Recent advances in musculoskeletal local drug delivery, Publication date: 15 July 2019 Source: Acta Biomaterialia, Volume 93 Author(s): Shichao Zhang, Malcolm Xing, Bingyun Li Abstract Musculoskeletal disorders are a significant burden on the global economy and public health. Advanced drug delivery plays a key role in the musculoskeletal field and holds the promise of enhancing the repair of degenerated and injured musculoskeletal tissues. Ideally, drug delivery should have the ability to directly deliver therapeutic agents to the diseased/injured sites with a desirable drug level over a period of time. Here, we present a mini-review of the current state-of-the-art research associated with local drug delivery and its use for the treatment of musculoskeletal disorders. First, an overview of drug delivery strategies, with a focus on issues related to musculoskeletal pathology, potential therapeutic strategies, conventional and non-conventional drugs, and various delivery systems, is introduced. Then, we highlight recent advances in the emerging fields of musculoskeletal local drug delivery, involving therapeutic drugs (e.g., genes, small molecule therapeutics, and stem cells), novel delivery vehicles (e.g., 3D printing and tissue engineering techniques), and innovative delivery approaches (e.g., multi-drug delivery and smart stimuli-responsive delivery). The review concludes with future perspectives and associated challenges for developing local drug delivery for musculoskeletal applications. Statement of Significance Three important aspects are highlighted in this manuscript: 1) The advanced musculoskeletal drug delivery is introduced from the aspects ranging from musculoskeletal disorders, potential therapeutic solutions, and various drug delivery systems. 2) The recent advances in the emerging fields of musculoskeletal local drug delivery, involving therapeutic drugs (e.g., genes, small molecule therapeutics, and stem cells), novel delivery vehicles (e.g., 3D printing and tissue engineering technique), and innovative delivery approaches (e.g., multi-drug delivery and smart stimuli-responsive delivery), are highlighted. 3) The challenges and perspectives of future research directions in the development of musculoskeletal local drug delivery are presented. Graphical abstract