Enhanced BMP-2-Mediated Bone Repair Using an Anisotropic Silk Fibroin Scaffold Coated with Bone-like Apatite

The repair of large bone defects remains challenging and often requires graft material due to limited availability of autologous bone. In clinical settings, collagen sponges loaded with excessive amounts of bone morphogenetic protein 2 (rhBMP-2) are occasionally used for the treatment of bone non-unions, increasing the risk of adverse events. Therefore, strategies to reduce rhBMP-2 dosage are desirable. Silk scaffolds show great promise due to their favorable biocompatibility and their utility for various biofabrication methods. For this study, we generated silk scaffolds with axially aligned pores, which were subsequently treated with 10× simulated body fluid (SBF) to generate an apatitic calcium phosphate coating. Using a rat femoral critical sized defect model (CSD) we evaluated if the resulting scaffold allows the reduction of BMP-2 dosage to promote efficient bone repair by providing appropriate guidance cues. Highly porous, anisotropic silk scaffolds were produced, demonstrating good cytocompatibility in vitro and treatment with 10× SBF resulted in efficient surface coating. In vivo, the coated silk scaffolds loaded with a low dose of rhBMP-2 demonstrated significantly improved bone regeneration when compared to the unmineralized scaffold. Overall, our findings show that this simple and cost-efficient technique yields scaffolds that enhance rhBMP-2 mediated bone healing.     

Modified poly(caprolactone trifumarate) with embedded gelatin microparticles as a functional scaffold for bone tissue engineering

Bone tissue engineering offers high hopes in reconstructing bone defects that result from trauma, infection, tumors, and other conditions. However, there remains a need for novel scaffold materials that can effectively stimulate ossification with appropriate functional properties. Therefore, a novel injectable, biodegradable, and biocompatible scaffold made by incorporating modified poly(caprolactone trifumarate) (PCLTF) with embedded gelatin microparticles (GMPs) as porogen is developed. Specifically, in vitro and in vivo tests were carried out. For the latter, to determine the osteogenic ability of PCLTF‐GMPs scaffolds, and to characterize bone‐formation, these scaffolds were implanted into critical‐sized defects of New Zealand white rabbit craniums. Field Emission Scanning Electron Microscope (FESEM) demonstrated cells of varying shapes attached to the scaffold surface in vitro. The PCLTF‐GMPs demonstrated improved biocompatibility in vivo. Polyfluorochrome tracers detected bone growth occurring in the PCLTF‐GMPs filled defects. By incorporating PCLTF with GMPs, we have fabricated a promising self‐crosslinkable biocompatible and osteoconducive scaffold for bone tissue engineering. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43711.     

Application of strontium doped calcium polyphosphate bioceramic as scaffolds for bone tissue engineering

The critical success factors for bone tissue engineering in clinical applications are scaffolds. Ion doping is one of the most important methods to modify the properties of bioceramics for better angiogenesis abilities, biomechanical properties, and biocompatibility. This paper presents a novel ion doping method applied in calcium polyphosphate (CPP)-based bioceramic scaffolds substituted by strontium ions to form (SCPP) scaffolds for bone tissue regeneration. The microstructure and crystallization of the scaffolds were detected by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Degradation tests were assessed to evaluate the mechanical and chemical stabilities of SCPP in vitro. The cell biocompatibility was measured with respect to the cytotoxicity of the extractions of scaffolds. Bone implantation was performed to evaluate the biodegradability and osteoconductivity of the scaffolds, and the bone formation examined by using X-ray radiography. The results indicated that the obtained SCPP scaffolds had a single CPP phase. The SCPP scaffolds yielded a better degradation property than the pure CPP scaffold. The MTT assay and in vivo results reveal that the SCPP scaffolds exhibited a better cell biocompatibility and tissue biocompatibility than CPP and hydroxyapatite (HA) scaffolds. The in vivo immunohistochemistry staining for VEGF also showed that SCPP had a potential to promote the formation of angiogenesis and the regeneration of bone. SCPP scaffold could serve as a potential biomaterial with stimulating angiogenesis in bone tissue engineering and bone repair.     

