Bone Defect Repair Material Research Articles

Anisotropic tough double network hydrogel from fish collagen and its spontaneous invivo bonding to bone.

Soft supporting tissues in the human body, such as cartilages and ligaments, are tough materials and firmly fixed to bones. These soft tissues, once injured, cannot regenerate spontaneously in vivo. Developing tough and biocompatible hydrogels as artificial soft supporting tissues would substantially improve outcomes after soft tissue injury. Collagen is the main rigid component in soft connective tissues which is organized in various hierarchical arrays. We have successfully developed a novel class of collagen fibril-based tough hydrogels based on the double network (DN) concept using swim bladder collagen (SBC) extracted from Bester sturgeon fish. The DN hydrogels, SBC/PDMAAm, are composed of physically/chemically crosslinked anisotropic SBC fibril as the first network and neutral, biocompatible poly(N,N'-dimethylacrylamide) (PDMAAm) as the second network. The anisotropic structure of SBC fibril network, which is well retained in the DN hydrogels, is formed by free injection method, taking advantage of the excellent fibrillogenesis capacity of SBC. The denaturation temperature of collagen is improved in the DN hydrogels. These DN gels possess anisotropic swelling behavior, exhibit excellent mechanical properties comparable to natural cartilage. The 4 weeks implantation of the gels in the osteochondral defect of rabbit knee also shows excellent biomechanical performance invivo. Furthermore, the hydroxyapatite (HAp) coated DN gels, HAp/SBC/PDMAAm gels, strongly bond to bone after 4 weeks. This new class of collagen-based hybrid DN gels, as soft and elastic ceramics, having good biomechanical performance and strong bonding ability with bone would expand the choice for designing next-generation orthopedic implants such as artificial cartilage, bone defect repair material in the load-bearing region of the body.

Systematical Evaluation of Mechanically Strong 3D Printed Diluted magnesium Doping Wollastonite Scaffolds on Osteogenic Capacity in Rabbit Calvarial Defects.

Wollastonite (CaSiO3; CSi) ceramic is a promising bioactive material for bone defect repair due to slightly fast degradation of its porous constructs in vivo. In our previous strategy some key features of CSi ceramic have been significantly improved by dilute magnesium doping for regulating mechanical properties and biodegradation. Here we demonstrate that 6 ~ 14% of Ca substituted by Mg in CSi (CSi-Mgx, x = 6, 10, 14) can enhance the mechanical strength (>40 MPa) but not compromise biological performances of the 3D printed porous scaffolds with open porosity of 60‒63%. The in vitro cell culture tests in vitro indicated that the dilute Mg doping into CSi was beneficial for ALP activity and high expression of osteogenic marker genes of MC3T3-E1 cells in the scaffolds. A good bone tissue regeneration response and elastoplastic response in mechanical strength in vivo were determined after implantation in rabbit calvarial defects for 6‒12 weeks. Particularly, the CSi-Mg10 and CSi-Mg14 scaffolds could enhance new bone regeneration with a significant increase of newly formed bone tissue (18 ~ 22%) compared to the pure CSi (~14%) at 12 weeks post-implantation. It is reasonable to consider that, therefore, such CSi-Mgx scaffolds possessing excellent strength and reasonable degradability are promising for bone reconstruction in thin-wall bone defects.

Enhancing the Gelation and Bioactivity of Injectable Silk Fibroin Hydrogel with Laponite Nanoplatelets.

