诱导多能干细胞
自愈水凝胶
脊髓
移植
生物医学工程
脊髓损伤
再生(生物学)
材料科学
组织工程
干细胞
医学
神经科学
外科
化学
胚胎干细胞
生物
细胞生物学
生物化学
高分子化学
基因
作者
Vanessa M. Doulames,Laura M. Marquardt,Meghan E. Hefferon,Neil Baugh,Riley A. Suhar,Alice Wang,Karen Dubbin,James M. Weimann,Theo D. Palmer,Giles W. Plant,Sarah C. Heilshorn
出处
期刊:Biomaterials
[Elsevier]
日期:2024-03-01
卷期号:305: 122400-122400
标识
DOI:10.1016/j.biomaterials.2023.122400
摘要
Cervical damage is the most prevalent type of spinal cord injury clinically, although few preclinical research studies focus on this anatomical region of injury. Here we present a combinatorial therapy composed of a custom-engineered, injectable hydrogel and human induced pluripotent stem cell (iPSC)-derived deep cortical neurons. The biomimetic hydrogel has a modular design that includes a protein-engineered component to allow customization of the cell-adhesive peptide sequence and a synthetic polymer component to allow customization of the gel mechanical properties. In vitro studies with encapsulated iPSC-neurons were used to select a bespoke hydrogel formulation that maintains cell viability and promotes neurite extension. Following injection into the injured cervical spinal cord in a rat contusion model, the hydrogel biodegraded over six weeks without causing any adverse reaction. Compared to cell delivery using saline, the hydrogel significantly improved the reproducibility of cell transplantation and integration into the host tissue. Across three metrics of animal behavior, this combinatorial therapy significantly improved sensorimotor function by six weeks post transplantation. Taken together, these findings demonstrate that design of a combinatorial therapy that includes a gel customized for a specific fate-restricted cell type can induce regeneration in the injured cervical spinal cord.
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