Department of Women's and Children's Health, Bioclinicum J10:20 Karolinska Institutet, 171 76 Stockholm, Sweden.
Laboratory of Tissue Engineering Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.
Int J Mol Sci. 2022 Oct 21;23(20):12703. doi: 10.3390/ijms232012703.
In severe malformations with a lack of native tissues, treatment options are limited. We aimed at expanding tissue in vivo using the body as a bioreactor and developing a sustainable single-staged procedure for autologous tissue reconstruction in malformation surgery. Autologous micro-epithelium from skin was integrated with plastically compressed collagen and a degradable knitted fabric mesh. Sixty-three scaffolds were implanted in nine rats for histological and mechanical analyses, up to 4 weeks after transplantation. Tissue integration, cell expansion, proliferation, inflammation, strength, and elasticity were evaluated over time in vivo and validated in vitro in a bladder wound healing model. After 5 days in vivo, we observed keratinocyte proliferation on top of the transplant, remodeling of the collagen, and neovascularization within the transplant. At 4 weeks, all transplants were fully integrated with the surrounding tissue. Tensile strength and elasticity were retained during the whole study period. In the in vitro models, a multilayered epithelium covered the defect after 4 weeks. Autologous micro-epithelial transplants allowed for cell expansion and reorganization in vivo without conventional pre-operative in vitro cell propagation. The method was easy to perform and did not require handling outside the operating theater.
在严重畸形且缺乏原生组织的情况下，治疗选择有限。我们旨在利用身体作为生物反应器来扩展组织，并为畸形手术中的自体组织重建开发一种可持续的单一阶段程序。将来自皮肤的自体微上皮与可塑压缩胶原和可降解的针织纤维网整合在一起。将 63 个支架植入 9 只大鼠中，进行组织学和机械分析，移植后最长可达 4 周。在体内随时间评估组织整合、细胞扩增、增殖、炎症、强度和弹性，并在膀胱伤口愈合模型中进行体外验证。在体内 5 天后，我们观察到移植物顶部的角质形成细胞增殖、胶原重塑和移植物内的新血管生成。4 周后，所有移植物均与周围组织完全整合。在整个研究期间，拉伸强度和弹性得以保留。在体外模型中，4 周后缺陷被复层上皮覆盖。自体微上皮移植允许细胞在体内扩增和重新组织，而无需传统的术前体外细胞繁殖。该方法易于操作，且不需要在手术室外进行处理。
