Abstract
We investigated the effects of a human umbilical cord mesenchymal stem cell-conditioned medium (MSC-CM)/chitosan/collagen/β-glycerophosphate (β-GP) thermosensitive hydrogel (MSC-CM/hydrogel) on mice with third-degree burns. MSC-CM was collected and mixed with chitosan, collagen, and β-GP to generate the thermosensitive MSC-CM/hydrogel, which was stored in the liquid phase at 4°C. The wounds of established third-degree burned mice were then externally covered with the MSC-CM/hydrogel, which formed a gel when placed on the wounds at physiological temperature. Injured mice in three additional groups were treated with unconditioned MSC medium (UM), MSC-CM, or UM/chitosan/collagen/β-GP thermosensitive hydrogels. Skin wound samples were obtained 4, 14, and 28 days after burning for further analysis by hematoxylin and eosin and Ki-67 staining. Wound healing rates and times, in addition to immunohistochemical results, were then compared and analyzed among the four groups. Application of the MSC-CM/hydrogel shortened healing time, limited the area of inflammation, enhanced reepithelialization, promoted the formation of high-quality, well-vascularized granulation tissue, and attenuated the formation of fibrotic and hypertrophic scar tissue. In summary, MSC-CM/hydrogel effectively promotes wound healing in third-degree burned mice.
Highlights
Severe burns are a common and highly lethal form of trauma and are associated with serious complications and poor prognosis [1]. e main priority for severe burn therapy is to facilitate wound healing as early as possible, and it has been reported that mesenchymal stem cell (MSC) therapy promotes wound healing [1,2,3,4].Most recent studies on MSC-based therapies have involved invasive operational procedures including intradermal injection of MSCs into or around the wound region and systemic intravenous injection, which contribute to patient suffering [3]
Ese characteristics implied that the thermosensitive mesenchymal stem cell-conditioned medium (MSC-CM)/hydrogel could be gelatinized under physiologically relevant conditions, which suggested its potential application for in vitro and in vivo research
On days 1, 3, 5, and 7, the cellular morphologies of MSCs cultured in MSC-CM/hydrogel were observed
Summary
Severe burns are a common and highly lethal form of trauma and are associated with serious complications and poor prognosis [1]. e main priority for severe burn therapy is to facilitate wound healing as early as possible, and it has been reported that mesenchymal stem cell (MSC) therapy promotes wound healing [1,2,3,4].Most recent studies on MSC-based therapies have involved invasive operational procedures including intradermal injection of MSCs into or around the wound region and systemic intravenous injection, which contribute to patient suffering [3]. E main priority for severe burn therapy is to facilitate wound healing as early as possible, and it has been reported that mesenchymal stem cell (MSC) therapy promotes wound healing [1,2,3,4]. Considering the intrinsic complexity of wound healing, the ideal wound dressing materials should feature good tissue conformity, a moist and occlusive environment, a low risk for infection, easy application and efficient removal of exudates, and the facilitation of healing [9]. Based on its lack of toxicity, mucoadhesion, biocompatibility, antimicrobial activity, biodegradability, and unique physicochemical properties, chitosan has received considerable attention for pharmaceutical and medical applications including drug delivery, cell encapsulation, and wound dressing [10]. Chitosan scaffolds combined with collagen have received considerable attention and were found to have favorable chemical, physical, and biological characteristics for skin engineering, partly due to its low immunogenicity, proper porous structure, and robust mechanical properties [14, 15]
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