Catechol-modified Poly(oxazoline)s with Tunable Degradability Facilitate Cell Invasion and Lateral Cartilage Integration

Abstract Tissue adhesives play an important role in clinical applications and may aid in the treatment of cartilage defects for improved cartilage integration. However, many fail to satisfy the demand for adequate adhesive strength on wet tissue surfaces and to facilitate sufficient cell migration and extracellular matrix (ECM) deposition at the defect site. Utilizing poly(2-alkyl-2-oxazoline) (POx)-based polymers equipped with mussel-inspired adhesion moieties and combining them with the natural wound sealant fibrinogen, we fabricated an adhesive biosynthethic hydrogel with tunable mechanical properties and improved bonding strength. Degradation of the hydrogels could be adjusted by the ratio of amide to ester linkages of the catecholic functional group at the POx side chain. In an in vitro disc/ring model for lateral cartilage integration, a benefit in long-term integration was observed with enhanced degradation of the adhesive without the expense of bonding strength. Incorporation of degradable ester linkages in the polymer facilitated cell invasion and strong deposition of cartilaginous ECM at the defect site. Overall, the results suggest that the presented injectable adhesive hydrogel, due to its easy tunability, holds great potential for cartilage defect treatment and other medical applications.