Gellan Gum-Hyaluronic Acid Spongy-like Hydrogels and Cells from Adipose Tissue Synergize Promoting Neoskin Vascularization

Abstract

Currently available substitutes for skin wound healing often result in the formation of nonfunctional neotissue. Thus, urgent care is still needed to promote an effective and complete regeneration. To meet this need, we proposed the assembling of a construct that takes 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 characterized by pore wall thickening and increased mean pore size. The proposed 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 rehydrated at the time of cell seeding then depicting features of both sponges and hydrogels, enabled the natural cell entrapment/encapsulation and attachment supported by cell-polymer interactions. Upon transplantation into mice full-thickness excisional wounds, GG-HA spongy-like hydrogels absorbed the early inflammatory cell infiltrate and led to the formation of a dense granulation tissue. Consequently, spongy-like hydrogel degradation was observed, and progressive wound closure, re-epithelialization, and matrix remodelling was improved in relation to the control condition. More importantly, GG-HA spongy-like hydrogels promoted a superior neovascularization, which was enhanced in the presence of human hAMECs, also found in the formed neovessels. These observations highlight the successful integration of a valuable matrix and prevascularization cues to target angiogenesis/neovascularization in skin full-thickness excisional wounds.

Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model

“…As fibroblast proliferation increased, collagen synthesis and deposition also increased 48. When the skin attachment was formed, re-epithelialization was considered to be promoted 49. Therefore, we confirmed that the wound-healing property of PRP-Exos is mediated by increasing collagen synthesis through YAP activation.…”

Cell-microenvironment interactions and architectures in microvascular systems

“…have modified 5% w/v hyaluronic acid, which is known to promote angiogenesis (Hanjaya-Putra et al, 2011), by adding methacrylate groups and used it to encapsulate cells within hydrogel and create cell docking templates for cell microarrays (Khademhosseini et al, 2006). Chitosan/β-glycerophosphate hydrogels were employed to deliver MSCs within decellularized arterial scaffolds (Sheridan et al, 2014), whereas gellan gum-hyaluronic acid spongy-like hydrogels with embedded human adipose stem cells and microvascular ECs were developed to promote neovascularization and wound closure (Cerqueira et al, 2014). Using a combination of two natural hydrogels, fibrinogen+thrombin and gelatin+transglutaminase, the quattroGel was developed by Aberle et al ., and its structural and mechanical properties were optimized to promote cell adhesion even though the proliferation rates of several cell types, including ECs, were generally unaffected.…”

High‐resolution synchrotronX‐ray analysis of bioglass‐enriched hydrogels

“…Addition of bioglass particles to a variety of noninjectable hydrogels resulted in enhanced apatite formation after incubation in SBF. [13][14][15][16][17][18] Furthermore, addition of bioglass particles to the anionic, calcium-binding polysaccharide gellan gum (GG), which has been investigated as a material for regeneration of skin, cartilage, and invertebral discs, [19][20][21][22][23] can promote GG hydrogel formation and increase compressive strength. 24 This is presumably due to the release of such ions as Ca 21 from bioglass particles, which ionically cross-link the anionic GG polymer chains.…”