PLGA/Gelatin/Hyaluronic Acid Fibrous Membrane Scaffold for Therapeutic Delivery of Adipose-Derived Stem Cells to Promote Wound Healing

Abstract

Hyaluronic acid (HA) has been suggested to be a preferential material for the delivery of adipose-derived stem cells (ASCs) in wound healing. By incorporating HA in electrospun poly (lactide-co-glycolide) (PLGA)/gelatin (PG) fibrous membrane scaffolds (FMS), we aim to fabricate PLGA/gelatin/HA (PGH) FMS to provide a milieu for 3D culture and delivery of ASCs. The prepared FMS shows adequate cytocompatibility and is suitable for attachment and growth of ASCs. Compared with PG, the PGH offers an enhanced proliferation rate of ASCs, shows higher cell viability, and better maintains an ASC-like phenotype during in vitro cell culture. The ASCs in PGH also show upregulated expression of genes associated with angiogenesis and wound healing. From a rat full-thickness wound healing model, a wound treated with PGH/ASCs can accelerate the wound closure rate compared with wounds treated with PGH, alginate wound dressing, and gauze. From H&E and Masson’s trichrome staining, the PGH/ASC treatment can promote wound healing by increasing the epithelialization rate and forming well-organized dermis. This is supported by immunohistochemical staining of macrophages and α-smooth muscle actin, where early recruitment of macrophages, macrophage polarization, and angiogenesis was found due to the delivered ASCs. The content of type III collagen is also higher than type I collagen within the newly formed skin tissue, implying scarless wound healing. Taken together, using PGH FMS as a topical wound dressing material for the therapeutic delivery of ASCs, a wound treated with PGH/ASCs was shown to accelerate wound healing significantly in rats, through modulating immunoreaction, promoting angiogenesis, and reducing scar formation at the wound sites.

Gelatin Microspheres Based on H8-Loaded Macrophage Membrane Vesicles to Promote Wound Healing in Diabetic Mice

“…The GMH8NV group exhibited a notable increase in the deposition of collagen I compared to the control group and other treatment groups ( p < 0.001), indicating that the promotion of collagen I expression was primarily observed with GMH8NV, rather than collagen III expression (Figure A,C). It has been shown that fetal skin contains a higher percentage of collagen III, but as the fetus develops, collagen types in adult skin show an increased collagen I/collagen III ratio . Thus, these results suggest that sustained release of H8NV in the GM significantly affects collagen remodeling and skin maturation in an MMP9 environment.…”

New insights into balancing wound healing and scarless skin repair

“…For example, a PLGA/gelatin/HA fiber membrane scaffold with adipose-derived stem cells accelerated wound healing by increasing the epithelialization rate and promoting the formation of robust dermis, angiogenesis, and macrophage polarization. 185 And a sodium hyaluronate-nanocellulose composite hydrogel loading plateletrich plasma enhances granulation tissue formation, promotes neovascularization and collagen deposition, and accelerates epithelialization, playing an important role in promoting full-thickness skin wound healing. 186 Fibrin, composed of fibrinogen, is a natural polymer that plays an important role in tissue engineering and wound healing.…”

Advances in wound dressing based on electrospinning nanofibers

“…While composite nanofibers based on electrospinning gelatin have already shown improved performance compared to pure gelatin nanofibers, subsequent crosslinking methods can be employed to stabilize the gelatin component and further enhance the properties of various composite nanofibers. Hsieh et al 147 fabricated nanofiber membranes using GE, HA, and PLGA. These nanofiber membranes were then cross‐linked by immersing them in 99.5% ethanol for 24 hours.…”