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首页> 外文期刊>Journal of Tissue Engineering >Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration
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Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration

机译:过程诱导的细胞外基质改变影响软组织修复和再生的机制

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Extracellular matrices derived from animal tissues for human tissue repairs are processed by various methods of physical, chemical, or enzymatic decellularization, viral inactivation, and terminal sterilization. The mechanisms of action in tissue repair vary among bioscaffolds and are suggested to be associated with process-induced extracellular matrix modifications. We compared three non-cross-linked, commercially available extracellular matrix scaffolds (Strattice, Veritas, and XenMatrix), and correlated extracellular matrix alterations to in vivo biological responses upon implantation in non-human primates. Structural evaluation showed significant differences in retaining native tissue extracellular matrix histology and ultrastructural features among bioscaffolds. Tissue processing may cause both the condensation of collagen fibers and fragmentation or separation of collagen bundles. Calorimetric analysis showed significant differences in the stability of bioscaffolds. The intrinsic denaturation temperature was measured to be 51°C, 38°C, and 44°C for Strattice, Veritas, and XenMatrix, respectively, demonstrating more extracellular matrix modifications in the Veritas and XenMatrix scaffolds. Consequently, the susceptibility to collagenase degradation was increased in Veritas and XenMatrix when compared to their respective source tissues. Using a non-human primate model, three bioscaffolds were found to elicit different biological responses, have distinct mechanisms of action, and yield various outcomes of tissue repair. Strattice permitted cell repopulation and was remodeled over 6 months. Veritas was unstable at body temperature, resulting in rapid absorption with moderate inflammation. XenMatrix caused severe inflammation and sustained immune reactions. This study demonstrates that extracellular matrix alterations significantly affect biological responses in soft tissue repair and regeneration. The data offer useful insights into the rational design of extracellular matrix products and bioscaffolds of tissue engineering.
机译:通过各种物理,化学或酶促脱细胞,病毒灭活和终末灭菌的方法处理源自动物组织的细胞外基质,以进行人体组织修复。在组织修复中的作用机制在生物支架之间有所不同,并被认为与过程诱导的细胞外基质修饰有关。我们比较了三种非交联的,可商购的细胞外基质支架(Strattice,Veritas和XenMatrix),并将细胞外基质改变与植入非人灵长类动物体内的生物反应相关联。结构评估显示,生物支架在保留天然组织细胞外基质的组织学和超微结构特征方面存在显着差异。组织处理可能会导致胶原纤维凝结和胶原束断裂或分离。量热分析显示生物支架的稳定性存在显着差异。对于Strattice,Veritas和XenMatrix,固有变性温度测得分别为51°C,38°C和44°C,这表明在Veritas和XenMatrix支架中细胞外基质的修饰更多。因此,与它们各自的来源组织相比,Veritas和XenMatrix对胶原酶降解的敏感性增加了。使用非人类的灵长类动物模型,发现了三个生物支架引发不同的生物学反应,具有不同的作用机制并产生各种组织修复结果。晶格允许细胞重聚,并在6个月内重塑。 Veritas在体温下不稳定,导致迅速吸收并伴有中度炎症。 XenMatrix引起严重的炎症和持续的免疫反应。这项研究表明,细胞外基质改变显着影响软组织修复和再生中的生物学反应。数据为细胞外基质产品和组织工程生物支架的合理设计提供了有用的见识。

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