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半月板修复的生物可吸收聚合物添加制造:从物理化学特性到 3D 打印聚(L-共-D、L 丙交酯-共-碳酸三亚甲基酯)与自体干细胞在兔体内的植入。

Meniscal repair with additive manufacture of bioresorbable polymer: From physicochemical characterization to implantation of 3D printed poly (L-co-D, L lactide-co-trimethylene carbonate) with autologous stem cells in rabbits.

机构信息

Laboratory of Biomaterials, Faculty of Medical Sciences and Health, Pontifical Catholic University of São Paulo (PUC-SP), Sorocaba, Brazil.

Post-Graduation Program of School of Mechanical Engineering (FEM), University of Campinas (UNICAMP), Campinas, Brazil.

出版信息

J Biomater Appl. 2024 Jul;39(1):66-79. doi: 10.1177/08853282241248517. Epub 2024 Apr 22.

DOI:10.1177/08853282241248517
PMID:38646887
Abstract

Three-dimensional (3D) structures are actually the state-of-the-art technique to create porous scaffolds for tissue engineering. Since regeneration in cartilage tissue is limited due to intrinsic cellular properties this study aims to develop and characterize three-dimensional porous scaffolds of poly (L-co-D, L lactide-co-trimethylene carbonate), PLDLA-TMC, obtained by 3D fiber deposition technique. The PLDLA-TMC terpolymer scaffolds (70:30), were obtained and characterized by scanning electron microscopy, gel permeation chromatography, differential scanning calorimetry, thermal gravimetric analysis, compression mechanical testing and study on in vitro degradation, which showed its amorphous characteristics, cylindrical geometry, and interconnected pores. The in vitro degradation study showed significant loss of mechanical properties compatible with a decrease in molar mass, accompanied by changes in morphology. The histocompatibility association of mesenchymal stem cells from rabbit's bone marrow, and PLDLA-TMC scaffolds, were evaluated in the meniscus regeneration, proving the potential of cell culture at in vivo tissue regeneration. Nine New Zealand rabbits underwent total medial meniscectomy, yielding three treatments: implantation of the seeded PLDLA-TMC scaffold, implantation of the unseeded PLDLA-TMC and negative control (defect without any implant). After 24 weeks, the results revealed the presence of fibrocartilage in the animals treated with polymer. However, the regeneration obtained with the seeded PLDLA-TMC scaffolds with mesenchymal stem cells had become intimal to mature fibrocartilaginous tissue of normal meniscus both macroscopically and histologically. This study demonstrated the effectiveness of the PLDLA-TMC scaffold in meniscus regeneration and the potential of mesenchymal stem cells in tissue engineering, without the use of growth factors. It is concluded that bioresorbable polymers represent a promising alternative for tissue regeneration.

摘要

三维(3D)结构实际上是为组织工程创建多孔支架的最先进技术。由于软骨组织的再生受到内在细胞特性的限制,因此本研究旨在开发和表征通过 3D 纤维沉积技术获得的聚(L-共-D,L 丙交酯-共-三亚甲基碳酸酯),PLDLA-TMC 的三维多孔支架。获得并通过扫描电子显微镜、凝胶渗透色谱法、差示扫描量热法、热重分析、压缩力学测试和体外降解研究对 PLDLA-TMC 共聚体支架(70:30)进行了表征,结果表明其具有无定形特征、圆柱几何形状和相互连接的孔。体外降解研究表明,机械性能显著丧失与摩尔质量下降相匹配,同时形态发生变化。兔骨髓间充质干细胞与 PLDLA-TMC 支架的组织相容性研究评估了半月板再生,证明了细胞在体内组织再生中的培养潜力。9 只新西兰兔接受了全内侧半月板切除术,产生了三种治疗方法:植入种子 PLDLA-TMC 支架、植入未种种子 PLDLA-TMC 和阴性对照(无任何植入物的缺陷)。24 周后,结果显示用聚合物处理的动物中有纤维软骨存在。然而,用间充质干细胞接种 PLDLA-TMC 支架进行的再生已在宏观和组织学上成为正常半月板的内膜成熟纤维软骨组织。本研究证明了 PLDLA-TMC 支架在半月板再生中的有效性和间充质干细胞在组织工程中的潜力,而无需使用生长因子。结论是,生物可吸收聚合物是组织再生的有前途的替代物。

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