Angiogenic Potential of Co-Cultured Human Umbilical Vein Endothelial Cells and Adipose Stromal Cells in Customizable 3D Engineered Collagen Sheets

Abstract

The wound healing process is much more complex than just the four phases of hemostasis, inflammation, proliferation, and maturation. Three-dimensional (3D) scaffolds made of biopolymers or ECM molecules using bioprinting can be used to promote the wound healing process, especially for complex 3D tissue lesions like chronic wounds. Here, a 3D-printed mold has been designed to produce customizable collagen type-I sheets containing human umbilical vein endothelial cells (HUVECs) and adipose stromal cells (ASCs) for the first time. In these 3D collagen sheets, the cellular activity leads to a restructuring of the collagen matrix. The upregulation of the growth factors Serpin E1 and TIMP-1 could be demonstrated in the 3D scaffolds with ACSs and HUVECs in co-culture. Both growth factors play a key role in the wound healing process. The capillary-like tube formation of HUVECs treated with supernatant from the collagen sheets revealed the secretion of angiogenic growth factors. Altogether, this demonstrates that collagen type I combined with the co-cultivation of HUVECs and ACSs has the potential to accelerate the process of angiogenesis and, thereby, might promote wound healing.

Hydrogel foam dressings with angiogenic and immunomodulatory factors from mesenchymal stem cells

“…Studies have shown that MSC‐conditioned medium can improve wound healing by releasing growth factors, immunoregulatory factors, chemokines, and extracellular vesicles 17–21 . Co‐culturing MSCs with endothelial cells and keratinocytes has shown improved angiogenesis and recovered epidermal barrier function 22–25 . The efficiency of MSC delivery to damaged tissue is limited by poor cell retention and viability after application 26 .…”

“…[17][18][19][20][21] Co-culturing MSCs with endothelial cells and keratinocytes has shown improved angiogenesis and recovered epidermal barrier function. [22][23][24][25] The efficiency of MSC delivery to damaged tissue is limited by poor cell retention and viability after application. 26 Furthermore, cell-laden dressings require special facilities and culture conditions that can limit access and increase cost.…”