Thiol-Ene/Yne Adhesives for Tissue Fixation

Abstract: The utilization of adhesives in surgery has not reached its full potential and research in the field is encouraged by the surgeons’ desire for improved alternatives to today’s tissue fixation strategies. Here, adhesive resins based on thiol-ene coupling (TEC) chemistry or thiol-yne coupling (TYC) chemistry are exploited to develop tissue adhesives that cure fast and on-demand via photoinitiation. In order to make safer adhesives, macromolecular components and systems with high conversion of functional groups were developed to minimize leakage of unreacted monomers.To develop macromolecular resin components, allyl-functional dendritic-linear-dendritic (DLD) co-polymers were synthesized with a poly(ethylene glycol) (PEG) core chain and hyperbranched structures of 2,2-bis(hydroxymethyl) propionic acid (bis-MPA) to capitalize on the rheological properties of dendritic structures. The dendritic structures interfered with the crystallization of the PEG segment and the DLD’s liquid appearance enabled their use as macromolecular components without solvent. The DLDs were cured with a thiol crosslinker and the strategy disclosed degradable soft tissue adhesives with good adhesion to wet porcine skin.Mussel inspired dopamine derivatives was evaluated as adhesion-enhancing primers for bone adhesives. The addition of NaOH to the primer solutions increased the shear bond strengths of the adhesive to bone. The highest bond strengths with the tested dopamine derivatives were obtained when a combination of thiol and ene-functional derivatives were used.With inspiration from dental resin adhesives, a fully TEC based adhesive system was developed with excellent shear bond strength to wet bone substrates. The adhesive system enabled superior fixation of phalangeal fracture models compared to the daily used Kirschner wires and could even compete with a screw fixated metal plate. The adhesive materials proved biocompatible in initial in vitro and in vivo studies.Strong and rigid materials for fracture fixation were developed via a strategy of using highly crosslinked triazine-trione monomers and TEC or TYC chemistry. The development resulted in TYC resin based materials with mechanical properties that very well can compete with poly(ether ether ketone) (PEEK) that is used in biomedical load bearing applications due to its high strength, toughness and inertness.