Imparato G, Casale C, Scamardella S, Urciuolo F, Bimonte M, Apone F, Colucci G, Netti P A
Centre for Advanced Biomaterials for Health Care, CRIB Istituto Italiano di Tecnologia, Naples, Italy.
Department of Chemical, Materials and Industrial Production (DICMAPI) and Interdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Naples, Italy.
J Tissue Eng Regen Med. 2017 Aug;11(8):2276-2285. doi: 10.1002/term.2125. Epub 2016 Feb 8.
The realization of biologically relevant human tissue equivalents as an in vitro model to investigate human diseases, as well as to test the efficacy or toxicity of novel compounds, is emerging as a new challenge in tissue engineering. Currently, the in vitro three-dimensional (3D) dermis model mainly involves the use of cells embedded in exogenous non-human matrices. However, such models feature biological and functional disparities with native dermis, therefore limiting their relevance to the in vivo situation. The purpose of this study was to provide a reliable endogenous human dermal equivalent (HDE) able to recapitulate the extracellular matrix (ECM) remodelling of the native dermis occurring after external damage. To this end, UVA irradiation was used to induce photodamage to both the HDE and to a fibroblast-populated collagen matrix. The photodamage was investigated at the cellular and ECM level and the results showed that, although a cellular response was detected in both systems, no ECM reorganization characteristic of the in vivo photo-aged dermis could be detected in the fibroblast-populated collagen matrix. In contrast in the HDE, the neosynthesized ECM recapitulated the characteristic ageing behaviour of the dermis found in vivo, in terms of collagen and hyaluronic acid synthesis as well as collagen organization remodelling. This study therefore demonstrates the role of the endogenous ECM in recapitulating in vitro the functionality of the human dermis and the proposed HDE as a novel tool for photoprotection trials. Copyright © 2016 John Wiley & Sons, Ltd.
作为一种体外模型来研究人类疾病以及测试新型化合物的功效或毒性,实现具有生物学相关性的人体组织等效物正成为组织工程中的一项新挑战。目前,体外三维(3D)真皮模型主要涉及使用嵌入外源性非人类基质中的细胞。然而,这类模型与天然真皮存在生物学和功能上的差异,因此限制了它们与体内情况的相关性。本研究的目的是提供一种可靠的内源性人体真皮等效物(HDE),能够重现外部损伤后天然真皮的细胞外基质(ECM)重塑过程。为此,采用紫外线A(UVA)照射对HDE和成纤维细胞填充的胶原基质进行光损伤诱导。在细胞和ECM水平对光损伤进行了研究,结果表明,虽然在两个系统中均检测到细胞反应,但在成纤维细胞填充的胶原基质中未检测到体内光老化真皮特有的ECM重组。相比之下,在HDE中,新合成的ECM在胶原蛋白和透明质酸合成以及胶原组织重塑方面重现了体内真皮特有的老化行为。因此,本研究证明了内源性ECM在体外重现人体真皮功能中的作用,并提出HDE作为光保护试验的一种新型工具。版权所有© 2016约翰威立父子有限公司。