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Abstract

The incidence of bone disorders and orthopedic surgeries are increasing worldwide representing a premier clinical need. The serious limitation in conventional therapies has led to a new discipline, the so-called bone tissue engineering (BTE), which aims to explore novel functional regeneration strategies via the synergistic combination of biomaterial design with cell and factor therapies. The core of BTE is the design of an “ideal” synthetic bone graft that mimics the tissue from macro- to nanoscale level, including the biochemical and biophysical cues of bone extracellular matrix. The engineering of natural polymers to obtain biomaterials is one of the most attractive options, mainly due to their similarities with the bone extracellular matrix (ECM), chemical versatility and good biological performance. In this chapter, the most relevant natural polymeric formulations for bone repair and the principal stimulus proposed as contributors or mediators for promoting cell activity and bone tissue formation are discussed. Finally, we bring up the current challenges and future directions in bone regeneration focused on the recent advances in 3D printing of customized bone grafts.

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... In vivo bone mineralization has inspired the design of advanced biomaterials, socalled biomimetic, mimicking the hierarchical organization and composition of native tissue at nanoscale level [8][9][10][11]. Bone is a nanocomposite made up of self-assembled collagen fibers (accounting for 35 wt.%) strengthened by inter and intrafibrillar mineralization of apatite (Ap) nanocrystals (65 wt.%) [12]. Ap nanoparticles consist on non-stoichiometric hydroxyapatite [HA, Ca10(PO4)6(OH)2] containing foreign ions in its structure, e.g., CO3 2-, Mg 2+ , Sr 2+ [13]. ...
... Herein, bioinspired scaffolds mimicking the osteogenic niche of cancellous bone have been designed through biomimetic mineralization of recombinant collagen and freezedrying. This technique is one of the most common methodologies used to fabricate tridimensional porous scaffolds with tailored pore size, porosity and pore distribution (aligned or isotropic structures) [10,35]. These are critical parameters that directly affect the fluid shear stress sensed by the cells when cell medium is perfused through the scaffold in the bioreactor [36]. ...
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In bone tissue engineering, the design of 3D systems capable of recreating composition, architecture and micromechanical environment of the native extracellular matrix (ECM) is still a challenge. While perfusion bioreactors have been proposed as potential tool to apply biomechanical stimuli, its use has been limited to a low number of biomaterials. In this work, we propose the culture of human mesenchymal stem cells (hMSC) in biomimetic mineralized recombinant collagen scaffolds with a perfusion bioreactor to simultaneously provide biochemical and biophysical cues guiding stem cell fate. The scaffolds were fabricated by mineralization of recombinant collagen in the presence of magnesium (RCP.MgAp). The organic matrix was homogeneously mineralized with apatite nanocrystals, similar in composition to those found in bone. X-Ray microtomography images revealed isotropic porous structure with optimum porosity for cell ingrowth. In fact, an optimal cell repopulation through the entire scaffolds was obtained after 1 day of dynamic seeding in the bioreactor. Remarkably, RCP.MgAp scaffolds exhibited higher cell viability and a clear trend of up-regulation of osteogenic genes than control (non-mineralized) scaffolds. Results demonstrate the potential of the combination of biomimetic mineralization of recombinant collagen in presence of magnesium and dynamic culture of hMSC as a promising strategy to closely mimic bone ECM.
... Regardless of the origin, they must be biocompatible to avoid the induction of immune response besides being sterilizable to be safely incorporated into the host tissues, biodegradable to disappear from the tissue after fulfilling their function, and bioactive to stimulate tissue responses ( Fig. 1) [36,37]. Natural polymers (chitosan, gelatin, collagen, cellulose, alginates, etc.) are more preferred than synthetic ones (polylactide-co-glycolide (PLGA), polycaprolactone (PCL), polylactic acid (PLA), fibronectin, polyurethane, etc.) as they have higher biocompatibility, excellent biodegradability, and minimal toxicity [38]. Moreover, plant-derived biomaterials have been explored widely to replace animal-derived ones due to major concerns regarding variability, ethical and environmental issues, also, animal-derived products are of higher cost and need more extraction and purification processes [39]. ...
