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The use of surface modified poly(glycerol-co-sebacic acid) in retinal transplantation

Pritchard, Christopher D.; Arnér, Karin LU ; Neal, Rebekah A.; Neeley, William L.; Bojo, Peter; Bachelder, Erika; Holz, Jessica; Watson, Nicki; Botchwey, Edward A. and Langer, Robert S., et al. (2010) In Biomaterials 31(8). p.2153-2162
Abstract
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... (More)
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 All 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. (C) 2009 Elsevier Ltd. All rights reserved. (Less)
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keywords
Polycaprolactone, Retina, Nanotopography, Laminin, Cell adhesion, Elastomer
in
Biomaterials
volume
31
issue
8
pages
2153 - 2162
publisher
Elsevier
external identifiers
  • wos:000275167300020
  • scopus:74449090637
ISSN
1878-5905
DOI
10.1016/j.biomaterials.2009.11.074
language
English
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yes
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b808d6c8-a7dc-4d50-aa0b-910120e40349 (old id 1589796)
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2010-04-19 14:11:51
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@article{b808d6c8-a7dc-4d50-aa0b-910120e40349,
  abstract     = {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 All 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. (C) 2009 Elsevier Ltd. All rights reserved.},
  author       = {Pritchard, Christopher D. and Arnér, Karin and Neal, Rebekah A. and Neeley, William L. and Bojo, Peter and Bachelder, Erika and Holz, Jessica and Watson, Nicki and Botchwey, Edward A. and Langer, Robert S. and Ghosh, Fredrik},
  issn         = {1878-5905},
  keyword      = {Polycaprolactone,Retina,Nanotopography,Laminin,Cell adhesion,Elastomer},
  language     = {eng},
  number       = {8},
  pages        = {2153--2162},
  publisher    = {Elsevier},
  series       = {Biomaterials},
  title        = {The use of surface modified poly(glycerol-co-sebacic acid) in retinal transplantation},
  url          = {http://dx.doi.org/10.1016/j.biomaterials.2009.11.074},
  volume       = {31},
  year         = {2010},
}