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Laura Koivusalo, Jennika Karvinen, Eetu Sorsa, Susanna Miettinen, Tanja Ilmarinen, Minna Kellomäki, Heli Skottman; Hyaluronic acid based hydrogels for therapeutic delivery of adipose stem cells to corneal defects. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1410.
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© ARVO (1962-2015); The Authors (2016-present)
Adipose stem cells (ASCs) have excellent therapeutic potential for treatment of corneal stromal defects, but feasible means of transplanting them is still lacking. In this study, we developed and compared two different hyaluronic acid (HA) hydrogels in order to evaluate their potential as a cell delivery vehicle to the corneal stroma. After preliminary tests, we then further modified the more promising HA-hydrogel by incorporating collagen I (CI) in the hydrogel structure. These HA based hydrogels are promising as corneal stromal biomaterials, as they form stable, crosslinked hydrogels rapidly in situ and are naturally degraded by enzymes in the body, without acidic degradation products.
We fabricated two hydrazone crosslinked HA hydrogels composed of differently synthesized HA components (HALD-HAADH and HAALD-HACDH). We then combined CI with the HAALD and HACDH components in order to increase the cellular inductivity of the hydrogel. The chemical structure of the crosslinked hydrogels was analyzed using Fourier transform infrared spectroscopy (FTIR). The hydrogels were also characterized for their swelling and degradation behavior and rheological, mechanical and optical properties. Human ASCs were incorporated into the hydrogels and cultured up to two weeks to determine cytocompatibility of the hydrogels, analyzed via PrestoBlue and Live/dead staining.
Comparison between the two HA hydrogel combinations revealed that HAALD-HACDH had improved stability and higher stiffness over HALD-HAADH. HAALD-HACDH also had a higher refractive index (1.341) than HALD-HAADH (1.335). The addition of CI lowered the swelling ratio of the HAALD-HACDH hydrogel and increased its stiffness. In cytocompatibility studies, HALD-HAADH failed after three days due to hydrolytic degradation, but both HAALD-HACDH and HAALD-HACDH-CI maintained hASC viability and showed elongated cell morphology.
The HAALD-HACDH and HAALD-HACDH-CI hydrogels showed good cytocompatibility with hASCs, and had excellent optical properties. The cells can be injected to the damage site within gel precursor, the components gelate within a few seconds without any external linking agents or heat, and the hydrogels are naturally cleared by enzymatic degradation. Thus, we suggest these hydrogels as potential materials for ASC delivery to treat corneal stromal damages.
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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