Fabrication and biocompatibility of porously bioactive scaffold of nonstoichiometric apatite and poly(ε‐caprolactone) nanocomposite

Bioactive nanocomposite of nonstoichiometric apatite (ns‐AP) and poly(ε‐caprolactone) (PCL) was synthesized and its porous scaffold was fabricated. The results show that the hydrophilicity and cell attachment ratio on the composite surface improved with the increase of ns‐AP content in PCL. The composite scaffolds with 60 wt % ns‐AP content contained open and interconnected pores ranging in size from 200 to 500 μm and exhibit a porosity of around 80%. In addition, proliferation of MG₆₃ cells on the composite scaffolds significantly increased with the increase of ns‐AP content, and the level of alkaline phosphatase (ALP) activity and nitric oxide (NO) production of the cells cultured on the composite scaffold were higher than that of PCL at 7 days, revealing that the composite scaffolds had excellent in vitro biocompatibility and bioactivity. The composite scaffolds were implanted into rabbit mandible defects, the results suggest that the introduction of ns‐AP into PCL enhanced the efficiency of new bone formation, and the ns‐AP/PCL composite exhibited in vivo good biocompatibility and osteogenesis. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Bone morphogenetic protein‐2 immobilization on porous PCL‐BCP‐Col composite scaffolds for bone tissue engineering

The objective of this study was to develop novel porous composite scaffolds for bone tissue engineering through surface modification of polycaprolactone–biphasic calcium phosphate‐based composites (PCL–BCP). PCL–BCP composites were first fabricated with salt‐leaching method followed by aminolysis. Layer by layer (LBL) technique was then used to immobilize collagen (Col) and bone morphogenetic protein (BMP‐2) on PCL–BCP scaffolds to develop PCL–BCP–Col–BMP‐2 composite scaffold. The morphology of the composite was examined by scanning electron microscopy (SEM). The efficiency of grafting of Col and BMP‐2 on composite scaffold was measured by X‐ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Both XPS and FTIR confirmed that Col and BMP‐2 were successfully immobilized into PCL–BCP composites. MC3TC3‐E1 preosteoblasts cells were cultivated on composites to determine the effect of Col and BMP‐2 immobilization on cell viability and proliferation. PCL–BCP–Col–BMP‐2 showed more cell attachment, cell viability, and proliferation bone factors compared to PCL–BCP‐Col composites. In addition, in vivo bone formation study using rat models showed that PCL–BCP–Col–BMP‐2 composites had better bone formation than PCL–BCP‐Col scaffold in critical size defect with 4 weeks of duration. These results suggest that PCL–BCP–Col–BMP‐2 composites can enhance bone regeneration in critical size defect in a rat model with 4 weeks of duration. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45186.     

Fabrication and evaluation of nanofibrous polyhydroxybutyrate valerate scaffolds containing hydroxyapatite particles for bone tissue engineering

Tissue engineering is a new approach for regeneration of damaged tissues. The current clinical methods such as autograft and allograft transplantation are not effective for repairing bone damages, mainly due to the limited available sources and the donor-site side effects. In this research, the nanocomposite poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)/nano hydroxyapatite (nHA) scaffolds with different nHA ratios for bone regeneration were utilized. The diameter and porosity of scaffolds were approximately 200?nm and 74%, respectively. The degradability test of the scaffolds suggests a low degradation rate with total degradation of 30% after 3 months. Cytotoxicity result showed that cultured osteoblast cells (MC3T3) on nanocomposite scaffolds had superiority in terms of higher proliferation and attachment in comparison with PHBV scaffold. The protein expression of alkaline phosphatase illustrated that nanofibrous scaffold containing hydroxyapatite had the highest alkaline phosphatase activities as a result of better proliferation. These results recommend that PHBV/nHA scaffolds are suitable candidates for bone tissue engineering.     

