Mechanically active polymeric adhesives (MAPAs) for tissue regeneration

Tissue adhesives have long been proposed as alternatives to sutures and staples, yet most existing formulations are mechanically passive, providing only static fixation. Recent advances, however, have introduced a new class of mechanically active polymeric adhesives (MAPAs) that can generate forces or dynamically modulate mechanical properties to engage cellular mechanotransduction. By integrating adhesive chemistry with biomechanics, MAPAs actively regulate inflammation, proliferation, and remodeling, thereby accelerating tissue regeneration in diverse applications—from skin closure to myocardial repair and musculoskeletal healing. This review defines the concept of MAPAs and situates them within the broader evolution of regenerative biomaterials. We highlight the biological foundations of mechanically guided regeneration and summarize design principles for adhesive matrices and interfaces. Particular attention is given to stimulation modalities—thermal, optical, electrical, magnetic, and chemical—that enable spatiotemporal control of mechanical cues, and to emerging AI-driven approaches that accelerate materials discovery and optimize mechanics–adhesion synergy. Applications in wound care, cardiac rehabilitation, and musculoskeletal repair illustrate the translational potential of MAPAs. Finally, we discuss key challenges, including the mechanistic understanding of mechanobiological coupling, clinical feasibility, reliability and safety in complex physiological environments, regulatory translation, and issues related to large-scale manufacturing and storage, while also highlighting opportunities for performance optimization and functional expansion. MAPAs thus represent a paradigm shift from passive sealants to active, mechano-therapeutic platforms poised to reshape regenerative medicine.