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Christiansen A.T.,Copenhagen University | Tao S.L.,CooperVision Inc. | Smith M.,NuVention Solutions Inc. | Wnek G.E.,Case Western Reserve University | And 6 more authors.
Stem Cells International | Year: 2012

Biodegradable scaffolds play an important adjunct role in transplantation of retinal progenitor cells (RPCs) to the subretinal space. Poly(μ- Caprolactone) (PCL) scaffolds with different modifications were subretinally implanted in 28 porcine eyes and evaluated by multifocal electroretinography (mfERG) and histology after 6 weeks of observation. PCL Short Nanowire, PCL Electrospun, and PCL Smooth scaffolds were well tolerated in the subretinal space in pigs and caused no inflammation and limited tissue disruption. PCL Short Nanowire had an average rate of preserved overlying outer retina 17 higher than PCL Electrospun and 25 higher than PCL Smooth. Furthermore, PCL Short Nanowire was found to have the most suitable degree of stiffness for surgical delivery to the subretinal space. The membrane-induced photoreceptor damage could be shown on mfERG, but the reductions in P1 amplitude were only significant for the PCL Smooth. We conclude that of the tested scaffolds, PCL Short Nanowire is the best candidate for subretinal implantation. Copyright © 2012 A. T. Christiansen et al.

Christiansen A.T.,Copenhagen University | Kiilgaard J.F.,Copenhagen University | Smith M.,NuVention Solutions Inc. | Ejstrup R.,Copenhagen University | And 6 more authors.
Stem Cells International | Year: 2012

To determine the effect of membrane brightness on multifocal electroretinograms (mfERGs), we implanted poly lactic-co-glycolic acid (PLGA) membranes in the subretinal space of 11 porcine eyes. We compared membranes with their native shiny white color with membranes that were stained with a blue dye (Brilliant Blue). Histological and electrophysiological evaluation of the overlying retina was carried out 6 weeks after implantation. Histologically, both white and blue membranes degraded in a spongiform manner leaving a disrupted outer retina with no preserved photoreceptor segments. Multifocal ERG revealed the white membranes to have a significantly higher P1-amplitude ratio than the blue (P = 0.027), and a correlation between brightness ratio and P1-amplitude ratio was found (r = 0.762). Based on our findings, we conclude that bright subretinal objects can produce normal mfERG amplitude ratios even when the adjacent photoreceptors are missing. Functional assessment with mfERG in scaffold implant studies should therefore be evaluated with care. © 2012 A. T. Christiansen et al.

Meng L.,Case Western Reserve University | Arnoult O.,Saint - Gobain | Smith M.,NuVention Solutions Inc. | Wnek G.E.,Case Western Reserve University
Journal of Materials Chemistry | Year: 2012

A simple one-step approach to electrospin Type I collagen in the presence of the chemical crosslinking agents 1-ethyl-3-(3-dimethyl-aminopropyl)-1- carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) has been developed to generate water-insoluble collagen nanofiber scaffolds without the need for post-crosslinking. SEM images indicate that fibrous surface morphology of collagen scaffolds was well retained after the in situ crosslinking process and following water treatment. The resultant collagen demonstrated a similar uniaxial tensile behavior of native tissue in mechanical testing. © 2012 The Royal Society of Chemistry.

Cai S.,Schepens Eye Research Institute | Smith M.E.,Case Western Reserve University | Smith M.E.,NuVention Solutions Inc. | Redenti S.M.,Schepens Eye Research Institute | And 3 more authors.
Journal of Biomaterials Science, Polymer Edition | Year: 2012

Age-related macular degeneration, retinitis pigmentosa and glaucoma are among the many retinal degenerative diseases where retinal cell death leads to irreversible vision loss and blindness. Working toward a cell-replacement-based therapy for such diseases, a number of research groups have recently evaluated the feasibility of using retinal progenitor cells (RPCs) cultured and transplanted on biodegradable polymer substrates to replace damaged retinal tissue. Appropriate polymer substrate design is essential to providing a three-dimensional environment that can facilitate cell adhesion, proliferation and post-transplantation migration into the host environment. In this study, we have designed and fabricated a novel, ultra-thin electrospun poly(ε-caprolactone) (PCL) scaffold with microscale fiber diameters, appropriate porosity for infiltration by RPCs, and biologically compatible mechanical characteristics. We have verified that our electrospun PCL scaffold supports robust mouse RPC proliferation, adhesion, and differentiation in vitro, as well as migration into mouse retinal explants. These promising results make PCL a strong candidate for further development as a cell transplantation substrate in retinal regenerative research. © 2011 Koninklijke Brill NV, Leiden.

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