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... There are various forms of chitosan-based scaffolds in bone tissue engineering, including films, particles, hydrogels, fibers, and sponges [117]. Chitosan is introduced as a linear polysaccharide and has favorable biocompatibility, bioactivity, and biodegradability features. ...
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... Currently, bone defect caused by pathological changes, aging, accidental injury, cancer and other reasons is one of the biggest problems in the field of biomedical engineering [1,2]. Different types of bone scaffolds including ceramics [3,4], metals [5], polymers [6] and composites [7] are used in bone tissue engineering. Despite the wide variety of scaffold technologies, it remains a challenge to select materials that can mimic the structural integrity and biocompatibility of natural bone. ...
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... A hybrid scaffold (Hy-scaffold) that mimics the bone composition, was developed by blending Gel/MgHA microparticles with a polymeric matrix consisting of Gel and Chit. The mineral component (Gel/MgHA) was developed through biomineralization, a process that allows the growth of biomimetic MgHA nanocrystals in the gelatin matrix via a neutralization reaction and a simultaneous pH variation, exploiting MgHA and gelatin functional groups aggregation abilities [13,28,29]. The mineralization of MgHA on gelatin produced mineralized flakes that were added to the polymer blend forming a hybrid hydrogel used as base matrix for the scaffold (Hy-scaffold) development (Fig. 1a). ...
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Fish gelatin is an important alternative gelatin which can be considered as Halal free and acceptable by all religions. It is made from fish by-products of which fish skin is the most widely used part. The collogan and gelatin-like property of fish bones and scales coupled with their readily availability make it a potential source for development into gelatin products. This review discusses the potentials for the development and utilization of fish bones and scales in the production of gelatins. It also looks at the raw materials, processes, properties and the improvement of fish gelatins for future commercial use.
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Silk/polyethylene glycol (PEG) hydrogels are studied as self-standing bioinks for 3D printing for tissue engineering. The two components of the bioink, silk fibroin protein (silk) and PEG, are both Food and Drug Administration approved materials in drug and medical device products. Mixing PEG with silk induces silk β-sheet structure formation and thus gelation and water insolubility due to physical crosslinking. A variety of constructs with high resolution, high shape fidelity, and homogeneous gel matrices are printed. When human bone marrow mesenchymal stem cells are premixed with the silk solution prior to printing and the constructs are cultured in this medium, the cell-loaded constructs maintain their shape over at least 12 weeks. Interestingly, the cells grow faster in the higher silk concentration (10%, w/v) gel than in lower ones (7.5 and 5%, w/v), likely due to the difference in material stiffness and the amount of residual PEG remaining in the gel related to material hydrophobicity. Subcutaneous implantation of 7.5% (w/v) bioink gels with and without printed fibroblast cells in mice reveals that the cells survive and proliferate in the gel matrix for at least 6 week postimplantation. The results suggest that these silk/PEG bioink gels may provide suitable scaffold environments for cell printing and function.
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Bone morphogenetic protein-2 (BMP-2) is a powerful osteoinductive protein; however, there is a need for the development of a safe and efficient BMP-2 release system for bone regeneration therapies. Recombinant extracellular matrix proteins are promising next generation biomaterials since the proteins are well-defined, reproducible and can be tailored for specific applications. In this study, we have developed a novel and versatile BMP-2 delivery system using microspheres from a recombinant protein based on human collagen I (RCP). In general, a two-phase release pattern was observed while the majority of BMP-2 was retained in the microspheres for at least two weeks. Among different parameters studied, the crosslinking and the size of the RCP microspheres changed the in vitro BMP-2 release kinetics significantly. Increasing the chemical crosslinking (hexamethylene diisocyanide) degree decreased the amount of initial burst release (24 h) from 23% to 17%. Crosslinking by dehydrothermal treatment further decreased the burst release to 11%. Interestingly, the 50 and 72 μm-sized spheres showed a significant decrease in the burst release compared to 207-μm sized spheres. Very importantly, using a reporter cell line, the released BMP-2 was shown to be bioactive. SPR data showed that N-terminal sequence of BMP-2 was important for the binding and retention of BMP-2 and suggested the presence of a specific binding epitope on RCP (KD: 1.2 nM). This study demonstrated that the presented RCP microspheres are promising versatile BMP-2 delivery vehicles.
