Objective To review the research progress on bone repair biomaterials with the function of recruiting endogenous mesenchymal stem cells (MSCs). Methods An extensive review of the relevant literature on bone repair biomaterials, particularly those designed to recruit endogenous MSCs, was conducted, encompassing both domestic and international studies from recent years. The construction methods and optimization strategies for these biomaterials were summarized. Additionally, future research directions and focal points concerning this material were proposed. Results With the advancement of tissue engineering technology, bone repair biomaterials have increasingly emerged as an ideal solution for addressing bone defects. MSCs serve as the most critical “seed cells” in bone tissue engineering. Historically, both MSCs and their derived exosomes have been utilized in bone repair biomaterials; however, challenges such as limited sources of MSCs and exosomes, low survival rates, and various other issues have persisted. To address these challenges, researchers are combining growth factors, bioactive peptides, specific aptamers, and other substances with biomaterials to develop constructs that facilitate stem cell recruitment. By optimizing mechanical properties, promoting vascular regeneration, and regulating the microenvironment, it is possible to create effective bone repair biomaterials that enhance stem cell recruitment. Conclusion In comparison to cytokines, phages, and metal ions, bioactive peptides and aptamers obtained through screening exhibit more specific and targeted recruitment functions. Future development directions for bone repair biomaterials will involve the modification of peptides and aptamers with targeted recruitment capabilities in biological materials, as well as the optimization of the mechanical properties of these materials to enhance vascular regeneration and adjust the microenvironment.
Polyetheretherketone is one of the most commonly used materials for the production of orthopaedic implants, but the osseointegration capacity of polyetheretherketone is poor because of its bioinert surface, which greatly limits its clinical application. In recent years, scholars have carried out a lot of research on the modification of polyetheretherketone materials in order to improve its osseointegration capacity. At present, the modification of polyetheretherketone is mainly divided into surface modification and blend modification. Therefore, this paper summarizes the research progress of polyetheretherketone material modification technology and its influence on osseointegration from two aspects of surface modification and blend modification for polyetheretherketone materials used in the field of bone repair, so as to provide a reference for the improvement and transformation of polyetheretherketone materials for bone repair in the future.
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.
ObjectiveTo summarize the application status of hypoxia mimetic agents in bone tissue engineering.MethodsThe related literature about the hypoxia mimetic agents in bone tissue engineering was reviewed and analyzed. And the application status and progress of hypoxia mimetic agents in bone tissue engineering were retrospectively analyzed.ResultsHypoxia mimetic agents have the same effect as hypoxia in up-regulating the level of hypoxia inducible factor 1α (HIF-1α). The combination of hypoxia mimetic agents and scaffolds can up-regulate the level of HIF-1α in bone tissue engineering, thus promoting early vascularization and bone regeneration of the bone defect area, which provides a new idea for using bone tissue engineering to repair bone defect. At present, the commonly used hypoxia mimetic agents include iron chelating agents, oxoglutarate competitive analogues, proline hydroxylase inhibitors, etc.ConclusionHypoxia mimetic agents have a wide application prospect in bone tissue engineering, but they have been used in bone tissue engineering for a short time, more attention should be paid to their possible side effects. In the future research, the hypoxia mimetic agents should be developed in the direction of higher targeting specificity and safety, and the exact mechanism of hypoxia mimetic agents in promoting bone regeneration should be further explored.
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 review the osteoimmunomodulatory effects and related mechanisms of inorganic biomaterials in the process of bone repair. Methods A wide range of relevant domestic and foreign literature was reviewed, the characteristics of various inorganic biomaterials in the process of bone repair were summarized, and the osteoimmunomodulatory mechanism in the process of bone repair was discussed. Results Immune cells play a very important role in the dynamic balance of bone tissue. Inorganic biomaterials can directly regulate the immune cells in the body by changing their surface roughness, surface wettability, and other physical and chemical properties, constructing a suitable immune microenvironment, and then realizing dynamic regulation of bone repair. Conclusion Inorganic biomaterials are a class of biomaterials that are widely used in bone repair. Fully understanding the role of inorganic biomaterials in immunomodulation during bone repair will help to design novel bone immunomodulatory scaffolds for 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 of urine derived stem cells (USCs) in regeneration of musculoskeletal system. Methods The original literature about USCs in the regeneration of musculoskeletal system was extensively reviewed and analyzed. Results The source of USCs is noninvasive and extensive. USCs express MSCs surface markers with stable proliferative and multi-directional differentiation capabilities, and are widely used in bone, skin, nerve, and other skeletal and muscle system regeneration fields and show a certain repair capacity. Conclusion USCs from non-invasive sources have a wide application prospect in the regeneration of musculoskeletal system, but the definite biological mechanism of its repair needs further study.
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 observe and compare the effects of peptides on the repair of rabbit skull defects through two different binding modes of non-covalent and covalent, and the combination of carboxyl (-COOH) and amino (-NH2) groups with materials.MethodsTwenty-one 3-month-old male ordinary New Zealand white rabbits were numbered 1 to 42 on the left and right parietal bones. They were divided into 5 groups using a random number table, the control group (group A, 6 sides) and the material group 1, 2, 3, 4 (respectively group B, C, D, E, 9 sides in each group). All animals were prepared with 12-mm-diameter skull defect models, and bone morphogenetic protein 2 (BMP-2) non-covalently bound multiwalled carbon nanotubes (MWCNT)-COOH+poly (L-lactide) (PLLA), BMP-2 non-covalently bound MWCNT-NH2+PLLA, BMP-2 covalently bound MWCNT-COOH+PLLA, and BMP-2 covalently bound MWCNT-NH2+PLLA were implanted into the defects of groups B, C, D, and E, respectively. At 4, 8, and 12 weeks after operation, the samples were taken for CT scanning and three-dimensional reconstruction, the ratio of bone tissue regeneration volume to total volume and bone mineral density were measured, and the histological observation of HE staining and Masson trichrome staining were performed to quantitatively analyze the volume ratio of new bone tissue.ResultsCT scanning and three-dimensional reconstruction showed that with the extension of time, the defects in groups A-E were filled gradually, and the defect in group E was completely filled at 12 weeks after operation. HE staining and Masson trichrome staining showed that the volume of new bone tissue in each group gradually increased with time, and regenerated mature bone tissue appeared in groups D and E at 12 weeks after operation. Quantitative analysis showed that at 4, 8, and 12 weeks after operation, the ratio of bone tissue regeneration volume to total volume, bone mineral density, and the volume ratio of new bone tissue increased gradually over time; and at each time point, the above indexes increased gradually from group A to group E, and the differences between groups were significant (P<0.05).ConclusionThrough covalent binding and using -NH2 to bound peptides with materials, the best bone repair effect can be achieved.