Next-generation strategies for anterior cruciate ligament repair: constructing biointelligent ligament grafts integrating biomimetic design, immune modulation, and sensory feedback

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Abstract
Anterior cruciate ligament (ACL) reconstruction conventionally prioritizes immediate mechanical stability; however, it does not fully prevent long-term post-traumatic osteoarthritis, residual neuromuscular deficits, or incomplete biological integration. This limitation reflects the gap between structural graft substitution and true functional regeneration, including insufficient ligament-bone interface healing, delayed graft vascularization and remodeling, loss of proprioceptive afferents, and the demanding intra-articular environment characterized by synovial fluid washout and high cyclic mechanical loading. To bridge this gap between conceptual biomaterials and clinical orthopedic practice, this review critically deconstructs the physiological bottlenecks of current ACL repair and reconstruction and outlines a translational roadmap for next-generation biointelligent ligament grafts. We evaluate emerging strategies including: (1) cross-scale hierarchical biomaterials designed to mitigate graft-tunnel micromotion, interfacial shear, and tunnel widening; (2) spatially retained and cell-responsive biological release systems that reduce the risk of uncontrolled intra-articular diffusion and ectopic ossification; (3) orthobiologic adjuncts, including platelet-rich plasma and platelet-rich fibrin, as clinically accessible but still insufficiently standardized tools for biological augmentation; (4) piezoelectric and mechanically shielded niches aimed at supporting proprioceptive neuralization; and (5) fluid-stable implantable sensors coupled with data-driven rehabilitation and digital twin concepts. By integrating biomimetic design, immune modulation, sensory restoration, and technology-readiness considerations, this review provides a clinically oriented framework for shifting ACL therapy from passive mechanical replacement toward active neuro-mechanical regeneration.

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