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Dramatic Improvement of the Mechanical Strength of Silane-Modified Hydroxyapatite–Gelatin Composites via Processing with Cosolvent
Abstract
Bone tissue engineering (BTE) requires a sturdy biomaterial for scaffolds for restoration of large bone defects. Ideally, the scaffold should have a mechanical strength comparable to the natural bone in the implanted site. We show that adding cosolvent during the processing of our previously developed composite of hydroxyapatite–gelatin with a silane cross-linker can significantly affect its mechanical strength. When processed with tetrahydrofuran (THF) as the cosolvent, the new hydroxyapatite–gelatin composite can demonstrate almost twice the compressive strength (97 vs 195 MPa) and biaxial flexural strength (222 vs 431 MPa) of the previously developed hydroxyapatite–gelatin composite (i.e., processed without THF), respectively. We further confirm that this mechanical strength improvement is due to the improved morphology of both the enTMOS network and the composite. Furthermore, the addition of cosolvents does not appear to negatively impact the cell viability. Finally, the porous scaffold can be easily fabricated, and its compressive strength is around 11 MPa under dry conditions. All these results indicate that this new hydroxyapatite–gelatin composite is a promising material for BTE application.
Supplementary resource (1)
... In this study, BHA/HA was formulated with gelatin (GEL) as the bone scaffold. 3,[24][25][26] The addition of GEL helps in increased the compressive strength of biomaterials, In general, the addition of polymers such as gelatine (GEL) helped increase the compressive strength and resulted in a controllable degradation rate of the scaffold. 27,28 The aim of this study was to investigate the in vivo performance of the BHA-based scaffold, specifically inflammatory response through M1 and M2, and osteoconductivity. ...
... This complex subsequently interacts with the PO 4 3and forms critical size nuclei, which are useful for HA crystal formation. 24,25 Moreover, the compressive strength of the BHA-GEL scaffold is the closest to that of the human cortical bone (100-230 MPa), and slightly higer than the human bone tensile strength reported by Fischer et al. 39 This compressive strength of BHA-GEL was also the closest to the rat femur bone, which was reported as 126.6 ± 19.7 and 167.3 ± 42.2 MPa for metaphyseal and diaphyseal specimens, respectively. 37 These hard characteristics of BHA-GEL scaffolds may prevent the premature degradation of the scaffold in vivo. ...
Hydroxyapatite (HA) is a biomaterial widely used to treat bone defect, such as due to traffic accident. The HA scaffold is obtained from synthetic HA or natural sources, such as bovine hydroxyapatite (BHA). This study aims to compare the characteristics and in vivo performance of BHA-based and HA-based scaffolds. For this purpose, the scaffold was formulated with gelatin (GEL) and characterised by SEM-EDX, FTIR and mini autograph. The defect model was carried out on the femur area of Wistar rats classified into three animal groups: defect, HA-GEL and BHA-GEL. Postoperatively (7, 14 and 28 days), the bone was radiologically evaluated, and stained with haematoxylin–eosin, anti-CD80 and anti-CD163. The BHA-GEL scaffold showed a regular surface and spherical particle shape, whereas the HA-GEL scaffold exhibited irregular surface. The BHA-GEL scaffold had higher pore size and compressive strength and lower calcium-to-phosphorus ratio than the HA-GEL scaffold. In vivo study showed that the expression of CD80 in the three experimental groups was not significantly different. However, the expression of CD163 differed significantly between the groups. The BHA-GEL group showed robust expression of CD163 on day 7, which rapidly decreased over time. It also showed increased osteoclasts, osteoblasts and osteocytes cell count that contributed to the integrity of the defect area. In conclusion, the BHA-based scaffold exhibited the desired physical and chemical characteristics that benefit in vivo performance versus the HA-based scaffold. Thus, the BHA-based scaffold may be used as a bone graft.
