Abstract
OBJECTIVES: Healing of meniscus tears is often limited by tear morphology as well tissue vascularity. We analyzed the regenerative capacity of meniscus defects in an ex-vivo model when repaired with a collagen scaffold seeded with human embryonic-derived mesenchymal stem cells (ES-MSC) and conjugated with different growth factors. METHODS: Synthetic Collagen scaffolds were created with a pneumatospinning technique and conjugated with different growth factors (TGFb1, TGFb3, PDGFbb). Scaffolds were then seeded with human ES-MSC and cultured in serum free differentiation medium. After 3 weeks, the scaffolds were placed into 3.5mm surgical defects made into ex vivo human osteoarthritic menisci explants and cultured for another 5 weeks. Implanted scaffolds were tested for 1) biomechanical integration with host meniscal tissue via push-out mechanical testing, 2) histological assessment, and 3) gene expression from ES-MSC seeded scaffolds. RESULTS: The ES-MSC seeded scaffolds were viable, able to colonize throughout the scaffold, and integrated with the host human meniscus tissues with robust neo-tissue formation. Growth factor conjugation enhanced tissue formation with greater safranin O staining and depositions of both collagen type I and II compared to controls (Fig 1). TGFb1 and TGFb3 led to a more avascular/chondrogenic profile with greatercollagen type II production. PDGF promoted a greater collagen type I deposition compared to the other treatments. Growth factors increased COL1A1, COMP, and ACAN expression reflecting the histology findings. Scaffolds without cells or growth factors resulted in significantly lower integration strength. CONCLUSIONS: Pneumatospun collagen scaffolds facilitated cell seeding, proliferation, migration, and differentiation of ES-MSC to an meniscogenic phenotype. This technique allowed for healing of meniscus defects with improved biomechanical strength, evidence of histologic tissue integration, and gene expression confirming cell viability. These findings support the potential for translation for repair of meniscal defects in situations where cell viability and vascularity may be limited.