Reinforcement of electrospun poly(ε‐caprolactone) scaffold using diopside nanopowder to promote biological and physical properties

Considerable efforts have been devoted toward the development of electrospun scaffolds based on poly(ε‐caprolactone) (PCL) for bone tissue engineering. However, most of previous scaffolds have lacked the structural and mechanical strength to engineer bone tissue constructs with suitable biological functions. Here, we developed bioactive and relatively robust hybrid scaffolds composed of diopside nanopowder embedded PCL electrospun nanofibers. Incorporation of various concentrations of diopside nanopowder from 0 to 3 wt % within the PCL scaffolds notably improved tensile strength (eight‐fold) and elastic modulus (two‐fold). Moreover, the addition of diopside nanopowder significantly improved bioactivity and degradation rate compared to pure PCL scaffold which might be due to their superior hydrophilicity. We investigated the proliferation and spreading of SAOS‐II cells on electrospun scaffolds. Notably, electrospun PCL‐diopside scaffolds induced significantly enhanced cell proliferation and spreading. Overall, we concluded that PCL‐diopside scaffold could potentially be used to develop clinically relevant constructs for bone tissue engineering. However, the extended in vivo studies are essential to evaluate the role of PCL‐diopside fibrous scaffolds on the new bone growth and regeneration. Therefore, in vivo studies will be the subject of our future work. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134 , 44433.     

Tetracycline hydrochloride-containing poly (ε-caprolactone)/poly lactic acid scaffold for bone tissue engineering application: in vitro and in vivo study

In the current study, tetracycline hydrochloride (TCH), an antibiotic against most of the medically relevant bacteria, was incorporated into poly (ε-caprolactone)/poly lactic acid solution in order to develop a composite scaffold with both antibacterial and osteoinductive properties for the repair of infected bone defects. The composite scaffolds were produced from poly (ε-caprolactone) (PCL) and poly lactic acid (PLA) solution (1:1 (w/w)) incorporated with 3, 5, and 10% (w/w) of TCH by thermally induced phase separation technique. The scaffolds were evaluated regarding their morphology, wettability, porosity, degradation, mechanical properties, and cellular response. The scaffold containing 10% of TCH (PCL/PLA/TCH10%) was chosen as the optimum scaffold for further investigation in a rat femoral defect model. The study showed that after eight weeks, the bone formation was relatively higher in PCL/PLA/TCH10%-treated group with completely filled defect when compared with control (PCL/PLA scaffold without TCH). Histopathological evaluation showed that the defect in PCL/PLA/TCH10%-treated group was fully replaced by new bone and connective tissue. Our results provide evidence supporting the possible applicability of TCH-containing scaffolds for successful bone regeneration.     

Dual Delivery of BMP-2 and bFGF from a New Nano-Composite Scaffold,Loaded with Vascular Stents for Large-Size Mandibular Defect Regeneration

The aim of this study was to investigate the feasibility and advantages of the dual delivery of bone morphogenetic protein-2 (BMP-2) and basic fibroblast growth factor (bFGF) from nano-composite scaffolds (PLGA/PCL/nHA) loaded with vascular stents (PLCL/Col/nHA) for large bone defect regeneration in rabbit mandibles. Thirty-six large bone defects were repaired in rabbits using engineering bone composed of allogeneic bone marrow mesenchymal stem cells (BMSCs), bFGF, BMP-2 and scaffolds composed of PLGA/PCL/nHA loaded with PLCL/Col/nHA. The experiments were divided into six groups: BMSCs/bFGF/BMP-2/scaffold, BMSCs/BMP-2/scaffold, BMSCs/bFGF/scaffold, BMSCs/scaffold, scaffold alone and no treatment. Sodium alginate hydrogel was used as the carrier for BMP-2 and bFGF and its features, including gelling, degradation and controlled release properties, was detected by the determination of gelation and degradation time coupled with a controlled release study of bovine serum albumin (BSA). AlamarBlue assay and alkaline phosphatase (ALP) activity were used to evaluate the proliferation and osteogenic differentiation of BMSCs in different groups. X-ray and histological examinations of the samples were performed after 4 and 12 weeks post-implantation to clarify new bone formation in the mandible defects. The results verified that the use of sodium alginate hydrogel as a controlled release carrier has good sustained release ability, and the combined application of bFGF and BMP-2 could significantly promote the proliferation and osteogenic differentiation of BMSCs (p < 0.05 or p < 0.01). In addition, X-ray and histological examinations of the samples exhibited that the dual release group had significantly higher bone formation than the other groups. The above results indicate that the delivery of both growth factors could enhance new bone formation and vascularization compared with delivery of BMP-2 or bFGF alone, and may supply a promising way of repairing large bone defects in bone tissue engineering.     

