自愈水凝胶
间充质干细胞
材料科学
旁分泌信号
细胞生物学
生物物理学
明胶
化学
生物化学
生物
受体
高分子化学
作者
Myung Chul Lee,Jae Seo Lee,Seong-Soo Kim,Anurag Jamaiyar,Winona Wu,Montserrat Legorreta Gonzalez,Tania Carolina Acevedo Durán,Andrea Donaxi Madrigal‐Salazar,Nicole Bassous,Violeta Carvalho,Cholong Choi,Da‐Seul Kim,Jeong Wook Seo,Nélson Rodrigues,Senhorinha Teixeira,Abdulhameed F. Alkhateeb,Javier Alejandro Lozano Soto,Mohammad Asif Hussain,Jeroen Leijten,Mark W. Feinberg,Su Ryon Shin
标识
DOI:10.1002/adma.202408488
摘要
Abstract Microporous hydrogels have been widely used for delivering therapeutic cells. However, several critical issues, such as the lack of control over the harsh environment they are subjected to under pathological conditions and rapid egression of cells from the hydrogels, have produced limited therapeutic outcomes. To address these critical challenges, cell‐tethering and hypoxic conditioning colloidal hydrogels containing mesenchymal stem cells (MSCs) are introduced to increase the productivity of paracrine factors locally and in a long‐term manner. Cell‐tethering colloidal hydrogels that are composed of tyramine‐conjugated gelatin prevent cells from egressing through on‐cell oxidative phenolic crosslinks while providing mechanical stimulation and interconnected microporous networks to allow for host‐implant interactions. Oxygenating microparticles encapsulated in tyramine‐conjugated colloidal microgels continuously generated oxygen for 2 weeks with rapid diffusion, resulting in maintaining a mild hypoxic condition while MSCs consumed oxygen under severe hypoxia. Synergistically, local retention of MSCs within the mild hypoxic‐conditioned and mechanically robust colloidal hydrogels significantly increased the secretion of various angiogenic cytokines and chemokines. The oxygenating colloidal hydrogels induced anti‐inflammatory responses, reduced cellular apoptosis, and promoted numerous large blood vessels in vivo. Finally, mice injected with the MSC‐tethered oxygenating colloidal hydrogels significantly improved blood flow restoration and muscle regeneration in a hindlimb ischemia (HLI) model.
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