Extracellular matrix dynamics associated with tissue-engineered intravascular sclerotherapy

Background: The extracellular dynamics after intravascular sclerotherapy with an injectable, fibroblast-based engineered construct is unknown. Methods: Rabbits underwent ethanol sclerotherapy of a jugular vein segment. Control animals (n = 40) underwent no further treatment or an acellular collagen hydrogel was injected. Experimental animals (n = 20) received a tissue-engineered construct. After 1, 2, 4, and 20 to 24 weeks, segments were evaluated for collagen, glycosaminoglycan (GAG), matrix metalloproteinase (MMP) 2 and 9, and tissue inhibitors of MMP (TIMPs) 1 and 2 and scored on a scale of 0 to 3. Groups and time points were compared using nonparametric statistical analysis. Results: Collagen content was higher in animals that received fibroblasts (P < .05). Glycosaminoglycan analysis showed a higher grade only at 1 week (P < .05). Collagen and GAG deposition were prominent at weeks 1 through 4, and decreased over time. Both MMP-2 and MMP-9 and TIMP-1 and TIMP-2 grade decreased with time (P < .01) in all groups, with no differences between groups. Conclusion: Enhancement of intravascular sclerotherapy by tissue engineering stems, at least in part, from increased local deposition of collagen and GAG. MMP and TIMPs may play a role in recanalization after experimental sclerotherapy. Tissue engineering may be a valuable adjunct for the treatment of vascular malformations.