Iorio Francesco, El Khatib Mohammad, Wöltinger Natalie, Turriani Maura, Di Giacinto Oriana, Mauro Annunziata, Russo Valentina, Barboni Barbara, Boccaccini Aldo R
Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Erlangen, Germany.
Department of Bioscience and Agro-Food and Environmental Technology, Unit of Basic and Applied Biosciences, University of Teramo, Teramo, Italy.
J Biomed Mater Res A. 2025 Jan;113(1):e37794. doi: 10.1002/jbm.a.37794. Epub 2024 Sep 18.
The electrospinning technique is a commonly employed approach to fabricate fibers intended for various tissue engineering applications. The aim of this study is to develop a novel strategy for tendon repair through the use of aligned poly(ε-caprolactone) (PCL) and poly(glycerol sebacate) (PGS) fibers fabricated in benign solvents, and further explore the potential application of PGS in tendon tissue engineering (TTE). The fibers were characterized for their morphological and physicochemical properties; amniotic epithelial stem cells (AECs) were used to assess the fibers teno-inductive and immunomodulatory potential due to their ability to teno-differentiate undergoing first a stepwise epithelial to mesenchymal transition, and due to their documented therapeutic role in tendon regeneration. The addition of PGS to PCL improved the spinnability of the polymer solution, as well as the uniformity and directionality of the so-obtained fibers. The mechanical properties were in the range of most TTE applications, specifically in the case of PCL/PGS 4:1 and 2:1 ratios. Compared to PCL alone, the same ratios also allowed a better AECs infiltration and growth over 7 days of culture, and triggered the activation of tendon-related genes (SCX, COL1, TNMD) and the expression of tenomodulin (TNMD) at the protein level. Concerning the immunomodulatory properties, both PCL and PCL/PGS fibers negatively affected the immunomodulatory profile of AECs, up-regulating both anti-inflammatory (IL-10) and pro-inflammatory (IL-12) cytokines over 7 days of culture. Overall, PCL/PGS 2:1 fibers fabricated with benign solvents proved to be the most suitable composition for TTE application based on their topographical cues, mechanical properties, biocompatibility, and teno-inductive properties.
静电纺丝技术是一种常用于制造适用于各种组织工程应用的纤维的方法。本研究的目的是开发一种新型策略，通过使用在良性溶剂中制造的排列的聚（ε-己内酯）（PCL）和聚（癸二酸甘油酯）（PGS）纤维来修复肌腱，并进一步探索PGS在肌腱组织工程（TTE）中的潜在应用。对纤维的形态和物理化学性质进行了表征；羊膜上皮干细胞（AECs）被用于评估纤维的腱诱导和免疫调节潜力，这是由于它们能够通过首先经历逐步的上皮-间充质转化进行腱分化，以及由于它们在肌腱再生中已被记载的治疗作用。向PCL中添加PGS提高了聚合物溶液的可纺性，以及所获得纤维的均匀性和方向性。力学性能在大多数TTE应用的范围内，特别是在PCL/PGS 4:1和2:1比例的情况下。与单独的PCL相比，相同的比例在7天的培养中也允许更好的AECs浸润和生长，并在蛋白质水平上触发了肌腱相关基因（SCX、COL1、TNMD）的激活和腱调蛋白（TNMD）的表达。关于免疫调节特性，PCL和PCL/PGS纤维在7天的培养中均对AECs的免疫调节谱产生负面影响，上调了抗炎（IL-10）和促炎（IL-12）细胞因子。总体而言，基于其形貌线索、力学性能、生物相容性和腱诱导特性，用良性溶剂制造的PCL/PGS 2:1纤维被证明是最适合TTE应用的组合物。
