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



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.
Experimental Pediatric Urology, Laboratory for Regenerative Medicine and Pharmacobiology, Institute for Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
E
E
Vardar
Experimental Pediatric Urology, Laboratory for Regenerative Medicine and Pharmacobiology, Institute for Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland; Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne 1011, Switzerland.
H M
HM
Larsson
Experimental Pediatric Urology, Laboratory for Regenerative Medicine and Pharmacobiology, Institute for Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
E M
EM
Engelhardt
Experimental Pediatric Urology, Laboratory for Regenerative Medicine and Pharmacobiology, Institute for Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland; Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne 1011, Switzerland.
K
K
Pinnagoda
Experimental Pediatric Urology, Laboratory for Regenerative Medicine and Pharmacobiology, Institute for Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
P S
PS
Briquez
Experimental Pediatric Urology, Laboratory for Regenerative Medicine and Pharmacobiology, Institute for Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland; Institute for Molecular Engineering, University of Chicago, Chicago, IL 60439, USA.
J A
JA
Hubbell
Experimental Pediatric Urology, Laboratory for Regenerative Medicine and Pharmacobiology, Institute for Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland. Electronic address: peter.frey@epfl.ch.
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P
Frey
D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D005260:Female; D005337:Fibrin / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects; D011923:Rats, Nude; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D001743:Urinary Bladder / Q000502:physiology* / Q000601:surgery
D001672:Biocompatible Materials; D007334:Insulin-Like Growth Factor I; D005337:Fibrin; D003094:Collagen
Bladder regeneration; Collagen; Fibrin; Human insulin-like growth factor-1