Nature-Inspired Bioelectric Stimuli-Based Electroactive Polymeric Therapeutics Technology for Osteoarthritis Treatment─A Review.

The self-healing capacity of severely damaged articular cartilage is inherently limited due to weak cellular signaling, low cell turnover, poor extracellular matrix synthesis, and a lack of vascularization. Such damage to cartilage can lead to severe pain and the progression of osteoarthritis, significantly impacting patients' physical and mental well-being. Current surgical and nonsurgical interventions for repairing and regenerating cartilage tissue have shown inadequate long-term efficacy. Recently, the intrinsic electrical properties of bone tissue inspired researchers to focus on designing and fabricating regenerative biomaterials with bioelectrical properties such as piezoelectric, pyroelectric, ferroelectric, and dielectric for more effective treatment of bone defects. Among these electrical cues, piezoelectricity, in particular, plays a critical role in fracture healing and joint mechanics. The loss of cartilage alters biomechanics and may disrupt essential mechanotransduction pathways. However, the potential of these piezoelectrically active biomaterials with a combination of electroactive polymeric and biomimetic inorganic materials for regenerating cartilage and alleviating osteoarthritis has not been thoroughly explored. Therefore, developing natural, innovative, and biofunctional biomaterials with electrical properties is imperative to treating osteoarthritis effectively. The advancement of biomaterials with electroactive and other features offers the potential to transmit direct electrical signals to cells and stimulate faster tissue regeneration. In this review, we aim to understand and explore the electroactive properties of polymeric-based biomaterials by analyzing their potential applications and challenges in treating osteoarthritis. Specifically, we discussed how electroactive polymers can serve as bioinks for 3D bioprinting, hydrogels, coatings, and scaffolds in combination with bioactive inorganic materials to repair and regenerate articular cartilage. This comprehensive review will aid researchers in gaining a deeper understanding of electroactive polymers and provide insightful information for the development and advancement of electroactive biomaterials like piezo-activated next-generation biomaterials for the treatment of osteoarthritis in an effective manner.