Yu Haiquan, Feng Meng, Mao Genwen, Li Qian, Zhang Zhifeng, Bian Weiguo, Qiu Yusheng
Department of Orthopedics, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, People's Republic of China.
Department of Orthopedics, Shijiazhuang People's Hospital, Shijiazhuang 050001, People's Republic of China.
ACS Biomater Sci Eng. 2022 Oct 10;8(10):4474-4485. doi: 10.1021/acsbiomaterials.2c00445. Epub 2022 Sep 8.
Cartilage defects caused by mechanical tear and wear are challenging clinical problems. Articular cartilage has unique load-bearing properties and limited self-repair ability. The current treatment methods, such as microfractures and autogenous cartilage transplantation to repair full-thickness cartilage defects, have apparent limitations. Tissue engineering technology has the potential to repair cartilage defects and directs current research development. To enhance the regenerative capacities of cartilage in weight-bearing areas, we attempted to develop a biomimetic scaffold loaded with a chondroprotective factor that can recreate structure, restore mechanical properties, and facilitate anabolic metabolism in larger joint defects. For enhanced spatial control over both bone and cartilage layers, it is envisioned that biomaterials that meet the needs of both tissue components are required for successful osteochondral repair. We used gelatin methacrylate (GELMA) and polyethylene glycol diacrylate (PEGDA) light-cured dual-network cross-linking modes that can significantly increase the mechanical properties of scaffolds and are capable of restoring function and prolonging the degradation time. Once the hydrogel complex was injected into the osteochondral defect, UV light curing was applied to seamlessly connect the defect repair tissue with the surrounding normal cartilage tissue. The small molecule active substance kartogenin (KGN) can promote cartilage repair. We encapsulated KGN in biomimetic scaffolds so that, as the scaffold degrades, scaffold-loaded KGN was slowly released to induce endogenous mesenchymal stem cells to home and differentiate into chondrocytes to repair defective cartilage tissue. Our experiments have proven that, compared with the control group, GELMA/PEGDA + KGN repaired cartilage defects and restored cartilage to hyaline cartilage. Our study suggests that implementing photosensitive, injectable, interpenetrating, and kartogenin-modified GELMA/PEDGA biomimetic scaffolds may be a novel approach to restore cartilage integrity in full-thickness osteochondral defects.
由机械性撕裂和磨损导致的软骨缺损是具有挑战性的临床问题。关节软骨具有独特的承重特性且自我修复能力有限。当前的治疗方法,如微骨折和自体软骨移植来修复全层软骨缺损,存在明显局限性。组织工程技术有修复软骨缺损的潜力并引领着当前的研究发展方向。为增强负重区域软骨的再生能力,我们尝试开发一种负载软骨保护因子的仿生支架,该支架能够重建结构、恢复力学性能并促进更大关节缺损处的合成代谢。为了增强对骨层和软骨层的空间控制,预计成功的骨软骨修复需要满足两种组织成分需求的生物材料。我们使用甲基丙烯酸明胶(GELMA)和聚乙二醇二丙烯酸酯(PEGDA)光固化双网络交联模式,这种模式能显著提高支架的力学性能,并能够恢复功能和延长降解时间。一旦将水凝胶复合物注入骨软骨缺损处,就应用紫外线光固化使其与周围正常软骨组织无缝连接缺损修复组织。小分子活性物质软骨生成素(KGN)能够促进软骨修复。我们将KGN包裹在仿生支架中,这样随着支架降解,负载在支架上的KGN会缓慢释放,诱导内源性间充质干细胞归巢并分化为软骨细胞以修复受损的软骨组织。我们的实验已证明,与对照组相比,GELMA/PEGDA + KGN修复了软骨缺损并将软骨恢复为透明软骨。我们的研究表明,采用光敏、可注射、互穿且经软骨生成素修饰的GELMA/PEDGA仿生支架可能是一种修复全层骨软骨缺损中软骨完整性的新方法。