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Statement of significance: The state-of-art of silk biomaterials in bone tissue engineering, covering their wide applications as cell scaffolding matrices to micro-nano carriers for delivering bone growth factors and therapeutic molecules to diseased or damaged site to facilitate bone regeneration, is emphasized here. The review rationalizes that the choice of silk protein as a biomaterial is not only because of its natural polymeric nature, mechanical robustness, flexibility, and wide range of cell compatibility but also because of its ability to template the growth of hydroxyapatite, the chief inorganic component of bone mineral matrix, resulting in improved osteointegration. The discussion extends to the role of inorganic ions such as Si and Ca as a matrix components in combination with silk to influence bone regrowth. The effect of ions or growth factor-loaded vehicle incorporation into regenerative matrix nanotopography is also included.
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Bioprinting of three-dimensional constructs mimicking natural-like extracellular matrix has revolutionized biomedical technology. Bioprinting technology circumvents various discrepancies associated with current tissue engineering strategies by providing an automated and advanced platform to fabricate various biomaterials through precise deposition of cells and polymers in a premeditated fashion. However, few obstacles associated with development of 3D scaffolds including varied properties of polymers used and viability, controlled distribution, and vascularization, etc. of cells hinder bioprinting of complex structures. Therefore, extensive efforts have been made to explore the potential of various natural polymers (e.g. cellulose, gelatin, alginate, and chitosan, etc.) and synthetic polymers in bioprinting by tuning their printability and cross-linking features, mechanical and thermal properties, biocompatibility, and biodegradability, etc. This review describes the potential of these polymers to support adhesion and proliferation of viable cells to bioprint cell laden constructs, bone, cartilage, skin, and neural tissues, and blood vessels, etc. for various applications in tissue engineering and regenerative medicines. Further, it describes various challenges associated with current bioprinting technology and suggests possible solutions. Although at early stage of development, the potential benefits of bioprinting technology are quite clear and expected to open new gateways in biomedical, pharmaceutics and several other fields in near future.
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Starch as a biopolymer directly extracted from nature has received much attention in recent years due to its strong advantages such as low cost, wide availability, renewability, and total compostability without toxic residues. Starch-based materials always display properties that are less satisfactory than those of traditional polymer materials, which can be ascribed to the inherent characteristics of starch. To make such materials to be truly competitive and to widen its applications, the development of starch-based nano-biocomposites could be a promising solution. This chapter provides the fundamental knowledge related to starch-based nano-biocomposites as well as the most recent developments in this area. Various types of nanofillers that have been used with plasticized starch are discussed such as montmorillonite, cellulose nanowhiskers, and starch nanoparticles. The preparation strategies for starch-based nano-biocomposites with these types of nanofillers and the corresponding dispersion state and related properties are also largely discussed.
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In the cell-printing process, bioink has been considered as an extremely important component for successful fabrication of macroscale cell-laden structures. Bioink should be non-toxic, biocompatible, and printable. To date, alginate has been widely used as a whole or partial component of bioink because it is non-toxic to embedded cells and even it can provide good printability with rapid gelation under calcium ions. However, alginate bioinks do not possess cell-activating ability. To overcome the shortcomings of alginate-based bioinks, a new collagen bioink, which was mixed with human adipose stem cells (hASCs) and crosslinked with a polyphenol (tannic acid), was proposed. The feasibility of the bioink was demonstrated using several in vitro assessments for comparison of the macroscale porous cell-laden collagen/polyphenol structure containing the hASCs with the conventional alginate-based cell-laden structure. The levels of the metabolic activity, including the cell viability and cell proliferation, of the cell-laden collagen structure were significantly higher than those of the control (alginate-based cell-laden structure). The results show that the newly designed bioink and cell-laden structure are potentially new outstanding components for regeneration of various tissues.
