Biomimetic Microstructured Scaffold with Release of Re‐Modified Teriparatide for Osteoporotic Tendon‐to‐Bone Regeneration via Balancing Bone Homeostasis

Abstract Osteoporotic tendon‐to‐bone interface healing is challenging, with a high surgical repair failure rate of up to 68%. Conventional tissue engineering approaches have primarily focused on promoting interface healing by stimulating regeneration in either the tendon or bone. However, these methods often fall short of achieving optimal therapeutic outcomes due to their neglect of balancing bone homeostasis and remodeling the microstructure at the osteoporotic tendon‐to‐bone interface. Herein, a series of site‐specific functional modifications are carried out on teriparatide to develop recombinant human parathyroid hormone (R‐PTH). A biomimetic microstructured reconstruction scaffold (BMRP) is constructed using a decalcified mussel shell scaffold, pre‐gel, and R‐PTH. The BMRP mimics the microstructures of the native tendon‐to‐bone interface and restores the original structure of the interface tissue by repairing injured cells, balancing bone homeostasis, and remodeling the microstructure of the osteoporotic tendon‐to‐bone interface. In an osteoporotic rotator cuff tear model, BMRP is in situ implanted at the injured site, resulting in structural reconstruction and functional recovery. The BMRP demonstrates excellent repair effects, representing a novel therapeutical alternative for treating osteoporotic tendon‐to‐bone injury potential for clinical application.