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Great interest has emerged in the use of non-antibiotic antimicrobials to reduce the rate of multiantibiotic-resistant bacterial infection and facilitate bone regeneration. The cationic antimicrobial peptide LL-37 is the sole human cathelicidin and has shown nonspecific activity against a broad spectrum of microorganisms. In this study, we fabricated the poly(lactic-co-glycolic acid)\/\u03b2-calcium phosphate\/peptide LL-37 (PLGA\/TCP\/LL-37, PTL) scaffold with low-temperature 3D-printing technology for the treatment of infected segmental bone defects. The prepared scaffolds were divided into three groups: a high LL-37 concentration group (PTHL), low LL-37 concentration group (PTLL) and blank control group (PT). The cytocompatibility and antimicrobial activity of the engineered scaffolds were tested in vitro, and their osteogenesis properties were assessed in vivo in a rat infected bone defect model. We found the fabricated PTL scaffold had a well-designed porous structure that could support a steady and prolonged LL-37 release. Furthermore, the PTHL group showed strong antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) without any inhibition of the proliferation or alkaline phosphatase activity of rat bone marrow mesenchymal stem cells (BMSCs) in vitro. In addition, the infected femoral defects implanted with PTHL group displayed new bone formation in four weeks without any evidence of residual bacteria, which showed similar antibacterial outcomes to the vancomycin and cancellous bone mixture group. In conclusion, the PTHL composite scaffold is a promising non-antibiotic antimicrobial graft with good biodegradability, biocompatibility, and osteogenic capability for infected bone defects.<\/jats:p>","DOI":"10.3390\/pharmaceutics15010088","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T08:42:22Z","timestamp":1672216942000},"page":"88","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["LL-37-Coupled Porous Composite Scaffold for the Treatment of Infected Segmental Bone Defect"],"prefix":"10.3390","volume":"15","author":[{"given":"Xialin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen 518052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen 518052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Li","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine Research & Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"},{"name":"Shenzhen Institutes of Advanced Technology, University of Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Emergency Department, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen 518052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihong","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen 518052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiao","family":"Lai","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine Research & Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"},{"name":"Shenzhen Institutes of Advanced Technology, University of Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen 518052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.actbio.2018.11.039","article-title":"Three-dimensional (3D) printed scaffold and material selection for bone repair","volume":"84","author":"Zhang","year":"2018","journal-title":"Acta Biomater."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11806","DOI":"10.1038\/s41598-019-48236-8","article-title":"Human Bone Marrow-Derived Mesenchymal Stromal Cell-Seeded Bone Biomaterial Directs Fast and Superior Mandibular Bone Augmentation in Rats","volume":"9","author":"Deluiz","year":"2019","journal-title":"Sci. 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