Composite Tissue Adhesive Containing Catechol-Modified Hyaluronic Acid and Poly-l-lysine

Commercial tissue adhesives such as fibrin, albumin-glutaraldehyde, and cyanoacrylates often suffer from the limitations of adverse inflammatory reactions, lack of bioactivity, and/or weak wet adhesion. There is a need to develop advanced tissue adhesives which possess adequate wet adhesion and appropriate biodegradability and biocompatibility. The wet adhesion of the catechol group to a variety of substrates is well-known. Further, it undergoes Michael addition with an amine or thiol group, which makes catechol-containing polymers appealing as tissue adhesives because there are abundant amine and thiol groups in native tissue. We present here a composite tissue adhesive based on a catechol-modified polymer that utilizes poly-l-lysine (PLL) as a bridging molecule to promote the interfacing with cells and tissues. Hyaluronic acid (HA) was chosen here as the polymer backbone for functionalization with catechol moieties, which is attributable to its multiple biological activities. The cross-linking conditions of catechol-functionalized HA (HACA) were optimized, and the swelling and degradation behavior of the cross-linked hydrogels were characterized. The PLL/HACA-based adhesive demonstrated good adhesion to hydrogels derived from collagen and gelatin that act as a simplified soft tissue model, and to porcine skin tissue. Moreover, the adhesive supported culture of a human umbilical vein endothelial cell line (HUV-EC-C) with high cell viability and formation of capillary-like structure. This may bring added benefit by means of promoting angiogenesis, therefore promoting the integration between host tissue and implant. Our results indicate that PLL/HACA could be a promising tissue adhesive for multiple internal uses.