The use of surface modified poly(glycerol-co-sebacic acid) in retinal transplantation.
Retinal transplantation experiments have advanced considerably during recent years, but remaining diseased photoreceptor cells in the host retina and inner retinal cells in the transplant physically obstruct the development of graft-host neuronal contacts which are required for vision. Recently, we developed methods for the isolation of donor photoreceptor layers in vitro, and the selective removal of host photoreceptors in vivo using biodegradable elastomeric membranes composed of poly(glycerol-co-sebacic acid) (PGS). Here, we report the surface modification of PGS membranes to promote the attachment of photoreceptor layers, allowing the resulting composite to be handled surgically as a single entity. PGS membranes were chemically modified with peptides containing an arginine-glycine-aspartic acid (RGD) extracellular matrix ligand sequence. PGS membranes were also coated with electrospun nanofiber meshes, containing laminin and poly(epsilon-caprolactone) (PCL). Following in vitro co-culture of biomaterial membranes with isolated embryonic retinal tissue, composites were tested for surgical handling and examined with hematoxylin and eosin staining and immunohistochemical markers. Electrospun nanofibers composed of laminin and PCL promoted sufficient cell adhesion for simultaneous transplantation of isolated photoreceptor layers and PGS membranes. Composites developed large populations of recoverin and rhodopsin labeled photoreceptors. Furthermore, ganglion cells, rod bipolar cells and AII amacrine cells were absent in co-cultured retinas as observed by neurofilament, PKC and parvalbumin labeling respectively. These results facilitate retinal transplantation experiments in which a composite graft composed of a biodegradable membrane adhered to an immature retina dominated by photoreceptor cells may be delivered in a single surgery, with the possibility of improving graft-host neuronal connections.
Pritchard
Christopher D
CD
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. cpritcha@mit.edu
Arnér
Karin M
KM
Neal
Rebekah A
RA
Neeley
William L
WL
Bojo
Peter
P
Bachelder
Erika
E
Holz
Jessica
J
Watson
Nicki
N
Botchwey
Edward A
EA
Langer
Robert S
RS
Ghosh
Fredrik K
FK
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D003651:Decanoates / Q000378:metabolism*; D005990:Glycerol / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008422:Materials Testing; D057139:Nanofibers / Q000737:chemistry; D016900:Neurofilament Proteins / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D010786:Photoreceptor Cells / Q000166:cytology / Q000378:metabolism; D011108:Polymers / Q000378:metabolism*; D051603:Recoverin / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D013499:Surface Properties; D013552:Swine; D014746:Vimentin / Q000378:metabolism
D001672:Biocompatible Materials; D003651:Decanoates; D016900:Neurofilament Proteins; D009842:Oligopeptides; D011108:Polymers; D014746:Vimentin; C469892:poly(glycerol-sebacate); D051603:Recoverin; C047981:arginyl-glycyl-aspartic acid; D005990:Glycerol