Regenerated silk fibroin (RSF) of Bombyx mori silk fiber is a promising natural material for bone defect repair. However, a lack of specific integrin and growth factor for osteoinduction significantly hinders its application in this area. In this study, the role of Laponite nanoplatelet (LAP), a bioactive clay that can promote osteoblast growth, in the formation of RSF hydrogel, as well as the various properties of RSF/LAP hybrid hydrogel, was closely investigated. The results indicate that LAP could serve as a medium to accelerate hydrophobic interaction among the RSF molecules and a disruptor to limit the growth of β-sheet domain during the gelation of RSF. Rheological measurement suggests that the RSF/LAP hydrogel is injectable as it displays thixotropy in the room temperature. Proliferation and differentiation results of the primary osteoblasts encapsulated in hydrogel show that RSF/LAP hydrogel can promote the cell proliferation and enhance the osteogenic differentiation. The transcript levels for alkaline phosphatase, osteocalcin, osteopontin, and collagen type I osteogenic markers obviously improve with RSF/LAP hydrogel compared to the controls at 14 days, especially with the higher contents of LAP. Overall, the results suggest that the RSF/LAP hydrogel have great potential to be utilized as an injectable biomaterial for irregular bone defect repair.

Effect of Resorbable Collagen Plug on Bone Regeneration in Rat Critical-Size Defect Model

The purpose of this investigation was to examine the effect of resorbable collagen plug (RCP) on bone regeneration in rat calvarial critical-size defects. About 5-mm-diameter calvarial defects were created in forty 12-week-old male Sprague-Dawley rats and implanted with or without RCP. Animals were killed at 1, 2, 4, and 8 weeks postoperatively. After being killed, specimens were collected and subjected to micro-computed tomography (μCT) and histological analysis. The μCT showed a significant increase of newly formed bone volume/tissue volume in RCP-implanted defect compared with controls at all designated time points. After 8 weeks, the defects implanted with RCP displayed almost complete closure. Hematoxylin and eosin staining of the decalcified sections confirmed these observations and evidenced active bone regeneration in the RCP group. In addition, Masson's trichrome staining demonstrated that RCP implantation accelerated the process of collagen maturation. The RCP enhances bone regeneration in rat critical-size cranial defects, which suggest it might be a desired material for bone defect repair.

Repair of rat cranial bone defect by using bone morphogenetic protein-2-related peptide combined with microspheres composed of polylactic acid/polyglycolic acid copolymer and chitosan

The effects of the transplanted bone morphogenetic protein-2 (BMP2) -related peptide P24 and rhBMP2 combined with poly(lactic-co-glycolic acid) (PLGA)/chitosan (CS) microspheres were investigated in promoting the repair of rat cranial bone defect. Forty white rats were selected and equally divided into four groups (group A: 1 μg of rhBMP2/PLGA/CS composite; group B: 3 mg of P24/PLGA/CS composite; group C: 0.5 μg of rhBMP2 + 1.5 mg of P24/PLGA/CS composite; group D: blank PLGA/CS material), and rat cranial bone defect models with a diameter of 5 mm were established. The materials were transplanted to the cranial bone defects. The animals were sacrificed on weeks 6 and 12 post-operation. Radiographic examinations (x-ray imaging and 3D CT scanning) and histological evaluations were performed. The repaired areas of cranial bone defects were measured, and the osteogenetic abilities of various materials were compared. Cranial histology, imaging, and repaired area measurements showed that the osteogenetic effects at two time points (weeks 6 and 12) in group C were better than those in groups A and B. The effects in groups A and B were similar. Group D achieved the worst repair effect of cranial bone defects, where a large number of fibrous connective tissues were observed. The PLGA/CS composite microspheres loaded with rhBMP2 and P24 had optimal concrescence and could mutually increase their osteogenesis capability. rhBMP2 + P24/PLGA/CS composite is a novel material for bone defect repair with stable activity to induce bone formation.

The effect of NovaBone combined with autologous iliac in the acetabular osteotomy of children with developmental dislocation of the hip

