Bioengineered hyaluronan-based hydrogels for retinal cell delivery

Event Abstract Back to Event Bioengineered hyaluronan-based hydrogels for retinal cell delivery Vianney Delplace1, Roger Y. Tam1, Brian G. Ballios1, Michael J. Cooke1, Derek Van Der Kooy1 and Molly Shoichet1 1 University of Toronto, Chemical Engineering & Applied Chemistry, Donnelly Centre, Canada Introduction: Blindness and visual impairment are largely caused by irreversible loss of light sensitive photoreceptors in the retina. Transplantation of photoreceptor cells and their progeny is one of the most promising strategies to restore vision[1]. But, using conventional injection strategies, the distribution, survival and integration of such cells in vivo remains a major impediment to clinical applications. To enhance retinal cell distribution and survival in vivo, we designed an injectable hyaluronan-based hydrogel that met with much success[2]-[7]. Yet, 90% (or more) of transplanted cells are still dying. In order to make a more significant difference, further chemical modifications of HAMC with various pro-survival factors are being investigated to deliver the cells in a more conducive environment for even greater survival and integration. Materials and Methods: A hydrogel formulation comprised of a physical blend of hyaluronan (HA) and methylcellulose (MC), HAMC, was developed and optimized for subretinal delivery. The injectable hydrogel was tested in vivo for transplantation of retinal cells and their photoreceptor progeny. HAMC was then chemically modified to allow thiol-maleimide and biotin–streptavidin chemistry, and conjugated with two pro-survival factors. The modified hydrogel is being tested with photoreceptor cells in vitro and in vivo. Results and Discussion: The HAMC hydrogel is particularly well-suited for delivery into the subretinal space as it is minimally swelling, bioresorbable within one week and it gels rapidly on injection[5]-[7]. When delivered in HAMC, retinal stem cells and their photoreceptor progeny were well-distributed in the subretinal space after injection (see Figure 1), and significantly better than those injected using conventional saline strategies, where the cells aggregated together[2]-[4]. Cell survival was doubled from approximately 4% to 8% when delivered in HAMC vs. saline controls. Figure 1. Delivery of retinal progenitor cells (RPCs) to the subretinal space, using hyaluronan/methylcellulose (HAMC) hydrogel as biomaterial support. To further enhance the properties of this hydrogel, HAMC was then covalently modified with two pro-survival factors. The success of the synthesis was assessed by mass spectroscopy and amino acid analysis, prior to a complete study of photoreceptor cell viability first in vitro and then in vivo. The HAMC hydrogel, conjugated with pro-survival factors, should enhance both distribution and survival of transplanted retinal photoreceptor cells. Conclusions: These data demonstrate that HAMC serves as a platform strategy for cell delivery, enabling minimally-invasive strategies and significantly better tissue and functional outcomes than controls. B.G.B. holds a CIHR Doctoral Canada Graduate Scholarship and McLaughlin Centre Graduate Fellowship; M.J.C. holds a Mitacs Elevate post-doctoral fellowship and thanks the Stem Cell Network for financial support; This work was supported in part by the CIHR, the Heart and Stroke Foundation, the NIH (R01 EY015716), the Foundation Fighting Blindness (FFB) Canada/Krembil Foundation, the McEwen Centre for Regenerative Medicine, and the Ontario Research FoundationReferences:[1] V. Delplace, S. Payne, M. Shoichet, Delivery strategies for treatment of age-related ocular diseases: from a biological understanding to biomaterial solutions., J. Control. Rel., (2015).[2] B.G. Ballios, M.J. Cooke, L. Donaldson, B.L. Coles, C.M. Morshead, D. van der Kooy, M.S. Shoichet, A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation, Stem Cell Reports, 4 (2015) 1031-1045.[3] B.G. Ballios, M.J. Cooke, D. van der Kooy, M.S. Shoichet, A hydrogel-based stem cell delivery system to treat retinal degenerative diseases, Biomaterials, 31 (2010) 2555-2564.[4] R.Y. Tam, T. Fuehrmann, N. Mitrousis, M.S. Shoichet, Regenerative therapies for central nervous system diseases: a biomaterials approach, Neuropsychopharmacology, 39 (2014) 169-188.[5] H. Kim, M.J. Cooke, M.S. Shoichet, Creating permissive microenvironments for stem cell transplantation into the central nervous system, Trends Biotechnol., 30 (2012) 55-63.[6] D. Gupta, C.H. Tator, M.S. Shoichet, Fast-gelling injectable blend of hyaluronan and methylcellulose for intrathecal, localized delivery to the injured spinal cord, Biomaterials, 27 (2006) 2370-2379.[7] M.D. Baumann, C.E. Kang, C.H. Tator, M.S. Shoichet, Intrathecal delivery of a polymeric nanocomposite hydrogel after spinal cord injury, Biomaterials, 31 (2010) 7631-7639. Keywords: Hydrogel, Tissue Regeneration, material design, Bioactive molecule Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Biomaterials for ophthalmic applications Citation: Delplace V, Tam RY, Ballios BG, Cooke MJ, Van Der Kooy D and Shoichet M (2016). Bioengineered hyaluronan-based hydrogels for retinal cell delivery. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.00844 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Vianney Delplace Roger Y Tam Brian G Ballios Michael J Cooke Derek Van Der Kooy Molly Shoichet Google Vianney Delplace Roger Y Tam Brian G Ballios Michael J Cooke Derek Van Der Kooy Molly Shoichet Google Scholar Vianney Delplace Roger Y Tam Brian G Ballios Michael J Cooke Derek Van Der Kooy Molly Shoichet PubMed Vianney Delplace Roger Y Tam Brian G Ballios Michael J Cooke Derek Van Der Kooy Molly Shoichet Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.