Injectable connective tissue matrices (CTMs) may promote tendon healing, given their minimally invasive properties, structural and biochemical extracellular matrix components, and capacity to fill irregular spaces. The purpose of this study is to evaluate the effects of placental CTMs on the cellular activities of human tenocytes. Decellularization, the removal of cells, cell fragments, and DNA from CTMs, has been shown to reduce the host’s inflammatory response. Therefore, the authors hypothesize that a decellularized CTM will provide a more cell-friendly matrix to support tenocyte functions. Three human placental CTMs were selected for comparison: AmnioFill® (A-CTM), a minimally manipulated, non-viable cellular particulate, BioRenew™ (B-CTM), a liquid matrix, and Interfyl® (I-CTM), a decellularized flowable particulate. Adhesion and proliferation were evaluated using cell viability assays and tenocyte migration using a transwell migration assay. Gene expression of tenocyte markers, cytokines, growth factors, and matrix metalloprotease (MMP) in tenocytes were assessed using quantitative polymerase chain reaction. Although A-CTM supported more tenocyte adhesion, I-CTM promoted significantly more tenocyte proliferation compared with A-CTM and B-CTM. Unlike A-CTM, tenocyte migration was higher in I-CTM than the control. The presence of I-CTM also prevented the loss of tenocyte phenotype, attenuated the expression of pro-inflammatory cytokines, growth factors, and MMP, and promoted the expression of antifibrotic growth factor, TGFβ3. Compared with A-CTM and B-CTM, I-CTM interacted more favorably with human tenocytes in vitro. I-CTM supported tenocyte proliferation with reduced de-differentiation and attenuation of the inflammatory response, suggesting that I-CTM may support tendon healing and regeneration in vivo.

中文翻译：

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脱细胞可流动胎盘结缔组织基质在体外支持人肌腱细胞的细胞功能

鉴于其微创特性、结构和生化细胞外基质成分以及填充不规则空间的能力，可注射结缔组织基质 (CTM) 可以促进肌腱愈合。本研究的目的是评估胎盘 CTMs 对人体肌腱细胞活性的影响。去细胞化，即从 CTM 中去除细胞、细胞碎片和 DNA，已被证明可以减少宿主的炎症反应。因此，作者假设去细胞化 CTM 将提供对细胞更友好的基质来支持肌腱细胞功能。选择了三种人类胎盘 CTM 进行比较：AmnioFill® (A-CTM)，一种微操作的非活性细胞颗粒，BioRenew™ (B-CTM)，一种液体基质，和 Interfyl® (I-CTM)，一种脱细胞可流动颗粒。使用细胞活力测定和使用 transwell 迁移测定的肌腱细胞迁移评估粘附和增殖。使用定量聚合酶链反应评估肌腱细胞中肌腱细胞标志物、细胞因子、生长因子和基质金属蛋白酶 (MMP) 的基因表达。尽管 A-CTM 支持更多的肌腱细胞粘附，但与 A-CTM 和 B-CTM 相比，I-CTM 显着促进了更多的肌腱细胞增殖。与 A-CTM 不同，I-CTM 中的肌腱细胞迁移高于对照。I-CTM 的存在还阻止了肌腱细胞表型的丧失，减弱了促炎细胞因子、生长因子和 MMP 的表达，并促进了抗纤维化生长因子 TGFβ3 的表达。与 A-CTM 和 B-CTM 相比，I-CTM 在体外与人肌腱细胞的相互作用更有利。