梯度人工骨修复支架调控骨骼系统组织的修复与再生

Gradient artificial bone repair scaffold regulates skeletal system tissue repair and regeneration

背景:梯度人工骨修复支架模拟了骨骼系统中的独特特征,在骨骼系统再生中具有巨大的应用潜力。目的:综述梯度人工骨修复支架在骨骼系统组织工程中的最新研究进展,并阐述了其优势与制造策略。方法:由第一作者检索Web of Science和PubMed数据库2000-2023年发表的文献,英文检索词为“gradient,bone regeneration,scaffold”,最终筛选后对76篇文献进行分析总结。结果与结论:①作为骨骼系统组织高效、高质量修复的重要手段,梯度人工骨修复支架目前针对骨组织、骨-软骨、肌腱-骨组织的天然梯度特征进行了仿生设计,这些支架能够一定程度地从结构、成分上模拟原生组织的细胞外基质,从而促进细胞黏附、迁移、增殖和分化,促进受损组织向原生状态再生恢复。②先进制造技术为梯度人工骨修复支架制备提供了更多可能;目前已经开发了通过空间差异化纤维排布和生物活性物质加载构建的梯度电纺纤维支架;分层叠加、分级孔隙率与生物3D打印技术制造的梯度3D打印支架;原位分层注射、简单逐层叠加、冷冻干燥法制造的梯度水凝胶支架;另外还包括其他方式或多方法联用的支架;这些支架在体外实验中展示了良好的生物相容性,在小型动物实验中能够加速组织再生并且观察到组织学结构明显改善。③目前开发的梯度人工骨修复支架仍需进一步优化,提高在梯度尺度上的匹配性,进一步明确材料与组织相互作用,避免降解产物导致的副反应等问题,未来需要结合相关学科优势与临床需求进一步优化。

BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues.OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies.METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms“gradient,bone regeneration,scaffold”.Finally,76 papers were analyzed and summarized after the screening.RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.