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

由于迄今为止，当前伤口敷料的临床适用性有限，特别是关于大的软组织缺损，并且有证据表明血管组分的影响在上皮再生背景下是有益的，因此位于材料科学-生命科学-界面的该组合项目最初旨在创建新型生物混合梯度分层非织造物（BGSV）作为用于治疗软组织缺损的细胞基质，包括大规模。在该项目的开发部分，生物力学BGSV性质将在制造过程中单独优化，涉及它们的E模量，使得它们成功地促进血管组分的建立，任选地包括（i）脐内皮细胞（HUVEC）或（ii）内皮祖细胞（EPC）。理想情况下，迭代生物力学优化将产生EPCs的内皮分化或BGSV内毛细血管内皮结构的形成，将在体外条件下对匹配的无血管对照进行临床前评价。通过采用组织特异性相互作用的人成纤维细胞-角质形成细胞系统，对口腔粘膜或皮肤上皮形态发生的推定改善和/或加速进行比较实验分析，定性进行该验证。与先前描述的临床前验证的操作方式类似，将在裸鼠伤口愈合模型中进行上皮再形成的体内验证，以解决意味着血管化BGSV的前瞻性临床利用的翻译水平。从临床前和体内验证中获得的关于两种不同上皮类型（即表皮和牙龈口腔粘膜）的研究结果在提供证据方面将是宝贵的，无论是关于上皮形态发生的结果（用各自的血管成分优化的BGSV详细说明），都可以推广到人体的上皮实体。

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.