TY - JOUR
T1 - A Heart Rate Matched Patch for Mechano-Chemical Treatment of Myocardial Infarction
T2 - Optimal Design and Transspecies Application
AU - Jia, Yuanbo
AU - Wei, Zhao
AU - Feng, Jinteng
AU - Lei, Meng
AU - Yang, Yanshen
AU - Liu, Jingyi
AU - Ma, Yufei
AU - Chen, Weiguo
AU - Huang, Guoyou
AU - Genin, Guy M.
AU - Guo, Xiaogang
AU - Li, Yan
AU - Xu, Feng
N1 - Publisher Copyright:
Copyright © 2024 Yuanbo Jia et al.
PY - 2024
Y1 - 2024
N2 - After myocardial infarction (MI), ventricular dilation and the microscopic passive stretching of the infarcted border zone is the meaning contributor to the continuous expansion of myocardial fibrosis. Epicardial hydrogel patches have been demonstrated to alleviate this sequela of MI in small-animal models. However, these have not been successfully translated to humans or even large animals, in part because of challenges in attaining both the greater stiffness and slower viscoelastic relaxation that mathematical models predict to be optimal for application to larger, slower-beating hearts. Here, using borate-based dynamic covalent chemistry, we develop an injectable “heart rate matched” viscoelastic gelatin (VGtn) hydrogel with a gel point tunable across the stiffnesses and frequencies that are predicted to transspecies and cross-scale cardiac repair after MI. Small-animal experiments demonstrated that, compared to heart rate mismatched patches, the heart rate matched VGtn patches inhibited ventricular bulging and attenuated stress concentrations in the myocardium after MI. In particular, the viscoelastic patch can coordinate the microscopic strain at the infarction boundary. VGtn loaded with anti-fibrotic agents further reduced myocardial damage and promoted angiogenesis in the myocardium. The tuned heart rate matched patches demonstrated similar benefits in a larger-scale and lower heart rate porcine MI model. Results suggest that heart rate matched VGtn patches may hold potential for clinical translation.
AB - After myocardial infarction (MI), ventricular dilation and the microscopic passive stretching of the infarcted border zone is the meaning contributor to the continuous expansion of myocardial fibrosis. Epicardial hydrogel patches have been demonstrated to alleviate this sequela of MI in small-animal models. However, these have not been successfully translated to humans or even large animals, in part because of challenges in attaining both the greater stiffness and slower viscoelastic relaxation that mathematical models predict to be optimal for application to larger, slower-beating hearts. Here, using borate-based dynamic covalent chemistry, we develop an injectable “heart rate matched” viscoelastic gelatin (VGtn) hydrogel with a gel point tunable across the stiffnesses and frequencies that are predicted to transspecies and cross-scale cardiac repair after MI. Small-animal experiments demonstrated that, compared to heart rate mismatched patches, the heart rate matched VGtn patches inhibited ventricular bulging and attenuated stress concentrations in the myocardium after MI. In particular, the viscoelastic patch can coordinate the microscopic strain at the infarction boundary. VGtn loaded with anti-fibrotic agents further reduced myocardial damage and promoted angiogenesis in the myocardium. The tuned heart rate matched patches demonstrated similar benefits in a larger-scale and lower heart rate porcine MI model. Results suggest that heart rate matched VGtn patches may hold potential for clinical translation.
UR - http://www.scopus.com/inward/record.url?scp=85209996014&partnerID=8YFLogxK
U2 - 10.34133/research.0517
DO - 10.34133/research.0517
M3 - Article
C2 - 39582687
AN - SCOPUS:85209996014
SN - 2096-5168
VL - 7
JO - Research
JF - Research
M1 - 0517
ER -