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

• Applicants: Professor Dr. Günter Finkenzeller (†); Professor Dr. Pascal Tomakidi
• Subject Area: Dentistry, Oral Surgery
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 255953801

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.

• DFG Programme: Research Grants