Biodegradable Nanofibrous Temperature‐Responsive Gelling Microspheres for Heart Regeneration

• Published in: Advanced functional materials 2020-05, Vol.30 (21), p.n/a
• Main Authors: Zhao, Chao, Tian, Shuo, Liu, Qihai, Xiu, Kemao, Lei, Ienglam, Wang, Zhong, Ma, Peter X.
• Format: Article
• Language: English
• Subjects: Biodegradability; Biomedical materials; block copolymers; cell transplantation; Cells (biology); Copolymers; Gelation; Heart; heart regeneration; Hydrogels; Lactic acid; Materials science; Microspheres; Myocardial infarction; Myocardium; nanofibers; Polyethylene glycol; Polyisopropyl acrylamide; Polysaccharides; Proteoglycans; Regeneration; Rodents; Transplantation
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.202000776

Myocardial infarction (heart attack) is the number‐one killer of heart patients. Existing treatments do not address cardiomyocyte (CM) loss and cannot regenerate the myocardium. Introducing exogenous cardiac cells is required for heart regeneration due to the lack of resident progenitor cells and very limited proliferative potential of adult CMs. Poor retention of transplanted cells is the critical bottleneck of heart regeneration. Here, the invention of a poly(l‐lactic acid)‐b‐poly(ethylene glycol)‐b‐poly(N‐Isopropylacrylamide) copolymer and its self‐assembly into nanofibrous gelling microspheres (NF‐GMS) is reported. The NF‐GMS undergo a thermally responsive transition to form not only a 3D hydrogel after injection in vivo, but also exhibit characteristics mimicking the native extracellular matrix (ECM) of nanofibrous proteins and gelling proteoglycans or polysaccharides. By integrating the ECM‐mimicking features, injectable form, and the capability of maintaining 3D geometry after injection, the transplantation of hESC‐derived CMs carried by NF‐GMS leads to a striking tenfold graft size increase over direct CM injection in rats, which is the highest reported engraftment to date. Furthermore, NF‐GMS‐carried CM transplantation dramatically reduces infarct size, enhances integration of transplanted CMs, stimulates vascularization in the infarct zone, and leads to a substantial recovery of cardiac function. The NF‐GMS may also be utilized in a variety of biomedical applications. A tri‐block copolymer is synthesized that self‐assembles into porous nanofibrous microspheres. These microspheres in an aqueous suspension form a hydrogel upon temperature increase to body temperature. These nanofibrous gelling microspheres are used to deliver cardiomyocytes into an infarcted rat heart and result in the highest cardiomyocyte engraftment to date, dramatically reduce infarct size, and lead to a substantial cardiac functional recovery.