Chen Hongying, Huang Jinyi, Li Xiaomeng, Zhao Weiwei, Hua Yujie, Song Zhenfeng, Wang Xianwei, Guo Zhikun, Zhou Guangdong, Ren Wenjie, Sun Yongkun
School of Basic Medical Sciences of Xinxiang Medical University, The Third Affiliated Hospital of Xinxiang Medical University, Henan Key Laboratory of Medical and Protective Products, Xinxiang, Henan, 453003, China.
The Key Laboratory of Medical Tissue Regeneration in Henan Province of Xinxiang Medical University, Xinxiang, Henan, 453003, China.
Mater Today Bio. 2024 Apr 10;26:101051. doi: 10.1016/j.mtbio.2024.101051. eCollection 2024 Jun.
Commonly, articular osteochondral tissue exists significant differences in physiological architecture, mechanical function, and biological microenvironment. However, the development of biomimetic scaffolds incorporating upper cartilage, middle tidemark-like, and lower subchondral bone layers for precise articular osteochondral repair remains elusive. This study proposed here a novel strategy to construct the trilayered biomimetic hydrogel scaffolds with dual-differential microenvironment of both mechanical and biological factors. The cartilage-specific microenvironment was achieved through the grafting of kartogenin (KGN) into gelatin -hydroxyphenylpropionic acid (HPA)-based enzyme crosslinking reaction as the upper cartilage layer. The bone-specific microenvironment was achieved through the grafting of atorvastatin (AT) into gelatin dual-crosslinked network of both HP-based enzyme crosslinking and glycidyl methacrylate (GMA)-based photo-crosslinking reactions as the lower subchondral bone layer. The introduction of tidemark-like middle layer is conducive to the formation of well-defined cartilage-bone integrated architecture. The experiments demonstrated the significant mechanical difference of three layers, successful grafting of drugs, good cytocompatibility and tissue-specific induced function. The results of experiments also confirmed the mechanical difference of the trilayered bionic scaffold and the ability of inducing osteogenesis and chondrogenesis. Furthermore, the articular osteochondral defects were successfully repaired using the trilayered biomimetic hydrogel scaffolds by the activation of endogenous recovery, which offers a promising alternative for future clinical treatment.
通常，关节软骨下骨组织在生理结构、力学功能和生物微环境方面存在显著差异。然而，用于精确关节软骨下骨修复的包含上层软骨、中层潮标样层和下层软骨下骨层的仿生支架的开发仍然难以实现。本研究在此提出了一种构建具有机械和生物因素双差异微环境的三层仿生水凝胶支架的新策略。通过将软骨生成素（KGN）接枝到明胶 - 羟基苯丙酸（HPA）基酶交联反应中作为上层软骨层，实现了软骨特异性微环境。通过将阿托伐他汀（AT）接枝到基于HP的酶交联和甲基丙烯酸缩水甘油酯（GMA）基光交联反应的明胶双交联网络中作为下层软骨下骨层，实现了骨特异性微环境。引入潮标样中间层有利于形成明确的软骨 - 骨整合结构。实验证明了三层的显著力学差异、药物的成功接枝、良好的细胞相容性和组织特异性诱导功能。实验结果还证实了三层仿生支架的力学差异以及诱导成骨和成软骨的能力。此外，通过激活内源性恢复，使用三层仿生水凝胶支架成功修复了关节软骨下骨缺损，这为未来的临床治疗提供了一种有前景的替代方案。
