Functional antimicrobial peptide-loaded 3D scaffolds for infected bone defect treatment with AI and multidimensional printing.

Infection is the most prevalent complication of fractures, particularly in open fractures, and often leads to severe consequences. The emergence of bacterial resistance has significantly exacerbated the burden of infection in clinical practice, making infection control a significant treatment challenge for infectious bone defects. The implantation of a structural stent is necessary to treat large bone defects despite the increased risk of infection. Therefore, there is a need for the development of novel antibacterial therapies. The advancement in antibacterial biomaterials and new antimicrobial drugs offers fresh perspectives on antibacterial treatment. Although antimicrobial 3D scaffolds are currently under intense research focus, relying solely on material properties or antibiotic action remains insufficient. Antimicrobial peptides (AMPs) are one of the most promising new antibacterial therapy approaches. This review discusses the underlying mechanisms behind infectious bone defects and presents research findings on antimicrobial peptides, specifically emphasizing their mechanisms and optimization strategies. We also explore the potential prospects of utilizing antimicrobial peptides in treating infectious bone defects. Furthermore, we propose that artificial intelligence (AI) algorithms can be utilized for predicting the pharmacokinetic properties of AMPs, including absorption, distribution, metabolism, and excretion, and by combining information from genomics, proteomics, metabolomics, and clinical studies with computational models driven by machine learning algorithms, scientists can gain a comprehensive understanding of AMPs' mechanisms of action, therapeutic potential, and optimizing treatment strategies tailored to individual patients, and through interdisciplinary collaborations between computer scientists, biologists, and clinicians, the full potential of AI in accelerating the discovery and development of novel AMPs will be realized. Besides, with the continuous advancements in 3D/4D/5D/6D technology and its integration into bone scaffold materials, we anticipate remarkable progress in the field of regenerative medicine. This review summarizes relevant research on the optimal future for the treatment of infectious bone defects, provides guidance for future novel treatment strategies combining multi-dimensional printing with new antimicrobial agents, and provides a novel and effective solution to the current challenges in the field of bone regeneration.