... The carbonate group is known to increase osteoblast proliferation, thus accelerating the synthesis of new bone matrix [5]. Gelatin (GEL) is a polymer similar to bone organic minerals and is useful for supporting apatite crystal formation in the synthesis of new bone matrix [6,7]. This makes BHA and GEL widely used as scaffold components for bone tissue engineering. ...
Objectives
Biomaterials are widely used as drug delivery systems targeting bone tissue, such as to treat bone infectious disease. However, the addition of drugs to biomaterials weakens their mechanical properties. Crosslinkers are compounds that improve the mechanical properties of biomaterials. This study aims to determine the effect of glutaraldehyde (GTA) as a crosslinker on the characteristics of bovine hydroxyapatite-gelatin-based bone scaffold with gentamicin as antibiotics (BHA-GEL-GEN-GTA).
Methods
BHA-GEL-GEN-GTA scaffold with GTA solid content ranging from 0.1 to 1.4 wt% was made by direct compression. The compressive strength test was carried out using autograph. Scaffold degradation test was carried out by dissolving the scaffolds in PBS. Scaffold toxicity was performed by MTT assay using BHK-21 fibroblast cells.
Results
There was a significant difference in the scaffolds’ compressive strength due to differences in GTA volume. Scaffold crosslinked using GTA with solid content 0.1 and 0.2 wt% in 2 mL solution had higher compressive strength than those in 1 mL solution. Furthermore, GTA with solid content 0.6, 1, 1.2, and 1.4 wt% showed higher compressive strength than those without GTA. Degradation test results showed that GTA increased the percentage of weight loss and swelling of the scaffold. The scaffold exhibited a nontoxic profile in MTT assay.
Conclusions
GTA with optimum solid content shows great compressive strength, stable swelling profile with low percentage of scaffold’s weight loss, and is considered as nontoxic.
Bone defects caused by various factors may cause morphological and functional disorders that can seriously affect patient’s quality of life. Autologous bone grafting is morbid, involves numerous complications, and provides limited volume at donor site. Hence, tissue-engineered bone is a better alternative for repair of bone defects and for promoting a patient’s functional recovery. Besides good biocompatibility, scaffolding materials represented by hydroxyapatite (HA) composites in tissue-engineered bone also have strong ability to guide bone regeneration. The development of manufacturing technology and advances in material science have made HA composite scaffolding more closely related to the composition and mechanical properties of natural bone. The surface morphology and pore diameter of the scaffold material are more important for cell proliferation, differentiation, and nutrient exchange. The degradation rate of the composite scaffold should match the rate of osteogenesis, and the loading of cells/cytokine is beneficial to promote the formation of new bone. In conclusion, there is no doubt that a breakthrough has been made in composition, mechanical properties, and degradation of HA composites. Biomimetic tissue-engineered bone based on vascularization and innervation show a promising future.
In the present study, a novel chitosan-functionalized graphene oxide decorated with glycidyl methacrylate (GO–CS–GMA) was synthesized and combined with nanohydroxyapatite particles (nHAp) to produce a novel hybrid synthetic natural material as a reinforcing phase for dental and biomedical purposes. In this process, the graphene oxide converted to GO–COCl, then reacted with chitosan (CS) to prepare GO–CS and final reaction of GO–CS with glycidyl methacrylate (GMA) gave methacrylate functionalized GO–CS–GMA. In another process, an alkyl bromide derivative of nanohydroxyapatite (nHAp-Br, radical initiator) was made from reaction of nHAP with 2-bromoisobutyryl bromide.
