in orthopedic use: stability of the host bone-graft junction, vitality of the bone support, and a favourable mode of constraint of the graft, which have to be protected by osteosynthesis, but should not, however, miss partial bearing.
A variety of bioactive composites have been investigated over the last two decades as substitute materials for diseased or damaged tissues in the human body. In this paper, the rationale and strategy of developing these composites are given. Major factors influencing the production and performance of bioactive composites are discussed. Some promising composites for tissue replacement and regeneration are reviewed. On the basis of past experience and newly gained knowledge, composite materials with tailored mechanical and biological performance can be manufactured and used to meet various clinical requirements.
The incorporation of silicate into hydroxyapatite (HA) has been shown to significantly increase the rate of bone apposition to HA bioceramic implants. However, uncertainty remains about the mechanism by which silicate increases the in vivo bioactivity of HA. In this study, high-resolution transmission electron microscopy was used to observe dissolution from HA, 0.8 wt% Si-HA and 1.5 wt% Si-HA implants after 6 and 12 weeks in vivo. Our observations confirmed that defects, in particular those involving grain boundaries, were the starting point of dissolution in vivo. Dissolution was observed to follow the order 1.5 wt% Si-HA>0.8 wt% Si-HA>pure HA and it was found to be particularly prevalent at grain boundaries and triple-junctions. These observations may help to explain the mechanism by which silicate ions increase the in vivo bioactivity of pure HA, and highlight the enhanced potential of these ceramics for biomedical applications.
Historically the function of biomaterials has been to replace diseased or damaged tissues. Recent findings show that controlled release of the ionic dissolution products of bioactive glasses results in regeneration of tissues. The mechanism for in situ tissue regeneration involves upregulation of seven families of genes that control the osteoblast cell cycle, mitosis and differentiation. In the presence of critical concentrations of Si and Ca ions, within 48 h osteoblasts that are capable of differentiating into a mature osteocyte phenotype begin to proliferate and regenerate new bone. Osteoblasts that are not in the correct phase of the cell cycle and unable to proceed towards differentiation are switched into apoptosis by the ionic dissolution products. A controlled release of soluble Ca and Si from bioactive glass--resorbable polymer composites leads to vascularised soft tissue regeneration. Gene activation by controlled ion release provides the conceptual basis for molecular design of a third generation of biomaterials optimised for in situ tissue regeneration.
Charnley [1] developed the first bone cement in the 1960s using poly(methyl methacrylate) (PMMA), which remains the most widely used material for fixation of orthopaedic joint replacements. In the field of dentistry, zinc polycarboxylate and glass polyalkenoate cements received major research interest from the 1970s to the present day. The discovery of a well-integrated intermediate layer between bone and many bioactive ceramic phases from the calcium-phosphate system, such as hydroxyapatite (HA), resulted in the development of new cements incorporating such phases. These investigations ranged from the development of castable bioactive materials to modified bioactive composites. This paper attempts to give a broad overview of the many different types of cements that have being developed in the past and those which are being researched at the present time. It has lead to a set of fundamental design criteria that should be considered prior to the development of a cement for use as a bone cement or in applications requiring a bone substitute.
Calcareous skeletal elements (ossicles) isolated from the seastar, Pisaster giganteus, were characterized and tested as potential biocompatible substrates for cellular attachment. These ossicles have a remarkably robust open-framework architecture with an interconnected network of ca. 10 microm diameter pores. Scanning electron and confocal microscopy was used to characterize the cell-substrate interaction. Cell culturing experiments revealed that the cells firmly attach to the ossicle surface, forming cell aggregates of several layers thick. The anchored cells extended to form 'bridges' between the openings in the bicontinuous framework and the degree of coverage increased as culture time progressed. Osteoblasts grown on the ossicles were found to be viable up to 32 days after initial seeding, as proven by assaying with AlamarBlue and FDA/PI staining indicating the ossicle's potential as an alternative highly effective tissue scaffold. Given the limitation in availability of this natural material, the results presented here should be seen as offering guidelines for future development of synthetic materials with physical and chemical properties strongly conducive to bone repair and restoration.
Particulate and ionic debris resulting from in vivo degradation of total joint replacement components are recognized as major factors limiting the longevity of the joint reconstruction and the overall success of the procedure. Particulate and ionic wear and corrosion debris have been associated with a locally aggressive biologic response that can lead to synovitis, periprosthetic bone loss, and aseptic loosening of the implants. Furthermore, concerns exist regarding the systemic dissemination of prosthetic debris, including potential effects resulting from end-organ retention. The long-term success of total disc arthroplasty may well depend, at least in part, on the ability to minimize implant debris generation and the subsequent local and systemic response.
The osseous response to silicon (Si) level (0, 0.2, 0.4, 0.8 and 1.5 wt% Si) within 5 batches of matched porosity silicate-substituted hydroxyapatite (SA) scaffold was assessed by implantation of 4.6 mm diameter cylinders in the femoral intercondylar notch of New Zealand White rabbits for periods of 1, 3, 6 and 12 weeks. Histological evaluation and histomorphometric quantification of bone ingrowth and mineral apposition rate (MAR) demonstrated the benefits to early (<1 week) bone ingrowth and repair through incorporation of Si, at all levels, in porous hydroxyapatite (HA) lattices as compared to stoichiometric (0 wt% Si) HA. The group containing 0.8 wt% Si supported significantly more bone ingrowth than all other groups at 3 and 6 weeks (P<0.05), initially through its elevated MAR between weeks 1 and 2, which was significantly higher than that of all other Si-containing groups (P<0.05). The level of silicate substitution also influenced the morphology and stability of the repair, with elevated levels of bone resorption and apposition apparent within other Si-containing groups at timepoints >3 weeks as compared to the 0 and 0.8 wt% Si groups. At 12 weeks, the net amount of bone ingrowth continued to rise in the 0, 0.8 and 1.5 wt% groups, apparently as a result of adaptive remodelling throughout the scaffold. Ingrowth levels remained highest in the 0.8 wt% Si group, was characterised by a dense trabecular morphology in the superficial region graduating to a more open network in the deep zone. These results highlight the sensitivity of healing response to Si level and suggest that an optimal response is obtained when SA is substituted with 0.8 wt% Si through its effect on the activity of both bone forming and bone resorbing cells.
Biological Staining Methods
- E. Gurr
Bone Cements and Fillers
- Kenny