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Bioprinting as an enabling technology for tissue engineering possesses the promises to fabricate highly mimicked tissue or organs with digital control. As one of the biofabrication approaches, bioprinting has the advantages of high throughput and precise control of both scaffold and cells. Therefore, this technology is not only ideal for translational medicine but also for basic research applications. Bioprinting has already been widely applied to construct functional tissues such as vasculature, muscle, cartilage, and bone. In this review, the authors introduce the most popular techniques currently applied in bioprinting, as well as the various bioprinting processes. In addition, the composition of bioink including scaffolds and cells are described. Furthermore, the most current applications in organ and tissue bioprinting are introduced. The authors also discuss the challenges we are currently facing and the great potential of bioprinting. This technology has the capacity not only in complex tissue structure fabrication based on the converted medical images, but also as an efficient tool for drug discovery and preclinical testing. One of the most promising future advances of bioprinting is to develop a standard medical device with the capacity of treating patients directly on the repairing site, which requires the development of automation and robotic technology, as well as our further understanding of biomaterials and stem cell biology to integrate various printing mechanisms for multi-phasic tissue engineering.
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The need of synthetic bone grafts that recreate from macro to nanoscale level the biochemical and biophysical cues of bone extracellular matrix (ECM) has been a major driving force for the development of new generation of biomaterials. In this study, synthetic bone substitutes have been synthesized via biomimetic mineralization of a recombinant collagen type I derived peptide (RCP), enriched in tri-amino acid sequence arginine-glycine-aspartate (RGD). 3D isotropic porous scaffolds of three different compositions are developed by freeze-drying: non-mineralized (RCP, as a control), mineralized (Ap/RCP) and mineralized scaffolds in presence of magnesium (MgAp/RCP) that closely imitate bone composition. The effect of mineral phase on scaffold pore size, porosity and permeability as well as on their in vitro kinetic degradation is evaluated. The ultimate goal is to investigate how chemical (i.e., surface chemistry and ion release from scaffold) together with physical signals (i.e., surface nano-topography) conferred via biomimetic mineralization can persuade and guide Mesenchymal Stem Cells (MSCs) interaction and fate. The three scaffold compositions showed optimum pore size and porosity for osteoconduction, without significant differences between them. The degradation tests confirmed that MgAp/RCP scaffolds presented higher reactivity under physiological condition compared to Ap/RCP ones. The in vitro study revealed an enhanced cell growth and proliferation on MgAp/RCP scaffolds at day 7, 14 and 21. Furthermore, MgAp/RCP scaffolds potentially promoted cell migration through the inner areas reaching the bottom of the scaffold after 14 days. MSCs cultured on MgAp/RCP scaffolds displayed higher gene and protein expressions of osteogenic markers when comparing them with the results of those MSCs grown on RCP or Ap/RCP scaffolds. This work highlights that mineralization of recombinant collagen mimicking bone mineral composition and morphology is a versatile approach to design smart scaffold interface in a 3D model guiding MSC fate. .
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This review is intended to give a state of the art description of scaffold-based strategies utilized in Bone Tissue Engineering. Numerous scaffolds have been tested in the orthopedic field with the aim of improving cell viability, attachment, proliferation and homing, osteogenic differentiation, vascularization, host integration and load bearing. The main traits that characterize a scaffold suitable for bone regeneration concerning its biological requirements, structural features, composition, and types of fabrication are described in detail. Attention is then focused on conventional and Rapid Prototyping scaffold manufacturing techniques. Conventional manufacturing approaches are subtractive methods where parts of the material are removed from an initial block to achieve the desired shape. Rapid Prototyping techniques, introduced to overcome standard techniques limitations, are additive fabrication processes that manufacture the final three-dimensional object via deposition of overlying layers. An important improvement is the possibility to create custom-made products by means of computer assisted technologies, starting from patient's medical images. As a conclusion, it is highlighted that, despite its encouraging results, the clinical approach of Bone Tissue Engineering has not taken place on a large scale yet, due to the need of more in depth studies, its high manufacturing costs and the difficulty to obtain regulatory approval. PUBMED search terms utilized to write this review were: “Bone Tissue Engineering”, “regenerative medicine”, “bioactive scaffolds”, “biomimetic scaffolds”, “3D printing”, “3D bioprinting”, “vascularization” and “dentistry”.
