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Medical Adhesives

Creating effective adhesives for internal tissue repair is an exceedingly challenging problem.  The adhesives must work in a wet physiological environment within a restricted temperature and pH range, be conveniently delivered to wet tissue, remain where it is applied, have a triggered set/cure mechanism, not produce toxic heat or large pH changes during cure, not shrink or swell substantially after placement, be non-toxic as applied, as it breaks down, and cannot induce persistent inflammation.  As practical considerations, the adhesive must be manufacturable at reasonable cost, sterilizable using industry standard methods, have a reasonable self life, and come in a simple user-friendly package.   

Our approach is based on synthetic polyelectrolytes that mimic the polyelectrolytic proteins in the sandcastle glue. Depending on the solution conditions and polymer structures, oppositely charged polyelectrolytes, when mixed, can associate into several supramolecular forms, ranging from colloidal polyelectrolyte complexes to insoluble flocs to ionic hydrogels.  In between is an intriguing material state, a dense, phase-separated fluid of condensed polymers—a complex coacervate—an example of which is shown in the figure above and in this video.  Electrostatic charge neutralization between polymeric charges displaces small counterions and water, providing an entropic driving force for condensation of the polyelectrolytes.  

Complex coacervates have ideal properties as the foundation for injectable, water-borne, non-toxic, wet tissue adhesives:

  • They are self-organized in water from pre-polymers so there are neither toxic solvents, nor exothermic nor promiscuous polymerization chemistry in situ.
  • Because they are denser than water (and blood), they sink onto the substrate and displace lighter fluids.
  • With an infinitesimal interfacial tension between the complex coacervate phase and water phase, they readily spread on submerged hydrophilic surfaces, which maximizes adhesive contact.
  • The polyelectrolyte constituents have multiple wet adhesion promoting functional groups that displace surface-associated water and counterions to chemically adhere to the substrate.
  • The supramolecular structure of complex coacervates results in a lower viscosity than an equivalent concentration of entangled polymers, which aids ejection through narrow gauge cannulae.
  • They are water immiscible.  The natural sandcastle glue does not dissolve into the sea before setting; likewise complex coacervate glues do not mix with physiological fluids, including blood and amniotic fluid before setting. 
  • Related to the previous quality, they are dimensionally stable in wet environments.  They do not absorb water and swell in part because they are water immiscible.  Swelling can cause tissue damage and pain. 
  • The complex coacervate phase is effectively a container for water-soluble components that can add functionality to the adhesive. Though partially dehydrated, the synthetic adhesive complex coacervates are still typically 40-60 wt% water.  The water and associated polyelectrolytes are not distributed homogeneously in the complex coacervate, but instead form bi-continuous phases, one mostly water, the other mostly polymer. This hydrated sponge-like internal structure of complex coacervates will contribute to their versatility for biomaterial applications.  Looking ahead, tissue adhesives that contain bioactives to prevent infections, decrease healing times, or otherwise modulate tissue responses seem feasible.

    Complex coacervation video

    Bonding bones underwater video