Finally, atom transfer radical polymerization (ATRP) was used to the grafting of GO–CS–GMA onto nHAp surface to give nanohybrid compounds that were utilized in the nanocomposite formulation. The structure, thermal stability, and mechanical properties of the nanocomposites were investigated by FTIR, XRD, CHN, FE-SEM, and TGA. The thermal stability of the final composite was higher than its precursor nHAp and GO–CS–GMA. A synergistic effect of graphene oxide, chitosan, and glycidyl methacrylate on reinforcing hydroxyapatite has been observed. The resulting nanocomposite revealed around 56% and 20% increases in compressive and flexural strength, respectively, in comparison with hydroxyapatite. In addition, both compressive and flexural strengths of new composites were improved in comparison with the conventional composites which are made from barium glass fillers. Cellular studies using human alveolar basal epithelial cells (A549 cell line) suggest that remarkable biocompatibility is shown by nHAp-g-GO–CS–GMA, which makes it an encouraging material for biomedical applications.Graphical abstract
Functionalized elastomeric networks were obtained via a polycondensation reaction between poly(dimethylsiloxane) (PDMS) containing Si(CH3)2OH as end groups and an imidazole- or benzimidazole-modified alkoxysilane. The structure of the polymeric materials was characterized via attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and solid-state 13C and 29Si NMR spectroscopy, which indicated the presence of silsesquioxane units that acted as nodes on the PDMS chains and linked the functional groups. Thermogravimetric analysis (TGA) of the product indicated high thermal stability with an initial weight-loss temperature around 450 K. The capacity for the removal of copper(II) from aqueous solution was estimated from adsorption isotherms, yielding values of 35.74 and 66.09 mg g-1, respectively, for benzimidazole- and imidazole-functionalized materials. The major adsorption models were evaluated to fit the removal data of copper(II) and the model elaborated by Sips was determined to provide the best fit for both prepared materials.
The sol-gel process is an inorganic polymerization considered a promising route for the design of new materials for optical, electrical, (bio)-medical and solar energy applications. Special attention is focused on the design of silica-based material by of sol-gel process. The aim of the paper is to investigate, in order to understand, the role of some important parameters (precursors type, pH, catalysts, temperature etc.) in sol-gel routes. It is proved that the textural and structural material properties are strongly influenced by synthesis and processing parameters.
To further improve the physical strength and biomedical applicability of bioceramics built on hydroxyapatite-gelatin (HAp-Gel) and siloxane sol-gel reactions, we incorporated mussel adhesive inspired polydopamine (PD) into our original composite based on HAp-Gel cross-linked with siloxane. Surprisingly, with the addition of PD, we observed that the processing conditions and temperatures play an important role in the structure and performance of these materials. A systematic study to investigate this temperature dependence behavior discloses that the rate of crosslinking of silane during the sol-gel process is significantly influenced by the temperature, whereas the polymerization of the dopamine only shows minor temperature dependence. With this discovery, we report an innovative thermal process for the design and application of these biocomposites.
Studies on sol–gel synthesis of monolithic silica and silicate glasses are summarized. Major research efforts have been devoted to avoid the fracture problems, associated with the extensive shrinkage of wet gels during drying. Supercritical drying, incorporation of silica fillers, and reduction of the surface tension of pore liquid have been used to form monolithic dried gels without fracture. More recent studies have shown that wet gels derived from alkoxides can be dried in a relatively short time without fracture at ambient pressure, by employing controlled drying accompanied by the cavitation of the pore liquid, macroscopic phase separation in parallel with gelation, and fluorine modification. By optimizing the synthesis procedure, it is also possible to reduce the use of reagents such as external alcohols, organic solvents, and other additives, which are removed during synthesis and are unnecessary in the final products. Another subject of considerable interest is the development of silica-based functional glasses that are difficult to form by conventional melt-quench and vapor-phase methods, by taking advantage of melt-free processes conducted at relatively low temperatures. Most of the recent studies on the functionalization of sol–gel-derived silica glasses are concerned with the doping of nanoparticles, rare earth ions, and/or fluorine.
Every day thousands of surgical procedures are performed to replace or repair tissue that has been damaged through disease or trauma. The developing field of tissue engineering (TE) aims to regenerate damaged tissues by combining cells from the body with highly porous scaffold biomaterials, which act as templates for tissue regeneration, to guide the growth of new tissue. This article describes the functional requirements, and types, of materials used in developing state of the art of scaffolds for tissue engineering applications. Furthermore, it describes the challenges and where future research and direction is required in this rapidly advancing field.
