Abstract
Biomaterial-based cell replacement approaches to regenerative medicine are emerging as promising treatments for a wide array of profound clinical problems. Here we report an interpenetrating polymer network (IPN) composed of gelatin-hydroxyphenyl propionic acid and hyaluronic acid tyramine that is able to enhance intravitreal retinal cell therapy. By tuning our bioinspired hydrogel to mimic the vitreous chemical composition and mechanical characteristics we were able to improve in vitro and in vivo viability of human retinal ganglion cells (hRGC) incorporated into the IPN. In vivo vitreal injections of cell-bearing IPN in rats showed extensive attachment to the inner limiting membrane of the retina, improving with hydrogels stiffness. Engrafted hRGC displayed signs of regenerating processes along the optic nerve. Of note was the decrease in the immune cell response to hRGC delivered in the gel. The findings compel further translation of the gelatin-hyaluronic acid IPN for intravitreal cell therapy.
Highlights
Cell replacement therapies critically depend on: the viability of the cells being delivered; maintenance of their phenotype; and their engraftment in the targeted tissue[1,2]
One recent study demonstrated substantial increases in viability and proliferation, and maintenance of phenotype, of retinal progenitor cells injected through a 31-gage needle when they were incorporated in gelatin conjugate with hydroxyphenyl propionic acid (Gtn-HPA) compared to saline, owing to the protection of the cells from the imparted shear stress offered by the gel[6,7]
Our results suggest that networks incorporating Gtn-HPA, and hyaluronic acid tyramine (HA)-Tyr have a superior biocompatibility and can be considered as candidate for retinal cell replacement therapy
Summary
Cell replacement therapies critically depend on: the viability of the cells being delivered; maintenance of their phenotype; and their engraftment in the targeted tissue[1,2]. While a host of hydrogels can meet these requirements, it is only a few that can undergo spontaneous covalent cross-linking in situ in a way that enables the control of gelation, degradation rate, and mechanical behavior[5]. One such polymer proven to be able to do so is a gelatin conjugate with hydroxyphenyl propionic acid (Gtn-HPA). One recent study demonstrated substantial increases in viability and proliferation, and maintenance of phenotype, of retinal progenitor cells injected through a 31-gage needle when they were incorporated in Gtn-HPA compared to saline, owing to the protection of the cells from the imparted shear stress offered by the gel[6,7]
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