Biological performance of mussel-inspired adhesive in extrahepatic islet transplantation

Abstract

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 extrahepatic 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 one minute 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.

Impact tolerance in mussel thread networks by heterogeneous material distribution

“…The structural and mechanical lessons gained by investigating the byssus network could provide us with important design principles that can be applied in the fabrication of interfacial materials that can function effectively under dynamic loadings, such as attachments to ships, submarines, in wind turbines, or for applications in space technologies 4,25,26 . From a slightly different perspective, we have found that the use of about 20% soft material in mussel threads is crucial in light of impact absorption and force reduction for the entire animal.…”

The microscopic network structure of mussel ( Mytilus ) adhesive plaques

“…The extraordinary ability of the byssus to bind to a variety of pristine and bio-fouled surfaces (e.g. glass, metal, plastic) in a matter of minutes while immersed in the high salt and basic pH conditions imposed by seawater has attracted the attention of many researchers and resulted in the creation of biomimetic glues for medical and broader use [2][3][4][5][6].…”

Recent Progress of Mussel‐Inspired Underwater Adhesives

“…In this figure, catechol, [22] dopamine [23] or dopa [24] was coupled to polymer chains ends or as side chains of polymerizable catechol monomers with the linear or branched polymer backbone, which are commonly made of polystyrene, [25] poly(ethylene glycol), [26] poly-(acrylate/methacrylate), [27] or poly(acrylamide/methacrylamide) [28] ( Figure 3). It is demonstrated that both of catechols and cations have a classic synergy for underwater adhesion.…”

“…[51] Based on the mussels protein, a mimetic biological adhesive was fabricated with a branched poly(ethylene glycol) (PEG) with catechol end groups ( Figure 9A). [22] After adding sodium periodate solution to induce gelation, the branched catechol-functional PEG (cPEG) solutions form hydrogels in less than 1 min ( Figure 9B). Subsequently, the cPEG adhesive elicited minimal acute or chronic inflammatory response in C57BL6 mice, and maintained an intact interface with supporting tissue up to one year.…”