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天然人胶原蛋白 I 为组织工程应用提供了一种可行的、具有生理相关性的异种来源替代物:体外和体内比较研究。

Native human collagen type I provides a viable physiologically relevant alternative to xenogeneic sources for tissue engineering applications: A comparative in vitro and in vivo study.

机构信息

Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.

Department of Biomedical and Chemical Engineering and Sciences, Florida Institute of Technology, Melbourne, Florida, USA.

出版信息

J Biomed Mater Res B Appl Biomater. 2022 Oct;110(10):2323-2337. doi: 10.1002/jbm.b.35080. Epub 2022 May 9.

DOI:10.1002/jbm.b.35080
PMID:35532208
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11103545/
Abstract

Xenogeneic sources of collagen type I remain a common choice for regenerative medicine applications due to ease of availability. Human and animal sources have some similarities, but small variations in amino acid composition can influence the physical properties of collagen, cellular response, and tissue remodeling. The goal of this work is to compare human collagen type I-based hydrogels versus animal-derived collagen type I-based hydrogels, generated from commercially available products, for their physico-chemical properties and for tissue engineering and regenerative medicine applications. Specifically, we evaluated whether the native human skin type I collagen could be used in the three most common research applications of this protein: as a substrate for attachment and proliferation of conventional 2D cell culture; as a source of matrix for a 3D cell culture; and as a source of matrix for tissue engineering. Results showed that species and tissue specific variations of collagen sources significantly impact the physical, chemical, and biological properties of collagen hydrogels including gelation kinetics, swelling ratio, collagen fiber morphology, compressive modulus, stability, and metabolic activity of hMSCs. Tumor constructs formulated with human skin collagen showed a differential response to chemotherapy agents compared to rat tail collagen. Human skin collagen performed comparably to rat tail collagen and enabled assembly of perfused human vessels in vivo. Despite differences in collagen manufacturing methods and supplied forms, the results suggest that commercially available human collagen can be used in lieu of xenogeneic sources to create functional scaffolds, but not all sources of human collagen behave similarly. These factors must be considered in the development of 3D tissues for drug screening and regenerative medicine applications.

摘要

由于易于获得,异种来源的 I 型胶原仍然是再生医学应用的常见选择。人和动物来源的胶原具有一些相似之处,但氨基酸组成的微小差异会影响胶原的物理性质、细胞反应和组织重塑。这项工作的目的是比较基于人 I 型胶原的水凝胶与基于商业可获得产品的动物来源的 I 型胶原水凝胶,评估天然人皮肤 I 型胶原是否可用于该蛋白的三种最常见的研究应用:作为常规 2D 细胞培养附着和增殖的基质;作为 3D 细胞培养的基质;以及作为组织工程的基质。结果表明,胶原来源的种属和组织特异性变异显著影响胶原水凝胶的物理、化学和生物学特性,包括凝胶形成动力学、溶胀比、胶原纤维形态、压缩模量、稳定性和 hMSC 的代谢活性。与人皮肤胶原相比,用肿瘤构建体配方的胶原对化疗药物的反应不同。与人尾胶原相比,人皮肤胶原表现出相似的性能,并能在体内组装可灌注的人血管。尽管胶原制造方法和供应形式存在差异,但结果表明,商业上可获得的人胶原可替代异种来源来制造功能性支架,但并非所有来源的人胶原都表现出相似的行为。在开发用于药物筛选和再生医学应用的 3D 组织时,必须考虑这些因素。

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