Graduate Department of Biomedical Engineering, Middle East Technical University, Ankara, Turkey.
MODSIMMER, Modeling and Simulation Research & Development Center, Middle East Technical University, Ankara, Turkey.
Biomed Mater. 2020 Oct 3;15(6):065014. doi: 10.1088/1748-605X/ab9550.
Tendon is a highly hierarchical and oriented tissue that provides high mechanical strength. Tendon injuries lead to loss of function, disability, and a decrease in quality of life. The limited healing capacity of tendon tissue leads to scar tissue formation, which can affect mechanical strength and cause a re-tear. Tissue engineering can be the solution to achieving complete and proper healing of tendon. The developed constructs should be mechanically strong while maintaining a suitable environment for cell proliferation. In this study, a dual-phase fibrous scaffold was produced by combining fibrous mats produced by rotary jet spinning (RJS) and wet electrospinning (WES), with the intent of improving the healing capacity of the construct. Dual-phase scaffolds were formed from aligned poly(ϵ-caprolactone) (PCL) fibers (Shell) produced by RJS and randomly oriented PCL or PCL/gelatin fibers (Core) produced by WES systems. The scaffolds mimicked i) the repair phase of tendon healing, in which randomly-oriented collagen type III is deposited by randomly-oriented WES fibers and ii) the remodeling stage, in which aligned collagen type I fibers are deposited by aligned RJS fibers. In vitro studies showed that the presence of randomly-oriented core fibers inside the aligned PCL fiber shell of the dual-phase scaffold increased the initial attachment and viability of cells. Scanning electron microscopy and confocal microscopy analysis showed that the presence of aligned RJS fibers supported the elongation of cells through aligned fibers which improves tendon tissue healing by guiding oriented cell proliferation and extracellular matrix deposition. Tenogenic differentiation of human adipose-derived mesenchymal stem cells on scaffolds was studied when supplemented with growth differentiation factor 5 (GDF-5). GDF-5 treatment improved the viability, collagen type III deposition and scaffold penetration of human adipose derived stem cells. The developed FSPCL/ESPCL-Gel 3:1 scaffold (FS = centrifugal force spinning/RJS, ES = wet electrospinning, Gel = gelatin) sustained high mechanical strength, and improved cell viability and orientation while supporting tenogenic differentiation.
肌腱是一种具有高度层次结构和取向的组织，提供了很高的机械强度。肌腱损伤会导致功能丧失、残疾和生活质量下降。肌腱组织的有限愈合能力导致疤痕组织形成，这会影响机械强度并导致再次撕裂。组织工程可以成为实现肌腱完全和适当愈合的解决方案。所开发的构建体应该具有足够的机械强度，同时为细胞增殖提供适宜的环境。在这项研究中，通过结合旋转射流纺丝（RJS）和湿法静电纺丝（WES）生产的纤维垫，开发了一种双相纤维支架，旨在提高构建体的愈合能力。双相支架由 RJS 生产的定向聚己内酯（PCL）纤维（Shell）和 WES 系统生产的无规取向的 PCL 或 PCL/明胶纤维（Core）组成。支架模拟了 i）肌腱愈合的修复阶段，其中无规取向的 WES 纤维沉积无规取向的 III 型胶原，ii）重塑阶段，其中定向的 RJS 纤维沉积定向的 I 型胶原。体外研究表明，双相支架中定向 PCL 纤维壳内的无规取向核纤维的存在增加了细胞的初始附着和活力。扫描电子显微镜和共聚焦显微镜分析表明，定向 RJS 纤维的存在支持细胞通过定向纤维的伸长，通过引导定向细胞增殖和细胞外基质沉积来改善肌腱组织愈合。当向支架中添加生长分化因子 5（GDF-5）时，研究了人脂肪间充质干细胞在支架上的腱细胞分化。GDF-5 处理提高了人脂肪干细胞的活力、III 型胶原沉积和支架穿透。开发的 FSPCL/ESPCL-Gel 3:1 支架（FS = 离心力纺丝/RJS，ES = 湿法静电纺丝，Gel = 明胶）保持了较高的机械强度，提高了细胞活力和定向性，同时支持腱细胞分化。