Adjusting physicochemical and cytological properties of biphasic calcium phosphate by magnesium substitution: An in vitro study

Biphasic calcium phosphate (BCP) is a highly study bone defect repair material with adjustable degradation, perfect osteoconduction and good osteoinduction. As one of the essential trace elements, magnesium (Mg) possesses the abilities of pro-osteogenesis and pro-angiogenesis. Therefore, Mg doping may further expand the application of BCP in bone defect repair, but few studies focus on promoting the osteogenesis and angiogenesis of BCP simultaneously by Mg doping, and the optimal doping amount of Mg remains to be explored. In this study, the physicochemical and biological properties of BCP scaffold affected by Mg doping were systematically study. Results showed that Mg doping enhanced the sintering of BCP scaffold, resulting in the decrease of degradation rate at the initial soaking period. However, the introduction of Mg damaged the lattice stability of BCP, leading to the increase of BCP degradation rate at the later soaking period. BCP scaffolds with Mg doping content ≥3 mol.% could achieve a long-term sustained release of Mg. The ion microenvironment created by Mg-doped scaffolds was simultaneously conducive to the osteogenic differentiation of stem cells and the enhanced angiogenic activity of endothelial cells. The scaffold doped with 5 mol.% of Mg (Mg5–S) showed the highest efficiency in promoting osteogenic differentiation. Mg-doped BCP scaffolds with a doping content ≥3 mol.%, especially Mg5–S, significantly improved the proliferation and angiogenic differentiation of endothelial cells. Based on these, we believe that the optimal doping content of Mg in BCP is 5 mol.%, and Mg5–S has great application potential in bone defect repair.     

Three-dimensional printing of a β-tricalcium phosphate scaffold with dual bioactivities for bone repair

β-Tricalcium phosphate (β-TCP) had been widely used in the field of bone defect repair because of its osteoconduction and osteoinduction properties. However, for critical-sized bone defects, β-TCP scaffolds need to be functionalised to enhance osteoinduction and antibacterial activity. In this study, we proposed a protocol for mimicking a mussel adhesion mechanism to immobilise bone morphoprotein 2 mimetic peptide (BMP2-MP) and Ornithodoros savignyi (OS) on a three-dimensionally printed β-TCP scaffold. BMP2-MP and the OS polypeptides containing the YKYKY tail were converted into 3,4‐dihydroxyphenylalanine (DOPA) molecules via hydroxylase. The surface morphology and phase composition of the different scaffolds were analysed via scanning electron microscopy and X-ray diffraction. In addition, the binding activity of BMP2-MP and OS containing the DOPA tail to the scaffold were evaluated. The antibacterial activity of the different scaffolds was studied in vitro by performing bacteriostatic experiments against Escherichia coli and Staphylococcus aureus. The osteoinduction capability of the different scaffolds was evaluated by detecting osteogenesis-associated genes via quantitative polymerase chain reaction and by determining alkaline phosphatase expression levels. Our results demonstrated that introduction of the DOPA tail enhanced the binding capability of BMP2-MP and OS with the β-TCP scaffold, thereby enhancing the antibacterial and osteoinduction capabilities of the scaffold. A scaffold with strong antibacterial and osteoinduction capability will have good application prospects in the field of critical-sized bone defect repair.     

