Objective To review the research progress of in-situ three dimensional (3D) bio-printing technology in the repair of bone and cartilage injuries. Methods Literature on the application of in-situ 3D bio-printing technology to repair bone and cartilage injuries at home and abroad in recent years was reviewed, analyzed, and summarized. Results As a new tissue engineering technology, in-situ 3D bio-printing technology is mainly applied to repair bone, cartilage, and skin tissue injuries. By combining biomaterials, bioactive substances, and cells, tissue is printed directly at the site of injury or defect. At present, the research on the technology mainly focuses on printing mode, bio-ink, and printing technology; the application research in the field of bone and cartilage mainly focuses on pre-vascularization, adjusting the composition of bio-ink, improving scaffold structure, printing technology, loading drugs, cells, and bioactive factors, so as to promote tissue injury repair. Conclusion Multiple animal experiments have confirmed that in-situ 3D bio-printing technology can construct bone and cartilage tissue grafts in a real-time, rapid, and minimally invasive manner. In the future, it is necessary to continue to develop bio-inks suitable for specific tissue grafts, as well as combine with robotics, fusion imaging, and computer-aided medicine to improve printing efficiency.
Objective To introduce the basic research and cl inical appl ication of the injectable bone repair biomaterials. Methods The recent original articles about the injectable bone repair biomaterials were extensively reviewed. Results The injectable bone repair biomaterials could fill irregularly shaped defects and might allow bone augmentation, both with minimal surgical intervention, and the injectable bone repair material had a good prospect by the medical profession and attach great importance to the academic material, but there were some deficiencies and shortcomings. Conclusion The injectable bone repair biomaterials may be a future approach to repair bone defect．
ObjectiveTo summarize the latest research progress of graphene and its derivatives (GDs) in bone repair. MethodsThe relevant research literature at home and abroad in recent years was extensively accessed. The properties of GDs in bone repair materials, including mechanical properties, electrical conductivity, and antibacterial properties, were systematically summarized, and the unique advantages of GDs in material preparation, functionalization, and application, as well as the contributions and challenges to bone tissue engineering, were discussed. ResultsThe application of GDs in bone repair materials has broad prospects, and the functionalization and modification technology effectively improve the osteogenic activity and material properties of GDs. GDs can induce osteogenic differentiation of stem cells through specific signaling pathways and promote osteogenic activity through immunomodulatory mechanisms. In addition, the parameters of GDs have significant effects on the cytotoxicity and degradation behavior.ConclusionGDs has great potential in the field of bone repair because of its excellent physical and chemical properties and biological properties. However, the cytotoxicity, biodegradability, and functionalization strategies of GDs still need to be further studied in order to achieve a wider application in the field of bone tissue engineering.
ObjectiveTo evaluate the in vivo biological safety of porous zinc oxide (ZnO)/hydroxyapatite (HA) composite materials.MethodsThe porous ZnO/HA composite materials and porous HA materials were prepared by the spark plasma sintering technology. First, the materials were characterized, including scanning electron microscopy to observe the material structure, in vitro degradation experiments to detect the degradation rate of the materials, and inductively coupled plasma emission spectrometer to detect the concentration of Zn2+ dissolved out of the composite material degradation. Then the two kinds of material extracts were prepared for acute systemic toxicity test. Fifteen male Kunming mice were randomly divided into groups A, B, and C (n=5) and injected intraperitoneally with normal saline, HA extracts, and ZnO/HA extracts, respectively. The body mass of the mice was recorded before injection and at 24, 48, and 72 hours after injection. The liver and kidney tissues were taken at 72 hours for HE staining to evaluate the safety of the composite material. Finally, the biological safety of the material in vivo was evaluated by implantation experiment. The eighteen male New Zealand white rabbits were randomly divided into HA group and ZnO/HA group (n=9); a bilateral radius defect model (1 cm) was established, and the right forelimbs of the two groups were implanted with porous HA materials and porous ZnO/HA composite materials, respectively; the left untreated as a blank control. The general condition of the animals were observed after operation. The rabbit blood was collected at 1 day before operation and at 1 day, 1 week, 4 weeks, and 8 weeks after operation for routine blood test (inflammation-related indicators) and blood biochemistry (liver and kidney function-related indicators). X-ray films were taken at 4, 8, and 12 weeks after operation to observe the repair of bone defects.ResultsMaterial characterization showed that porous ZnO/HA composite materials had interconnected large and small pore structures with a pore size between 50 and 500 μm, which degraded faster than porous HA materials, and continuously and slowly dissolved Zn2+. The acute systemic toxicity test showed that the mice in each group had no abnormal performance after injection, and the body mass increased (P<0.05). HE staining showed that the cells shape and structure of liver and kidney tissue were normal. Animal implantation experiments showed that all rabbits survived until the experiment was completed; routine blood tests showed inflammation in each group (neutrophils, monocytes, and lymphocytes increased) at 1 day after operation, and all returned to normal at 8 weeks (P>0.05); compared with 1 day before operation, the content of inflammatory cells in the HA group increased at 1 day, 1 week, and 4 weeks after operation (P<0.05), and the ZnO/HA group increased at 1 day after operation (P<0.05); blood biochemistry showed that the liver and kidney function indexes were in the normal range; X-ray films showed that the ZnO/HA group had better osseointegration than the HA group at 4 weeks after operation.ConclusionThe porous ZnO/HA composite material has good in vivo biological safety and good bone repair ability, which is a potential bone repair material.
