Cultured human fetal dermal extracellular matrix for scarless wound healing

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Dysfunctional skin wound healing, including underhealing, overhealing and scarring causes significant long-term morbidity including pain, functional restriction, and severe psychological outcomes, all of which translates to a tremendous burden on the US healthcare system. Fetal scarless wound repair is capable of healing with restoration of normal skin architecture and preservation of both tissue strength and function. Extracellular matrices (ECM) deposited by fetal dermal fibroblasts and extracted from fetal tissues have shown to be superior in supporting functional wound healing than ECM from aged tissues, but the availability of healthy fetal human tissues is extremely limited. Here, we propose a solution of large 3D human tissues grown in the lab with human cells that can be an unlimited and reliable source for the extraction of human ECM. The objectives of this project are to 1) biofabricate microtissues with commercially available fetal or adult human dermal fibroblasts to generate cultured ECM, 2) integrate with bioinformatics of the phenome (proteomics, biochemistry, mechanics, etc) of the secreted ECM with microtissue transcriptome to elucidate the key ECM-associated pathways involved in controlling the fetal ECM niche, and 3) evaluate the in vivo therapeutic efficacy of adult and fetal cultured ECMs against scarring of skin wounds.