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Tao Lowe, Sri Chandana Damera; Injectable Hydrogels for Stem Cell Based Regenerative Treatment of Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4567.
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© ARVO (1962-2015); The Authors (2016-present)
Intravitreally injected adipose derived stem cells (ADSC) have shown potential to rescue the neural retina from hyperglycemia-induced degeneration, resulting in improved visual function. Hydrogel biomaterials have shown to improve the cell attachment, viability/proliferation, and differentiation of stem cells when used as scaffolds in various regenerative treatment studies. However, currently no injectable hydrogels scaffolds for ADSCs for the ocular application are available. The purpose of this study is to design injectable hydrogels as scaffolds for enhanced performance of ADSC based regenerative therapy for DR.
A series of thermoresponsive and biodegradable hydrogels were synthesized by photo-polymerization of N-isopropylacrylamide monomer and oligolactate 2-hydroxyethyl methacrylate macromer. Different weight ratios of the reactants (19:1~16:4, w:w), and amounts of Irgacure 2959 photo initiator (0.0125, 0.025, 0.05 wt%), UV intensity (100-750 mW/cm2), and reaction time (3, 10 min) were used to synthesize the hydrogels. The chemical structure and thermoresponsive property of the hydrogels were characterized by FTIR and UV-Vis spectrometer, respectively. The time dependent hydrolytic degradation of the hydrogels was evaluated by FTIR and dynamic mechanical analyzer. The rheological property including storage and loss moduli of the hydrogels was measured by rheometer. The cytotoxicity of the hydrogels to ADSCs at 37 °C was assessed by MTT assay. In vivo retinal histopathological studies of the ADSCs-loaded injectable hydrogels for the decrease in vascular leakage and apoptotic cells in the diabetic rat eyes are under investigation.
FTIR measurements confirmed the successful synthesis of the hydrogels. The thermo-responsive, biodegradable and rheological properties of the hydrogels strongly depended on the hydrogel composition and reaction conditions. The higher were the amount of the Irgacure 2959 initiator, UV intensity, reaction time, and the reactants, the higher were the storage and loss moduli of the hydrogels at 37 °C. The hydrogels were not cytotoxic to ADSCs at concentration up to at least 10 mg per mL.
The developed hydrogels can be tuned to have different degradation and mechanical properties to promote ADSC growth inside their matrices. Successful completion of this project will have significant impact on development of injectable biomaterials to treat DR.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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