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Biodegradable Nanofibrous Temperature‐Responsive Gelling Microspheres for Heart Regeneration
Author(s) -
Zhao Chao,
Tian Shuo,
Liu Qihai,
Xiu Kemao,
Lei Ienglam,
Wang Zhong,
Ma Peter X.
Publication year - 2020
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.202000776
Subject(s) - regeneration (biology) , materials science , extracellular matrix , ethylene glycol , transplantation , biomedical engineering , in vivo , tissue engineering , progenitor cell , myocardial infarction , microbiology and biotechnology , biophysics , stem cell , chemistry , biology , surgery , medicine , organic chemistry
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.