Study on the influence of scaffold morphology and structure on osteogenic performance.

The number of patients with bone defects caused by various bone diseases is increasing yearly in the aging population, and people are paying increasing attention to bone tissue engineering research. Currently, the application of bone tissue engineering mainly focuses on promoting fracture healing by carrying cytokines. However, cytokines implanted into the body easily cause an immune response, and the cost is high; therefore, the clinical treatment effect is not outstanding. In recent years, some scholars have proposed the concept of tissue-induced biomaterials that can induce bone regeneration through a scaffold structure without adding cytokines. By optimizing the scaffold structure, the performance of tissue-engineered bone scaffolds is improved and the osteogenesis effect is promoted, which provides ideas for the design and improvement of tissue-engineered bones in the future. In this study, the current understanding of the bone tissue structure is summarized through the discussion of current bone tissue engineering, and the current research on micro-nano bionic structure scaffolds and their osteogenesis mechanism is analyzed and discussed.

Study of PLGA microspheres loaded with pOsx/PEI nanoparticles for repairing bone defects in vivo and in vitro.

BACKGROUND: Autogenous or allogenic bone transplantation is the main treatment for bone defects and nonunions. However, the shortcomings of autogenous or allogenic bone transplantation limit its wide application in clinical use. OBJECTIVES: This study investigated the effect of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with pOsterix (pOsx)/polyethylenimine (PEI) nanoparticles in repairing bone defects and explored its mechanism. MATERIAL AND METHODS: Poly(lactic-co-glycolic acid) microspheres loaded with pOsx/PEI nanoparticles were constructed. The Osx transfection effect was detected by fluorescence quantitative PCR and western blotting methods. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide (MTT) and flow cytometry methods were used to detect cell proliferation. The collagen I (Col-1), osteopontin (OPN) and osteocalcin (OC) expression levels were detected using real-time polymerase chain reaction (RT-PCR) and western blotting methods. Bone defect model was constructed. Bone repair was detected using X-ray, hematoxylin and eosin (H&E) staining, and Mason staining methods. RESULTS: PLGA@pOsx/PEI has transfection effect both in vitro and in vivo, does not affect cell proliferation and is safe for cells. PLGA@pOsx/PEI could promote the expression of Col-1, OPN and OC in vitro and in vivo. PLGA@pOsx/PEI could promote osteogenesis in vivo. CONCLUSIONS: PLGA@pOsx/PEI with high Osx expression could promote the expression of OC, OPN, and COL-I. PLGA@pOsx/PEI can be used as a material for repairing bone defects and can promote bone formation. These results provide a theoretical and practical basis for its further clinical application.

The mechanism research of non-Smad dependent TAK1 signaling pathway in the treatment of bone defects by recombination BMP-2-loaded hollow hydroxyapatite microspheres/chitosan composite.

AIMS: The present study aimed to evaluate whether the non-Smad dependent TAK1 signaling pathway (BMP-2-TAK1-p38-Osx signaling pathway) played an important role in bone repair mediated by hollow hydroxyapatite (HA) microspheres/chitosan (CS) composite. METHODS: Firstly, the biological activity of rhBMP-2 released from the complex was investigated. Then, differentiation test of osteoblasts including ALP activity and calcium deposition, X-ray scoring and three-point bending test were performed. Finally, the mRNAs expression of TAK1, p38, Osx and osteogenic markers was tested by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: RhBMP-2 could be loaded and released from the complex in bioactive form. Additionally, the complex provided a prolonged period of time compared with HA/CS scaffolds. Serum ALP activity was significantly decreased in the TAK1 inhibitor group and p38 inhibitor group. In the X-ray radiography, bone callus was observed in rhBMP-2-loaded hollow HA microspheres/CS composite group. In the three-point bending test, load values in p38 inhibitor group decreased. In the animal model, the mRNA expression of BSP on day 90 was significantly decreased in the p38 inhibitor group and TAK1 inhibitor group. In MC3T3-E1 cells, the mRNA expression of OSX was remarkably up-regulated in both rhBMP-2 group or rhBMP-2-loaded hollow HA microspheres/CS composite group; while the mRNA expression of OSX was significantly down-regulated in TAK1 inhibitor group and p38 inhibitor group. CONCLUSION: The BMP-2-TAK1-p38-OSX signaling pathway may play an important role in bone formation and repair mediated by rhBMP-2-loaded hollow HA microspheres/CS composite.

Study of bone repair mediated by recombination BMP-2/ recombination CXC chemokine Ligand-13-loaded hollow hydroxyapatite microspheres/chitosan composite.

