Cultured human fetal dermal extracellular matrix for scarless wound healing

功能障碍性皮肤伤口愈合，包括愈合不良、过度愈合和瘢痕形成 导致显著的长期发病率，包括疼痛、功能限制和严重的 所有这些都给美国带来了巨大的负担 医疗保健系统。胎儿无瘢痕伤口修复能够愈合， 正常的皮肤结构和组织强度和功能的保持。细胞外 由胎儿真皮成纤维细胞沉积并从胎儿组织中提取的基质（ECM）， 显示出在支持功能性伤口愈合方面比来自老化组织的ECM优越上级， 但是健康的胎儿人体组织的可用性极其有限。 在这里，我们提出了一种在实验室中用人类细胞生长的大型3D人体组织的解决方案， 可以成为提取人ECM的无限和可靠的来源。这一目标 项目是1）用商业上可获得的胎儿或成人生物制造微组织 真皮成纤维细胞以产生培养的ECM，2）整合表型组的生物信息学 （蛋白质组学、生物化学、力学等） 转录组，以阐明关键ECM相关的途径参与控制胎儿 ECM生态位，以及3）评估成人和胎儿培养的ECM的体内治疗功效 防止皮肤伤口结疤。

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.