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用于骨修复的可降解动力学控制和组织再生匹配的光交联海藻酸盐水凝胶。

Degradation-Kinetics-Controllable and Tissue-Regeneration-Matchable Photocross-linked Alginate Hydrogels for Bone Repair.

机构信息

Center of Stomatology, Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China.

Hefei Stomatological Clinic Hospital, Anhui Medical University & Hefei Stomatological Hospital, Hefei 230001, Anhui, China.

出版信息

ACS Appl Mater Interfaces. 2022 May 18;14(19):21886-21905. doi: 10.1021/acsami.2c01739. Epub 2022 May 4.

Abstract

Photocross-linked alginate hydrogels, due to their biodegradability, biocompatibility, strong control for gelling kinetics in space and time, and admirable adaptability for in situ polymerization with a minimally invasive approach in surgical procedures, have created great expectations in bone regeneration. However, hydrogels with suitable degradation kinetics that can match the tissue regeneration process have not been designed, which limits their further application in bone tissue engineering. Herein, we finely developed an oxidation strategy for alginate to obtain hydrogels with more suitable degradation rates and comprehensively explored their physical and biological performances in vitro and in vivo to further advance the clinical application for the hydrogels in bone repair. The physical properties of the gels can be tuned via tailoring the degree of alginate oxidation. In particular, in vivo degradation studies showed that the degradation rates of the gels were significantly increased by oxidizing alginate. The activity, proliferation, initial adhesion, and osteogenic differentiation of rat and rabbit bone marrow stromal cells (BMSCs) cultured with/in the hydrogels were explored, and the results demonstrated that the gels possessed excellent biocompatibility and that the encapsulated BMSCs were capable of osteogenic differentiation. Furthermore, in vivo implantation of rabbit BMSC-loaded gels into tibial plateau defects of rabbits demonstrated the feasibility of hydrogels with appropriate degradation rates for bone repair. This study indicated that hydrogels with increasingly controllable and matchable degradation kinetics and satisfactory bioproperties demonstrate great clinical potential in bone tissue engineering and regenerative medicine and could also provide references for drug/growth-factor delivery therapeutic strategies for diseases requiring specific drug/growth-factor durations of action.

摘要

光交联海藻酸盐水凝胶由于其生物可降解性、生物相容性、在空间和时间上对凝胶动力学的强控制能力,以及在手术中微创方法与原位聚合的极好适应性,在骨再生中寄予厚望。然而,尚未设计出具有合适降解动力学的水凝胶,使其能够与组织再生过程相匹配,这限制了其在骨组织工程中的进一步应用。在此,我们精细地开发了一种海藻酸盐的氧化策略,以获得具有更合适降解速率的水凝胶,并在体外和体内全面探索其物理和生物学性能,以进一步推进水凝胶在骨修复中的临床应用。通过调整海藻酸盐的氧化程度,可以调节凝胶的物理性质。特别是,体内降解研究表明,通过氧化海藻酸盐可以显著提高凝胶的降解速率。研究了在水凝胶中培养的大鼠和兔骨髓基质细胞(BMSCs)的活性、增殖、初始黏附以及成骨分化情况,结果表明,凝胶具有良好的生物相容性,且包封的 BMSCs 能够进行成骨分化。此外,将负载兔 BMSC 的凝胶植入兔胫骨平台缺损部位的体内实验表明,具有适当降解速率的凝胶在骨修复中具有可行性。本研究表明,具有越来越可控和匹配的降解动力学以及令人满意的生物特性的水凝胶在骨组织工程和再生医学中具有巨大的临床潜力,也可为需要特定药物/生长因子作用时间的疾病的药物/生长因子输送治疗策略提供参考。

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