Zhang Xu, Li Ke, Wang Chenyang, Rao Ying, Tuan Rocky S, Wang Dan Michelle, Ker Dai Fei Elmer
Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong.
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong.
Bioact Mater. 2024 Apr 25;37:439-458. doi: 10.1016/j.bioactmat.2024.03.036. eCollection 2024 Jul.
Facile and rapid 3D fabrication of strong, bioactive materials can address challenges that impede repair of large-to-massive rotator cuff tears including personalized grafts, limited mechanical support, and inadequate tissue regeneration. Herein, we developed a facile and rapid methodology that generates visible light-crosslinkable polythiourethane (PHT) pre-polymer resin (∼30 min at room temperature), yielding 3D-printable scaffolds with tendon-like mechanical attributes capable of delivering tenogenic bioactive factors. characterization confirmed successful fabrication, robust human supraspinatus tendon (SST)-like tensile properties (strength: 23 MPa, modulus: 459 MPa, at least 10,000 physiological loading cycles without failure), excellent suture retention (8.62-fold lower than acellular dermal matrix (ADM)-based clinical graft), slow degradation, and controlled release of fibroblast growth factor-2 (FGF-2) and transforming growth factor-β3 (TGF-β3). studies showed cytocompatibility and growth factor-mediated tenogenic-like differentiation of mesenchymal stem cells. studies demonstrated biocompatibility (3-week mouse subcutaneous implantation) and ability of growth factor-containing scaffolds to notably regenerate at least 1-cm of tendon with native-like biomechanical attributes as uninjured shoulder (8-week, large-to-massive 1-cm gap rabbit rotator cuff injury). This study demonstrates use of a 3D-printable, strong, and bioactive material to provide mechanical support and pro-regenerative cues for challenging injuries such as large-to-massive rotator cuff tears.
快速简便地制造坚固的生物活性材料可以应对阻碍大面积至巨大肩袖撕裂修复的挑战,包括个性化移植物、有限的机械支撑和不足的组织再生。在此,我们开发了一种快速简便的方法,可生成可见光交联的聚硫氨酯(PHT)预聚物树脂(室温下约30分钟),从而得到具有类似肌腱机械特性且能够递送成腱生物活性因子的3D可打印支架。表征证实了成功制造,具有类似人冈上肌腱(SST)的强大拉伸性能(强度:23兆帕,模量:459兆帕,至少10000次生理加载循环无失效),出色的缝线保留能力(比基于脱细胞真皮基质(ADM)的临床移植物低8.62倍),缓慢降解以及成纤维细胞生长因子-2(FGF-2)和转化生长因子-β3(TGF-β3)的可控释放。细胞研究显示了间充质干细胞的细胞相容性和生长因子介导的成腱样分化。体内研究证明了生物相容性(3周小鼠皮下植入)以及含生长因子的支架能够显著再生至少1厘米具有类似天然生物力学特性的肌腱,如同未受伤的肩部(8周,大面积至巨大1厘米间隙兔肩袖损伤)。这项研究证明了使用3D可打印、坚固且生物活性的材料为大面积至巨大肩袖撕裂等具有挑战性的损伤提供机械支撑和促再生线索。