Zhou Jiaqi, Ji Xiongfa, Xue Yu, Yang Wenjie, Zhong Guoqing, Zhou Zhiyang, Chen Xingmei, Lei Zehua, Lu Teliang, Zhang Yu, Liu Ji, Ma Limin
Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, 510080, China.
Guang Dong Engineering Technology Research Center of Functional, Repair of Bone Defects and Biomaterials, Guangzhou, 510080, China.
Bioact Mater. 2025 Mar 1;49:23-38. doi: 10.1016/j.bioactmat.2025.02.035. eCollection 2025 Jul.
Osteochondral autograft transfer system (OATS) can effectively improve cartilage injuries by obtaining bone-cartilage grafts from healthy sites and implanting them into the defective areas. However, in up to 40 % of patients, the lack of a stable adhesive interface between the osteochondral graft and the normal tissue surface reduces the repair efficiency. In this work, we report an injectable and biocompatible poly (N-hydroxyethyl acrylamide-N-hydroxy succinimide)/Gelatin (PHE-Gel) hydrogel, featuring the instant formation of a tough bio-interface, which allows for robust adhesion with osteochondral grafts. Through physicochemical characterization, we found that a system composed of 10%PHE-Gel possesses superior interfacial toughness and excellent biocompatibility. In vitro, mechanistic studies and RNA-seq analysis had shown that 10%PHE-Gel promotes the expression of cartilage anabolic metabolism genes by upregulating the hypoxia-inducible factor alpha (HIF-α) signaling pathway and downregulating the tumor necrosis factor (TNF) signaling pathway. Dimethyloxalylglycine (DMOG) loaded liposome (DMOG-Lip) promotes the transition of M1 macrophages to M2 macrophages, shifting the microenvironment towards a pro-repair direction. Studies on a rabbit OATS model indicated that DMOG-Lip loaded 10%PHE-Gel (10%PHE-Gel@DMOG-Lip) effectively modulated the immune microenvironment, facilitated the repair of the hyaline cartilage, and inhibited further degeneration of cartilage. This composite hydrogel offers a promising solution for enhancing OATS repair in tissue engineering and has the potential to improve outcomes in cartilage restoration procedures.
骨软骨自体移植系统（OATS）可通过从健康部位获取骨软骨移植物并将其植入缺损区域，有效改善软骨损伤。然而，高达40%的患者中，骨软骨移植物与正常组织表面之间缺乏稳定的黏附界面，降低了修复效率。在这项工作中，我们报道了一种可注射且具有生物相容性的聚（N-羟乙基丙烯酰胺-N-羟基琥珀酰亚胺）/明胶（PHE-Gel）水凝胶，其特点是能即时形成坚韧的生物界面，可与骨软骨移植物实现牢固黏附。通过物理化学表征，我们发现由10%PHE-Gel组成的体系具有优异的界面韧性和良好的生物相容性。在体外，机制研究和RNA测序分析表明，10%PHE-Gel通过上调缺氧诱导因子α（HIF-α）信号通路和下调肿瘤坏死因子（TNF）信号通路，促进软骨合成代谢基因的表达。负载二甲基乙二酰甘氨酸（DMOG）的脂质体（DMOG-Lip）可促进M1巨噬细胞向M2巨噬细胞的转变，使微环境向促修复方向转变。对兔OATS模型的研究表明，负载DMOG-Lip的10%PHE-Gel（10%PHE-Gel@DMOG-Lip）可有效调节免疫微环境，促进透明软骨修复，并抑制软骨进一步退变。这种复合水凝胶为增强组织工程中OATS修复提供了一种有前景的解决方案，并且有潜力改善软骨修复手术的效果。
