Pre-vascularized dermis model for fast and functional anastomosis with host vasculature

• DOI: 10.5281/zenodo.6460404
• Publication Date: 2022-04-14
• Authors: Claudia Mazio; Costantino Casale; Giorgia Imparato; Francesco Urciuolo; Chiara Attanasio; María de los Ánge...; Francesca Rescigno; Paolo A. Netti
• Keywords: 0301 basic medicine; Anastomosis; Biophysics; Neovascularization, Physiologic; Bioengineering; Anastomosis; Capillary like structures; Dermis substitutes; Endogenous matrix; Skin engineering; Vascularization; Bioengineering; Ceramics and Composites; Biophysics; Biomaterials; Mechanics of Materials; Biomaterials; Skin engineering; Mice; 03 medical and health sciences; Human Umbilical Vein Endothelial Cells; Animals; Humans; Cells, Cultured; Dermis substitutes; Skin, Artificial; Wound Healing; 0303 health sciences; Tissue Engineering; Vascularization; Endothelial Cells; Dermis; Fibroblasts; Extracellular Matrix; Endogenous matrix; Mechanics of Materials; Capillary like structures; Ceramics and Composites

Skin engineering for clinical applications has gained numerous advances, however, most of the available dermis substitutes are exogenous matrices acting for a limited time. Indeed, after implantation these matrices need to be colonized by host cells such as fibroblast and endothelial cells which respectively produce their own extracellular matrix and set a vascular network within the construct. These steps are essential to guarantee implant efficacy, but they may require a long time depending on tissue dimension and lesion severity. Here we show the pre-vascularization process of a dermis equivalent featured by an endogenous matrix produced by human dermal fibroblasts. In this environment, endothelial cells were able to develop mature capillary-like-structures (CLS) as demonstrated by both the inner lumen and the positivity for alpha-SMA, laminin and collagen. The pre-vascularized dermis model (PVD) so obtained had a human matrix populated by fibroblasts as well as a complex capillary network making the construct ready to be implanted. These features make the graft very easy to handle during the surgery. In vivo results showed that 7 days after implantation CLS effectively anastomosed with host vessels. Therefore we argue that the proposed PVD may represent a new class of dermis substitute of strong clinical interest.