Chondroitinase ABC Treatment Improves the Organization and Mechanics of 3D Bioprinted Meniscal Tissue

The meniscus is a fibrocartilage tissue that is integralto thecorrect functioning of the knee joint. The tissue possesses a uniquecollagen fiber architecture that is integral to its biomechanicalfunctionality. In particular, a network of circumferentially alignedcollagen fibers function to bear the high tensile forces generatedin the tissue during normal daily activities. The limited regenerativecapacity of the meniscus has motivated increased interest in meniscustissue engineering; however, the in vitro generationof structurally organized meniscal grafts with a collagen architecturemimetic of the native meniscus remains a significant challenge. Herewe used melt electrowriting (MEW) to produce scaffolds with definedpore architectures to impose physical boundaries upon cell growthand extracellular matrix production. This enabled the bioprintingof anisotropic tissues with collagen fibers preferentially orientedparallel to the long axis of the scaffold pores. Furthermore, temporallyremoving glycosaminoglycans (sGAGs) during the early stages of in vitro tissue development using chondroitinase ABC (cABC)was found to positively impact collagen network maturation. Speciallywe found that temporal depletion of sGAGs is associated with an increasein collagen fiber diameter without any detrimental effect on the developmentof a meniscal tissue phenotype or subsequent extracellular matrixproduction. Moreover, temporal cABC treatment supported the developmentof engineered tissues with superior tensile mechanical propertiescompared to empty MEW scaffolds. These findings demonstrate the benefitof temporal enzymatic treatments when engineering structurally anisotropictissues using emerging biofabrication technologies such as MEW andinkjet bioprinting.

Automated summary

The meniscus is a crucial tissue in the knee joint, but its limited regenerative capacity has driven the development of tissue engineering approaches. In this study, melt electrowriting was used to create structured scaffolds, and enzymatic treatment was employed to enhance collagen network maturity. This resulted in the development of engineered meniscus tissues with improved mechanical properties.