biostudies-literatureUnknownCurry CWNEI NIH HHSNCRR NIH HHSNIDDK NIH HHSNIA NIH HHSNCI NIH HHSNINDS NIH HHSCritical limb ischemia (CLI) occurs when blood flow is restricted through the arteries, resulting in ulcers, necrosis, and chronic wounds in the downstream extremities. The development of collateral arterioles (i.e. arteriogenesis), either by remodeling of pre-existing vascular networks or <i>de novo</i> growth of new vessels, can prevent or reverse ischemic damage, but it remains challenging to stimulate collateral arteriole development in a therapeutic context. Here, we show that a gelatin-based hydrogel, devoid of growth factors or encapsulated cells, promotes arteriogenesis and attenuates tissue damage in a murine CLI model. The gelatin hydrogel is functionalized with a peptide derived from the extracellular epitope of Type 1 cadherins. Mechanistically, these "GelCad" hydrogels promote arteriogenesis by recruiting smooth muscle cells to vessel structures in both <i>ex vivo</i> and <i>in vivo</i> assays. In a murine femoral artery ligation model of CLI, delivery of <i>in situ</i> crosslinking GelCad hydrogels was sufficient to restore limb perfusion and maintain tissue health for 14 days, whereas mice treated with gelatin hydrogels had extensive necrosis and autoamputated within 7 days. A small cohort of mice receiving the GelCad hydrogels were aged out to 5 months and exhibited no decline in tissue quality, indicating durability of the collateral arteriole networks. Overall, given the simplicity and off-the-shelf format of the GelCad hydrogel platform, we suggest it could have utility for CLI treatment and potentially other indications that would benefit from arteriole development.bioRxiv : the preprint server for biology2023.05.24.542150https://www.ebi.ac.uk/biostudies/studies/S-EPMC10245920biostudies-literatureGrowth factor-free, peptide-functionalized gelatin hydrogel promotes arteriogenesis and attenuates tissue damage in a murine model of critical limb ischemia.PMC10245920S10 RR025677T32 AG058524P30 CA068485P30 DK058404R01 NS110665P30 EY008126Gibson-Corley KNSchmeckpeper JSchoenecker JGPaige HACurry CWMowery LSHawkes AStiefbold MRYates AKKatdare KAMoore-Lotridge SKjar AMlouk KKawabata APatel RVO'Grady BJMcKee RMKusunose JLippmann ESSturgeon SMCaskey CFVafaie-Partin SfalseGrowth factor-free, peptide-functionalized gelatin hydrogel promotes arteriogenesis and attenuates tissue damage in a murine model of critical limb ischemia.Critical limb ischemia (CLI) occurs when blood flow is restricted through the arteries, resulting in ulcers, necrosis, and chronic wounds in the downstream extremities. The development of collateral arterioles (i.e. arteriogenesis), either by remodeling of pre-existing vascular networks or <i>de novo</i> growth of new vessels, can prevent or reverse ischemic damage, but it remains challenging to stimulate collateral arteriole development in a therapeutic context. Here, we show that a gelatin-based hydrogel, devoid of growth factors or encapsulated cells, promotes arteriogenesis and attenuates tissue damage in a murine CLI model. The gelatin hydrogel is functionalized with a peptide derived from the extracellular epitope of Type 1 cadherins. Mechanistically, these "GelCad" hydrogels promote arteriogenesis by recruiting smooth muscle cells to vessel structures in both <i>ex vivo</i> and <i>in vivo</i> assays. In a murine femoral artery ligation model of CLI, delivery of <i>in situ</i> crosslinking GelCad hydrogels was sufficient to restore limb perfusion and maintain tissue health for 14 days, whereas mice treated with gelatin hydrogels had extensive necrosis and autoamputated within 7 days. A small cohort of mice receiving the GelCad hydrogels were aged out to 5 months and exhibited no decline in tissue quality, indicating durability of the collateral arteriole networks. Overall, given the simplicity and off-the-shelf format of the GelCad hydrogel platform, we suggest it could have utility for CLI treatment and potentially other indications that would benefit from arteriole development.2023-01-01T00:00:00Z2023 May2024-11-07T04:09:51.259Z2024-11-07T04:09:51.259ZS-EPMC102459203729289810.1101/2023.05.24.542150