A novel strategy to engineer pre-vascularized 3-dimensional skin substitutes to achieve efficient, functional engraftment
A novel strategy to engineer pre-vascularized 3-dimensional skin substitutes to achieve efficient, functional engraftment
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DOI：
10.1038/s41598-019-44113-6
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发表时间：
2019-05-24
影响因子：
4.6
通讯作者：
Saitoh, Daizoh
中科院分区：
文献类型：
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作者：
Miyazaki, Hiromi;Tsunoi, Yasuyuki;Saitoh, Daizoh
自体中厚皮移植是切除的烧伤创面的首选治疗方法，但在大面积烧伤的患者中，自体移植的供区往往有限。许多替代疗法已经被用于治疗大面积烧伤和溃疡。尽管大力发展组织工程皮肤，但血管形成延迟或缺失是组织工程皮肤植入失败的主要原因之一。为了克服这些问题，基于我们的逐层细胞涂层技术，我们开发了一种无支架三维(3D)皮肤替代品，其中包含结合真皮成纤维细胞、内皮细胞和表皮角质形成细胞的血管网络。我们将预先血管化的3D皮肤替代物移植到严重联合免疫缺陷小鼠的全层皮肤缺损上，以评估它们与宿主组织的整合和对伤口愈合的影响。我们使用非血管化3D皮肤替代物作为对照。14天时，非血管化对照组的血管明显含有红血球。然而，在移植后7天内，可以检测到人源性血管的血液灌流。此外，血管化前的3D皮肤替代物具有较高的移植物存活率，其表皮层逐渐被小鼠表皮所替代。我们认为，一种新型的含有血管的真皮-表皮3D皮肤替代物可以促进全层皮肤缺损的有效重建。
Autologous split-thickness skin grafts are the preferred treatment for excised burn wounds, but donor sites for autografting are often limited in patients with extensive burns. A number of alternative treatments are already in use to treat large burns and ulcers. Despite intense efforts to develop tissue-engineered skin, delayed or absent vascularization is one of the major reasons for tissue-engineered skin engraftment failure. To overcome these problems, we developed a scaffold-free 3-dimensional (3D) skin substitute containing vascular networks that combine dermal fibroblasts, endothelial cells, and epidermal keratinocytes based on our layer-by-layer cell coating technique. We transplanted the pre-vascularized 3D skin substitutes onto full-thickness skin defects on severe combined immunodeficiency mice to assess their integration with the host tissue and effects on wound healing. We used non-vascularized 3D skin substitutes as a control. Vessels containing red blood cells were evident in the non-vascularized control by day 14. However, blood perfusion of the human-derived vasculature could be detected within 7 days of grafting. Moreover, the pre-vascularized 3D skin substitutes had high graft survival and their epidermal layers were progressively replaced by mouse epidermis. We propose that a novel dermo-epidermal 3D skin substitute containing blood vessels can promote efficient reconstruction of full-thickness skin defects.