Laboratory and preclinical evaluation of a novel wound dressing patch for treatment of wounds in the elderly

Author:

Arjunan Subramanian1,Teo Nelson1,Claudine Stephanie1,Tam Kimberley2,Feng Pan1,Lim Jane1,Biswas Arijit1,Bongso Ariff1,Fong Chui Yee1,Choolani Mahesh1ORCID

Affiliation:

1. National University of Singapore

2. Singapore-MIT Alliance for Research and Technology Centre

Abstract

Abstract Background Elderly patients develop pressure ulcers that are very difficult to treat and current treatments have several limitations. Native skin stem cells diminish with age and may explain poor skin renewal in the elderly. Hence, an exogenous supply of stem cells to wounds in the elderly may produce a successful therapy. We evaluated the wound healing potential of an aloe vera-polycaprolactone nanocarrier impregnated with human Wharton’s jelly stem cells (hWJSCs + AV/PCL) or its conditioned medium (hWJSC-CM + AV/PCL) on elderly human skin using in vitro wound assays and on excisonal wounds created in an elderly preclinical mouse model. Methods hWJSCs and human skin fibroblasts (HSFs) were derived and characterized using our previously published protocols. The influence of hWJSC-CM on elderly human skin fibroblasts (eHSFs) were compared with that of young HSFs (yHSFs) and untreated eHSF controls. The healing of excisonal wounds created in elderly mice over a 21 day period was evaluated using various methods. Results Scratch wounds of hWJSC-CM-treated eHSFs completely closed by day 2 compared to untreated eHSF controls. Collagen and elastin levels were significantly increased while senescence-related genes were significantly downregulated in hWJSC-CM-treated eHSFs compared to untreated eHSFs. Angiogenesis assays produced significantly greater tubule numbers and ring formation in the presence of CM from hWJSC-CM-treated eHSFs. Excisional wounds in elderly mice treated with hWJSC + AV/PCL and hWJSC-CM + AV/PCL completely healed by day 21 and wound closure rates were significantly greater compared to controls. Histology of elderly mice wounds treated with hWJSC + AV/PCL and hWJSC-CM + AV/PCL showed changes in skin structure. Epidermal and dermal thickness, CD31 and gene expression levels of ECM, collagen, angiogenesis, scarless, granulation and immune cell chemoattraction were significantly greater in elderly mice treated with hWJSC + AV/PCL and hWJSC-CM + AV/PCL. Conclusions The results confirmed that hWJSCs in combination with the stem cell niches in nanoscaffolds and the antimicrobial properties of aloe vera provide an attractive wound dressing patch for treatment of chronic wounds in the elderly.

Publisher

Research Square Platform LLC

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