Biomaterials 27 (2006) 745–751 Tannic acid mimicking dendrimers as small intestine submucosa stabilizing nanomordants Vladimir Kasyanov a,b , Jason Isenburg c , Robert A. Draughn a , Starr Hazard a , Jason Hodde d , Iveta Ozolanta b , Modra Murovska b , S. Bart Halkes e , Ioannis Vrasidas e , Rob M.J. Liskamp e , Roland J. Pieters e , Dan Simionescu c , Roger R. Markwald a , Vladimir Mironov a,Ã a Medical University of South Carolina, Charleston, SC 29425, USA b Riga Stradins University, Riga, LV-1007, Latvia c Clemson University, Clemson, SC 29634, USA d Cook Biotech Inc., West Lafayette, IN 47906, USA e Utrecht University, NL—3508 TB, Utrecht, The Netherlands Received 25 March 2005; accepted 28 June 2005 Available online 18 August 2005 Abstract Chemical stabilization resulting in increased resistance to proteolytic degradation is one of the approaches in prevention of post- implantational aneurysm development in decellularized natural vascular scaffolds. Recently, tannic acid (TA) and tannic acid mimicking dendrimers (TAMD) have been suggested as potential stabilization agents for collagen and elastin. The aim of this work was to determine the stabilizing effects of TAMD on decellularized natural scaffolds. Vascular scaffolds fabricated from small intestine submucosa (SIS) and SIS plane sheets (Cook Biotech Inc.) were used. The biomechanical properties of the SIS vascular graft segments treated with TA and TAMD were tested. The effect of TAMD treatment on resistance to proteolytic degradation was evaluated by measuring biomechanical properties of TAMD stabilized and non-stabilized SIS specimens after incubation in collagenase solution. It was shown that treatment with TA as well as with TAMD increased the strength of tubular SIS as well as their resistance to proteolytic biodegradation manifested by preservation of biomechanical properties after collagenase treatment. Transmission electron microscopy demonstrated that treatment with TAMD increased the periodical pattern typical of collagen fiber ultrastructure as a result of the ‘‘mordant’’ effect. The possible collagen cross-linking effect of TAMD on SIS was investigated by differential scanning calorimetry (DSC). The treatment with TAMD induced a small, but detectable cross-linking effect, suggesting that TAMD do not establish extensive covalent cross links within the extracellular matrix but rather interact with collagen, thus rendering SIS scaffolds more resistant to proteolytic degradation. r 2005 Elsevier Ltd. All rights reserved. Keywords: Dendrimer; Tannic acid; Acellular scaffold; Vascular prosthesis; Biomechanical properties; Nanomordant 1. Introduction The small diameter vascular graft is the ‘‘holy grail’’ of cardiovascular surgery [1]. However, all existing synthetic vascular grafts have failed as coronary bypasses due to early thrombosis and late anastomotic intimal thickening [2]. The emerging field of vascular tissue engineering has made impressive progress during the last decade [3–7]. The decellularized natural scaf- folds in vascular tissue engineering have certain ad- vantages as compared with synthetic scaffolds. For instance, they are biomechanically more ideal [8], are available ‘‘off the shelf’’, can be endothelialized, and can ARTICLE IN PRESS www.elsevier.com/locate/biomaterials 0142-9612/$-see front matter r 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2005.06.022 Ã Corresponding author. Tel.: +8437927630; fax: +8437920664. E-mail address: mironovv@musc.edu (V. Mironov).