March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
A porous poly(-caprolactone) tissue engineering scaffold for RPE Transplantation
Author Affiliations & Notes
  • Kevin J. McHugh
    Schepens Eye Research Institute, Boston, Massachusetts
    Biomedical Engineering, Boston University, Boston, Massachusetts
  • Carrie Spencer
    Schepens Eye Research Institute, Boston, Massachusetts
  • Patricia A. D'Amore
    Schepens Eye Research Institute, Boston, Massachusetts
    Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • Sarah L. Tao
    The Charles Stark Draper Laboratory, Inc., Cambridge, Massachusetts
    Advanced Development Center, Current Affiliation: CooperVision, Inc., Pleasanton, California
  • Magali Saint-Geniez
    Schepens Eye Research Institute, Boston, Massachusetts
    Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Kevin J. McHugh, None; Carrie Spencer, None; Patricia A. D'Amore, 61/499,909 (P); Sarah L. Tao, 61/499,909 (P); Magali Saint-Geniez, 61/499,909 (P)
  • Footnotes
    Support  NIH Grant 1 DP 20D 006649
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 3641. doi:
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      Kevin J. McHugh, Carrie Spencer, Patricia A. D'Amore, Sarah L. Tao, Magali Saint-Geniez; A porous poly(-caprolactone) tissue engineering scaffold for RPE Transplantation. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3641.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Transplantation of retinal pigment epithelium (RPE) is a promising approach for the treatment of retinal diseases including dry age-related macular degeneration (AMD). Past replacement strategies using RPE cell suspensions or sheets have failed largely due to poor adhesion or lack of organization on a Bruch’s Membrane (BrM) that is aged or itself diseased. In this study, we developed and tested a thin film, porous poly(ε-caprolactone) (PCL) scaffold to act as a biomimetic BrM substitute for RPE culture and potential implantation into the sub-retinal space.

Methods: : A nanopatterned mold was created using a combined process of photolithography and reactive ion etching. Porous PCL scaffolds were then produced from the mold by spin-assisted templating and mounted on transwell inserts. Fetal human RPE cells (fhRPE) were maintained at confluence on the scaffolds for up to 8 weeks and compared to non-porous PCL and porous polyester (PET) transwells (Costar) using transepithelial resistance, gene expression, phagocytic capacity, and immunohistochemistry.

Results: : fhRPE transepithelial resistance significantly increased on porous PCL compared to PET transwells beginning at 5 days and persisting through the end of the 8 week experiment. Cells on porous PCL also displayed significant upregulation of key RPE proteins including a 6.45-fold increase in RPE65 and 2.19-fold increase in CRALBP compared to the PET control at 4 weeks. Alternately, cells on non-porous PCL fail to show a significant change in major RPE markers compared to the control. fhRPE cultured on porous PCL and PET displayed similar levels of binding and phagocytosis of fluorescently-labeled photoreceptor outer segments after four weeks of culture. In addition, the greatest degree of pigmentation was observed in cells on the porous PCL followed by non-porous PCL, and finally PET.

Conclusions: : Both material and porosity are important factors in RPE maturation and function in vitro. Our porous PCL thin film scaffold exploits both characteristics to promote the development of a mature RPE monolayer as evaluated by gene expression profile, organization, and polarization while allowing transport across the membrane.

Keywords: retinal pigment epithelium • Bruch's membrane • age-related macular degeneration 

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