title: Covalent surface heparinization potentiates porous polyurethane scaffold vascularization.
abstract: Porous scaffolds play an integral role in many tissue-engineering approaches, and the ability to improve vascularization, without eliciting an excessive inflammatory response, would constitute an important step towards achieving long-term healing and function of devices made from these materials. After having previously optimized the dimensional requirements of the well-defined pores, the present study aimed at a further shift from inflammation to vascularization via surface immobilization with heparin. Porous polyurethane disks were produced to contain well-defined pores (147 +/- 2 microm) with abundant interconnecting windows (67 +/- 2 microm). After heparinization via copolymer grafting and amination to contain 32 microg of heparin, the modification appeared as a uniform layer on all exposed surfaces, with no signs of pore obliteration or significant changes in pore size. After 28 days implantation in a rat subcutaneous model, the scaffolds were assessed for vascularization/arteriolization and inflammation using CD31/actin and ED-1 staining, respectively. Heparinization resulted in a significant increase in vascularization: capillaries increased by 62% in number (66.2 +/- 0.8 to 107.3 +/- 1.4 vessels/mm( 2); p < 0.03) and 56% in total area (0.9 +/- 0.1 to 1.4 +/- 0.02%; p<0.02). Arteriolization also increased in absolute terms (200% in number; p<0.03), but did not change significantly when normalized to capillary number. Heparinization did not significantly affect the inflammatory response at this time-point, as quantified by ED-1 positive macrophage and foreign body giant cell (FBGC) content. Thus, the in vivo vascularization of porous scaffolds could be increased without concomitant increase in the inflammatory response by employing a simple surface modification technique. This could be a valuable tool for in vivo tissue engineering applications where enhanced vascularization is required.
authors.affiliation: Cardiovascular Research Unit, Chris Barnard Division of Cardiothoracic Surgery, Faculty of Health Sciences University of Cape Town, Cape Town, South Africa. deon.bezuidenhout@uct.ac.za
authors.forename: Deon
authors.initials: D
authors.lastname: Bezuidenhout
authors.forename: Neil
authors.initials: N
authors.lastname: Davies
authors.forename: Melanie
authors.initials: M
authors.lastname: Black
authors.forename: Christian
authors.initials: C
authors.lastname: Schmidt
authors.forename: Anel
authors.initials: A
authors.lastname: Oosthuysen
authors.forename: Peter
authors.initials: P
authors.lastname: Zilla
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000254:growth & development; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D018919:Neovascularization, Physiologic; D011140:Polyurethanes; D051381:Rats; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D020099:Coated Materials, Biocompatible; D011140:Polyurethanes; D006493:Heparin