Self-adaptive Dual-Inducible Nanofibers Scaffolds for Tendon-To-Bone Interface Synchronous Regeneration

It has been established that one major cause of retear following rotator cuff repair is the failure of regeneration of the native tendon-to-bone interface. Therefore, identification of noval strategies to promote synchronous regeneration of different tissues at the inhomogeneous tendon-to-bone interface is a critical challenge for tendon-bone healing after rotator cuff repair. Both chondrogenic and osteogenic induction microenvironment coexist in the tendon-to-bone interface, however, it is inadequate to support the fibrocartilage and bone regeneration during tendon-bone healing. Thus, inspired by intrinsic induction microenvironments present at the tendon-to-bone interface, self-adaptive dual-inducible nanofibers scaffolds (SDNS) were designed to significantly improve chondrogenic and osteogenic ability in response to local induction microenvironments. Strontium-doped mesoporous bioglass nanoparticles (Sr-MBG) were first synthesized by modulated sol-gel method, and then loaded into nanofibers of SDNS. SDNS were capable of releasing strontium ions continuously and thereby improving osteogenic and chondrogenic differentiation of the mesenchymal stem cells in response to specific induction microenvironments. SDNS stimulated synchronous regeneration of the fibrocartilage and bone layers at the tendon-to-bone interface after implantation in the torn rotator cuff, improving the biomechanical strength of the supraspinatus tendon–humerus complexes significantly. Our study provided a novel perspective for promoting inhomogeneous tissue in situ regeneration by regulating the local intrinsic microenvironments through metal ions.