Gellan Gum-Hyaluronic Acid Spongy-like hydrogels and cells from adipose tissue synergize promoting neoskin vascularization

Non-functional skin tissue has been the most common outcome of the healing of wounds treated with the currently available substitutes. Thus, urgent care is needed to promote an effective and complete regeneration. To meet this, we proposed the assembling of a construct that take advantage of cell-adhesive gellan gum-hyaluronic acid (GG-HA) spongy-like hydrogels and a powerful cell-machinery obtained from adipose tissue, human adipose stem cells (hASCs) and microvascular endothelial cells (hAMECs). In addition to a cell-adhesive character, GG-HA spongy-like hydrogels overpass limitations of traditional hydrogels, such as reduced physical stability and limited manipulation, due to improved microstructural arrangement and ameliorated mechanical performance. The pruposed constructs combining cellular mediators of the healing process within the spongy-like hydrogels that intend to recapitulate skin matrix, aim to promote neoskin vascularization. Stable and off-the-shelf dried GG-HA polymeric networks, rapidly re-hydrated at the time of cell seeding, then depicting features of both sponges and hydrogels, enabled the natural cell entrapment/encapsulation and consequent attachment and cell-polymer interactions. Upon transplantation into mice full-thickness excisional wounds, GG-HA spongy-like hydrogels absorbed the early inflammatory cell infiltrate and lead to the formation of a dense granulation tissue. Consequently, spongy-like hydrogel degradation was observed and progressive wound closure, re-epithelialization and matrix remodel was improved in relation to control condition. More importantly, GG-HA spongy-like hydrogels promoted a superior neovascularization, which was enhanced in the presence of human hAMECs, also found incorporated in the formed neovessels. These observations highlight the successful integration of a valuable matrix and pre-vascularization cues to target angiogenesis/neovascularization in skin full-thickness excisional wounds.