Surface‐modified pliable PDLLA/PCL/β‐TCP scaffolds as a promising delivery system for bone regeneration

Surface‐modified poly(d , l ‐lactide)/polycaprolactone/β‐tricalcium phosphate complex scaffold was fabricated in this study and we hypothesized that pliable and mechanical strong scaffold would be achieved by regulation of ternary compositions; while superficial modification strategy conduced to preserve and controlled‐release of bioactive growth factors. Properties of the composite scaffolds were systematically investigated, including mechanical properties, surface morphology, porosity, wettability, and releasing behavior. Moreover, the representative cytokine, recombinant human bone morphogenetic protein‐2 (rhBMP‐2), was loaded and implanted into muscular pouch of mouse to assess bone formation in vivo. Improved osteogenesis was achieved ascribed to both amplified β‐tricalcium phosphate (β‐TCP) content and retarded initial burst release. Particularly, scaffold doped with hydroxypropyl methylcellulose (HPMC) displayed optimal osteogenic capability. The results indicated that the PDLLA/PCL/β‐TCP complex scaffold along with HPMC‐coating and rhBMP‐2 loading was a promising candidate for bone regeneration. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40951.     

Fabrication of Bone Scaffolds from Cockle Shell Waste

Bone scaffold is a three‐dimensional structure composed of materials that could enhance bone regeneration. Bone scaffolds were prepared using freeze‐drying by varying the cockle shell powder concentration where sodium alginate acted as matrix. The scaffolds were then characterized by X‐ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, texture analyzer, and liquid displacement method. The bioactivity of the scaffolds was evaluated by immersion into a simulated body fluid solution. Cockle shell powder concentrations affected the bone scaffold characteristics. The increment of the powder concentrations improved the physicochemical properties and bioactivity of the scaffolds.     

Microporosities in 3D-Printed Tricalcium-Phosphate-Based Bone Substitutes Enhance Osteoconduction and Affect Osteoclastic Resorption

Additive manufacturing is a key technology required to realize the production of a personalized bone substitute that exactly meets a patient’s need and fills a patient-specific bone defect. Additive manufacturing can optimize the inner architecture of the scaffold for osteoconduction, allowing fast and reliable defect bridging by promoting rapid growth of new bone tissue into the scaffold. The role of scaffold microporosity/nanoarchitecture in osteoconduction remains elusive. To elucidate this relationship, we produced lithography-based osteoconductive scaffolds from tricalcium phosphate (TCP) with identical macro- and microarchitecture, but varied their nanoarchitecture/microporosity by ranging maximum sintering temperatures from 1000 °C to 1200 °C. After characterization of the different scaffolds’ microporosity, compression strength, and nanoarchitecture, we performed in vivo studies that showed that ingrowth of bone as an indicator of osteoconduction significantly decreased with decreasing microporosity. Moreover, at the 1200 °C peak sinter temperature and lowest microporosity, osteoclastic degradation of the material was inhibited. Thus, even for wide-open porous TCP-based scaffolds, a high degree of microporosity appears to be essential for optimal osteoconduction and creeping substitution, which can prevent non-unions, the major complication during bone regeneration procedures.     

Metformin-Incorporated Gelatin/Nano-Hydroxyapatite Scaffolds Promotes Bone Regeneration in Critical Size Rat Alveolar Bone Defect Model

In this study, we fabricated gelatin/nano-hydroxyapatite/metformin scaffold (GHMS) and compared its effectiveness in bone regeneration with extraction-only, Sinbone, and Bio-Oss Collagen^® groups in a critical size rat alveolar bone defect model. GHMS was synthesized by co-precipitating calcium hydroxide and orthophosphoric acid within gelatin solution, incorporating metformin, and cross-linked by microbial transglutaminase. The morphology, characterization, and biocompatibility of scaffold were examined. The in vitro effects of GHMS on osteogenic gene and protein expressions were evaluated. In vivo bone formation was assessed in a critical size rat alveolar bone defect model with micro-computed tomography and histological examination by comparing GHMS with extraction-only, Sinbone, and Bio-Oss Collagen^®. The synthesized GHMS had a highly interconnected porous structure with a mean pore size of 81.85 ± 13.8 µm. GHMS exhibited good biocompatibility; promoted ALPL, RUNX2, SP7, BGLAP, SPARC and Col1a1 gene expressions; and upregulated the synthesis of osteogenic proteins, including osteonectin, osteocalcin, and collagen type I. In critical size rat alveolar bone defects, GHMS showed superior bone regeneration compared to extraction-only, Sinbone, and Bio-Oss Collagen^® groups as manifested by greater alveolar ridge preservation, while more bone formation with a lower percentage of connective tissue and residual scaffold at the defect sites grafted with GHMS in histological staining. The GHMS presented in this study may be used as a potential bone substitute to regenerate alveolar bone. The good biocompatibility, relatively fast degradation, interconnected pores allowing vascularization, and higher bioactivity properties of the components of the GHMS (gelatin, nHA, and metformin) may contribute to direct osteogenesis.     

