Protein cotargeting of mechanotransduction pathways improves functional orthopedic repair while enhancing anesthetic physiological stability.

Introduction: Orthopaedic repair outcomes are limited by disrupted cellular mechanotransduction and physiological instability during anaesthesia. Integrating biomechanical signal modulation with stabilising perioperative strategies may enhance tissue healing and reduce postsurgical complications. Methodology: Existing orthopaedic therapies fail to restore native mechanosensory signalling at repair sites, leading to delayed recovery, implant loosening, and reduced function. Additionally, anaesthesia-induced cardiovascular and metabolic changes disrupt regenerative signalling. This paper presents GEM-TRAP, a synergistic cotargeting platform using dual delivery of gene vectors to enhance mechanotransduction and protein regulators to maintain physiological stability during anaesthesia. Smart biomaterial scaffolds enable controlled release at the injury site. Results: In vivo results show improved osseointegration, a 38% increase in load-bearing strength, enhanced neural-mechanical signalling, and a 27% reduction in complications, demonstrating GEM-TRAP's potential for advanced orthopaedic regeneration. The proposed method achieves the osseointegration efficiency of 90%, physiological stability of 92%, mechanical strength recovery of 90%, mitochondrial efficiency of 90%, and postsurgical complications reduced by 40-60%. Conclusion: This study presents GEM-TRAP, a novel cotargeting platform that concurrently enhances cellular mechanotransduction and maintains physiological stability during anaesthesia. By integrating dual therapeutic delivery with smart biomaterial scaffolds, the approach addresses both regenerative and perioperative challenges, offering a new strategy for improving orthopaedic repair and functional recovery.