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

由于到目前为止，目前创面敷料的临床适用性有限，特别是对于大型软组织缺损，而且有证据表明血管成分的影响在再上皮化环境中是有益的。这个组合项目位于材料科学-生命科学-界面，最初的目标是创造一种新型的生物杂化梯度层状非织造布(BGSV)作为细胞基质用于治疗软组织缺损，包括大规模的软组织缺损。在该项目的开发部分，BGSV的生物力学性能将在制造过程中进行单独优化，涉及它们的E-模数，以便它们成功地促进血管组件的建立，可选地包括(I)脐静脉内皮细胞(HUVECs)或(Ii)内皮祖细胞(EPC)。理想情况下，迭代的生物力学优化将产生内皮祖细胞的内皮分化或在BGSV内形成毛细血管内皮结构，与匹配的无血管对照将在体外条件下进行临床前评估。这一验证将通过使用组织特异性的人成纤维细胞-角质形成细胞系统对口腔粘膜或皮肤上皮形态发生的假定改善和/或加速的对比实验分析来进行定性地进行。与前面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体内重新上皮化的验证，以解决翻译水平，这意味着有血管的BGSV有望在临床上使用。从临床前和体内验证中获得的两种不同的上皮类型，即表皮和牙龈口腔粘膜的研究结果，对于提供证据将是宝贵的，为用各自的血管成分优化的BGSVs阐述的关于上皮形态发生的结果是否可以推广到人体的上皮实体提供证据。

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.