4.8 Article

Biological performance of mussel-inspired adhesive in extrahepatic islet transplantation

Journal

BIOMATERIALS
Volume 31, Issue 3, Pages 420-427

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2009.09.062

Keywords

Biomimetic material; Tissue adhesive; Islet; Diabetes; Hydrogel; Biocompatibility

Funding

  1. National Institutes of Health [EB003806, DE014193]
  2. Northwestern University Regenerative Medicine Training Program [NIH DA022881]
  3. NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R01EB003806] Funding Source: NIH RePORTER
  4. NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R37DE014193] Funding Source: NIH RePORTER
  5. NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [R01DE014193] Funding Source: NIH RePORTER
  6. NATIONAL INSTITUTE ON DRUG ABUSE [T90DA022881] Funding Source: NIH RePORTER

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There is significant need for effective medical adhesives that function reliably on wet tissue surfaces with minimal inflammatory insult. To address these performance characteristics, we have generated a synthetic adhesive biomaterial inspired by the protein glues of marine mussels. In-vivo performance was interrogated in a murine model of extrathepatic syngeneic islet transplantation, as an alternative to standard portal administration. The adhesive precursor polymer consisted of a branched poly(ethylene glycol) (PEG) core, whose endgroups were derivatized with catechol, a functional group abundant in mussel adhesive proteins. Under oxidizing conditions, adhesive hydrogels formed in less than 1 min from catechol-derivatized PEG (cPEG) solutions. Upon implantation, the cPEG adhesive elicited minimal acute or chronic inflammatory response in C57BL6 mice, and maintained an intact interface with supporting tissue for up to one year. in-situ cPEG adhesive formation was shown to efficiently immobilize transplanted islets at the epididymal fat pad and external liver surfaces, permitting normoglycemic recovery and graft revascularization. These findings establish the use of synthetic, biologically-inspired adhesives for islet transplantation at extrahepatic sites. (C) 2009 Elsevier Ltd. All rights reserved.

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