Preclinical in vitro validation and in vivo evaluation of a new Biohybrid-Gradient-Layersystem-non woven as a carrier matrix for a vascular component for the supply of epithelial soft tissue defects

迄今为止，目前伤口敷料的临床适用性是有限的，特别是对于大型软组织缺陷，并且有证据表明血管成分的影响在再上皮环境中是有益的，这个组合项目，位于材料科学-生命科学界面，最初旨在创造一种新型生物杂交梯度分层非织造布（BGSV）作为细胞基质，用于治疗软组织缺陷，包括大规模。在该项目的开发部分，生物力学BGSV特性将在制造过程中单独优化，涉及其e模量，这样它们就能成功地促进血管成分的建立，可选地包括(i)脐带内皮细胞（HUVECs）或（ii）内皮祖细胞（EPCs）。理想情况下，迭代的生物力学优化将产生内皮细胞的内皮分化或BGSV内毛细血管内皮结构的形成，与匹配的无血管对照将在体外条件下进行临床前评估。通过采用组织特异性的人成纤维细胞-角质形成细胞系统，通过对口腔黏膜或皮肤上皮形态发生的推定改善和/或加速的比较实验分析，将进行定性验证。与先前描述的临床前验证的操作方法类似，将在裸鼠伤口愈合模型中进行再上皮化的体内验证，以解决翻译水平，这意味着血管化BGSVs的前瞻性临床应用。临床前和体内验证对表皮和牙龈口腔黏膜两种不同上皮类型的研究结果，将为分别优化血管组分的BGSVs阐述的上皮形态发生结果是否可以推广到人体上皮实体提供宝贵的证据。

Since to date, clinical applicability of current wound dressings is limited, particularly regarding large soft tissue defects, and there is evidence that impact of a vascular component is beneficial in the re-epithelisation context, this combinatorial project, located at the material science-life science-interface, initially aims at creating a novel biohybrid gradient layered nonwoven (BGSV) as cell matrix for treatment of soft tissue defects, including large scale. In the developmental part of the project, the biomechanical BGSV properties will be individually optimized during the manufacturing process, concerning their E-moduli, such that they successfully facilitate establishment of a vascular component, optionally comprising (i) umbilical endothelial cells (HUVECs) or (ii) endothelial progenitor cells (EPCs). Ideally, iterative biomechanics optimization will yield endothelial differentiation of EPCs or formation of capillary endothelial structures inside the BGSV, which with matched avascular controls will be preclinically evaluated under in vitro conditions. This validation will be conducted qualitatively, by comparative experimental analysis of putative improvement and/or acceleration of oral mucosa or skin epithelial morphogenesis, by employing tissue-specific interactive human fibroblast-keratinocyte cell systems. In analogy to the previously described modus operandi for the preclinical validation, in vivo validation of re-epithelization will be carried out in a nude mouse wound healing model, to address the translational level that means a prospective clinical utilisation of vascularised BGSVs. The findings on two divergent epithelial types, namely epidermis and gingival oral mucosa, obtained from preclinical as well as in vivo validation will be precious in providing evidence, whether the results on epithelial morphogenesis, elaborated with the respective vascular component-optimized BGSVs, can be generalized on epithelial entities of the human body.