Materials that enhance bone regeneration have a wealth of potential clinical applications from the treatment of nonunion fractures to spinal fusion. The use of porous material scaffolds from bioceramic and polymer components to support bone cell and tissue growth is a longstanding area of interest. Current challenges include the engineering of materials that can match both the mechanical and biological context of real bone tissue matrix and support the vascularization of large tissue constructs. Scaffolds with new levels of biofunctionality that attempt to recreate nanoscale topographical and biofactor cues from the extracellular environment are emerging as interesting candidate biomimetic materials.
The worldwide incidence of bone disorders and conditions has trended steeply upward and is expected to double by 2020, especially in populations where aging is coupled with increased obesity and poor physical activity. Engineered bone tissue has been viewed as a potential alternative to the conventional use of bone grafts, due to their limitless supply and no disease transmission. However, bone tissue engineering practices have not proceeded to clinical practice due to several limitations or challenges. Bone tissue engineering aims to induce new functional bone regeneration via the synergistic combination of biomaterials, cells, and factor therapy. In this review, we discuss the fundamentals of bone tissue engineering, highlighting the current state of this field. Further, we review the recent advances of biomaterial and cell-based research, as well as approaches used to enhance bone regeneration. Specifically, we discuss widely investigated biomaterial scaffolds, micro- and nano-structural properties of these scaffolds, and the incorporation of biomimetic properties and/or growth factors. In addition, we examine various cellular approaches, including the use of mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), adult stem cells, induced pluripotent stem cells (iPSCs), and platelet-rich plasma (PRP), and their clinical application strengths and limitations. We conclude by overviewing the challenges that face the bone tissue engineering field, such as the lack of sufficient vascularization at the defect site, and the research aimed at functional bone tissue engineering. These challenges will drive future research in the field.
Causes of bone deficiency are numerous, but biomimetic alloplastic grafts provide an alternative to repair tissue naturally. Previously, a hydroxyapatite-gelatin modified siloxane (HAp-Gemosil) composite was prepared by cross-linking (N, N'-bis[(3-trimethoxysilyl)propyl]ethylene diamine (enTMOS) around the HAp-Gel nanocomposite particles, to mimic the natural composition and properties of bone. However, the tensile strength remained too low for many orthopedic applications. It was hypothesized that incorporating a polymer chain into the composite could help improve long range interaction. Furthermore, designing this polymer to interact with the enTMOS siloxane cross-linked matrix would provide improved adhesion between the polymer and the ceramic composite, and improve mechanical properties. To this end, copolymers of L-Lactide (LLA), and a novel alkyne derivatized trimethylene carbonate, propargyl carbonate (PC), were synthesized. Incorporation of PC during copolymerization affects properties of copolymers such as molecular weight, T(g), and % PC incorporation. More importantly, PC monomers bear a synthetic handle, allowing copolymers to undergo post-polymerization functionalization with graft monomers to specifically tailor the properties of the final composite. For our investigation, P(LLA-co-PC) copolymers were functionalized by an azido-silane (AS) via copper catalyzed azide-alkyne cycloaddition (CuAAC) through terminal alkyne on PC monomers. The new functionalized polymer, P(LLA-co-PC)(AS) was blended with HAp-Gemosil, with the azido-silane linking the copolymer to the silsesquioxane matrix within the final composite.These HAp-Gemosil/P(LLA-co-PC)(AS) composites were subjected to mechanical and biological testing, and the results were compared with those from the HAp-Gemosil composites. This study revealed that incorporating a cross-linkable polymer served to increase the flexural strength of the composite by 50%, while maintaining the biocompatibility of HAp-Gemosil ceramics.
Bone disorders are of significant concern due to increase in the median age of our population. Traditionally, bone grafts have been used to restore damaged bone. Synthetic biomaterials are now being used as bone graft substitutes. These biomaterials were initially selected for structural restoration based on their biomechanical properties. Later scaffolds were engineered to be bioactive or bioresorbable to enhance tissue growth. Now scaffolds are designed to induce bone formation and vascularization. These scaffolds are often porous, made of biodegradable materials that harbor different growth factors, drugs, genes, or stem cells. In this review, we highlight recent advances in bone scaffolds and discuss aspects that still need to be improved.
