Monsuur Hanneke N, Weijers Ester M, Gibbs Susan, van den Broek Lenie J
Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Oral Cell Biology, Academic Center for Dentistry Amsterdam (ACTA), University of Amsterdan and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
BMC Biomed Eng. 2019 Jul 17;1:18. doi: 10.1186/s42490-019-0018-8. eCollection 2019.
Therapy resistant ulcers are wounds that remain open for a long time period and often arise from chronic venous disease, prolonged pressure or diabetes. For healing of chronic wounds, revitalization of the inert wound bed, which is achieved by angiogenic sprouting of new blood vessels is of great importance. An alternative treatment option to conventional therapies is the use of skin substitutes: dermal (DS), epidermal (ES) or bi-layered skin substitutes (SS). The aim of this study was to determine the mode of action of an autologous SS, ES and DS with regards to endothelial cell proliferation, migration and angiogenic sprouting into a fibrin hydrogel.
SS consists of a fully differentiated epidermis expanding over the acellular donor dermis (AD) which has become repopulated with fibroblasts. DS is the same construct as SS but without the epidermis and ES is the same construct as SS but without the fibroblasts. As a control, AD was used throughout. It was found that the bi-layered SS was the most potent substitute in inducing migration and sprouting of endothelial cells. The cross talk between dermis and epidermis resulted in the strongest induction of sprouting via VEGF and uPAR. ES stimulated sprouting more than DS again via VEGF and uPAR. The slight induction of sprouting mediated by DS was not mediated by VEGF, but was in part stimulated through uPAR.
This in vitro study supports our clinical observations that a bi-layered SS is a strong stimulator of angiogenesis and therefore has the potential to revitalize an inert wound bed.
治疗抵抗性溃疡是长期不愈合的伤口，通常由慢性静脉疾病、长期压力或糖尿病引起。对于慢性伤口的愈合，通过新生血管的血管生成芽来实现惰性伤口床的复苏非常重要。传统疗法的一种替代治疗选择是使用皮肤替代物：真皮替代物（DS）、表皮替代物（ES）或双层皮肤替代物（SS）。本研究的目的是确定自体SS、ES和DS在内皮细胞增殖、迁移以及向纤维蛋白水凝胶中血管生成芽方面的作用方式。
SS由覆盖在已重新填充有成纤维细胞的无细胞供体真皮（AD）上的完全分化的表皮组成。DS与SS结构相同，但没有表皮，ES与SS结构相同，但没有成纤维细胞。整个实验过程中均使用AD作为对照。发现双层SS是诱导内皮细胞迁移和芽生的最有效替代物。真皮和表皮之间的相互作用通过VEGF和uPAR导致最强的芽生诱导。ES再次通过VEGF和uPAR比DS更能刺激芽生。DS介导的轻微芽生诱导不是由VEGF介导的，而是部分通过uPAR刺激的。
这项体外研究支持了我们的临床观察结果，即双层SS是血管生成的强刺激剂，因此有潜力使惰性伤口床复苏。
