Combined use of chondroitinase-ABC, TGF-β1, and collagen crosslinking agent lysyl oxidase to engineer functional neotissues for fibrocartilage repair

Abstract

Patients suffering from damaged or diseased fibrocartilages currently have no effective long-term treatment options. Despite their potential, engineered tissues suffer from inferior biomechanical integrity and an inability to integrate in vivo. The present study identifies a treatment regimen (including the biophysical agent chondroitinase-ABC, the biochemical agent TGF-β1, and the collagen crosslinking agent lysyl oxidase) to prime highly cellularized, scaffold-free neofibrocartilage implants, effecting continued improvement in vivo. We show these agents drive in vitro neofibrocartilage matrix maturation toward synergistically enhanced Young’s modulus and ultimate tensile strength values, which were increased 245% and 186%, respectively, over controls. Furthermore, an in vitro fibrocartilage defect model found this treatment regimen to significantly increase the integration tensile properties between treated neofibrocartilage and native tissue. Through translating this technology to an in vivo fibrocartilage defect model, our results indicate, for the first time, that a pre-treatment can prime neofibrocartilage for significantly enhanced integration potential in vivo, with interfacial tensile stiffness and strength increasing by 730% and 745%, respectively, compared to integration values achieved in vitro. Our results suggest that specifically targeting collagen assembly and organization is a powerful means to augment overall neotissue mechanics and integration potential toward improved clinical feasibility.

The Yucatan Minipig Temporomandibular Joint Disc Structure–Function Relationships Support Its Suitability for Human Comparative Studies

“…The GAG content of minipig discs was low (1%/DW) in comparison to articular cartilage (30%/DW) 32 or knee meniscus (17%/DW) 33 ; similarly, low GAG content was found in human and FP discs. 13 The collagen/GAG ratio for the minipig disc was 28.9, which is more similar to humans (43.0) than FPs (67.3) (Fig.…”

Harnessing Biomechanics to Develop Cartilage Regeneration Strategies

“…Additionally, the subcutaneous implantation of native-to-engineered cartilage assemblies pretreated with a two LOX applications and one C-ABC and TGF-b1 treatment increased interfacial Tensile modulus and ultimate tensile strength by 4.3-fold and 4.7-fold, respectively (Fig. 17) [82]. This study showed that LOX treatment primes the integration of highly cellularized and metabolically active neofibrocartilage, a promising approach to the significant obstacle of cartilage integration.…”

“…These enhancements persisted at 12 weeks of culture. Collagen fibril diameter was also synergistically increased by 104% at 12 weeks [82].…”

Tissue Engineering and Regenerative Medicine Technologies in the Treatment of Articular Cartilage Defects

“…В этом случае развитие новой ткани происходит лишь под действием гипоксии, факторов роста, связывающе-го агента лизилоксидазы и биомеханической сти-муляции, как правило, гидростатического давления [53][54][55][56][57].…”