An ideal bone graft for restoring critical size defects (CSDs) should be sturdy enough to tolerate physiological loads, be malleable enough to fit into defects in the patient's bone, and stimulate bone regeneration. Here, we report a new nanocomposite material called Gemussel, made of gelatinous hydroxyapatite (HAP-GEL) with polydopamine crosslinking. We found that the mechanical performance of Gemussel is superior to calcium phosphate cement, can harden within aqueous environment, and is suitable for chair side applications. Gemussel is injectable and suitable for scaffolding. The combined physical properties of Gemussel were equivalent to that of cortical bone. Our result also showed that Gemussel had a compressive strength (120MPa), a biaxial flexure strength (110Mpa), and a compressive modulus (2.2GPa) that are approximating 80%, 50%, and 60% of cortical bone, respectively. We also found experimental evidence indicating that the polydopamine material in Gemussel may be bioactive and might play a role in stimulating bone formation. In support of this hypothesis, we found that osteoblasts express specific dopamine receptor subunits and adding polydopamine increased in vitro osteoblastic cell proliferation and differentiation. Mineralization and osteocalcin expression were increased by dopamine, suggesting an osteoconductive effect. To our knowledge, this is the first report which shows that osteoblasts express dopamine receptors and respond to dopamine. Taken together, our data demonstrate that polydopamine crosslinking significantly reduces brittleness of the previous HPA-GEL system and improves osteoconductivity possibly by stimulating bone formation through bioactive dopamine. Therefore, our new Gemussel bioceramics is an ideal material for restoring CSDs and bone regeneration.
This paper aims to provide useful and practical information on the design of composite prostheses for healing bone fractures and describes the material properties of living tissues such as cartilage, structural materials and loading conditions according to various cases, and modeling techniques for the simulation of tissue differentiation during bone healing. In addition, the present review paper provides an overview of composite materials for the design of prostheses and highlights the merits of using composites. The history and recent trends in fixation methods and types, types of materials used for prostheses, loading conditions, mechano-regulation theories, and modeling techniques for finite element analyses to estimate the healing of bone fractures are also introduced. The healing process of bone fractures is fully influenced by the biomechanical characteristics of an orthopedic prosthesis and the injured bone such as fracture configurations, prosthesis shape, material properties, and degradation rate of the material. The appropriate parameters are highlighted for the optimal design of composite prostheses to heal bone fractures successfully.
Monolithic gels can be more easily obtained when prepared with drying control chemical additives (DCCAs). The influence of formamide DCCA on the hydrolysis and early condensation of tetramethoxysilane has been studied by 29Si NMR. It was found that formamide decreases the hydrolysis rate by 6 × but increases the polymerization rate slightly. The rate constants for both hydrolysis and condensation reactions depend upon the concentration of formamide and solution pH.
Effects produced by changing the solvent medium on the sol-gel polymerization process have been investigated by Raman spectroscopy, the molybdenum chemical reaction and electron microscopy methods. The mechanism of particle aggregation as well as the extent of condensation of the polymeric network have been shown to be dramatically affected by the presence of organic additives, such as formamide, dimethyl formamide, acetonitrile and dioxane. These observations have been explained in terms of hydrogen bonding and electrostatic interactions which modulate the nucleophilic substitution mechanism associated with the sol-gel condensation process.
