Smart Healing for Wound Repair: Emerging Multifunctional Strategies in Personalized Regenerative Medicine and Their Relevance to Orthopedics.

To address the challenges in wound healing, clinical management increasingly demands targeted, adaptive, responsive, and patient-centered strategies. This is especially true for wounds characterized by delayed healing and a high risk of infection. Advances in regenerative medicine and biomaterial technologies are fostering the development of multifunctional approaches that integrate tissue regeneration, antibacterial/antibiofilm activity, immunomodulation, and real-time monitoring. This paper surveys emerging platforms, including both natural and synthetic scaffolds, hydrogels enriched with platelet-derived growth factors, glycosaminoglycan mimetics, bioactive peptides (such as GHK-Cu and antimicrobial peptides), nanoscaffolds, and stimuli-responsive systems. The paper also explores cutting-edge technologies such as water-powered, electronics-free dressings that deliver localized electrical stimulation; biodegradable bioelectric sutures that produce self-sustained mechano-electrical signals; and sensory bandages that monitor pH, moisture, temperature, and bacterial contamination in real-time while enabling on-demand drug release with pro-regenerative, antibacterial, and other therapeutic functionalities. Further therapeutic approaches include natural matrices, exosomes, gene editing, 3D bioprinting, and AI-assisted design. Particular attention is paid to orthopedic applications and orthopedic implant infection. A brief section addresses the still unresolved challenge of articular cartilage regeneration. Interdisciplinary innovation, integrating insights from molecular biology through engineering, plays a central role in translating novel strategies into tailored, clinically effective wound management solutions.