title: An effective treatment of experimental osteomyelitis using the antimicrobial titanium/silver-containing nHP66 (nano-hydroxyapatite/polyamide-66) nanoscaffold biomaterials.
abstract: Effective treatment of osteomyelitis remains a formidable clinical challenge. The rapid emergence of multidrug-resistant bacteria has renewed interest in developing antimicrobial biomaterials using antiseptic silver ions to treat osteomyelitis. However, inadequate local retention and severe cytotoxic effects have limited the clinical use of ionic silver for bone grafts. We recently developed novel porous nano-hydroxyapatite/polyamide 66 (nHP66)-based nanoscaffold materials containing varied concentrations of silver ions (Ag+) (TA-nHAPA66) and oxidized titanium (TiO2), which was added as a second binary element to enhance antibacterial activity and biocompatibility. In this study, we establish a large cohort of rabbit model of experimental osteomyelitis and investigate the in vivo antimicrobial and therapeutic effects of TA-nHP66 biomaterials and their in vivo silver release kinetics. We find the TA-nHP66 scaffolds exhibit potent antibacterial activities against E. coli and S. aureus, support cell adhesion and cell proliferation of pre-osteoblasts, and stimulate osteogenic regulator/marker expression. Moreover, the TA2-nHP66 scaffold exerts potent antibacterial/anti-inflammation effects in vivo and promotes bone formation at the lesion site of osteomyelitis. We further demonstrate that TA2-nHP66 exhibits excellent biosafety profile without apparent systemic toxicities. Therefore, the TA-nHP66 scaffold biomaterials may be further explored as an effective adjuvant therapy for infected bone defects and/or osteomyelitis debridement.
authors.affiliation: Department of Orthopaedic Surgery, The Children's Hospital, Chongqing Medical University, Chongqing 400010, China.|Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Minpeng
authors.initials: M
authors.lastname: Lu
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.|Department of Orthopaedic Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of Orthopaedic Surgery, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Orthopaedic Surgery, The Children's Hospital, Chongqing Medical University, Chongqing 400010, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Orthopaedic Surgery, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Department of Orthopaedic Surgery, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu 610064, China.
authors.forename: Jidong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Dianming
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Orthopaedic Surgery, The Children's Hospital, Chongqing Medical University, Chongqing 400010, China.|Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Zhengxue
authors.initials: Z
authors.lastname: Quan
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D017886:Durapatite / Q000737:chemistry*; D004926:Escherichia coli / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D009757:Nylons / Q000737:chemistry*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010019:Osteomyelitis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D011817:Rabbits; D012834:Silver / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects; D014025:Titanium / Q000737:chemistry*
chemical_list: D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D015415:Biomarkers; D009757:Nylons; C009495:titanium dioxide; D012834:Silver; D017886:Durapatite; D014025:Titanium