Bone tissue regeneration and blood vessel formation are inseparable. How to realize the vascularization of bone repair scaffolds is an urgent problem in bone tissue engineering. The growth and development, mineralization maturity, reconstruction and remodeling, and tissue regeneration of bone are all based on forming an excellent vascularization network. In recent years, more and more researchers have used hydrogels to carry different cells, cytokines, metal ions and small molecules for in vitro vascularization and application in bone regeneration. Based on this background, this article reviews the hydrogel-based vascularization strategies in bone tissue engineering.
In recent years, 3D printing technology, as a new material processing technology, can precisely control the macroscopic and microstructure of biological scaffolds and has advantages that traditional manufacturing methods cannot match in the manufacture of complex bone repair scaffolds. Magnesium ion is one of the important trace elements of the human body. It participates in many physiological activities of the body and plays a very important role in maintaining the normal physiological function of the organism. In addition, magnesium ions also have the characteristics of promoting the secretion of osteogenic proteins by osteoblasts and osteogenic differentiation of mesenchymal stem cells. By combining with 3D printing technology, more and more personalized magnesium-based biological scaffolds have been produced and used in bone regeneration research in vivo and in vitro. Therefore, this article reviews the application and research progress of 3D printing magnesium-based biomaterials in the field of bone regeneration and repair.
Objective To review the research and application progress of bioactive glass in bone repair. Methods The recently published literature concerning bioactive glass in bone repair was reviewed and summarized. Results Bioactive glass can classified different types, such as bioactive glass particulate, bioactive glass scaffold, bioactive glass coating, injectable bioactive glass cement, and bioactive glass delivery system. Bioactive glass has been well studied in the field of bone repair due to its excellent biological properties. Also, the remarkable progress has been made in various aspects. Conclusion Bioactive glass is a reliable material of bone repair and will play an even more important role in the future.
Objective To investigate the physicochemical properties, osteogenic properties, and osteogenic ability in rabbit model of femoral condylar defect of acellular dermal matrix (ADM)/dicalcium phosphate (DCP) composite scaffold. Methods ADM/DCP composite scaffolds were prepared by microfibril technique, and the acellular effect of ADM/DCP composite scaffolds was detected by DNA residue, fat content, and α-1, 3-galactosyle (α-Gal) epitopes; the microstructure of scaffolds was characterized by field emission scanning electron microscopy and mercury porosimetry; X-ray diffraction was used to analyze the change of crystal form of scaffold; the solubility of scaffolds was used to detect the pH value and calcium ion content of the solution; the mineralization experiment in vitro was used to observe the surface mineralization. Twelve healthy male New Zealand white rabbits were selected to prepare the femoral condylar defect models, and the left and right defects were implanted with ADM/DCP composite scaffold (experimental group) and skeletal gold? artificial bone repair material (control group), respectively. Gross observation was performed at 6 and 12 weeks after operation; Micro-CT was used to detect and quantitatively analyze the related indicators [bone volume (BV), bone volume/tissue volume (BV/TV), bone surface/bone volume (BS/BV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), bone mineral density (BMD)], and HE staining and Masson staining were performed to observe the repair of bone defects and the maturation of bone matrix. Results Gross observation showed that the ADM/DCP composite scaffold was a white spongy solid. Compared with ADM, ADM/DCP composite scaffolds showed a significant decrease in DNA residue, fat content, and α-Gal antigen content (P<0.05). Field emission scanning electron microscopy showed that the ADM/DCP composite scaffold had a porous structure, and DCP particles were attached to the porcine dermal fibers. The porosity of the ADM/DCP composite scaffold was 76.32%±1.63% measured by mercury porosimetry. X-ray diffraction analysis showed that the crystalline phase of DCP in the ADM/DCP composite scaffolds