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

IF 8.2 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Shengnan Qin, Wen Wang, Liang Chen, Ming Yu, Cailing Zhao, Haiquan Zeng, Hanyu Chu, Kexin Zhang, Simin Wu, Rui Cui, Yinfeng Zheng, Ying Bai, Jiake Xu
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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 support in-situ tissue 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. In vitro 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 the in vitro findings, the bottom GelMA/HAP scaffold facilitated bone formation, while the top-layer with preloaded collagen markedly augmented hyaline cartilage formation in vivo. Furthermore, it was evident that the biphasic scaffolds effectively modulated bone remodeling dynamics via inhibiting hyperactive osteoclast activities. Considering that such combinatorial biphasic scaffolds were easily prepared and successfully utilized for cartilage defect repair, this cell-free tissue-engineered strategy holds great promise in future clinical translation.

3D打印骨软骨谱系特异性双相支架在负重区全层关节软骨缺损功能修复中的应用
负重关节软骨全层缺损的功能修复一直是骨科的主要挑战之一。然而,先进的3D打印技术允许构建支持原位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3d打印和冻干制造。为了促进骨生成和骨形成,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打印多孔支架。为了协同刺激软骨形成和透明软骨再生,将胶原蛋白注入3d打印的GelMA/HAP结构的顶层。体外培养的骨髓间充质干细胞(BMSCs)显示,上层胶原层优先促进BMSCs的软骨分化,而GelMA/HAP复合材料主要促进BMSCs的成骨分化。这种定制的双相支架随后在兔全层关节软骨的缺损负重区域内进行了检查,在植入后6周和12周发现了新软骨、骨形成和重塑。与体外实验结果一致,底部的GelMA/HAP支架促进了骨形成,而顶部预载胶原的支架在体内显著增强了透明软骨的形成。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。考虑到这种组合双相支架易于制备并成功用于软骨缺损修复,这种无细胞组织工程策略在未来的临床转化中具有很大的前景。
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来源期刊
Biofabrication
Biofabrication ENGINEERING, BIOMEDICAL-MATERIALS SCIENCE, BIOMATERIALS
CiteScore
17.40
自引率
3.30%
发文量
118
审稿时长
2 months
期刊介绍: Biofabrication is dedicated to advancing cutting-edge research on the utilization of cells, proteins, biological materials, and biomaterials as fundamental components for the construction of biological systems and/or therapeutic products. Additionally, it proudly serves as the official journal of the International Society for Biofabrication (ISBF).
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