Injectable nanofiber microspheres modified with metal phenolic networks for effective osteoarthritis treatment

Osteoarthritis (OA) is one of the most common chronic musculoskeletal diseases, which accounts for a large proportion of physical disabilities worldwide. Herein, we fabricated injectable gelatin/poly(L-lactide)-based nanofibrous microspheres (MS) via electrospraying technology, which were further modified with tannic acid (TA) named as TMS or metal phenolic networks (MPNs) consisting of TA and strontium ions (Sr²⁺) and named as TSMS to enhance their bioactivity for OA therapy. The TA-modified microspheres exhibited stable porous structure and anti-oxidative activity. Notably, TSMS showed a sustained release of TA as compared to TMS, which exhibited a burst release of TA. While all types of microspheres exhibited good cytocompatibility, TSMS displayed good anti-inflammatory properties with higher cell viability and cartilage-related extracellular matrix (ECM) secretion. The TSMS microspheres also showed less apoptosis of chondrocytes in the hydrogen peroxide (H₂O₂)-induced inflammatory environment. The TSMS also inhibited the degradation of cartilage along with the considerable repair outcome in the papain-induced OA rabbit model in vivo as well as suppressed the expression level of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1β). Taken together, TSMS may provide a highly desirable therapeutic option for intra-articular treatment of OA. STATEMENT OF SIGNIFICANCE: Osteoarthritis (OA) is a chronic disease, which is caused by the inflammation of joint. Current treatments for OA achieve pain relief but hardly prevent or slow down the disease progression. Microspheres are at the forefront of drug delivery and tissue engineering applications, which can also be minimal-invasively injected into the joint. Polyphenols and therapeutic ions have been shown to be beneficial for the treatment of diseases related to the joints, including OA. Herein, we prepared gelatin/poly(L-lactide)-based nanofibrous microspheres (MS) via electrospinning incorporated electrospraying technology and functionalized them with the metal phenolic networks (MPNs) consisting of TA and strontium ions (Sr²⁺), and assessed their potential for OA therapy both in vitro and in vivo.