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Acellular Hydrogels for Regenerative Burn Wound Healing: Translation from a Porcine Model.

ABSTRACT: Currently available skin grafts and skin substitutes for healing following third-degree burn injuries are fraught with complications, often resulting in long-term physical and psychological sequelae. Synthetic treatment that can promote wound healing in a regenerative manner would provide an off-the-shelf, non-immunogenic strategy to improve clinical care of severe burn wounds. Here, we demonstrate the vulnerary efficacy and accelerated healing mechanism of a dextran-based hydrogel in a third-degree porcine burn model. The model was optimized to allow examination of the hydrogel treatment for clinical translation and its regenerative response mechanisms. Hydrogel treatment accelerated third-degree burn wound healing by rapid wound closure, improved re-epithelialization, enhanced extracellular matrix remodeling, and greater nerve reinnervation, compared with the dressing-treated group. These effects appear to be mediated through the ability of the hydrogel to facilitate a rapid but brief initial inflammatory response that coherently stimulates neovascularization within the granulation tissue during the first week of treatment, followed by an efficient vascular regression to promote a regenerative healing process. Our results suggest that the dextran-based hydrogels may substantially improve healing quality and reduce skin grafting incidents and thus pave the way for clinical studies to improve the care of severe burn injury patients.

SUBMITTER: Shen YI

PROVIDER: S-EPMC4570841 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Acellular Hydrogels for Regenerative Burn Wound Healing: Translation from a Porcine Model.

Shen Yu-I YI Song Hyun-Ho Greco HG Papa Arianne A Burke Jacqueline J Volk Susan W SW Gerecht Sharon S

The Journal of investigative dermatology 20150508 10

Currently available skin grafts and skin substitutes for healing following third-degree burn injuries are fraught with complications, often resulting in long-term physical and psychological sequelae. Synthetic treatment that can promote wound healing in a regenerative manner would provide an off-the-shelf, non-immunogenic strategy to improve clinical care of severe burn wounds. Here, we demonstrate the vulnerary efficacy and accelerated healing mechanism of a dextran-based hydrogel in a third-de ...[more]

PMID: 26358387

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Project description:Acellular cornea derived hydrogels provide significant advantages in preserving native corneal stromal keratocyte cells and endothelial cells. However, for clinical application, hydrogel physical properties need to be improved, and their role in corneal epithelial wound healing requires further investigation. In this study, an acellular porcine corneal stroma (APCS) hydrogel (APCS-gel) was successfully prepared from 20 mg/ml APCS, demonstrated optimal light transmittance and gelation kinetic properties and retained critical corneal ECM of collagens and growth factors. Compared with fibrin gel, the APCS-gel had a higher porosity ratio and faster nutrition diffusion with an accompanying improvement in the proliferation of primary rabbit corneal epithelial cells (RCECs) and stromal cells (RCSCs). These corneal cell types also displayed improved viability and cellular infiltration. Furthermore, the APCS-gel provides significant advantages in the preservation of RCECs stemness and enhancement of corneal wound healing in vitro and in vivo. After 7 days of culture, 3-4 layers of RCECs were formed on the APCS-gel in vitro, while only 1-2 layers were found on the fibrin gel. More corneal stem/progenitor cell phenotypes (K12-, p63+, ABCG2+) and proliferation phenotypes (Ki67+) were detected on the APCS-gel than fibrin gel. Using a corneal epithelial wound healing model, we also found faster reepithelization in corneas that received APCS-gel compared to fibrin gel. Additionally, our APCS-gel demonstrated better physical and biological properties when compared to Tisseel, a clinically used type of fibrin gel. In conclusion, our APCS-gel provided better corneal epithelial and stromal cell biocompatibility to fibrin gels and due to its transparency and faster gelation time could potentially be superior for clinical purposes. STATEMENT OF SIGNIFICANCE: Extracellular matrix (ECM) can be used to provide tissue specific physical microstructure and biochemical cues for tissue regeneration. Here, we produced an ECM hydrogel derived from acellular porcine cornea stroma (APCS-gel) that retained critical biological characteristics of the native tissue and provided significant transparency and fast gelation time. Our data demonstrated that the APCS-gel was superior to clinically used fibrin gel, as the APCS-gel showed high porosity and permeability, better corneal stromal keratocytes infiltration, increased cellular proliferation and retention of corneal epithelial cells stemness. The APCS-gel improved corneal wound healing in vitro and in vivo. This APCS-gel may have clinical utility for corneal diseases, and the more general approach used to make this hydrogel might be used in other tissues.

Project description:Objective: The use of noncultured autologous stromal vascular fraction or clinical grade adipose-derived regenerative cells (ADRCs) is a promising strategy to promote wound healing and tissue repair. Nevertheless, issues regarding the optimal mode of administration remain unclear. The purpose of this study was to compare the effects of local injection and topical spray delivery of ADRCs in a porcine model of thermal burns. Approach: Full-thickness thermal burns were created on the dorsum of 10 Gottingen minipigs. Two days following injury, wounds underwent fascial excision and were randomized to receive control vehicle or freshly isolated autologous ADRCs delivered by either multiple injections into or surrounding the wound bed, or by spray onto the wound surface (0.25?×?106 viable cells/cm2). Healing was evaluated by planimetry, histopathology, and immunohistochemistry at day 7, 12, 16, 21, and 28 posttreatment. Results:In vitro analysis demonstrated that there was no substantial loss of cell number or viability attributable to the spray procedure. Planimetric assessment revealed that delivery of ADRCs by either local injection or topical spray increased wound reepithelialization relative to control at day 14. No significant difference in wound reepithelialization was observed between both delivery approaches. In addition, on day 7 posttreatment, blood vessel density was greater in wounds receiving local or topical spray ADRCs than in the wounds treated with vehicle control. Histopathologic analysis suggests that ADRC treatment may modulate the inflammatory response by reducing neutrophil infiltration at day 7 and 12 posttreatment, irrespective of the route of administration. Conclusions: These data demonstrate that local injection and spray delivery of ADRCs modulate inflammation and improve wound angiogenesis and epithelialization. Importantly, both delivery routes exhibited similar effects on wound healing. Given the greater ease-of-use associated with topical spray delivery, these data support the use of a spray system for autologous ADRC delivery.

Dataset Information

Acellular Hydrogels for Regenerative Burn Wound Healing: Translation from a Porcine Model.

Publications

Acellular Hydrogels for Regenerative Burn Wound Healing: Translation from a Porcine Model.

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