title: Autoclaving-Derived Surface Coating with In Vitro and In Vivo Antimicrobial and Antibiofilm Efficacies.
abstract: Biomedical device-associated infections which engender severe threat to public health require feasible solutions. In this study, block copolymers consisting of antimicrobial, antifouling, and surface-tethering segments in one molecule are synthesized and grafted on polymeric substrates by a facile plasma/autoclave-assisted method. Hetero-bifunctional polyethylene glycol (PEG) with allyl and tosyl groups (APEG-OTs) is first prepared. PEGs with different molecular weights (1200 and 2400 Da) are employed. Polyhexamethylene guanidine (PHMG) which has excellent broad-spectrum antimicrobial activity and thermal/chemical stability, is conjugated with APEG-OTs to generate the block copolymer (APEG-PHMG). Allyl terminated PHMG (A-PHMG) without PEG segments is also synthesized by reacting PHMG with allyl glycidyl ether. The synthesized copolymers are thermal initiated by autoclaving and grafted on plasma pretreated silicone surface, forming permanently bonded bottlebrush-like coatings. Both A-PHMG and APEG1200/2400-PHMG coatings exhibit potent antimicrobial activity against gram-positive/negative bacteria and fungus, whereas APEG1200/2400-PHMG coatings show superior antifouling activity and long-term reusability to A-PHMG coating. APEG2400-PHMG coating demonstrates the most effective in vitro antibiofilm and protein/platelet-resistant properties, as well as excellent hemo/biocompatibility. Furthermore, APEG2400-PHMG greatly reduces the bacteria number with 5-log reduction in a rodent subcutaneous infection model. This rationally designed dual-functional antimicrobial and antifouling coating has great potential in combating biomedical devices/implant-associated infections.
authors.affiliation: Center for Biomedical Engineering and Regenerative Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Su
authors.affiliation: Key Laboratory of Flexible Electronics (KLOFE) and Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University (NanjingTech), Nanjing, 211816, China.
authors.forename: Zelun
authors.initials: Z
authors.lastname: Zhi
authors.affiliation: Center for Biomedical Engineering and Regenerative Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Center for Biomedical Engineering and Regenerative Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China.
authors.forename: Meihua
authors.initials: M
authors.lastname: Xie
authors.affiliation: Center for Biomedical Engineering and Regenerative Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Yu
authors.affiliation: Center for Biomedical Engineering and Regenerative Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Lei
authors.affiliation: Center for Biomedical Engineering and Regenerative Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China.|Key Laboratory of Flexible Electronics (KLOFE) and Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University (NanjingTech), Nanjing, 211816, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.|Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA.|Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI, 48109, USA.|Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Peter X
authors.initials: PX
authors.lastname: Ma
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D002460:Cell Line; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D008422:Materials Testing; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000502:physiology*
chemical_list: D000890:Anti-Infective Agents; D020099:Coated Materials, Biocompatible; D011092:Polyethylene Glycols
keywords: antifouling; antimicrobial; block copolymer; polyhexamethylene guanidine (PHMG); surface coating