OBJECTIVE To enhance the in vitro integration of self-assembled articular cartilage to native articular cartilage using chondroitinase ABC. DESIGN 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. RESULTS 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. CONCLUSIONS 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.

中文翻译：

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软骨素酶ABC增强自组装关节软骨的整合，但其剂量需要根据新软骨成熟度来调节。

目的 使用软骨素酶 ABC 增强自组装关节软骨与天然关节软骨的体外整合。设计 为了检验软骨素酶 ABC (C-ABC) 整合治疗 (C-ABCint) 会增强不同成熟度新软骨整合的假设，本研究分两个阶段进行。在第一阶段，通过 2 因子全因子设计检查了对 TCL（TGF-β1、C-ABC 和赖氨酰氧化酶样 2）和 C-ABCint 两种治疗整合的影响。在第二阶段，构建成熟度（2 个水平）和 C-ABCint 浓度（3 个水平）是全因子设计中的因素，以确定有效 C-ABCint 剂量是否取决于新软骨成熟度水平。将根据上述因素形成或处理的新软骨置于天然软骨环中，培养 2 周，并且，然后，对整合进行了组织学和机械研究。在整合之前，在阶段 II 中，还分析了一组处理过的构建体以提供特性基线。结果在第一阶段，与对照相比，C-ABCint 和 TCL 处理协同增强了界面杨氏模量 6.2 倍（P = 0.004），界面拉伸强度增加了 3.8 倍（P = 0.02）。在第二阶段，因素 C-ABCint 和构建体成熟度的相互作用是显着的（P = 0.0004），表明提高界面杨氏模量的有效 C-ABCint 剂量取决于构建体成熟度。无论 C-ABCint 剂量如何，都保留了构建体的机械性能。结论 将 C-ABCint 应用于新软骨是一种具有转化潜力的有效整合策略，