This study aims to explore the vascularization of hydroxyapatite/tricalcium phosphate (HA/TCP) biomaterials implanted in mice during osteoinduction. The HA/TCP biomaterials were implanted in muscle of mice, and 2, 4, 6, 8, 10 and 12 weeks after the implantation, the materials were harvested to prepare serial sections and hematoxylin-eosin (HE) staining. The process of vascularization was dynamically described, and the area percentage of neovascularization was quantitatively analyzed. The results showed that neovascularization formation was a continuous and dynamic process. The neovascularization appeared largely in the first two weeks, with a rising trend in week 4, reached peak in week 6, and gradually reduced in week 8. The results provide ideas for improving the success rate of bone tissue engineering, and indicate the mechanism of osteoinduction.
Objective To review the recent advances in the application of graphene oxide (GO) for bone tissue engineering. Methods The latest literature at home and abroad on the GO used in the bone regeneration and repair was reviewed, including general properties of GO, degradation performance, biocompatibility, and application in bone tissue engineering. Results GO has an abundance of oxygen-containing functionalities, high surface area, and good biocompatibility. In addition, it can promote stem cell adhesion, proliferation, and differentiation. Moreover, GO has many advantages in the construction of new composite scaffolds and improvement of the performance of traditional scaffolds. Conclusion GO has been a hot topic in the field of bone tissue engineering due to its excellent physical and chemical properties. And many problems still need to be solved.
ObjectiveTo summarize the clinical application and research status of bioactive glass (BAG) in bone repair.MethodsThe recently published literature concerning BAG in bone repair at home and abroad was reviewed and summarized.ResultsBAG has been widely used in clinical bone repair with a favorable effectiveness. In the experimental aspect, to meet different clinical application needs, BAG has been prepared in different forms, such as particles, prosthetic coating, drug and biological factor delivery system, bone cement, and scaffold. And the significant progress has been made.ConclusionBAG has been well studied in the field of bone repair due to its excellent bone repair performance, and it is expected to become a new generation of bone repair material.
ObjectiveTo review the research progress of in vivo bioreactor (IVB) for bone tissue engineering in order to provide reference for its future research direction.MethodsThe literature related to IVB used in bone tissue engineering in recent years was reviewed, and the principles of IVB construction, tissue types, sites, and methods of IVB construction, as well as the advantages of IVB used in bone tissue engineering were summarized.ResultsIVB takes advantage of the body’s ability to regenerate itself, using the body as a bioreactor to regenerate new tissues or organs at injured sites or at ectopic sites that can support the regeneration of new tissues. IVB can be constructed by tissue flap (subcutaneous pocket, muscle flap/pocket, fascia flap, periosteum flap, omentum flap/abdominal cavity) and axial vascular pedicle (axial vascular bundle, arteriovenous loop) alone or jointly. IVB is used to prefabricate vascularized tissue engineered bone that matched the shape and size of the defect. The prefabricated vascularized tissue engineered bone can be used as bone graft, pedicled bone flap, or free bone flap to repair bone defect. IVB solves the problem of insufficient vascularization in traditional bone tissue engineering to a certain extent.ConclusionIVB is a promising method for vascularized tissue engineered bone prefabrication and subsequent bone defect reconstruction, with unique advantages in the repair of large complex bone defects. However, the complexity of IVB construction and surgical complications hinder the clinical application of IVB. Researchers should aim to develop a simple, safe, and efficient IVB.
In bone tissue engineering, fabrication of scaffold materials that are biodegradable with regenerative functions is one of the most important research fields. Silk fibroin exhibits many favorable characteristics used as scaffold materials. Among them, hybrid silk fibroin/inorganic composites prepared by biomimetic mineralization have better biocompatibility, biomechanical properties, and biodegradability. At the same time, the hybrid silk fibroin/inorganic materials have much better osteoinduction and conduction properties than silk fibroin. Here, the recent advances in the preparation of silk fibroin/silica hybrid materials by combination or biomimetic silicification are reviewed, and the future research prospects of silicification of silk fibroin are discussed.