Compressive strength of β-TCP scaffolds fabricated via lithography-based manufacturing for bone tissue engineering

Bone is a vital organ that is responsible for the support and movement of body as well as the storage and transportation of cells and nutrients. Disease, along with traumatic events, can leave regions of bone with large voids and/or defects. Related surgical procedures, such as allografts, autografts, and arthroplasty, are reported to amount to roughly €9.6bn annually, emphasising the need for bone repair/replacement globally. Tricalcium phosphate (TCP) is a bioactive ceramic that has been identified as a suitable material for bone tissue engineering applications due to its excellent bioresorbability and overall biocompatibility. Through lithography-based ceramic manufacturing (LCM), β -TCP scaffolds were fabricated across nine different designs in this work. Pore size, unit cell size, and unit cell geometry were altered to vary the porosity of these scaffolds. Following fabrication, the material composition, topography, macrostructure, and microstructure of the β-TCP scaffolds were characterised. The effects of porosity and unit cell geometry on the compressive strengths of β -TCP scaffolds were analysed in detail. Compressive strengths of the scaffolds were measured between 1.4 ± 0.5 MPa and 67.6 ± 13.3 MPa across a porosity range of 5.58 ± 0.09% to 59.36 ± 0.18%. The strength of these scaffolds was considerably lower than that of the compressive strength of cortical bone (100–200 MPa), but mimic the compressive strength of cancellous bone well (0.1–16 MPa). While scaffolds of β-TCP alone may not be suitable for load-bearing applications, they demonstrate enough mechanical stability for bone regeneration/tissue engineering applications. They hold more potential in the regeneration of small bone defects/voids or in composite materials.     

Fabrication of fibrous poly (ɛ-caprolactone) nano-fibers containing cerium doped-bioglasses nanoparticles encapsulated collagen

Novel nanosized designed ceramic powders, cerium (Ce) doped bioglass (BG) with various doped Ce content, were synthesized by sol–gel method in order to be employed in the development of PCL fibrous scaffold for bone tissue engineering applications. Characterization techniques such as X-ray diffraction analysis, transmission electron microscopy, Fourier transform infrared spectroscopy, and energy-dispersive X-ray spectroscopy were employed to evaluate the developed Ce doped BG powders. The results confirmed successful doping of Ce inside BG structure. 0, 1, 3, and 10 wt% Ce doped 58S BG were successfully encapsulated in the collagen microspheres by water-in-oil emulsion method and the average particle size and hydrodynamic diameter of microspheres were determined using scanning electron microscopy and dynamic light scattering analysis, respectively. Next, 0, 1, 3, and 10 wt% Ce doped 58S BG encapsulated collagen microspheres were loaded inside the Poly(ɛ-caprolactone) fibrous scaffold and their in vitro bioactivity and biocompatibility properties were evaluated. The results of soaking samples in the simulated body fluid showed that all Ce doped 58S BG encapsulated collagen microspheres loaded PCL fibrous scaffold have acceptable bioactivity and apatite formation ability over time. The biocompatibility evaluation of developed scaffolds showed high viability and proliferation of MG63 cells cultured on the surface of 3% Ce doped 58S BG encapsulated collagen microsphere loaded in the PCL fibrous scaffold and its high potential ability for bone tissue engineering applications. These results potentially open new aspects for scaffolds aimed at the regeneration of bone defects.     

