Osteoarthritis (OA) is a progressive chronic inflammation that leads to cartilage degeneration. OA Patients are commonly given pharmacological treatment, but the available treatments are not sufficiently effective. The development of sustained-release drug delivery systems (DDSs) for OA may be an attractive strategy to prevent rapid drug clearance and improve the half-life of a drug at the joint cavity. Such delivery systems will improve the therapeutic effects of anti-inflammatory effects in the joint cavity. Whereas, for disease-modifying OA drugs (DMOADs) which target chondrocytes or act on mesenchymal stem cells (MSCs), the cartilage-permeable DDSs are required to maximize their efficacy. This review provides an overview of joint structure in healthy and pathological conditions, introduces the advances of the sustained-release DDSs and the permeable DDSs, and discusses the rational design of the permeable DDSs for OA treatment. We hope that the ideas generated in this review will promote the development of effective OA drugs in the future.

Rationale: Photothermal therapy employs the photoabsorbers to generate heat under the near-infrared (NIR) irradiation for thermal tumor ablation. However, NIR irradiation might damage the adjacent tissue due to the leakage of the photoabsorbers and the residual materials after treatment might hinder the local healing process. A bifunctional hydrogel that holds both photothermal property and potent pro-healing ability provides a viable option to resolve this issue.