Polymer Microneedles for Localized Drug Delivery in Musculoskeletal Tissue Regeneration.

Musculoskeletal (MSK) disorders-osteoporosis, osteoarthritis, rheumatoid arthritis, intervertebral disc degeneration, tendinopathy, and skeletal muscle injury-contribute the largest share of years lived with disability worldwide. Conventional therapy relies on systemic dosing or repeated intra-articular and peri-tissue injections, which suffer from off-target toxicity, poor lesional bioavailability, and low adherence. Polymer microneedles (MNs)-micron-scale projections of biodegradable, dissolving, hydrogel-forming, or composite polymers-have rapidly matured into a versatile platform for minimally invasive, spatially localized, and temporally programmable delivery of small molecules, biologics, nucleic acids, extracellular vesicles, and cells to MSK tissues. This review synthesizes 2018-2026 advances in polymer MN systems engineered specifically for MSK regeneration. We classify dominant polymer chemistries and MN architectures; map fit-for-purpose across bone, cartilage, joint, intervertebral disc, tendon, and skeletal muscle; and survey "smart" MN designs that exploit reactive oxygen species, pH, mechanical, triboelectric, optogenetic, and ultrasonic triggers. We close with a concise conclusion and forward perspective that identifies the key design levers-hybrid MN-scaffold combination products, stimuli-responsive platforms tuned to the MSK micro-environment, and cell- and EV-loaded formats-most likely to have clinical impact.