ABSTRACT
Surgical reattachment of tendon to bone is a clinical challenge, with unacceptably high retear rates in the early period after repair. A primary reason for these repeated tears is that the multiscale toughening mechanisms found at the healthy tendon enthesis are not regenerated during tendon-to-bone healing. The need for technologies to improve these outcomes is pressing, and the tissue engineering community has responded with many advances that hold promise for eventually regenerating the multiscale tissue interface that transfers loads between the two dissimilar materials, tendon, and bone. This review provides an assessment of the state of these approaches, with the aim of identifying a critical agenda for future progress.
ABSTRACT
A reliable method for fabricating biomimetic scaffolds with a controllable mineral gradient to facilitate the surgical repair of tendon-to-bone injuries and the regeneration of the enthesis is reported. The gradient in mineral content is created by sequentially spin-coating with hydroxyapatite/poly(ε-caprolactone) suspensions containing hydroxyapatite nanoparticles in decreasing concentrations. To produce pores and facilitate cell infiltration, the spin-coated film is released and patterned with an array of funnel-shaped microchannels by laser machining. The unique design provided both mechanical (i.e., substrate stiffness) and biochemical (e.g., hydroxyapatite content) cues to spatially control the graded differentiation of mesenchymal stem cells. Immunocytochemical analysis of human mesenchymal stem cell-seeded scaffolds after 14 days of culture demonstrated the formation of a spatial phenotypic cell gradient from osteoblasts to mineralized chondrocytes based on the level of mineralization in the scaffold. By successfully recreating compositional and cellular features of the native tendon enthesis, the biomimetic scaffolds offer a promising avenue for improved tendon-to-bone repair.