Interaction of functional groups in tissue adhesive : experimental analysis and computational modeling

223 p.The development of new tissue adhesives (TAs) has been very slow, to say the least, for the past decade. Synthesis of new TAs is by and large through trial and error and therefore very costly and time consuming. This thesis introduces some new aspects of study into the field of TA with the intent of assisting and even guiding the choice of functional groups that may promote adhesiveness in TAs. Atomistic modeling and simulation is an increasingly potential tool in studying the origins of observable phenomena. Here, it is introduced to study TAs for the first time. Of all theories available, classical molecular mechanics and dynamics (MM/MD) were implemented as it is most suitable to handle the size of the system of interest and the time of simulations. As an introductory work, the thesis studied the (i) physical interactions of small functional molecules with collagen triple-helix; and (ii) the physical interactions of oligomer molecules with collagen surface in both dry and wet conditions. From there, a hypothesis of tissue adhesion was formulated. The simulation works, based on classical theory, were then examined by two experimental adhesion measurements. They were atomic force measurements in AFM (atomic force microscope) and lap shear tests. The former was also unprecedented in the field and it measured the interaction forces at molecular level. A few types of functional groups were tested on collagenous tendon substrates in dry and wet environments. The latter is a typical test used by many to assess adhesive joint strengths. Different adhesives were used to bond dry and wet collagenous substrates together and the joint strength was assessed by stressing in shear direction. Results showed that small molecules, in general, have strong physical adsorption on collagen but this interaction weakens as the molecules polymerize or cross-linked. Presence of water is indeed very unfavorable to adhesiveness in TAs and interactions are seriously perturbed, as observed in simulations and experiments. Also, peptide/amide group shows strong adhesiveness, and therefore protein glues have great potential. Finally, while adsorption is crucial, diffusion mechanism, which could be equally important, is proposed for future study.DOCTOR OF PHILOSOPHY (MSE