UC San Diego

Meniscus injury and degeneration have been linked to the development of secondary osteoarthritis. Therapies that successfully repair or replace the meniscus are therefore likely to prevent or delay OA progression. We investigated the novel approach of building layers of aligned polylactic acid (PLA) electrospun scaffolds with human meniscus cells embedded in extracellular matrix (ECM) hydrogel to lead to formation of neotissues that resemble meniscus-like tissue. PLA ES scaffolds with randomly oriented or aligned fibers were seeded with human meniscus cells derived from vascular or avascular regions. Morphology and mechanical properties of PLA scaffolds (with and without cells) were influenced by fiber direction of the scaffolds. Also, the self-healing capacity of an injured meniscus is limited to the vascularized regions and is especially challenging in the inner avascular regions. Thus, we investigated the use of human meniscus cell-seeded electrospun collagen type I scaffolds to produce meniscus tissue and explored whether these cell seeded scaffolds can be implanted in repair defects created in meniscus avascular tissue explants. To determine potential for repair of meniscal defects, meniscus cells were seeded and cultured on aligned electrospun collagen scaffolds for 4 weeks before implantation. Surgical defects resembling "longitudinal tears" were created in the avascular zone of live bovine meniscus explants and implanted with cell-seeded collagen scaffolds and cultured for 3 weeks. Ex-vivo implantation with cell-seeded collagen scaffolds resulted in neo-tissue that was significantly better integrated with the native tissue. Meniscus cell-seeded electrospun collagen scaffolds may therefore be useful in facilitating meniscal repair in the repair of avascular meniscus tears. Hydrogels and electrospun scaffolds materials support cell attachment and neo tissue development and can be tuned to structurally and mechanically resemble native ECM by altering either electrospun fiber or hydrogel properties. We examined meniscus tissue generation from different cell sources including several human meniscus, bone-marrow mesenchymal stem, synovial, and infrapatellar fat pad cells. All cells were seeded onto electrospun collagen scaffolds while encapsulated in an ECM hydrogel or directly seeded on the scaffolds. Collagen scaffolds supported meniscus tissue formation and cell seeded scaffolds generated higher stiffness relative to acellular scaffolds. Overall, electrospun materials support neotissue formation and show potential for use in cell- based meniscus regeneration strategies