PC3015: Injectable Hydrogel for Cardiac Regeneration

Background: Regenerative medicine is an emerging field offering numerous innovative strategies to repair damaged cells, tissues, and organs and restore normal function. Among different approaches in the field, scaffold fabrication using hydrogel has long received attention and found use in biomedical applications such as drug delivery systems, medical dressing, cutaneous correction for scars and wrinkles. Specifically, due to a large proportion of water and the ability to hybridize into a polymeric network, hydrogel can be designed to resemble the extracellular matrix of myocardiocytes, showing the potential as a regenerative therapy for cardiovascular diseases. In this study, we hypothesized that a minimally invasive hydrogel system, fabricated with biocompatible polymers of desired properties, could improve cardiac regeneration following myocardial infarction. Herein, we focused on the crosslinking and interpenetration chemistry for fabricating the three-dimensionally cross-linked scaffold of the polymeric injectable hydrogel system.

Methods: The polymeric hydrogel was synthesized by cross-linking natural and synthetic materials in a formulated ratio to achieve desired properties. The synthesis process was monitored, and gelation times were recorded. Characterization for chemical, physical, biological properties of the hydrogel scaffold was evaluated by infrared (IR) spectral analysis, water content and holding capacity, contact angle measurements, and standard direct contact assay.

Results: A new formula for hydrogel was discovered that allowed deliberate gelation upon injection with an optimized average gelation time of 4 to 5 minutes. The polymeric network formation of this formula was confirmed through IR spectral analysis of freeze-dried samples. The results showed the following: -OH stretch at 3400 cm-1, -CH stretch at 2800 cm-1, -CO stretch at 1700 cm-1, and -C-O-C- stretch at 1080 cm-1. These functional groups indicate favorable cell adhesion and migration. Surface hydrophilicity was determined through contact angle measurements of the water swollen hydrogel. The average advancing contact angle was 39.7 deg ± 8.4, and the average receding contact angle was 45.1 deg ± 6.7, indicating amphiphilic nature crucial for biocompatibility. Evaluation of the cell survival and proliferation in hydrogel network using direct contact assay showed no characteristic change in morphology upon contact, suggesting non-toxicity and cytocompatibility in vivo systems.

Conclusion: A new formulation of hydrogel with great resemblance to the physiologic extracellular matrix environment was synthesized and characterized. Analysis confirmed the fabricated scaffold using biosynthetic polymers was amphipathic, homogenous, and cytocompatible. This injectable hydrogel system has potential as a template for new applications in minimally invasive regenerative therapy for cardiac regeneration and other future clinical uses.