As a worldwide challenge in the field of neurosurgery, there is no effective treatment method for pediatric skull defects repair in clinic. Currently clinical used cranioplasty materials couldn’t undergo adjustment in response to skull growth and deformation. An ideal material for pediatric cranioplasty should fulfill the requirements of achieving complete closure, good osseointegration, biodegradability and conformability, sufficient cerebral protection and optimal aesthetic, and functional restoration of calvaria. Biomimetic mineralized collagen-based bone material is a kind of material that simulates the microstructural unit of natural bone on the nanometer scale. Because of its high osteogenic activity, it is widely used in repair of all kinds of bone defects. Recently, the biomimetic mineralized collagen-based bone materials have successfully been applied for cranial regeneration and repair with satisfactory results. This review mainly introduces the characteristics of the biomimetic mineralized collagen-based bone materials, the advantages for the repair of pediatric skull defects, and the related progresses.
Objective To review the research progress on the role of Schwann cells in regulating bone regeneration. MethodsThe domestic and foreign literature about the behavior of Schwann cells related to bone regeneration, multiple tissue repair ability, nutritional effects of their neurotrophic factor network, and their application in bone tissue engineering was extensively reviewed. ResultsAs a critical part of the peripheral nervous system, Schwann cells regulate the expression level of various neurotrophic factors and growth factors through the paracrine effect, and participates in the tissue regeneration and differentiation process of non-neural tissues such as blood vessels and bone, reflecting the nutritional effect of neural-vascular-bone integration. ConclusionTaking full advantage of the multipotent differentiation ability of Schwann cells in nerve, blood vessel, and bone tissue regeneration may provide novel insights for clinical application of tissue engineered bone.
Objective To review the progress of cell sheet technology and its application in bone and cartilage engineering. Methods The recent literature concerning the cell sheet technology used in treatment of bone and cartilage defects was extensively reviewed and summarized. Results Cell sheet built through many different ways can protect extracellular matrix from proteolytic enzymes. As a three-dimensional structure, cell sheet can repair bone and cartilige defects via folding, wrapping scaffold, or be created by the layering of individual cell sheets. Conclusion The cell sheet technology would have a very broad prospects in bone and cartilage tissue engineering in future.
ObjectiveTo investigate the preparation and osteogenic properties of poly (L-lactic acid)(PLLA)/lecithin porous scaffolds with open pore structure.MethodsPLLA/lecithin porous scaffolds with different lecithin contents (0, 5%, 10%, 20%, 30%, 40%, 50%) were prepared by thermally induced phase separation (groups A, B, C, D, E, F, and G, respectively). Scanning electron microscopy (SEM) was used to observe the surface morphology of the scaffolds. Wide-angle X-ray diffraction (XRD) and differential scanning calorimetry (DSC) were used to detect the crystallinity of the scaffolds. The water uptake ability of the scaffolds was measured. The cell growth and viability of bone marrow mesenchymal stem cells (BMSCs) of mouse on each scaffold was assessed by cell counting kit 8 (CCK-8) method. The osteogenic differentiation ability of BMSCs on each scaffold was evaluated by alkaline phosphatase (ALP) activity. Finally, a critical-size rat calvarial bone defect model was used to evaluate the osteogenesis of the scaffolds in vivo. Micro-CT was used to reconstruct the three-dimensional model of the defect area, and the bone volume and bone mineral density were quantitatively analyzed.ResultsSEM results showed that the lecithin could slightly reduce the pore size; when lecithin content was 50%, platelet-like structure could be observed on the scaffolds. Wide angle XRD and DSC showed that the crystallinity of scaffolds gradually decreased with the increase of lecithin content. The water uptake ability test showed that the hydrophilicity of scaffolds increased with the increase of lecithin content. CCK-8 assay showed that cell activity gradually increased with the increase of culture time. After 7 days of culture, the absorbance (A) value of groups C, D, E, and F were significantly higher than that of groups A, B, and G (P<0.05), but no significant difference was found among groups C, D, E, and F (P>0.05). After 14 days of osteogenic induction, with the increase of lecithin content, there was a significant difference in ALP activity of each group. The ALP activity in groups D, E, F, and G were significantly higher than that in groups A, B, and C (P<0.05).In vivo, the results of Micro-CT examination and bone volume and bone mineral density showed that the scaffolds with 30% lecithin had the best repairing effect.ConclusionPrepared by thermally induced phase separation, the cytocompatibility, osteogenic differentiation, and bone repair ability of the PLLA/lecithin porous scaffold is obviously better than that of pure PLLA scaffold. PLLA/lecithin porous scaffold with suitable lecithin content is a promising scaffold material for bone tissue engineering.
