Bone defects combined with tumors, infections, or other bone diseases are challenging in clinical practice. Autologous and allogeneic grafts are two main traditional remedies, but they can cause a series of complications. To address this problem, researchers have constructed various implantable biomaterials. However, the original pathological microenvironment of bone defects, such as residual tumors, severe infection, or other bone diseases, could further affect bone regeneration. Thus, the rational design of versatile biomaterials with integrated bone therapy and regeneration functions is in great demand. Many strategies have been applied to fabricate smart stimuli-responsive materials for bone therapy and regeneration, with stimuli related to external physical triggers or endogenous disease microenvironments or involving multiple integrated strategies. Typical external physical triggers include light irradiation, electric and magnetic fields, ultrasound, and mechanical stimuli. These stimuli can transform the internal atomic packing arrangements of materials and affect cell fate, thus enhancing bone tissue therapy and regeneration. In addition to the external stimuli-responsive strategy, some specific pathological microenvironments, such as excess reactive oxygen species and mild acidity in tumors, specific pH reduction and enzymes secreted by bacteria in severe infection, and electronegative potential in bone defect sites, could be used as biochemical triggers to activate bone disease therapy and bone regeneration. Herein, we summarize and discuss the rational construction of versatile biomaterials with bone therapeutic and regenerative functions. The specific mechanisms, clinical applications, and existing limitations of the newly designed biomaterials are also clarified.

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Background: The maxilla position is essential for the aesthetic and functional outcomes of orthognathic surgery. Previous studies demonstrated the advantages of patient-specific implants in orthognathic surgery. However, more data are needed to confirm the superiority of patient-specific implants over surgical splints created with computer-aided design/computer-aided manufacturing (CAD/CAM). This randomized controlled trial aimed to compare the accuracy of patient-specific implants and CAD/CAM splints for maxilla repositioning in orthognathic surgery. Methods: Patients ( n = 64) who required orthognathic surgery were randomly assigned to use either patient-specific implants (patient-specific implant group) or CAD/CAM surgical splints (splint group) to reposition the maxilla. The outcome evaluation was completed by comparing virtual plans with actual results. The primary outcome was the discrepancies of the centroid position of the maxilla. Other translation and orientation discrepancies of the maxilla were also assessed. Results: The authors analyzed 27 patients in the patient-specific implant group and 31 in the splint group. The maxilla position discrepancy was 1.41 ± 0.58 mm in the patient-specific implant group and 2.20 ± 0.94 mm in the splint group; the between-group difference was significant ( p < 0.001). For the patient-specific implant group, the largest translation discrepancy was 1.02 ± 0.66 mm in the anteroposterior direction, and the largest orientation discrepancy was 1.85 ± 1.42 degrees in pitch. For the splint group, the largest translation discrepancy was 1.23 ± 0.93 mm in the mediolateral direction, and the largest orientation discrepancy was 1.72 ± 1.56 degrees in pitch. Conclusion: The result showed that using patient-specific implants in orthognathic surgery resulted in a more accurate maxilla position than CAD/CAM surgical splints. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.