Engineering retinal progenitor cell and scrollable poly(glycerol-sebacate) composites for expansion and subretinal transplantation

Abstract

Retinal degenerations cause permanent visual loss and affect millions world-wide. Presently, a novel treatment highlights the potential of using biodegradable polymer scaffolds to induce differentiation and deliver retinal progenitor cells for cell replacement therapy. In this study, we engineered and analyzed a micro-fabricated polymer, poly(glycerol sebacate) (PGS) scaffold, whose useful properties include biocompatibility, elasticity, porosity, and a microtopology conducive to mouse retinal progenitor cell (mRPC) differentiation. In vitro proliferation assays revealed that PGS held up to 86,610 (±9993) mRPCs per square millimeter, which were retained through simulated transplantations. mRPCs adherent to PGS differentiated toward mature phenotypes as evidenced by changes in mRNA, protein levels, and enhanced sensitivity to glutamate. Transplanted composites demonstrated long-term mRPC survival and migrated cells exhibited mature marker expression in host retina. These results suggest that combining mRPCs with PGS scaffolds for subretinal transplantation is a practical strategy for advancing retinal tissue engineering as a restorative therapy.

Nanofibrous composite scaffolds of poly(ester amides) with tunable physicochemical and degradation properties

“…To date, biodegradable synthetic thermoset elastomer PGS has been widely explored for various tissue engineering applications [6,8,[20][21][22][23][24][25][26][27][28][29][30]. PGS exhibits faster degradation rate of 17% in 9 weeks in PBS, elastic modulus of around 0.282 MPa, and it's tensile strength is above 0.5…”

Synthetic Polymer Scaffolds for Stem Cell Transplantation in Retinal Tissue Engineering

“…Collagen-functionalized nanofibers improved cell adhesion and migration compared to non-functionalized nanofibers [69]. Polymer scaffolds made from PLGA [1,46], PMMA [49] and PGS [52,54] required protein modification of the surface with either laminin or a combination of laminin and poly-L-lysine to achieve RPC attachment. Additionally, PLLA/PLGA scaffolds needed a concentrated cell solution in order to achieve appropriate levels of cell attachment [46].…”

“…By using PGS scaffolds as a cell delivery vehicle, 13% and 7% of grafted cells migrated into the C57BL/6 and Rho-/-mouse retinal explants at one week. 1.5% and 0.8% of grafted cells migrated into the C57BL/6 and Rho-/-mouse retina four weeks post-transplantation [54].…”

Electrospun chitosan-graft-poly (ε-caprolactone)/poly (ε-caprolactone) nanofibrous scaffolds for retinal tissue engineering

“…One of the most promising therapies for late-stage retinal degeneration is to deliver retinal stem or progenitor cells to the subretina. 3,4 Several studies indicate that a typical bolus injection of mouse retinal progenitor cells (mRPCs) leads to massive new cell loss through efflux and death. 3,5 Recently it was demonstrated that a tissue engineering approach, the usage of a biocompatible polymer scaffold, improved the mRPCs survival and promoted the integration of transplanted mRPCs in host retinal tissue following transplantation.…”