Aminosilane has been explored as an alternative chemical linker to facilitate the binding and solidification of hydroxyapatite-gelatin Aminosilane has been explored as an alternative chemical linker to facilitate the binding and solidification of hydroxyapatite-gelatin
nanocomposite at room temperature, which was synthesized using co-precipitation method in the presence of gelatin. This aminosilane nanocomposite at room temperature, which was synthesized using co-precipitation method in the presence of gelatin. This aminosilane
treatment was found effective at low concentration (~25μL/mL) and the solidification and dehydration of hydroxyapatite-gelatin treatment was found effective at low concentration (~25μL/mL) and the solidification and dehydration of hydroxyapatite-gelatin
slurry completes within hours depending on the amount of aminosilane. The resulting sample exhibits compressive strength of slurry completes within hours depending on the amount of aminosilane. The resulting sample exhibits compressive strength of
133MPa, about 40% higher than glutaraldehyde treated samples, and shows good biocompatibility based on cell adhesion, proliferation, 133MPa, about 40% higher than glutaraldehyde treated samples, and shows good biocompatibility based on cell adhesion, proliferation,
alkaline phosphate synthesis, and mineralization studies. alkaline phosphate synthesis, and mineralization studies.
We obtained silica gel membranes by sol–gel processing. In order to study the effect of some drying control chemical additives, we used an alkoxide/additive molar ratio of 1/1. The performance of the drying additives in obtaining crack-free gels was evaluated through monolithicity measurements. The structural evolution occurring in the interconnected network of the membranes during thermal treatment was monitored by Fourier transform infrared spectroscopy, structural density measurements and nitrogen gas sorption. The degree of cross-linking of the silica network was inferred from the frequency of the Si–O(Si) vibration in the range. We noted that in the presence of formamide and N,N-dimethylformamide, the Si–O–Si bonds are stronger and belong to a more cross-linked structure. Changes in the chemical properties of the membranes, evaluated by quantities of molecular water and silanol groups on their surface, were monitored by absorption bands in the range of 3800–3000 cm−1. Membranes obtained with additives have surfaces covered by a large content of isolated silanol groups even when annealed at 800 °C. The membrane obtained in the presence of amide has larger pore volume and its pore structure is in the range of mesoporosity. The membranes without additive and with propylene carbonate are microporous. Formamide and N,N-dimethylformamide allowed the preparation of crack-free membranes stabilized at high temperatures.
High-resulution 29Si NMR has been employed to investigate the role of chemical additives in the dynamics of the sol-gel hydrolysis process. The chemical additives selected for the study are formamide, dimethyl formamide, dioxane and acetonitrile. The kinetics of the hydrolysis reaction have been shown to be strongly dependent upon the viscosity of the sol-gel system, and consequently upon the viscosity of the chemical additive considered.
In the present work we studied the influence of formamide on the structural and textural characteristics of tetramethoxysilane-derived silica gels by Raman spectroscopy, small angle X-ray scattering, Mo acidic test, and N2 adsorption-desorption isotherms. It was shown that sols are made of primary particles of about 20 Å in diameter. These primary structural units agglomerate in secondary particles of about 60 Å in diameter. Gelation occurs when the secondary structural units agglomerate with each other and form a three-dimensional network throughout the sample.The evolution of the relative Raman intensity of the SiOSi peak at 830 cm−1 confirms that polycondensation still takes place after gelation, until a reduced time (reaction time/gelation time) t/tG of about 2, after which no significant variation of the Raman intensity is observed.The structural and textural characteristics were found to be dependent on the concentration of formamide. The particle size, pore volume, and average pore radius increase when the concentration of formamide increases. These results are in very good agreement with previous work which showed that formamide decreases the hydrolysis rate but increases the polycondensation rate of tetramethoxysilane.
The use of a tranversely isotropic model is tested for the elastic behavior of bovine and human bone and the five independent constants of this model are determined. The accuracy of the model is tested for eight cases by comparing the off-axis modulus predicted by a rotation of stiffness matrix with an experimentally determined off-axis modulus. Ultimate properties are presented for bovine and human bone for tension, compression, and torsional loads. A Hankinson type failure criterion is proposed for off-axis ultimate stress and this predicted value compared with experimental values for nine cases.
