Tissue Mimetic Membranes for Healing Augmentation of Tendon–Bone Interface in Rotator Cuff Repair

The globally prevalent rotator cuff tear has a high re-rupture rate, attributing to the failure to reproduce the interfacial fibrocartilaginous enthesis. Herein, a hierarchically organized membrane is developed that mimics the heterogeneous anatomy and properties of the natural enthesis and finely facilitates the reconstruction of tendon–bone interface. A biphasic membrane consisting of a microporous layer and a mineralized fibrous layer is constructed through the non-solvent induced phase separation (NIPS) strategy followed by a co-axial electrospinning procedure. Cationic kartogenin (KGN)-conjugated nanogel (nGel-KGN) and osteo-promotive struvite are incorporated within the membranes in a region-specific manner. During in vivo repair, the nGel-KGN-functionalized microporous layer is adjacent to the tendon which intends to suppress scar tissue formation at the lesion and simultaneously heightens chondrogenesis. Meanwhile, the struvite-containing fibrous layer covers the tubercula minus to enhance stem cell aggregation and bony ingrowth. Such tissue-specific features and spatiotemporal release behaviors contribute to effective guidance of specific defect-healing events at the transitional region, further leading to the remarkably promoted regenerative outcome in terms of the fibrocartilaginous tissue formation, collagen fiber alignment, and optimized functional motion of rotator cuff. These findings render a novel biomimetic membrane as a promising material for clinical rotator cuff repair.