Biodegradable nanofibrous temperature-responsive gelling microspheres for heart regeneration

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Cardiovascular Research

Background:

• Myocardial infarction causes cardiomyocyte loss, with limited treatment options for myocardial regeneration.
• Current heart attack treatments do not address cardiomyocyte loss or regenerate heart tissue.
• Transplanted cell retention is a major challenge in cardiac regeneration strategies.

Purpose of the Study:

• To develop an injectable, ECM-mimicking biomaterial for enhanced cardiac cell transplantation.
• To investigate the efficacy of nanofibrous gelling microspheres (NF-GMS) in improving cardiac cell engraftment and cardiac function.
• To evaluate NF-GMS as a platform for delivering cardiomyocytes (CMs) for heart repair.

Main Methods:

• Synthesized a novel poly(l-lactic acid)-b-poly(ethylene glycol)-b-poly(N-Isopropylacrylamide) copolymer.
• Self-assembled the copolymer into thermally responsive nanofibrous gelling microspheres (NF-GMS).
• Transplanted human embryonic stem cell-derived cardiomyocytes (hESC-CMs) using NF-GMS in a rat myocardial infarction model.

Main Results:

• NF-GMS formed an injectable 3D hydrogel in vivo, mimicking native extracellular matrix (ECM) structure.
• NF-GMS significantly increased graft size (10-fold) and cell retention compared to direct injection.
• Transplantation with NF-GMS reduced infarct size, improved CM integration, enhanced vascularization, and restored cardiac function.

Conclusions:

• NF-GMS are effective injectable biomaterials that promote cardiac cell survival and integration.
• This technology offers a promising strategy for enhancing myocardial regeneration after heart attack.
• NF-GMS hold potential for diverse cell and biomolecule delivery applications in medicine.