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负载卡托金纳米颗粒的重组胶原蛋白/甲基丙烯酸壳聚糖/纳米粘土水凝胶的3D打印用于软骨再生

3D printing of recombinant collagen/chitosan methacrylate/nanoclay hydrogels loaded with Kartogenin nanoparticles for cartilage regeneration.

作者信息

Zhang Wanting, Shi Kejia, Yang Jianfeng, Li Wenjing, Yu Yang, Mi Yu, Yao Tianyu, Ma Pei, Fan Daidi

机构信息

Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an 710069, China.

Shaanxi Key Laboratory of Degradable Biomedical Materials and Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi'an 710069, China.

出版信息

Regen Biomater. 2024 Aug 28;11:rbae097. doi: 10.1093/rb/rbae097. eCollection 2024.

Abstract

Cartilage defects are frequently caused by trauma, illness and degradation of the cartilage. If these defects are not sufficiently treated, the joints will degrade irreversibly, possibly resulting in disability. Articular cartilage lacks blood vessels and nerves and is unable to regenerate itself, so the repair of cartilage defects is extremely challenging in clinical treatment. Tissue engineering technology is an emerging technology in cartilage repair and cartilage regeneration. 3D-printed hydrogels show great potential in cartilage tissue engineering for the fabrication of 3D cell culture scaffolds to mimic extracellular matrix. In this study, we construct a 3D-printed hydrogel loaded with nanoparticles by electrostatic interaction and photo cross-linking for the regeneration of cartilage, which has adaptable and drug-continuous release behavior. A photopolymerizable bioink was prepared using recombinant collagen, chitosan, nanoclay Laponite-XLG and nanoparticles loaded with Kartogenin (KGN). This bioink was added with KGN, a small molecule drug that promotes cartilage differentiation, and as a result, the 3D-printed CF/CM/3%LAP/KGN scaffolds obtained by extrusion printing is expected to be used for cartilage repair. It was shown that the 3D-printed scaffolds had good cytocompatibility for human bone marrow mesenchymal stem cells (hBMSCs) and exhibited excellent antimicrobial properties, the continuous release of KGN in the scaffold induced the hBMSCs differentiation into chondrocytes, which significantly enhanced the expression of collagen II and glycosaminoglycan. studies have shown that implantation of KGN-loaded scaffolds into cartilage-injured tissues promoted cartilage tissue regeneration. This study demonstrated that 3D-printed CF/CM/3%LAP/KGN scaffolds can be used for cartilage repair, which is expected to lead to new healing opportunities for cartilage injury-based diseases.

摘要

软骨缺损常由创伤、疾病及软骨退变引起。若这些缺损得不到充分治疗,关节将发生不可逆退变,可能导致残疾。关节软骨缺乏血管和神经,自身无法再生,因此软骨缺损的修复在临床治疗中极具挑战性。组织工程技术是软骨修复和再生领域的一项新兴技术。3D打印水凝胶在软骨组织工程中具有巨大潜力,可用于制造模拟细胞外基质的3D细胞培养支架。在本研究中,我们通过静电相互作用和光交联构建了一种负载纳米颗粒的3D打印水凝胶用于软骨再生,该水凝胶具有适应性和药物持续释放行为。使用重组胶原蛋白、壳聚糖、纳米黏土Laponite-XLG和负载有软骨生成素(KGN)的纳米颗粒制备了一种可光聚合的生物墨水。向这种生物墨水中添加了促进软骨分化的小分子药物KGN,通过挤出打印得到的3D打印CF/CM/3%LAP/KGN支架有望用于软骨修复。结果表明,该3D打印支架对人骨髓间充质干细胞(hBMSCs)具有良好的细胞相容性,并表现出优异的抗菌性能,支架中KGN的持续释放诱导hBMSCs分化为软骨细胞,显著增强了II型胶原蛋白和糖胺聚糖的表达。研究表明,将负载KGN的支架植入软骨损伤组织可促进软骨组织再生。本研究证明3D打印CF/CM/3%LAP/KGN支架可用于软骨修复,有望为基于软骨损伤的疾病带来新的治愈机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecec/11364519/1bf7ced4bf1a/rbae097f8.jpg

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