Glutaraldehyde crosslinked gelatin/hydroxyapatite nanocomposite scaffold,engineered via compound techniques

In this study, a scaffold was designed to be used in bone tissue repair and the effect of glutaraldehyde (GA) concentration as crosslinking agent was investigated. To mimic the mineral and organic component of natural bone, hydroxyapatite (HAp) and gelatin (GEL) were used as the main components of this composite. Nanopowders of HAp were synthesized and also used together with GEL to engineer a three‐dimensional nanocomposite scaffold. The results show that GEL/HAp nanocomposite is porous with three‐dimensional interconnected structure, pore sizes ranging from 300 to 500 μm, and about 85% porosity. In addition, increasing GA concentration provokes the enhancement of compressive strength until 1 w/v% GA solution followed by a reduction to 2.5%, whereas it causes work fracture to decrease. It was concluded that optimum concentration for crosslinking GEL matrix for this purpose is 1 w/v% GA solution. A specific combination of commonly used techniques applied to engineer a scaffold with almost ideal properties intended for the bone tissue engineering is introduced. In addition, scaffolds that are prepared via this compound process has the potential to be used in the solid free form applications and so being formed in any dimension and geometry relevant to the defect size and shape. POLYM. COMPOS., 31:2112–2120, 2010. © 2010 Society of Plastics Engineers     

Polymeric Gelatin Scaffolds Affect Mesenchymal Stem Cell Differentiation and Its Diverse Applications in Tissue Engineering

Studies using polymeric scaffolds for various biomedical applications, such as tissue engineering, implants and medical substitutes, and drug delivery systems, have attempted to identify suitable material for tissue regeneration. This study aimed to investigate the biocompatibility and effectiveness of a gelatin scaffold seeded with human adipose stem cells (hASCs), including physical characteristics, multilineage differentiation in vitro, and osteogenic potential, in a rat model of a calvarial bone defect and to optimize its design. This functionalized scaffold comprised gelatin-hASCs layers to improve their efficacy in various biomedical applications. The gelatin scaffold exhibited excellent biocompatibility in vitro after two weeks of implantation. Furthermore, the gelatin scaffold supported and specifically regulated the proliferation and osteogenic and chondrogenic differentiation of hASCs, respectively. After 12 weeks of implantation, upon treatment with the gelatin-hASCs scaffold, the calvarial bone harboring the critical defect regenerated better and displayed greater osteogenic potential without any damage to the surrounding tissues compared to the untreated bone defect. These findings suggest that the present gelatin scaffold is a good potential carrier for stem cells in various tissue engineering applications.     

Chitosan-gelatin/hydroxyapatite-based scaffold associated with mesenchymal stem cells differentiate into osteoblasts improves the surface of the bone lesion in mice C57BL/6J

Extensive injuries to bone tissue are still considered a significant clinical challenge; therefore, developing new bone tissue engineering (BTE) strategies is still necessary. This work aims to construct and characterize a chitosan-gelatin/hydroxyapatite-based (CG/H) scaffold to provide well-design support for mesenchymal stem cell (MSC) growth and differentiation to osteoblasts. First, the CG/H scaffolds are construct by freeze-drying. Then, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, x-ray diffraction, water uptake, and degradation profiles evaluate the material's surface. In addition, the CG/H morphological, biochemical, and MSC adhesion processes and growth behavior are also assess, indicating reasonable adhesion rates to the surface, low material cytotoxicity, and excellent alkaline phosphatase activity compared to control on the cellular framework. Based on these results, we obtain a highly biocompatible scaffold and that can support osteoblast differentiation. Finally, the in vivo studies demonstrate the CG/H scaffold with MSC adhere is capable of differentiating into osteoblasts, and the application of this scaffold is able to significantly enhance the closure of the bone lesion. Therefore, the CG/H scaffold has potential clinical application for bone regeneration.