无细胞聚合物复合支架的机械加载可增强兔模型中完全功能性跟腱的原位再生。

Mechanical loading on cell-free polymer composite scaffold enhances in situ regeneration of fully functional Achilles tendon in a rabbit model.

机构信息

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering Research, National Tissue engineering Center of China, Shanghai, PR China.

Department of Plastic Surgery, The 1st affiliated hospital of Sun Yat-sen University. Guangzhou, PR China.

出版信息

Biomater Adv. 2024 Oct;163:213950. doi: 10.1016/j.bioadv.2024.213950. Epub 2024 Jul 2.

Abstract

Traditional tendon engineering using cell-loaded scaffold has limited application potential due to the need of autologous cells. We hypothesize that potent mechanical loading can efficiently induce in situ Achilles tendon regeneration in a rabbit model by using a cell-free porous composite scaffold. In this study, melt-spinning was used to fabricate PGA (polyglycolic acid) and PLA (polylactic acid) filament fibers as well as non-woven PGA fibers. The PLA/PGA (4:2) filament fibers were further braided into a hybrid yarn,which was knitted into a PLA/PGA tubular mesh with potent mechanical property for sustaining natural tendon strain. The results showed that a complete cross-section of Achilles tendon created a model of full mechanical loading on the bridging scaffold, which could efficiently induce in situ tendon regeneration by promoting host cell infiltration, matrix production and tissue remodeling. Histologically, mechanical loading assisted in forming parallel aligned collagen fibers and tenocytes in a fashion similar to those of native tendon. Transmission electron microscope further demonstrated that mechanical strain induced collagen fibril development by increasing fibril diameter and forming bipolar structure, which resulted in enhanced mechanical properties. Interestingly, the synergistic effect between mechanical loading and hyaluronic acid modification was also observed on the induced tenogenic differentiation of infiltrated host fibroblasts. In conclusion, potent mechanical loading is the key inductive microenvironment for in situ tendon regeneration for this polymer-based composite scaffold with proper matrix modification, which may serve as a universal scaffold product for tendon regeneration.

摘要

传统的细胞负载支架肌腱工程由于需要自体细胞,其应用潜力有限。我们假设,通过使用无细胞多孔复合支架,强大的机械负荷可以有效地在兔模型中诱导原位跟腱再生。在这项研究中,熔融纺丝被用于制造 PGA(聚乙醇酸)和 PLA(聚乳酸)长丝纤维以及非织造 PGA 纤维。PLA/PGA(4:2)长丝纤维进一步编织成混合纱线,然后编织成具有强大机械性能的 PLA/PGA 管状网,以维持天然肌腱应变。结果表明,完整的跟腱横截面为桥接支架上的全机械加载创建了一个模型,通过促进宿主细胞浸润、基质产生和组织重塑,有效地诱导了原位腱再生。组织学上,机械加载有助于形成与天然肌腱相似的平行排列的胶原纤维和腱细胞。透射电子显微镜进一步表明,机械应变通过增加纤维直径和形成双极结构来诱导胶原纤维的发育,从而提高了机械性能。有趣的是,在浸润宿主成纤维细胞的诱导成肌腱分化方面,机械加载和透明质酸修饰之间也存在协同作用。总之,对于这种具有适当基质修饰的基于聚合物的复合支架,强大的机械加载是原位腱再生的关键诱导微环境,它可能成为一种通用的肌腱再生支架产品。

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