TABLE 4.

Biohybrids/TI, Biomaterials-encapsulated RPE cells, in vivo studies.

Product	Cell types	Description	Format	Model	Cell survival
Collagen [1]	Human RPE cells	Non-crosslinked collagen + supported RPE integrated with host RPE over crosslinked collagen	scaffold	rabbit	<6 w
Fibrinogen [2]	Human fetal RPE	RPE cells with crosslinked fibrinogen particles survived after transplantation into the subretinal space, retinal degeneration was noted in areas of particles	particles	rabbit	4 w
Gelatin [3]	RPE grafts	Subretinal transplant of an allogeneic RPE grafts embedded in gelatin, no infiltration of the graft site with inflammatory cells	film	pig	12 w
Parylene [4]	hESCs-derived RPE	hESCs-derived RPE survived post-implantation	film	rat	–
Parylene-C [5]	hESC-derived RPE cells	Safe and useful implantation of synthetic sheets seeded with organized retinal cells	film	rat	>1 w
PDMS-PmL [6]	iPSC derived RPE	Subretinal scaffold showed biocompatibility and preserved macular function up to 2 years after implantation with no inflammation	scaffold	pig	*
PET or P(LA-co-CL) [7]	hESC-derived RPE cells	Showed subretinal biocompatibility, some migration of native RPE cells into nanofibers, reactive gliosis with some photoreceptor degeneration	film	rabbit	>2 w
Polyester [8]	hESCs-derived RPE	hESCs-derived RPE maintained their structure and polarity on polyester matrix	matrix	rabbit	4 w
Polyester (PET) [7] [9]	Adult human RPE stem cell (hRPESC) and fetal human RPE stem cells	Subretinal implantation of a polarized monolayer of adult hRPESC-derived RPE, after implantation cells survived and maintained key properties, no graft proliferation.	film	rabbit	>4 w
Polyimide (PI) [10]	hESCs-derived RPE	Membrane well tolerated but hESCs-derived RPE showed loss of pigmentation over time	scaffold	rabbit	–
Silk Fibroin/PLC/Gelatin [11]	Human primary RPE cells	Subscleral implantation with no inflammation or rejection	scaffold	rabbit	>12 w

ESC, embryonic stem cells; RPE, retinal pigment epithelium; hESCs-RPE, human embryonic stem cell-derived RPE cells; iPSC, induced pluripotent stem cell; PDMS-PmL, plasma modified polydimethylsiloxane coated with laminin; PET, poly(ethylene terephthalate); P(LA-co-CL), poly(l-lactide-co-ε-caprolactone); PCL, poly caprolactone. [1] (Bhatt et al., 1994); [2] (Oganesian et al., 1999); [3] (Del Priore et al., 2004): [4] (Hu et al., 2012); [5] (Liu et al., 2012; Lu et al., 2012; Diniz et al., 2013); [6] (Peng et al., 2016); [7] (Liu et al., 2014); [8] (Giordano et al., 1997); [9] (Stanzel et al., 2014); [10] (Ilmarinen et al., 2015) [11] (Xiang et al., 2014). *no cell viability assay performed after implantation.