Injectable Citrate-Based Hydrogel as an Angiogenic Biomaterial Improves Cardiac Repair after Myocardial Infarction

• Published in: ACS applied materials & interfaces 2019-10, Vol.11 (42), p.38429-38439
• Main Authors: Yuan, Zhize, Tsou, Yung-Hao, Zhang, Xue-Qing, Huang, Shixing, Yang, Yang, Gao, Mingzhu, Ho, William, Zhao, Qiang, Ye, Xiaofeng, Xu, Xiaoyang
• Format: Article
• Language: English
• Subjects: angiogenesis; Animals; biocompatible materials; Biocompatible Materials - chemistry; Biocompatible Materials - pharmacology; Biocompatible Materials - therapeutic use; Cell Adhesion - drug effects; Cell Proliferation - drug effects; citrates; Citric Acid - chemistry; Disease Models, Animal; Echocardiography; encapsulation; heart; Heart - diagnostic imaging; Human Umbilical Vein Endothelial Cells; Humans; hydrogels; Hydrogels - chemistry; Hydrogels - pharmacology; infarction; Interleukins - chemistry; Interleukins - therapeutic use; medicine; Mice; myocardial infarction; Myocardial Infarction - diagnostic imaging; Myocardial Infarction - drug therapy; Myocardial Infarction - pathology; Neovascularization, Physiologic - drug effects; NIH 3T3 Cells; polyesters; Polyethylene Glycols - chemistry; Positron-Emission Tomography; Rats; Rheology; therapeutics; tissue repair
• ISSN: 1944-8244; 1944-8252; 1944-8252
• DOI: 10.1021/acsami.9b12043

Implanted medical biomaterials are closely in contact with host biological systems via biomaterial–cell/tissue interactions, and these interactions play pivotal roles in regulating cell functions and tissue regeneration. However, many biomaterials degrade over time, and these degradation products also have been shown to interact with host cells/tissue. Therefore, it may prove useful to specifically design implanted biomaterials with degradation products which greatly improve the performance of the implant. Herein, we report an injectable, citrate-containing polyester hydrogel which can release citrate as a cell regulator via hydrogel degradation and simultaneously show sustained release of an encapsulated growth factor Mydgf. By coupling the therapeutic effect of the hydrogel degradation product (citrate) with encapsulated Mydgf, we observed improved postmyocardial infarction (MI) heart repair in a rat MI model. Intramyocardial injection of our Mydgf-loaded citrate-containing hydrogel was shown to significantly reduce scar formation and infarct size, increase wall thickness and neovascularization, and improve heart function. This bioactive injectable hydrogel-mediated combinatorial approach offers myriad advantages including potential adjustment of delivery rate and duration, improved therapeutic effect, and minimally invasive administration. Our rational design combining beneficial degradation product and controlled release of therapeutics provides inspiration toward the next generation of biomaterials aiming to revolutionize regenerative medicine.