ObjectiveTo investigate the mechanical properties of the novel compound calcium phosphate cement (CPC) biological material as well as the biological activity and osteogenesis effects of induced pluripotent stem cells (iPS) seeding on scaffold and compare their bone regeneration efficacy in cranial defects in rats.MethodsAc- cording to the different scaffold materials, the experiment was divided into 4 groups: pure CPC scaffold group (group A), CPC∶10%wt chitosan as 2∶1 ratio mixed scaffold group (group B), CPC∶10%wt chitosan∶whisker as 2∶1∶1 ratio mixed scaffold group (group C), and CPC∶10%wt chitosan∶whisker as 2∶1∶2 ratio mixed scaffold group (group D). Mechanical properties (bending strength, work-of-fracture, hardness, and modulus of elasticity) of each scaffold were detected. The scaffolds were cultured with fifth generation iPS-mesenchymal stem cells (MSCs), and the absorbance (A) values of each group were detected at 1, 3, 7, and 14 days by cell counting kit 8 (CCK-8) method; the alkaline phosphatase (ALP) activity, Live/Dead fluorescence staining and quantitative detection, ALP, Runx2, collagen typeⅠ, osteocalcin (OC), and bone morphogenetic protein 2 (BMP-2) gene expressions by RT-PCR were detected at 1, 7, and 14 days; and the alizarin red staining were detected at 1, 7, 14, and 21 days. Twenty-four 3-month-old male Sprague Dawley rats were used to establish the 8 mm-long skull bone defect model, and were randomly divided into 4 groups (n=6); 4 kinds of scaffold materials were implanted respectively. After 8 weeks, HE staining was used to observe the repair of bone defects and to detect the percentage of new bone volume and the density of neovascularization.ResultsThe bending strength, work-of-fracture, hardness, and modulus of elasticity in groups B, C, and D were significantly higher than those in group A, and in groups C, D than in group B, and in group D than in group C (P<0.05). CCK-8 assay showed that cell activity gradually increased with the increase of culture time, theA values in groups B, C, and D at 3, 7, 14 days were signifiantly higher than those in group A, and in groups C, D than in group B (P<0.05), but no significant difference was found between groups C and D (P>0.05). Live/Dead fluorescence staining showed that the proportion of living cells in groups B, C, and D at 7 and 14 days was significantly higher than that in group A (P<0.05), and in groups C, D at 7 days than in group B (P<0.05); but no significant difference was found between groups C and D (P>0.05). RT-PCR showed that the relative expressions of genes in groups B, C, and D at 7 and 14 days were significantly higher than those in group A, and in groups C, D than in group B (P<0.05); but no significant difference was found between groups C and D (P>0.05). Alizarin red staining showed that the red calcium deposition on the surface of scaffolds gradually deepened and thickened with the prolongation of culture time; theA values in groups B, C, and D at 14 and 21 days were significantly higher than those in group A (P<0.05), and in groups C and D than in group B (P<0.05), but no significant difference was found between groups C and D (P>0.05).In vivo repair experiments in animals showed that the new bone in each group was mainly filled with the space of scaffold material. Osteoblasts and neovascularization were surrounded by new bone tissue in the matrix, and osteoblasts were arranged on the new bone boundary. The new bone in groups B, C, and D increased significantly when compared with group A, and the new bone in groups C and D was significantly higher than that in group B. The percentage of new bone volume and the density of neovascularization in groups B, C, and D were significantly higher than those in group A, and in groups C and D than in group B (P<0.05); but no significant difference was found between groups C and D (P>0.05).ConclusionThe mechanical properties of the new reinforced composite scaffold made from composite chitosan, whisker, and CPC are obviously better than that of pure CPC scaffold material, which can meet the mechanical properties of cortical bone and cancellous bone. iPS-MSCs is attaching and proliferating on the new reinforced composite scaffold material, and the repair effect of bone tissue is good. It can meet the biological and osteogenic activity requirements of the implant materials in the bone defect repair.