Chondroitinase ABC Enhances Integration of Self-Assembled Articular Cartilage, but Its Dosage Needs to Be Moderated Based on Neocartilage Maturity.

Abstract

To enhance the in vitro integration of self-assembled articular cartilage to native articular cartilage using chondroitinase ABC. To examine the hypothesis that chondroitinase ABC (C-ABC) integration treatment (C-ABCint) would enhance integration of neocartilage of different maturity levels, this study was conducted in 2 phases. In phase I, the impact on integration of 2 treatments, TCL (TGF-β1, C-ABC, and lysyl oxidase like 2) and C-ABCint, was examined via a 2-factor, full factorial design. In phase II, construct maturity (2 levels) and C-ABCint concentration (3 levels) were the factors in a full factorial design to determine whether the effective C-ABCint dose was dependent on neocartilage maturity level. Neocartilages formed or treated per the factors above were placed into native cartilage rings, cultured for 2 weeks, and, then, integration was studied histologically and mechanically. Prior to integration, in phase II, a set of treated constructs were also assayed to provide a baseline of properties. In phase I, C-ABCint and TCL treatments synergistically enhanced interface Young's modulus by 6.2-fold (P = 0.004) and increased interface tensile strength by 3.8-fold (P = 0.02) compared with control. In phase II, the interaction of the factors C-ABCint and construct maturity was significant (P = 0.0004), indicating that the effective C-ABCint dose to improve interface Young's modulus is dependent on construct maturity. Construct mechanical properties were preserved regardless of C-ABCint dose. Applying C-ABCint to neocartilage is an effective integration strategy with translational potential, provided its dose is calibrated appropriately based on implant maturity, that also preserves implant biomechanical properties.