An electrospun fiber reinforced scaffold promotes total meniscus regeneration in rabbit meniscectomy model

Abstract

Low vascularization in meniscus limits its regeneration ability after injury, and tissue engineering is the most promising method to achieve meniscus regeneration. In this study, we fabricated a kind of composite scaffold by decellularized meniscus extracellular matrix/polycaprolactone (DMECM/PCL) electrospinning fibers and porous DMECM, in which DMECM/PCL fibers were used as reinforcing component. The tensile modulus of the composite scaffold in longitudinal and crosswise directions were 8.5 ± 1.9 and 2.3 ± 0.3 MPa, respectively. Besides that, the DMECM/PCL electrospinning fibers enhanced suture resistance of the composite scaffold more than 5 times than DMECM scaffold effectively. In vitro cytocompatibility showed that the porous structure provided by DMECM component facilitated meniscus cells’ proliferation. DMECM was also the main component to regulate cell behaviors, which promoted meniscus cells expressing extracellular matrix related genes such as COL I, COL II, SOX9 and AGG. Rabbits with total meniscectomy were used as animal model to evaluated the composited scaffolds performance in vivo at 3 and 6 months. Results showed that rabbits with scaffold implanting could regenerate neo-menisci in both time points. The neo-menisci had similar histology structure and biochemical content with native menisci. Although neo-menisci had inferior tensile modulus than native ones, its modulus was improved with implanting time prolonging. MRI imaging showed the signal of neo-meniscus in the body is clear, and X-ray imaging of knee joints demonstrated the implantation of scaffolds could relief joint space narrowing. Moreover, rabbits with neo-menisci had better cartilage condition in femoral condyle and tibial plateau compared than meniscectomy group. Statement of SignificanceWe fabricated the meniscus scaffold by combining porous decellularized meniscus extracellular matrix (DMECM) and DMECM/PCL electrospinning fibers together, which used the porous structure of DMECM, and the good tensile property of electrospinning fibers. We believe single material cannot satisfy increasing needs of scaffold. Therefore, we combined not only materials but also fabrication methods together to develop scaffold to make good use of each part. DMECM in electrospinning fibers also made these two components possible to be integrated through crosslinking. Compared to existing meniscus scaffold, the composite scaffold had (1) soft structure and extrusion would not happen after implantation, (2) ability to be trimmed to suitable shape during surgery, and (3) good resistance to suture.