Objective To compare the effect of application of autologous iliac alone and NovaBone combined with autologous iliac in the acetabular osteotomy of children with developmental dislocation of the hip (DDH). Methods Data of 113 cases of children with DDH who had undergone open reduction and acetabular osteotomy surgery from 2007 to 2011 were retrospectively analyzed. According to bone material using after acetabular osteotomy, the patients were divided into autogenous iliac bone graft group (52 cases, 60 hips) and NovaBone combined with autologous iliac bone graft group (61 cases, 67 hips). There were no statistical differences in gender, age, side, dislocation type, osteotomy and acetabular index between the two groups. The patients were evaluated by Lane's scoring criteria, Severin standards and McKay standards at 6 weeks, 3 months, 6 months, 1-year and 2-year post-operation follow-up. The bone healing of acetabular osteotomy zone, radiography and function of hip were compared. Results 6 weeks and 3 months after operation, Lane bone healing score in NovaBone combined with autologous iliac bone graft group (6.4± 1.3 points and 9.6±1.7 points respectively) was obviously superior to autogenous iliac bone graft group (4.7±1.5 points and 7.8±1.2 points respectively). And 6 months and 1 year after operation, the two groups were basically reached bone healing. The Severin standard results showed that the rate (94%, 63/67) of Excellent and Good in NovaBone combined with autologous iliac bone graft group (excellent: 41 hips, good: 22 hips, Fair: 4 hips) was significantly higher than the rate (83.3%, 50/60) in autogenous iliac bone graft group (excellent: 28 hips, good: 22 hips, Fair: 10 hips). The rate (16.7%, 10/60) of Fair in autogenous iliac bone graft group was significantly higher than the rate (6.0%, 4/67) in NovaBone combined with autologous iliac bone graft group. McKay standard results were consistent with the results of radiological evaluation. Conclusion As a novel bone defect repair material, NovaBone can promote early bone healing process of acetabular osteotomy areas. It also can improve the resistance of osteotomy area. NovaBone can get a satisfied result in acetabular osteotomy in children with DDH. Key words: Hip dislocation, congenital; Child; Osteotomy

Criteria of biocompatibility of materials for bone defect repair.

We analyzed and systematized the criteria of biocompatibility of materials intended for reconstruction of bone defects on the basis of previously studied synthetic, natural, and composite biomaterials (carbonate hydroxyapatite, calcium phosphate cement, silica, natural corals, freshwater pearls, chitosan/carbonate hydroxyapatite) in the model of subcutaneous implantation to small laboratory animals.

Novel highly bioactive and biodegradable gypsum/calcium silicate composite bone cements: from physicochemical characteristics to in vivo aspects.

Gypsum is a promising material for bone defect repair due to its osteoconductivity, whereas it is still limited in orthopedic and dental surgeries due to its low bioactivity and too rapid resorption so that one major concern is the significant loss in microstructural stability in vivo. In the present strategy some key features were significantly improved by introducing rapidly biodegradable but highly bioactive calcium silicate (CS) for regulating the physicochemical properties and biological performances of the gypsum-based cements at the same liquid/solid ratio. We demonstrated that introduction of 23% CS into β-calcium sulfate hemihydrate (CSH) could improve the physicochemical properties but would not compromise the mechanical strength of the composite. The surface bioactivity was significantly enhanced by introducing 23% CS, and these biphasic composites were favorable for decelerating the biodegradation rate by nearly 18.5% in 28 days in vitro. A mild bioresorption rate, with 39.6% of composite residual 4 weeks after operation, was determined when implanted in subcutaneous tissue of rats. 8 weeks after implantation, the composite cement containing 23% CS significantly enhanced new bone tissue regeneration with a much higher relative bone content (∼68.6%) than pure gypsum in critical size femoral defects in rabbits. The novel CSH-CS biocements represent promising candidates for rapid bone resconstruction and repair in trauma and pathological conditions.

Development of multi-walled carbon nanotubes reinforced monetite bionanocomposite cements for orthopedic applications

In this study, we present results of our research on biodegradable monetite (DCPA, CaHPO4) cement with surface-modified multi-walled carbon nanotubes (mMWCNTs) as potential bone defect repair material. The cement pastes showed desirable handling properties and possessed a suitable setting time for use in surgical setting. The incorporation of mMWCNTs shortened the setting time of DCPA and increased the compressive strength of DCPA cement from 11.09±1.85MPa to 21.56±2.47MPa. The cytocompatibility of the materials was investigated in vitro using the preosteoblast cell line MC3T3-E1. An increase of cell numbers was observed on both DCPA and DCPA-mMWCNTs. Scanning electron microscopy (SEM) results also revealed an obvious cell growth on the surface of the cements. Based on these results, DCPA-mMWCNTs composite cements can be considered as potential bone defect repair materials.

