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Review
. 2025 Jan;14(2):e2402737.
doi: 10.1002/adhm.202402737. Epub 2024 Nov 6.

Therapeutic Controlled Release Strategies for Human Osteoarthritis

Dan Wang  1 , Wei Liu  1 , Jagadeesh K Venkatesan  1 , Henning Madry  1 , Magali Cucchiarini  1
Affiliations
Review

Therapeutic Controlled Release Strategies for Human Osteoarthritis

Dan Wang et al. Adv Healthc Mater. 2025 Jan.

Abstract

Osteoarthritis is a progressive, irreversible debilitating whole joint disease that affects millions of people worldwide. Despite the availability of various options (non-pharmacological and pharmacological treatments and therapy, orthobiologics, and surgical interventions), none of them can definitively cure osteoarthritis in patients. Strategies based on the controlled release of therapeutic compounds via biocompatible materials may provide powerful tools to enhance the spatiotemporal delivery, expression, and activities of the candidate agents as a means to durably manage the pathological progression of osteoarthritis in the affected joints upon convenient intra-articular (injectable) delivery while reducing their clearance, dissemination, or side effects. The goal of this review is to describe the current knowledge and advancements of controlled release to treat osteoarthritis, from basic principles to applications in vivo using therapeutic recombinant molecules and drugs and more innovatively gene sequences, providing a degree of confidence to manage the disease in patients in a close future.

Keywords: biomaterials; controlled release; drugs; gene sequences; in vivo; osteoarthritis; recombinant molecules.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Representation of normal and osteoarthritic knee joints and tissues. The anatomical representation of the knee joint (top panels) and the schematic composition of the osteochondral unit (bottom panels) are illustrated for normal (left panels) and osteoarthritic (right panels) knee joints, tissues, and zones (created with BioRender).
Figure 2
Figure 2
Principles of therapeutic controlled release. Therapeutic controlled release involves 1) a biocompatible material and one (or more) therapeutic agent(s) (elements), with 2) specific interactions (methods) and release in response to 3) various parameters (stimuli) upon 4) specific steps of material degradation (degradation mechanisms), leading to release profiles in three phases (phase I: rapid agent release; phase II: slow, controlled release of the agent; phase III: fast agent release with material degradation) (created with BioRender).
Figure 3
Figure 3
Controlled release systems for osteoarthritis. Recombinant molecules (top left) and gene sequences (top right) have been applied to relevant models of OA in vivo using various controlled release systems (middle) supporting over time cargo release as convenient injectable therapies for human OA (bottom). Abbreviations: NSAIDs, non‐steroidal anti‐inflammatory drugs; SADOAs, slow‐acting drugs in OA; OA, osteoarthritis; DNA: deoxyribonucleic acid; ASO: antisense oligonucleotide; rAAV, recombinant adeno‐associated virus; siRNA, small interfering RNA; RNA, ribonucleic acid; mRNA, messenger RNA; miRNA, microRNA; MPs, microparticles; NPs, nanoparticles; NDs, nanodiamonds (created with BioRender).
See this image and copyright information in PMC

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