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3D bioprinting is a booming method to obtain scaffolds of different materials with predesigned and customized morphologies and geometries. In this review we focus on the experimental strategies and recent achievements in bioprinting major structural proteins (collagen, silk, fibrin), as a particularly interesting technology to reconstruct the biochemical, biophysical composition and hierarchical morphology of natural scaffolds. The flexibility in molecular design offered by structural proteins, combined with the flexibility in mixing, deposition and mechanical processing inherent to bioprinting technologies enables the fabrication of highly functional scaffolds and tissue mimics with a degree of complexity and organization which has just been started to be explored. Here we describe the printing parameters and physical (mechanical) properties of bioinks based on structural proteins, including the biological function of the printed scaffolds. We describe applied printing techniques and cross-linking methods, highlighting the modification implemented to improve scaffold properties. The used cell types, cell viability, and possible construct applications are also reported. We envision that the application of printing technologies to structural proteins will enable unprecedented control over their supramolecular organization, conferring printed scaffolds biological properties and functions close to natural ones.
Article
A bio-inspired mineralisation process was investigated and applied to develop novel hybrid magnetic materials by heterogeneous nucleation of Fe2+/Fe3+-doped hydroxyapatite nanocrystals onto a biopolymeric matrix made of a Type I collagen-based recombinant peptide (RCP). The effect of the synthesis temperature on the phase composition, crystallinity and magnetic properties of the nucleated inorganic phase was studied. The as-obtained magnetic materials were then engineered, by using a water-in-oil emulsification process, into hybrid magnetic microspheres, which were stabilized by de-hydrothermal treatment yielding cross-linking of the macromolecular matrix. Thorough investigation of the physicochemical, morphological and biological properties of the new hybrid microspheres, as induced by the presence of the inorganic nanophase and controlled iron substitution into hydroxyapatite lattice, revealed bone-like composition, good cytocompatibility, designed shape and size, and tailored magnetization. Such features are interesting and promising for application as new biomaterials with ability of remote activation and control by using external magnetic fields, for smart and personalized applications in medicine, particularly in bone tissue regeneration.
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Statement of significance: Additive manufacturing techniques have given tissue engineers the ability to precisely recapitulate the native architecture present within tissue. In addition, these techniques can be leveraged to create scaffolds with both physical and chemical gradients. This work offers insight into several techniques that can be used to generate graded scaffolds, depending on the desired gradient. Furthermore, it outlines methods to determine if the designed gradient was achieved. This review will help to condense the abundance of information that has been published on the creation and characterization of gradient scaffolds and to provide a single review discussing both methods for manufacturing gradient scaffolds and evaluating the establishment of a gradient.
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Natural and synthetic polymeric materials have been widely used in bone tissue engineering due to their similarity with extracellular matrices and considerable biocompatibility and biodegradability. A variety of techniques has been applied to modify the physicochemical, structural, and biological properties of polymeric materials to meet the specific requirements of bone regeneration. This review aims to provide a brief overview of recent progress on the synthesis and fabrication of polymeric materials for bone tissue engineering. Commonly used and innovative processing techniques to fabricate different structural polymer scaffolds and bioactive surface modification of polymer scaffolds to promote bone regeneration are introduced. The mechanical stimulation and immunomodulatory effect of polymeric materials to cells are also discussed.
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The basic building block of the extra-cellular matrix in native tissue is collagen. As a structural protein, collagen has an inherent biocompatibility making it an ideal material for regenerative medicine. Cellular response, mediated by integrins, is dictated by the structure and chemistry of the collagen fibers. Fiber formation, via fibrillogenesis, can be controlled in vitro by several factors: pH, ionic strength, and collagen structure. After formation, fibers are stabilized via cross-linking. The final bioactivity of collagen scaffolds is a result of both processes. By considering each step of fabrication, scaffolds can be tailored for the specific needs of each tissue, improving their therapeutic potential.
