@article {19253, title = {Biomimetic tissue sealants from glycosaminoglycans}, journal = {FoReCaST 1st Workshop}, year = {2017}, month = {2017-11-15 00:00:00}, address = {Porto (Portugal)}, abstract = {

Medical adhesives and sealants that form in situ offer a minimally invasive alternative to the common surgical procedures such as suturing and stapling. These systems are based on either synthetic polymers, e.g. cyanoacrylates, or on proteins, such as collagen and fibrin. The main limitation of the synthetic adhesives is associated with their cytotoxicity, while allergic reactions and poor mechanical properties are major concerns when applying/developing protein sealants.

Herein, we propose an alternative class of biomolecules {\textendash} glycosaminoglycans (GAGs) - as a main constituent of adhesives and sealants for biomedical applications. We expected that the high affinity of GAGs to different extracellular matrix (ECM) proteins will result in high adhesive strength when biosubstrates, e.g. biological tissues, are used.

We tested three GAGs {\textendash} heparin (HEP), chondroitin sulfate (CS), and hyaluronic acid (HA) that differ by their charge (largely dependent on sulfation degree) and specificity towards different ECM proteins. Because GAGs are water soluble, we applied them as polyelectrolyte complexes with poly-L-lysine (PLL). The weight ratio of PLL/GAG that is optimal for the formation of stable complexes was determined for each system by zeta-potential measurements and titration assays; the PLL/HEP, PLL/CS, and PLL/HA complexes were prepared using 1.47:1, 1.10:1, and 1.13:1 weight ratios, respectively. The complexes were isolated (centrifugation at 14000g for 30 min at 37 {\textordmasculine}C) and applied on the surface of two polystyrene substrates (12.7{\texttimes}6.35 mm2). After drying, the lap shear strength in air for PLL/HEP, PLL/CS and PLL/HA was 897.4{\textpm}283.19 kPa, 840.5{\textpm}40.30 kPa, and 579.3{\textpm}67.86 kPa, respectively. The higher lap shear strength of PLL/HEP and PLL/CS was attributed to the higher charge density of these GAGs: they are strong polyelectrolytes and form more rigid polyelectrolyte complexes (PECs) than HA, which is a weak polyelectrolyte that forms loose, highly hydrated PECs. Upon drying, PLL/GAG PECs retain solely their solid fraction which is lower in the case of PLL/HA glues. When tested in their hydrated state, PLL/HEP and PLL/HA PECs do not retain their adhesiveness, whereas surprisingly PLL/CS show tacky properties that keep the surfaces sticking together. In the future, we envisage that the measurement of viscoelastic properties and assays with biosimulated substrates will validate PLL/GAG PECs as sealants and adhesives for soft tissues in biological environments, such as skin, cartilage, and cardiac valves.

}, keywords = {Biomimetics, Glycosaminoglycans, Polyelectrolyte complexation}, author = {Costa, R. R. and Reis, R. L. and Pashkuleva, I.} }