Zhang Miao, Wang Ziyu, Zhang Anyu, Liu Linyang, Mithieux Suzanne M, Bilek Marcela M M, Weiss Anthony S
Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia.
School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
Regen Biomater. 2022 Oct 27;10:rbac087. doi: 10.1093/rb/rbac087. eCollection 2023.
The highly organized extracellular matrix (ECM) of musculoskeletal tissues, encompassing tendons, ligaments and muscles, is structurally anisotropic, hierarchical and multi-compartmental. These features collectively contribute to their unique function. Previous studies have investigated the effect of tissue-engineered scaffold anisotropy on cell morphology and organization for musculoskeletal tissue repair and regeneration, but the hierarchical arrangement of ECM and compartmentalization are not typically replicated. Here, we present a method for multi-compartmental scaffold design that allows for physical mimicry of the spatial architecture of musculoskeletal tissue in regenerative medicine. This design is based on an ECM-inspired macromolecule scaffold. Polycaprolactone (PCL) scaffolds were fabricated with aligned fibers by electrospinning and mechanical stretching, and then surface-functionalized with the cell-supporting ECM protein molecule, tropoelastin (TE). TE was attached using two alternative methods that allowed for either physisorption or covalent attachment, where the latter was achieved by plasma ion immersion implantation (PIII). Aligned fibers stimulated cell elongation and improved cell alignment, in contrast to randomly oriented fibers. TE coatings bound by physisorption or covalently following 200 s PIII treatment promoted fibroblast proliferation. This represents the first cytocompatibility assessment of novel PIII-treated TE-coated PCL scaffolds. To demonstrate their versatility, these 2D anisotropic PCL scaffolds were assembled into 3D hierarchical constructs with an internally compartmentalized structure to mimic the structure of musculoskeletal tissue.
肌肉骨骼组织的细胞外基质（ECM）高度有序，包括肌腱、韧带和肌肉，其结构具有各向异性、层次性和多室性。这些特征共同促成了它们独特的功能。以往的研究探讨了组织工程支架各向异性对肌肉骨骼组织修复和再生中细胞形态和组织的影响，但ECM的层次排列和分隔通常没有被复制。在此，我们提出了一种多室支架设计方法，可在再生医学中对肌肉骨骼组织的空间结构进行物理模拟。这种设计基于一种受ECM启发的大分子支架。通过静电纺丝和机械拉伸制备了具有排列纤维的聚己内酯（PCL）支架，然后用细胞支持性ECM蛋白分子原弹性蛋白（TE）进行表面功能化。采用两种替代方法连接TE，一种是物理吸附，另一种是共价连接，后者通过等离子体离子浸没注入（PIII）实现。与随机取向的纤维相比，排列的纤维刺激细胞伸长并改善细胞排列。经200秒PIII处理后通过物理吸附或共价结合的TE涂层促进成纤维细胞增殖。这是对新型PIII处理的TE涂层PCL支架的首次细胞相容性评估。为了展示其多功能性，将这些二维各向异性PCL支架组装成具有内部隔室结构的三维层次结构，以模拟肌肉骨骼组织的结构。