Chapter
Tissue engineering is one of the fields of action of regenerative medicine and usually employs a triad of interconnected strategies, namely: the employment of biomaterials to provide suitable physical and chemical environments; the use of cells to establish communication between living tissues and scaffold materials; and the appliance of bioactive agents such as growth factors to stimulate local and/or implanted cell responses. The main objective is to assist the regeneration of tissues damaged by disease or trauma and, in some cases, creating new tissues to replace failing or malfunctioning tissues or organs. Starch can be processed through several techniques to form 3D porous scaffolds, microparticles, and bone cements for a wide range of applications in the biomedical field. Using different synthetic components of starch-based blends tailored by different processing methods and/or incorporation of reinforcement materials/additives, one can achieve distinct structural forms and/or properties.
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This study offers new bioactive composite scaffolds from carboxylated starch-chitosan for bone regeneration. In order to introduce COOH groups into the scaffolds, chitosan was first dissolved in citric acid and then mixed with different amounts of starch. Various characterization techniques were used to analyze the structure, morphology, compressive strength, and apatite mineralization of the composites, which were compared to pure chitosan scaffolds. The results indicated that chitosan scaffolds showed the highest pore size and porosity, while no apatite deposition was observed even after 14 days of soaking in simulated body fluid. For composite samples, the pore size and porosity decreased as the starch content increased. In spite of such decrease, the pore size measurements were in the optimal range for bone regeneration. The bone-like apatite mineralization, compressive strength, carboxyl content, and swelling ratio of the composites increased with additional starch. Cell culture experiments demonstrated that higher starch content can enhance proliferation, ALP activity, and mineralization of osteoblast-like cells (MG63).
Book
Collagen: Structure and Mechanics provides a cohesive introduction to collagen-rich tissues, such as tendon, bone, cornea or arterials walls. Written in a clear and didactic manner, this volume reviews current knowledge on hierarchical structure, mechanical properties, deformation and strengthening mechanisms, and discusses many applications in biomaterials and tissue engineering. Researchers in the fields of materials, (bio-)engineering, physics, chemistry and biology will gain an understanding of the structure and mechanical behavior of type I collagen and collagen-based tissues in vertebrates, across all length scales from the molecular (nano) to the organ (macro) level. Collagen: Structure and Mechanics is a reference for new researchers entering this area and can serve also as a basis for lecturing in the interdisciplinary field of biological materials science. © 2008 Springer Science+Business Media, LLC. All rights reserved.
Article
The clinical demand for scaffolds and the diversity of available polymers provide freedom in the fabrication of scaffolds to achieve successful progress in bone tissue engineering (BTE). Chitosan (CS) has drawn much of the attention in recent years for its use as graft material either as alone or in a combination with other materials in BTE. The scaffolds should possess a number of properties like porosity, biocompatibility, water retention, protein adsorption, mechanical strength, biomineralization and biodegradability suited for BTE applications. In this review, CS and its properties, and the role of CS along with other polymeric and ceramic materials as scaffolds for bone tissue repair applications are highlighted.
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Bio-inspired synthesis of smart biomaterials is an emerging nano-technological approach to develop new solutions for an ever-raising number of patients affected by degenerative and disabling pathologies. Particularly for purpose of tissue regeneration, the new materials should function as scaffolds with high mimicry of host tissues, in order to instruct cells to perform their task. Due to the complexity of living tissues and limitations of the current fabrication methods, synthesis methods reproducing the biologic processes may exploit the huge information inherent in macromolecular matrices, to build complex nano-composites with regenerative ability. As an example the assembling/mineralization phenomena involved in hard tissues can be mimicked to achieve smart devices able to regenerate different tissues such as joints and periodontium. Besides, the implementation of this approach with remote activation by low magnetic fields of bio-resorbable superparamagnetic apatite nano-phases, may provide new devices enabling activation on demand suitable for non-invasive and more effective therapies.
Article
The rising incidence of bone disorders has resulted in the need for more effective therapies to meet this demand, exacerbated by an increasing ageing population. Bone tissue engineering is seen as a means of developing alternatives to conventional bone grafts for repairing or reconstructing bone defects by combining biomaterials, cells and signalling factors. However, skeletal tissue engineering has not yet achieved full translation into clinical practice as a consequence of several challenges. The use of additive manufacturing techniques for bone biofabrication is seen as a potential solution, with its inherent capability for reproducibility, accuracy and customisation of scaffolds as well as cell and signalling factor delivery. This review highlights the current research in bone biofabrication, the necessary factors for successful bone biofabrication, in addition to the current limitations affecting biofabrication, some of which are a consequence of the limitations of the additive manufacturing technology itself.
