Reliable Fabrication of Mineral‐Graded Scaffolds by Spin‐Coating and Laser Machining for Use in Tendon‐to‐Bone Insertion Repair

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.