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pH-Sensitive and Thermosensitive Hydrogels as Stem-Cell Carriers for Cardiac Therapy
Zhenqing Li1,2, Zhaobo Fan1,2, Yanyi Xu1,2
1Department of Materials Science and Engineering and ⊥Department of Emergency Medicine, Davis Heart Lung Research Institute, The Ohio State University , Columbus, Ohio 43210, United States.
ACS Applied Materials & Interfaces
|April 12, 2016
Summary
New injectable hydrogels offer improved stem cell retention for cardiac repair after heart attacks. These dual-sensitive hydrogels rapidly solidify in infarcted heart tissue, enhancing cell survival and cardiac differentiation.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Cardiovascular Research
Background:
- Stem cell therapy shows promise for regenerating heart tissue post-myocardial infarction.
- Current injectable hydrogels face limitations as stem cell carriers, including poor cell retention due to slow gelation and potential blood vessel blockage.
- Inefficient cell retention leads to the expulsion of cells and hydrogels from the damaged cardiac tissue.
Purpose of the Study:
- To develop novel injectable hydrogels with rapid, pH-triggered solidification for enhanced stem cell delivery in cardiac tissue.
- To create hydrogel carriers that improve cell retention and support the survival and differentiation of encapsulated cardiac cells.
- To evaluate the injectability, gelation properties, degradation, mechanical characteristics, and in vitro performance of the developed hydrogels.
Main Methods:
- Hydrogels were synthesized using free-radical polymerization of N-isopropylacrylamide, propylacrylic acid, hydroxyethyl methacrylate-co-oligo(trimethylene carbonate), and methacrylate poly(ethylene oxide) methoxy ester.
- Injectability was tested through 0.2-mm-diameter catheters at physiological conditions (pH 8.0, 37 °C).
- Gelation kinetics were assessed at pH 6.5 and 7.4 at 37 °C. Degradation and mechanical properties were evaluated at different pH values. Cardiosphere-derived cells (CDCs) were encapsulated to assess viability and cardiac differentiation.
Main Results:
- The developed hydrogels demonstrated rapid solidification at the infarcted heart's pH (6-7) but not in blood (pH 7.4), ensuring localized gelation.
- Hydrogels were injectable via small-diameter catheters and exhibited pH-dependent degradation and mechanical strength, with better integrity at lower pH.
- Encapsulated CDCs survived for 7 days and differentiated into cardiac cells, confirmed by cardiac marker expression. Gel integrity positively influenced differentiation.
Conclusions:
- The novel dual-sensitive hydrogels provide a promising solution for overcoming limitations of current stem cell carriers in cardiac tissue engineering.
- Rapid, localized gelation and improved cell retention facilitate enhanced survival and cardiac differentiation of encapsulated stem cells.
- These hydrogels represent a clinically attractive platform for minimally invasive cardiac cell therapy.
