用于负重区全层关节软骨缺损功能修复的3D打印骨软骨谱系特异性双相支架

3D printed osteochondral lineage-specific biphasic scaffolds for functional repair of full-thickness articular cartilage defects in weight-bearing area.

作者信息

Qin Shengnan, Wang Wen, Chen Liang, Yu Ming, Zhao Cailing, Zeng Haiquan, Chu Hanyu, Zhang Kexin, Wu Simin, Cui Rui, Zheng Yinfeng, Bai Ying, Xu Jiake

机构信息

Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou, People's Republic of China.

Harry Perkins Institute of Medical Research, Perth, Australia.

出版信息

Biofabrication. 2025 Jul 10;17(3). doi: 10.1088/1758-5090/ade8a9.

Abstract

Functional repair of full-thickness defects in the weight-bearing articular cartilage has been one of the major challenges in orthopeadics. Whereas the advanced 3D printing technique allows the construction of bionic bioscaffolds that supporttissue regeneration. Herein, we developed a sort of lineage-specific biphasic scaffolds for osteochondral regeneration, fabricated via consecutive 3D-printing and lyophilization. To facilitate osteogenesis and bone formation, a porous scaffold was 3D-printed fabricated using a composite ink consisting of gelatin methacrylate (GelMA) and hydroxyapatite (HAP). To synergistically stimulate chondrogenesis and hyaline cartilage regeneration, collagen was infused into the top layers of the 3D-printed GelMA/HAP construct.culture of bone marrow mesenchymal stem cells (BMSCs) showed that the top collagen layer preferentially promoted BMSCs chondrogenic differentiation, while the GelMA/HAP composite mostly contributed to their osteogenic differentiation. This customized biphasic scaffold was then examined within the defected weight-bearing regions of full-thickness articular cartilage in rabbits, in which neocartilage, bone formation and remodeling were identified at six and twelve weeks post-implantation. Consistently to thefindings, the bottom GelMA/HAP scaffold facilitated bone formation, while the top-layer with preloaded collagen markedly augmented hyaline cartilage formation. Furthermore, it was evident that the biphasic scaffolds effectively modulated bone remodeling dynamics via inhibiting hyperactive osteoclast activities. Considering that such combinatorial biphasic scaffolds have been easily prepared and successfully utilized for cartilage defect repair, this cell-free tissue-engineered strategy holds great promise in future clinical translation.

摘要

负重关节软骨全层缺损的功能修复一直是骨科领域的主要挑战之一。而先进的3D打印技术能够构建支持组织再生的仿生生物支架。在此,我们开发了一种用于骨软骨再生的谱系特异性双相支架,通过连续的3D打印和冻干制备而成。为促进成骨和骨形成,使用由甲基丙烯酸明胶(GelMA)和羟基磷灰石(HAP)组成的复合墨水3D打印制备了一种多孔支架。为协同刺激软骨生成和透明软骨再生,将胶原蛋白注入3D打印的GelMA/HAP构建体的顶层。骨髓间充质干细胞(BMSCs)培养表明,顶层胶原蛋白层优先促进BMSCs的软骨分化,而GelMA/HAP复合材料主要促进其成骨分化。然后在兔全层关节软骨缺损的负重区域内检查这种定制的双相支架,在植入后六周和十二周时在其中发现了新软骨、骨形成和重塑。与研究结果一致,底部的GelMA/HAP支架促进骨形成,而预加载胶原蛋白的顶层显著增加透明软骨形成。此外,很明显双相支架通过抑制过度活跃的破骨细胞活性有效地调节骨重塑动力学。鉴于这种组合双相支架易于制备并已成功用于软骨缺损修复,这种无细胞组织工程策略在未来临床转化中具有巨大潜力。

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