remained intact. Mineralization results in vitro showed that the hydroxyapatite layer of ADM/DCP composite scaffolds was basically mature. The repair experiment of rabbit femoral condyle defect showed that the incision healed completely after operation without callus or osteophyte. Micro-CT showed that bone healing was complete and a large amount of new bone tissue was generated in the defect site of the two groups, and there was no difference in density between the defect site and the surrounding bone tissue, and the osteogenic properties of the two groups were equivalent. There was no significant difference in BV, BV/TV, BS/BV, Tb.Th, Tb.N, and BMD between the two groups (P>0.05), except that the Tb.Sp in the experimental group was significantly higher than that in the control group (P<0.05). At 6 and 12 weeks after operation, HE staining and Masson staining showed that the new bone and autogenous bone fused well in both groups, and the bone tissue tended to be mature. Conclusion The ADM/DCP composite scaffold has good biocompatibility and osteogenic ability similar to the artificial bone material in repairing rabbit femoral condylar defects. It is a new scaffold material with potential in the field of bone repair.
Objective To investigate the effect of domestic porous tantalum encapsulated with pedicled fascial flap on repairing of segmental bone defect in rabbits’ radius. Methods A total of 60 New Zealand white rabbits (aged 6- 8 months and weighing 2.5-3.0 kg) were randomly divided into the experimental group and control group (30 rabbits each group). A 1.5 cm segmental bone defect in right radius was established as the animal model. The porous tantalums encapsulated with pedicled fascial flaps (30 mm×20 mm) were implanted in the created bone defect in the experimental group, and the porous tantalums were only implanted in the control group. X-ray films were observed at the day after operation and at 4, 8, and 16 weeks after operation. Specimens were taken out at 4, 8, and 16 weeks after operation for HE staining and toluidine blue staining observation. The maximum load force and bending strength were detected by three point bending biomechanical test, and the Micro-CT analysis and quantitative analysis of the new bone volume fraction (BV/TV) were performed at 16 weeks after operation to compare the bone defect repair abilityin vivo in 2 groups. Results All incisions healed by first intention without wound infection. At 4, 8, and 16 weeks after operation, the X-ray films showed that the implants were well maintained without apparent displacement. As followed with time, the combination between the implants and host bone became more and more closely, and the fracture line gradually disappeared. HE staining and toluidine blue staining showed that new bone mass and maturity gradually increased at the interface and inside materials in 2 groups, and the new bone gradually growed from the interface to internal pore. At 16 weeks after operation, the three point bending biomechanical test showed that the maximum load force and bending strength in the experimental were (96.54±7.21) N and (91.26±1.76) MPa respectively, showing significant differences when compared with the control group [(82.65±5.65) N and (78.53±1.16) MPa respectively] (t=3.715, P=0.004; t=14.801, P=0.000). And Micro-CT analysis exhibited that there were a large amount of new bone at the interface and the surface of implant materials and inside the materials. The new bone BV/TV in the experimental group (32.63%±3.56%) was significantly higher than that in control group (25.07%±4.34%) (t=3.299, P=0.008). Conclusion Domestic porous tantalum encapsulated with pedicled fascial flap can increase local blood supply, strengthen material bone conduction ability, and promote the segmental bone defect repair.
Objective To review the application and research progress of in-situ tissue engineering technology in bone and cartilage repair. Methods The original articles about in-situ tissue engineering technology in bone and cartilage repair were extensively reviewed and analyzed. Results In-situ tissue engineering have been shown to be effective in repairing bone defects and cartilage defects, but biological mechanisms are inadequate. At present, most of researches are mainly focused on animal experiments, and the effect of clinical repair need to be further studied. Conclusion In-situ tissue engineering technology has wide application prospects in bone and cartilage tissue engineering. However, further study on the mechanism of related cytokines need to be conducted.