ROS‐Responsive Microneedles Loaded With Biomimetic Nanozymes for Rotator Cuff Repair and Adipose Infiltration Prevention

ABSTRACT The difficulty in tendon‐bone interface repair and surrounding muscle adipose infiltration after rotator cuff injuries present significant clinical challenges, necessitating the development of biomaterials capable of repairing the interface and preventing adipose deposition. In this study, we developed a reactive oxygen species (ROS)‐responsive microneedle patch (Cu/MnTA‐HP) designed to facilitate rotator cuff injuries repair and reduce adipose tissue deposition. Utilizing the natural metal prosthetic groups Cu 2+ and Mn 2+ of superoxide dismutase (SOD) enzyme, we coordinated with tannic acid (TA) to form metal polyphenol nanoparticles (Cu/MnTA), which mimic the structure and function of natural SOD enzymes. Subsequently, dynamic covalent boronate ester bonds between Cu/MnTA and phenylboronic acid‐modified hyaluronic acid (HP) ensured the microneedles' intelligent response to ROS. The constructed mimetic SOD nanozymes‐Cu/MnTA, on the one hand, release TA to eliminate endogenous reactive oxygen, and on the other hand, participate in a series of natural enzymatic reactions (Superoxide dismutase‐like, Peroxidase‐like), thereby rescuing mitochondrial function (enhancing mitochondrial membrane potential levels and reducing mitochondrial ROS production) in tendon‐derived stem cells, promoting tenogenic differentiation, and inhibiting adipose accumulation. This approach promotes the repair of the tendon‐bone interface in rotator cuff injuries and reduces fatty infiltration in surrounding muscles.