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Physicochemically Tuned Myofibroblasts for Wound Healing Strategy.

ABSTRACT: Normal healing of skin wounds involves a complex interplay between many different cellular constituents, including keratinocytes, immune cells, fibroblasts, myofibroblasts, as well as extracellular matrices. Especially, fibroblasts play a critical role in regulating the immune response and matrix reconstruction by secreting many cytokines and matrix proteins. Myofibroblasts, which are differentiated form of fibroblasts, feature high cellular contractility and encourage the synthesis of matrix proteins to promote faster closure of the wounds. We focus on the functional characteristics of these myofibroblasts as the healing strategy for severe wounds where the surplus amount of matrix proteins could be beneficial for better regeneration. In this study, we first employed multiple physicochemical cues, namely topographical alignment, TGF-?1, and electrical field (EF), to induce differentiation of dermal fibroblasts into myofibroblasts, and to further activate the differentiated cells. We then used these cells in a mouse wound model to verify their potential as a transplantable substitute for the severe wound. Our results confirmed that physicochemically stimulated myofibroblasts promoted faster healing of the wound compared to the case with non-stimulated myofibroblasts through elevated matrix reconstruction in the mouse model. Conclusively, we propose the utilization of physicochemically tuned myofibroblasts as a novel strategy for promoting better healing of moderate to severe wounds.

SUBMITTER: Ko UH

PROVIDER: S-EPMC6831678 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Physicochemically Tuned Myofibroblasts for Wound Healing Strategy.

Ko Ung Hyun UH Choi Jongjin J Choung Jinseung J Moon Sunghwan S Shin Jennifer H JH

Scientific reports 20191105 1

Normal healing of skin wounds involves a complex interplay between many different cellular constituents, including keratinocytes, immune cells, fibroblasts, myofibroblasts, as well as extracellular matrices. Especially, fibroblasts play a critical role in regulating the immune response and matrix reconstruction by secreting many cytokines and matrix proteins. Myofibroblasts, which are differentiated form of fibroblasts, feature high cellular contractility and encourage the synthesis of matrix pr ...[more]

PMID: 31690789

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Project description:Co-encapsulated econazole nitrate-triamcinolone acetonide loaded biocompatible, physically stable, and non-irritating mesoporous silica nanoparticles (EN-TA-loaded MSNs) were prepared and optimized by using a central composite rotatable design (CCRD) for providing better therapeutic efficacy against commonly prevailed resistant fungal infections. These drugs loaded MSNs can significantly overcome the deficiencies and problems like short duration of action, requirement of frequent administration, erythema, and burning sensation and irritation associated with conventional drug delivery systems. The stability of optimized drugs loaded MSNs prepared with 100 gm of oil at pH 5.6 with a stirring time of 2 h was confirmed from a zeta potential value of -25 mV. The remarkable compatibility of formulation ingredients was depicted by X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR) spectra while scanning electron microscopy (SEM) and size analysis represented a very fine size distribution of nanoparticles ranging from 450-600 nm. The CCRD clearly predicted that the optimized parameters of drugs loaded MSNs have better values of percentage yield (85%), EN release (68%), and TA release (70%). Compared to pure drugs, the decreased cytotoxicity of EN-TA-loaded MSNs was quite evident because they showed a cell survival rate of 90%, while in the case of pure drugs, the survival rate was 85%. During in vivo antifungal testing against Candida albicans performed on three different groups, each consisting of six rabbits, the EN-TA-loaded MSNs were relatively superior in eradicating the fungal infection as a single animal exhibited a positive culture test. Rapid recovery of fungal infection and a better therapeutic effect of EN-TA-loaded MSN were quite evident in wound healing and histopathology studies. Likewise, on the 14th day, a larger inhibitory zone was measured for optimized nanoparticles (15.90 mm) compared to the suspension of pure drugs (13.90 mm). In skin irritation studies, MSNs did not show a grade of erythema compared to pure drugs, which showed a four-fold grade of erythema. As a result, MSNs loaded with combination therapy seem to have the potential of improving patient compliance and tolerability by providing enhanced synergistic antifungal effectiveness at a reduced dose with accelerated wound healing and reduced toxicity of therapeutics.

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Physicochemically Tuned Myofibroblasts for Wound Healing Strategy.

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Physicochemically Tuned Myofibroblasts for Wound Healing Strategy.

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