Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan.
Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital at Keelung, Keelung 20401, Taiwan; Department of Plastic and Reconstructive Surgery and Craniofacial Research Center, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Kwei-San, Taoyuan 33305, Taiwan.
Int J Biol Macromol. 2022 Nov 30;221:314-333. doi: 10.1016/j.ijbiomac.2022.09.001. Epub 2022 Sep 6.
This study develops a spiral wound scaffold based on gelatin/PCL/heparin (GPH) nanofiber membranes for tendon tissue engineering. By embedding sutures in dual layers of aligned GPH nanofiber membranes, prepared from mixed electrospinning of gelatin and PCL/heparin solutions, we fabricate a high resilience scaffold intended for the high loading environment experienced by tendons. The basic fibroblast growth factor (bFGF) was anchored to GPH scaffold through bioaffinity between heparin and bFGF, aim to provide biological cues for maintenance of tenogenic phenotype. In addition, the aligned nanofiber morphology is expected to provide physical cues toward seeded tenocytes. With sustained release of bFGF, GPH-bFGF can enhance proliferation, up-regulate tenogenic gene expression, and increase synthesis of tendon-specific proteins by tenocytes in vitro. Furthermore, by properly maintaining tendon phenotypes, GPH-bFGF/tenocytes constructs showed improved mechanical properties over GPH-bFGF. From in vivo study using GPH-bFGF/tenocytes constructs to repair rabbit Achilles tendon defects, neotendon tissue formation was confirmed from histological staining and biomechanical analysis. These findings collectively demonstrate that the newly designed GPH-bFGF scaffold could provide a niche for inducing tendon tissue regeneration by effectively restoring the tendon tissue structure and function.
本研究基于明胶/PCL/肝素(GPH)纳米纤维膜开发了一种螺旋缠绕支架,用于肌腱组织工程。通过将缝线嵌入由明胶和 PCL/肝素溶液混合电纺制备的双层定向 GPH 纳米纤维膜中,我们制造了一种高弹性支架,旨在适应肌腱所经历的高负载环境。碱性成纤维细胞生长因子(bFGF)通过肝素和 bFGF 之间的生物亲和力锚定到 GPH 支架上,旨在为维持肌腱形成表型提供生物学线索。此外,定向纳米纤维形态有望为接种的肌腱细胞提供物理线索。通过持续释放 bFGF,GPH-bFGF 可以增强体外肌腱细胞的增殖、上调肌腱形成基因表达,并增加肌腱特异性蛋白的合成。此外,通过适当维持肌腱表型,GPH-bFGF/肌腱细胞构建体在机械性能方面优于 GPH-bFGF。通过使用 GPH-bFGF/肌腱细胞构建体修复兔跟腱缺损的体内研究,从组织学染色和生物力学分析证实了新形成的腱组织。这些发现共同表明,新设计的 GPH-bFGF 支架可以通过有效恢复肌腱组织的结构和功能,为诱导肌腱组织再生提供一个合适的场所。