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. 2016 Sep 1:41:75-85.
doi: 10.1016/j.actbio.2016.06.010. Epub 2016 Jun 7.

IGF-1-containing multi-layered collagen-fibrin hybrid scaffolds for bladder tissue engineering

E Vardar  1 , H M Larsson  2 , E M Engelhardt  1 , K Pinnagoda  2 , P S Briquez  1 , J A Hubbell  3 , P Frey  4
Affiliations

IGF-1-containing multi-layered collagen-fibrin hybrid scaffolds for bladder tissue engineering

E Vardar et al. Acta Biomater. .

Abstract

Clinical success of bladder reconstructive procedures could be promoted by the availability of functional biomaterials. In this study, we have developed a multi-layered scaffold consisting of a bioactive fibrin layer laminated between two collagen sheets all having undergone plastic compression. With this construct we performed bladder augmentation in a nude rat model after partial bladder excision and evaluated the morphological and functional behavior of the implant. The fibrin was functionalized with a recombinant human insulin-like growth factor-1 (IGF-1) variant that covalently binds fibrin during polymerization and has a matrix metalloproteinase-cleavage insert to enable cell-mediated release. The purified IGF-1 variant showed similar bioactivity in vitro compared to commercially available wild type (wt) IGF-1, inducing receptor phosphorylation and induction of human smooth muscle cell proliferation. In vivo, the multi-layered bioactive collagen-fibrin scaffolds loaded with the IGF-1 variant triggered dose-dependent functional host smooth muscle cell invasion and bundle formation with re-urothelialization 4weeks after surgery in a rat model.

Statement of significance: The design of new bio-functional scaffolds that can be employed for bladder reconstructive procedures is a growing focus in the field of tissue engineering. In this study, a fibrin binding form of human insulin-like growth factor-1 (IGF-1) was produced and used to functionalize a multi-layered collagen-fibrin scaffold consisting of bioactive fibrin layer, sandwiched between two collagen gels. An effective dosage of our IGF-1 variant was successfully determined via a nude rat bladder model, which may play a critical role in estimating its therapeutic dosage in clinical trials. Thus, this new bioactive scaffold may offer an advanced approach to accelerate bladder regeneration.

Keywords: Bladder regeneration; Collagen; Fibrin; Human insulin-like growth factor-1.

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