Meniscus injury and meniscectomy are strongly correlated with osteoarthritis. There is an unmet need for functional meniscus replacements. The purpose of this study is to create a meniscus construct with micro-scale circumferential and radial fibres, inspired by native tissue architecture and using clinical grade materials. Secondly, we aim to seed the construct with a clinically relevant cell number and cell type for potential translation in one-stage treatment. In order to assess bio-compatibility, we compare the in vitro meniscus extracellular matrix formation in the construct.
Materials And Methods
Scaffolds were made from medical-grade polycaprolactone (Corbion) using melt-electrowriting (MEW) technology. Two different architectures were deposited with a programmed inter fibre spacing of 225 µm or 160 µm. The ratio of circumferential : radial fibres was 14:2 or 12:4. Printability was assessed using scanning electron microscopy (SEM). The scaffolds were seeded with co-cultures of primary human osteoarthritic meniscus cells and bone marrow mesenchymal stromal cells (MSCs) in fibrin glue (3 donor combinations; 5 technical replicates). The constructs were compared to a CMI® that was reduced to the same form and size and 2 Fused Deposition Modelling constructs. Elastic properties were assessed under uniaxial confined compression. After 4 weeks of culture, proteoglycan and DNA content were quantified. Cell distribution throughout the scaffold was assessed at 3 locations and 2 orientations using Hematoxylin and Eosin (H&E) staining. Micro Computed Tomography (uCT) was used to assess contruct dimensions.
After 28 days of co-culture, a basal level of proteoglycan production was demonstrated in MEW scaffolds, the CMI®, and fibrin gel control, yet within the FDM scaffolds less proteoglycan production was observed. The MEW scaffolds showed a higher Young’s modulus compared to the CMI® scaffolds and a higher yield point compared to FDM scaffolds. During 28 days of culture the cell-seeded scaffolds increased in yield stress and ultimate strength. Histology indicated distribution of cells across the construct.
This study shows feasibility of creating a wedge-shaped meniscus scaffold with MEW using medical-grade materials, and seeding the scaffold with a clinically-feasible cell number and -type for potential translation as a one-stage treatment