Growth factor release from a chemically modified elastomeric poly(1,8-octanediol-co-citrate) thin film promotes angiogenesis in vivo

Sharma, A. K.; Bury, M. I.; Fuller, N. J.; Rozkiewicz, D. I.; Hota, P. V.; Kollhoff, D. M.; Webber, M. J.; Tapaskar, N.; Meisner, J. W.; Lariviere, P. J.; Destefano, S.; Wang, D.; Ameer, G. A.; Cheng, E. Y.

J Biomed Mater Res A. 2011 Dec 14; 100(3):561-70


The ultimate success of in vivo organ formation utilizing ex vivo expanded "starter" tissues relies heavily upon the level of vascularization provided by either endogenous or artificial induction of angiogenic or vasculogenic events. To facilitate proangiogenic outcomes and promote tissue growth, an elastomeric scaffold previously shown to be instrumental in the urinary bladder regenerative process was modified to release proangiogenic growth factors. Carboxylic acid groups on poly(1,8-octanediol-co-citrate) films (POCfs) were modified with heparan sulfate creating a heparan binding POCf (HBPOCf). Release of proangiogenic growth factors vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), and insulin-like growth factor 1 (IGF-1) from HBPOCfs demonstrated an approximate threefold increase over controls during a 30-day time course in vitro. Atomic force microscopy demonstrated significant topological differences between films. Subcutaneous implantation of POCf alone, HBPOCf, POCf-VEGF, and HBPOCf-VEGF within the dorsa of nude rats yielded increased vascular growth in HBPOCf-VEGF constructs. Vessel quantification studies revealed that POCfs alone contained 41.1 +/- 4.1 vessels/mm(2) , while HBPOCf, POCf-VEGF, and HBPOCF-VEGF contained 41.7 +/- 2.6, 76.3 +/- 9.4, and 167.72 +/- 15.3 vessels/mm(2) , respectively. Presence of increased vessel growth was demonstrated by CD31 and vWF immunostaining in HBPOCf-VEGF implanted areas. Data demonstrate that elastomeric POCfs can be chemically modified and possess the ability to promote angiogenesis in vivo. (c) 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.

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