Article
Collagen-based biomedical materials have developed into important, clinically effective materials used in a range of devices that have gained wide acceptance. These devices come with collagen in various formats, including those based on stabilized natural tissues, those that are based on extracted and purified collagens, and designed composite, biosynthetic materials. Further knowledge on the structure and function of collagens has led to on-going developments and improvements. Among these developments has been the production of recombinant collagen materials that are well defined and are disease free. Most recently, a group of bacterial, non-animal collagens has emerged that may provide an excellent, novel source of collagen for use in biomaterials and other applications. These newer collagens are discussed in detail. They can be modified to direct their function, and they can be fabricated into various formats, including films and sponges, while solutions can also be adapted for use in surface coating technologies. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015.
Article
In recent years, stereolithographic fabrication has advanced greatly in the quality, resolution, and accuracy of manufactured parts. The concurrent development of photocurable resins that are biocompatible, biodegradable, and bioactive has enabled a vast array of biomedical and translation medical applications of stereolithography-based fabrication technologies. Stereolithographic techniques have been readily integrated with medical imaging technologies in order to improve disease diagnosis, preoperative planning, quality and morphology of prosthetics and implants, and functional success of complex surgeries. Furthermore, stereolithography has established itself as one of the primary enabling tools that will be useful for regenerative medicine applications in the coming years. As a whole, the versatility in design, scale, resolution, and broad applicability of stereolithographic technologies render them the ideal enabling technology for biomedical and translational medical applications.
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The musculoskeletal system, which includes bone, cartilage, tendon/ligament, and skeletal muscle, is becoming the targets for tissue engineering because of the high need for their repair and regeneration. Numerous factors would affect the use of musculoskeletal tissue engineering for tissue regeneration ranging from cells used for scaffold seeding to the manufacture and structures of materials. The essential function of the scaffolds is to convey growth factors as well as cells to the target site to aid the regeneration of the injury. Among the variety of biomaterials used in scaffold engineering, silk fibroin is recognized as an ideal material for its impressive cytocompatibility, slow biodegradability, and excellent mechanical properties. The current review describes the advances made in the fabrication of silk fibroin scaffolds with different forms such as films, particles, electrospun fibers, hydrogels, three-dimensional porous scaffolds, and their applications in the regeneration of musculoskeletal tissues.
Article
Several synthetic scaffolds are being developed using polymers, ceramics and their composites to overcome the limitations of auto- and allografts. Polymer-ceramic composites appear to be the most promising bone graft substitute since the natural bone itself is a composite of collagen and hydroxyapatite. Ceramics provide strength and osteoconductivity to the scaffold while polymers impart flexibility and resorbability. Natural polymers have an edge over synthetic polymers because of their biocompatibility and biological recognition property. But, very few natural polymer-ceramic composites are available as commercial products, and those few are predominantly based on type I collagen. Disadvantages of using collagen include allergic reactions and pathogen transmission. The commercial products also lack sufficient mechanical properties. This review summarizes the recent developments of biocomposite materials as bone scaffolds to overcome these drawbacks. Their characteristics, in vitro and in vivo performance are discussed with emphasis on their mechanical properties and ways to improve their performance.
Article
There is a growing demand for three-dimensional scaffolds for expanding applications in regenerative medicine, tissue engineering, and cell culture techniques. The material requirements for such three-dimensional structures are as diverse as the applications themselves. A wide range of materials have been investigated in the recent decades in order to tackle these requirements and to stimulate the anticipated biological response. Among the most promising class of materials are inorganic/organic hydrogel composites for regenerative medicine. The generation of synergetic effects by hydrogel composite systems enables the design of materials with superior properties including biological performance, stiffness, and degradation behavior in vitro and in vivo. Here, we review the most important organic and inorganic materials used to fabricate hydrogel composites. We highlight the advantages of combining different materials with respect to their use for biofabrication and cell encapsulation as well as their application as injectable materials for tissue enhancement and regeneration. [GRAPHICS] .