טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentBitton Ronit
SubjectBiomimetic Phenolic-Based Soft Tissue Adhesive
DepartmentDepartment of Biotechnology
Supervisor Professor Havazelet Bianco-Peled
Full Thesis textFull thesis text - English Version


Abstract

A challenging aspect of developing new tissue adhesive is to create a material that can glue wet surfaces. The success of synthetic glues under such an environment is very limited. On the contrary, many marine sessile organisms produce adhesives that effectively stick to almost any wet surface. We have studied adhesive materials formulated from natural materials extracted from the brown alga Fucus Serratus. These glues were suspected to be composed of two cross linked polymers: a phenolic polymer, cross linked via an enzymatic reaction in the presence of KI and H2O2, and alginate, cross linked by divalent calcium ions.  Adhesion tests have shown that the cross-linked phenolic polymers could become useful adhesives, capable of adhering to a variety of surfaces, as long as their cohesive strength is modified by the addition of alginate and calcium ions.  Further insight into the mechanism of glue formation was obtained from scattering and electron microscopy experiments. These have shown that the phenolic polymer self-assembles and forms flexible chain-like objects. This structure does not change upon enzymatic cross-linking or addition of alginate. However, once the alginate is cross-liked with calcium ions, a rigid network is formed. Presumably, this network is responsible for the cohesive strength of the glue. Replacing KI with KBr did not alter the polyphenols' organization nor the glues' structure. Yet, slight differences in the aggregate size were detected. The halogen type did, however, affect the adhesion properties of the glue. QCM-D results showed that the kinetics of the oxidation was faster with iodide than with bromide. Moreover, oxidation with iodide generates stiffer networks, suggesting that the interaction between the alginate and the polyphenol could be the cause for the KI containing glues' reduced adhesion.

Inspired by these findings, we have developed a bio-mimetic analog by replacing the algal-born polyphenol with phloroglucinol, a low-molecular weigh synthetic monomer. The biomimetic glue formulations were capable of adhering to a variety of surfaces, including porcine tissues. The adherence of the phloroglucinol glue to hydrophilic surfaces was improved by omitting the phloroglucinol oxidation. Rheology measurements showed that the presence of phloroglucinol lowered the amount of ca+2 ions required for the induction of a sol-gel transition, indicating interactions between the alginate and the phloroglucinol. SAXS experiments support this claim.