Advanced Polymer-Based Drug Delivery Strategies for Meniscal Regeneration

The meniscus plays a critical role in maintaining knee joint homeostasis. Injuries to the meniscus, especially considering the limited self-healing capacity of the avascular region, continue to be a challenge and are often treated by (partial) meniscectomy, which has been identified to cause osteoarthritis. Currently, meniscus tissue engineering focuses on providing extracellular matrix (ECM)-mimicking scaffolds to direct the inherent meniscal regeneration process, and it has been found that various stimuli are essential. Numerous bioactive factors present benefits in regulating cell fate, tissue development, and healing, but lack an optimal delivery system. More recently, bioengineers have developed various polymer-based drug delivery systems (PDDSs), which are beneficial in terms of the favorable properties of polymers as well as novel delivery strategies. Engineered PDDSs aim to provide not only an ECM-mimicking microenvironment but also the controlled release of bioactive factors with release profiles tailored according to the biological concerns and properties of the factors. In this review, both different polymers and bioactive factors involved in meniscal regeneration are discussed, as well as potential candidate systems, with examples of recent progress. This article aims to summarize drug delivery strategies in meniscal regeneration, with a focus on novel delivery strategies rather than on specific delivery carriers. The current challenges and future prospects for the structural and functional regeneration of the meniscus are also discussed. Impact statement Meniscal injury remains a clinical Gordian knot owing to the limited healing potential of the region, restricted surgical approaches, and risk of inducing osteoarthritis. Existing tissue engineering scaffolds that provide mechanical support and a favorable microenvironment also lack biological cues. Advanced polymer-based delivery strategies consisting of polymers incorporating bioactive factors have emerged as a promising direction. This article primarily reviews the types and applications of biopolymers and bioactive factors in meniscal regeneration. Importantly, various carrier systems and drug delivery strategies are discussed with the hope of inspiring further advancements in this field.