A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury  

作　　者：Qi Liu Jianye Xie Runxue Zhou Jin Deng Weihong Nie Shuwei Sun Haiping Wang Chunying Shi 

机构地区：[1]Department of Human Anatomy,Histology and Embryology,School of Basic Medicine,Qingdao University,Qingdao,Shandong Province,China [2]Department of Neurology,The Affiliated Hospital of Qingdao University,Qingdao,Shandong Province,China [3]Department of General Practice,The Affiliated Hospital of Qingdao University,Qingdao,Shandong Province,China

出　　处：《Neural Regeneration Research》2025年第2期503-517,共15页中国神经再生研究（英文版）

基　　金：supported by the Natural Science Foundation of Shandong Province,No.ZR2023MC168;the National Natural Science Foundation of China,No.31670989;the Key R&D Program of Shandong Province,No.2019GSF107037(all to CS).

摘　　要：Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

关 键 词：angiogenesis biomaterial blood-brain barrier cerebral ischemia/reperfusion injury control release drug delivery inflammation QK peptides matrix metalloproteinase-2 NEUROPROTECTION self-assembling nanofiber hydrogel 

分 类 号：R743[医药卫生—神经病学与精神病学]