Cultured human fetal dermal extracellular matrix for scarless wound healing

培养的人胎儿真皮细胞外基质用于无疤痕伤口愈合

• 批准号: 10527429
• 负责人: Blanche C IP
• 金额: $ 17.16万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10527429
• 关键词: 3-Dimensional; Adult; Affect; Age; Animals; Architecture; Atomic Force Microscopy; Biochemical; Biochemistry; Biocompatible Materials; Bioinformatics; Biomechanics; Biomedical Engineering; Biomimetics; Boston; Cardiac; Cell Culture Techniques; Cells; Chondroitin Sulfates; Cicatrix; Collagen; Data; Data Set; Deposition; Dermal; Dipeptidyl-Peptidase IV; Elastin; Engineering; Environment; Exhibits; Extracellular Matrix; Fetal Tissues; Fibrillar Collagen; Fibroblasts; Fibronectins; Funding; Glycoproteins; Goals; Healthcare Systems; Histology; Human; Immune response; In Vitro; Mechanics; Medicine; Methods; Microscopy; Molecular Biology; Morbidity - disease rate; Mus; National Institute of General Medical Sciences; Normal tissue morphology; Operative Surgical Procedures; Pain; Pathologic; Pathway interactions; Patients; Pediatric Hospitals; Performance; Phenotype; Population; Proteins; Proteomics; Rattus; Reproducibility; Research; Resources; Skin; Skin wound healing; Source; Splint Device; Surface; Therapeutic Effect; Time; Tissue Engineering; Tissues; Translating; Treatment Efficacy; Work; aged; data integration; experience; fetal; healing; human fetus tissue; human tissue; improved; in vivo; innovation; insight; mouse model; novel therapeutics; phenome; physical property; postnatal; prenatal; preservation; psychological outcomes; regenerative; regenerative therapy; research and development; restoration; skin wound; tissue regeneration; tissue repair; transcriptome; transcriptome sequencing; transcriptomics; two-dimensional; wound healing

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.

皮肤伤口愈合功能障碍，包括愈合不足、愈合过度和结疤 导致显着的长期发病率，包括疼痛、功能限制和严重的 心理后果，所有这些都转化为美国的巨大负担 医疗保健系统。胎儿无疤痕伤口修复能够愈合并恢复 正常的皮肤结构以及组织强度和功能的保存。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）具有 与来自老化组织的 ECM 相比，在支持功能性伤口愈合方面表现出更好的效果， 但健康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使用人体细胞生长大型 3D 人体组织的解决方案， 可以成为提取人体 ECM 的无限且可靠的来源。本次活动的目标 项目是 1）用市售的胎儿或成人生物制造微组织 真皮成纤维细胞产生培养的 ECM，2) 与现象组的生物信息学整合 微组织分泌的 ECM（蛋白质组学、生物化学、力学等） 转录组阐明参与控制胎儿的关键 ECM 相关途径 ECM 生态位，3) 评估成人和胎儿培养的 ECM 的体内治疗效果 防止皮肤伤口留下疤痕。