Original article. Development of chitosan/nanosized apatite composites for bone cements

Abstract Background: Calcium phosphate cements (CPC) is a promising materials for bone defect repair. Nanosized apatite or calcium orthophosphate has a better bioactivity than coarser crystals. Chitosan is produced commercially from chitin that is the structural element in the exoskeleton of crustaceans such as crabs and shrimp. The mixing of nanosized apatite and chitosan may provide the consistency cement, improving mechanical properties of the set bone cement. Objective: Develop nanosized apatite powder with chitosan for bone composite cement. Materials and method: Nanosized apatite was synthesized by chemical method at low temperature and used as the single-component for bone cement. The nanosized apatite powder was characterized using X-ray diffraction method, Fourier transform infrared spectroscopy, and transmission electron microscopy. CPCs were developed based on chitosan/nanosized apatite and calcium sulfate hemihydrate. The compressive strength of the set cement was measured after one to four weeks. The phase composition and the morphology of the set cements were investigated. Results: Calcium sulfate hemihydrate was effective in increasing the compressive strength after setting in a simulated body fluid for seven days. The compressive strength of chitosan/nanosized apatite composite was about 18 MPa after soaking. Conclusion: The workability and setting time of this composite were suitable to handling for bone cement. These composite cements had a significant clinical advantage for substitution of the regenerated bone.

Development of chitosan/nanosized apatite composites for bone cements

Background: Calcium phosphate cements (CPC) is a promising materials for bone defect repair. Nanosized apatite or calcium orthophosphate has a better bioactivity than coarser crystals. Chitosan is produced commercially from chitin that is the structural element in the exoskeleton of crustaceans such as crabs and shrimp. The mixing of nanosized apatite and chitosan may provide the consistency cement, improving mechanical properties of the set bone cement. Objective: Develop nanosized apatite powder with chitosan for bone composite cement. Materials and method: Nanosized apatite was synthesized by chemical method at low temperature and used as the single-component for bone cement. The nanosized apatite powder was characterized using X-ray diffraction method, Fourier transform infrared spectroscopy, and transmission electron microscopy. CPCs were developed based on chitosan/nanosized apatite and calcium sulfate hemihydrate. The compressive strength of the set cement was measured after one to four weeks. The phase composition and the morphology of the set cements were investigated. Results: Calcium sulfate hemihydrate was effective in increasing the compressive strength after setting in a simulated body fluid for seven days. The compressive strength of chitosan/nanosized apatite composite was about 18 MPa after soaking. Conclusion: The workability and setting time of this composite were suitable to handling for bone cement. These composite cements had a significant clinical advantage for substitution of the regenerated bone. Keywords: Apatite, bone cements, calcium phosphate cement, chitosan, composites, nanosized apatite

Adhesion and Proliferation of Chondrocytes on Nano- HA/PDLLA Scaffolds for Bone Tissue Engineering

In this paper, three different scale HA/PDLLA porous scaffolds, nano-HA/PDLLA, micro-HA/PDLLA and pure PDLLA were successfully fabricated using solvent casting/particulate leaching method. Chondrocytes adhesion and proliferation on these scaffolds were investigated. In detail, the cells attachment rate and proliferation on nano-HA/PDLLA, micro-HA/PDLLA and pure PDLLA were quantitatively evaluated by cytometry. The interaction between the scaffolds and chondrocytes were observed by optical microscope with HE staining and FE-SEM. The results exhibited that nano-HA/PDLLA scaffold has a modified cell adhesion property, and cells on the nano-scaffold grow much better both in biological and morphological characteristics than on the micro-HA/PDLLA and pure PDLLA scaffolds. This work suggested that nano-HA/PDLLA composite scaffold can significantly improved cell adhesion and proliferation tendency with the existing of nano-effects，and could be used as a potential scaffold material for bone defect repair.