AIMS: The present study aimed to investigate the mechanism of bone repair mediated by recombination BMP-2 (rhBMP-2)/recombination CXC chemokine ligand-13 (rhCXCL13)-loaded hollow hydroxyapatite (HA) microspheres/chitosan (CS) composite. MATERIALS AND METHODS: Firstly, the biological activity of rhBMP-2 and rhCXCL13 released from the complex was investigated. Secondly, the effect of rhBMP-2 sustained release solution on ALP activity and rhCXCL13 sustained release solution on cell migration of rat bone marrow mesenchyme stem cells was tested. Thirdly, osteoblasts differentiation test, X-ray scoring and three-point bending test were performed. Finally, the mRNAs expression of osteogenic marker genes and the protein expression of Runx2 was tested by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting (WB), respectively. KEY FINDINGS: RhBMP-2 could significantly promote the proliferation and differentiation, and RhCXCL13 could promote the migration of rat bone marrow MSCs. Detection of ALP activity and calcium salt deposition showed that rhBMP-2 and rhCXCL13 could significantly improve the biological activity and promote cell differentiation ability. X-ray scoring of radius and flexural strength test showed that rhBMP-2 and rhCXCL13 could promote bone healing and improve the bending resistance of bone tissue. The in vitro molecular experiments including RT-PCR and WB further demonstrated the roles of rhBMP-2 and rhCXCL13 in bone formation and bone repair. SIGNIFICANCE: Our results indicated that the hollow HA microspheres/CS composite could be effective as a delivery vehicle for rhBMP-2 and rhCXCL13 in bone regeneration and bone repair. In this process, rhBMP-2 may promote bone regeneration by regulating bone marrow MSCs cells recruited by rhCXCL13.

Bone repair scaffold coated with bone morphogenetic protein-2 for bone regeneration in murine calvarial defect model: Systematic review and quality evaluation.

To systematically assess the effects of hydroxyapatite bone repair scaffold coated with bone morphogenetic protein-2 on murine calvarial defect models and to determine the quality of studies according to the Animal Research Reporting in In Vivo Experiments guidelines. Internet search was performed in duplicate using PubMed, MEDLINE, Ovid and Embase databases (without restrictions on publication date). The Animal Research Reporting in In Vivo Experiments guidelines were used to evaluate the quality of selected studies. Following screening, 12 studies were eligible for the review. Studies with average quality coefficients predominated (66.67%), followed by poor (25%) and excellent (8.33%) quality coefficients. Minimum quality scores were assigned to the Animal Research Reporting in In Vivo Experiments guideline items: housing and husbandry (9), allocation (11), outcomes (12), interpretation (18) and generalizability (19). Sprague-Dawley rats were the most frequently used (50%) species, and most studies had a sample size of more than 30 (58.33%). A defect dimension of 5 mm was the most common (33.33%). The biological hydroxyapatite composite scaffold was common (50%), and the bioactive factors were bone morphogenetic protein-2 (50%) and recombinant human bone morphogenetic protein-2 (50%). Histomorphometric results showed that bone morphogenetic protein-2 enhanced the capacity to regenerate bone considerably. In addition, scaffolds with bone morphogenetic protein-2 resulted in a significant increase in the blood vessel in the new bone. The findings suggested that data on animal experiments of hydroxyapatite scaffold coated with bone morphogenetic protein-2 in murine calvarial defect models lack homogeneity. Animal experiment should follow the Animal Research Reporting in In Vivo Experiments guidelines to promote the high quality, integrity and reproducibility. This systematic review suggested that bone morphogenetic protein-2 enhanced the capacity to regenerate bone and the angiogenesis in the new bone.

Scaffolds for the repair of bone defects in clinical studies: a systematic review.

BACKGROUND: This systematic review aims to summarize the clinical studies on the use of scaffolds in the repair of bony defects. METHODS: The relevant articles were searched through PubMed database. The following keywords and search terms were used: "scaffolds," "patient," "clinic," "bone repair," "bone regeneration," "repairing bone defect," "repair of bone," "osteanagenesis," "osteanaphysis," and "osteoanagenesis." The articles were screened according to inclusion and exclusion criteria, performed by two reviewers. RESULTS: A total of 373 articles were obtained using PubMed database. After screening, 20 articles were identified as relevant for the purpose of this systematic review. We collected the data of biological scaffolds and synthetic scaffolds. There are eight clinical studies of biological scaffolds included collagen, gelatin, and cellular scaffolds for bone healing. In addition, 12 clinical studies of synthetic scaffolds on HAp, TCP, bonelike, and their complex scaffolds for repairing bone defects were involved in this systematic review. CONCLUSIONS: There are a lot of clinical evidences showed that application of scaffolds had a good ability to facilitate bone repair and osteogenesis. However, the ideal and reliable guidelines are insufficiently applied and the number and quality of studies in this field remain to be improved.

Effects of Thermal Cross-Linking on the Structure and Property of Asymmetric Membrane Prepared from the Polyacrylonitrile.

Improving the thermal and chemical stabilities of classical polymer membranes will be beneficial to extend their applications in the high temperature or aggressive environment. In this work, the asymmetric ultrafiltration membranes prepared from the polyacrylonitrile (PAN) were used to fabricate the cross-linking asymmetric (CLA) PAN membranes via thermal cross-linking in air to improve their thermal and chemical stabilities. The effects of thermal cross-linking parameters such as temperature and holding time on the structure, gas separation performance, thermal and chemical stabilities of PAN membranes were investigated by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), positron annihilation lifetime spectroscopy (PALS), scanning electron microscopy (SEM), thermogravimetic analysis (TGA) and gas permeation test. The thermal cross-linking significantly influences the chemical structure, microstructure and pore structure of PAN membrane. During the thermal cross-linking, the shrinkage of membrane and coalescence or collapse of pore and microstructure make large pores diminish, small pores disappear and pore volumes reduce. The gas permeances of CLA-PAN membranes increase as the increasing of cross-linking temperature and holding time due to the volatilization of small molecules. The CLA-PAN membranes demonstrate excellent thermal and chemical stabilities and present good prospects for application in ultrafiltration for water treatment and for use as a substrate for nanofiltration or gas separation with an aggressive and demanding environment.