Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 10, Issue 44, Pages 37783-37796Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b09757
Keywords
injectable hydrogels; NIPAM microgel; thermo-responsive microgel; cardiac stromal cells; multicellular spheroids; heart repair
Funding
- University of Adelaide
- ARC Discovery Project [DP160104632]
- Medical Advances Without Animals (MAWA) Trust
- National Institute of Health [HL123920, HL137093]
- American Heart Association [18TPA34230092]
- University of North Carolina General Assembly Research Opportunities Initiative grant
- National Natural Science Foundation of China [81370216]
- University of Adelaide-NCSU Starter Grant
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL137093, R01HL123920] Funding Source: NIH RePORTER
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To tune the chemical, physical, and mechanical microenvironment for cardiac stromal cells to treat acute myocardial infarction (MI), we prepared a series of thermally responsive microgels with different surface charges (positive, negative, and neutral) and different degrees of hydrophilicity, as well as functional groups (carboxyl, hydroxyl, amino, and methyl). These microgels were used as injectable hydrogels to create an optimized micro environment for cardiac stromal cells (CSCs). Our results indicated that a hydrophilic and negatively charged microenvironment created from poly(N-isopropylacrylamide-co-itaconic acid) was favorable for maintaining high viability of CSCs, promoting CSC proliferation and facilitating the formation of CSC spheroids. A large number of growth factors, such as vascular endothelial growth factor (VEGF), insulin-like growth factor I (IGF-1), and stromal-derived factor-1 (SDF-1) were released from the spheroids, promoting neonatal rat cardiomyocyte activation and survival. After injecting the poly(N-isopropylacrylamide-co-itaconic acid) microgel into mice, we examined their acute inflammation and T-cell immune reactions. The microgel itself did not elicit obvious immune response. We then injected the same microgel-encapsulated with CSCs into MI mice. The result revealed the treatment-promoted MI heart repair through angiogenesis and inhibition of apoptosis with an improved cell retention rate. This study will open a door for tailoring poly(N-isopropylacrylamide)-based microgel as a delivery vehicle for CSC therapy.
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