Experimental determination of the elastic modulus and ultimate strength of human tibial trabecular bone as a function of metaphyseal location is presented. A 1 cm cubic matrix with planes parallel to the subchondral plate was defined on five fresh frozen cadaver tibias. Approximately 400, 7 mm X 10 mm cylindrical bone plugs were cut from the locations defined by the matrix and tested in uniaxial compressive stress at a strain rate of 0.1%S-1. Results of the study indicate that the trabecular bone properties vary as much as two orders of magnitude from one location to another. As might be predicted from Wolff's law, and noted by previous investigators, concentrations of strength arise from the medial and lateral metaphyseal cortices toward the major medial and lateral contact regions. These results may be valuable for improved analytical modeling and optimal prosthetic design.
A nanocomposite of gelatin[GEL]-hydroxyapatite[HAp] was prepared using the biomimetic process. The hydroxyapatite nanocrystals were precipitated in aqueous solution of gelatin at pH 8 and 38 degrees C. The chemical bonding between calcium ions of HAp and carboxyl ions of GEL molecules induced a red-shift of the 1339 cm(-1) band of GEL in FT-IR analysis. TEM images and electron diffraction patterns for the nanocomposite strongly indicate the self-organization of HAp nanocrystals along the GEL fibrils. Electron diffraction for the nanocomposites showed a strong preferred orientation of the (002) plane in HAp nanocrystals. The development of HAp nanocrystals in an aqueous GEL solution was highly influenced by the concentration ratio of GEL to HAp. A higher concentration of GEL induced the formation of tiny crystallites (4 nm x 9 nm size), while a lower concentration of GEL contributed to the development of bigger crystallites (30 nm x 70 nm size). From DT/TGA data, the HAp-GEL nanocomposite showed typically three exothermic temperatures. The increase in decomposition temperatures indicates the formation of a primary chemical bond between HAp and GEL. The higher concentration of GEL supplies abundant reaction sites containing groups such as carboxyl, which can bind with calcium ions. The abundant supply of reaction sites leads to a very large number of HAp nuclei. However, the formation of a large number of nuclei depletes the concentration of calcium ions that available for growth to the extent that the nuclei cannot grow very large. This in turn will lead to the creation of a large number of tiny nanocrystals at this higher GEL concentration.
The hydroxyapatite (HAp)/gelatin (GEL) nanocomposite was prepared through the coprecipitation and then cross-linked by using glutaraldehyde (GA). From FT-IR measurement the spectral features for amide bands and phosphate bands were severely modified by the cross-linkage and the organic content increased with the degree of cross-linkage. From Transmission Electron Microscopy (TEM) and electron diffraction analyses we could confirm the preferentially directional growth of needle-like HAp particles, which were embedded in GEL by the mineralization. Also we could observe worm-like stria patterns of contrast, which were revealed by the mineralization on the individual GEL fibrils. Moiré images were observed in a highly cross-linked HAp/GEL nanocomposite sample and we think the cross-linkage induced the assembly of unordered individual fibrils along the preferential direction.
The field of tissue engineering integrates the latest advances in molecular biology, biochemistry, engineering, material science, and medical transplantation. Researchers in the developing field of regenerative medicine have identified bone tissue engineering as an attractive translational target. Clinical problems requiring bone regeneration are diverse, and no single regeneration approach will likely resolve all defects. Recent advances in the field of tissue engineering have included the use of sophisticated biocompatible scaffolds, new postnatal multipotent cell populations, and the appropriate cellular stimulation. In particular, synthetic polymer scaffolds allow for fast and reproducible construction, while still retaining biocompatible characteristics. These criteria relate to the immediate goal of determining the ideal implant. The search is becoming a reality with widespread availability of biocompatible scaffolds; however, the desired parameters have not been clearly defined. Currently, most research focuses on the use of bone morphogenetic proteins (BMPs), specifically BMP-2 and BMP-7. These proteins induce osteogenic differentiation in vitro, as well as bone defect healing in vivo. Protein-scaffold interactions that enhance BMP binding are of the utmost importance, since prolonged BMP release creates the most osteogenic microenvironment. Transition into clinical studies has had only mild success and relies on large doses of BMPs for bone formation. Advances within the field of bone tissue engineering will likely overcome these challenges and lead to more clinically relevant therapies.