PMID- 30408337 OWN - NLM STAT- MEDLINE DCOM- 20190820 LR - 20190820 IS - 1616-5195 (Electronic) IS - 1616-5187 (Linking) VI - 18 IP - 12 DP - 2018 Dec TI - Silk-Based Antimicrobial Polymers as a New Platform to Design Drug-Free Materials to Impede Microbial Infections. PG - e1800262 LID - 10.1002/mabi.201800262 [doi] AB - Surgical site infections (SSI) represent a serious health problem that occur after invasive surgery, thus new antimicrobial biomaterials able to prevent SSI are needed. Silks are natural biopolymers with excellent biocompatibility, low immunogenicity and controllable biodegradability. Spider silk-based materials can be bioengineered and functionalized with specific peptides, such as antimicrobial peptides, creating innovative polymers. Herein, we explored new drug-free multifunctional silk films with antimicrobial properties, specifically tailored to hamper microbial infections. Different spider silk domains derived from the dragline sequence of the spider Nephila clavipes (6mer and 15mer, 27 and 41 kDa proteins, respectively) were fused with the two antimicrobial peptides, Hepcidin (Hep) and Human Neutrophil peptide 1 (HNP1). The self-assembly features of the spider silk domains (beta-sheets) were maintained after functionalization. The bioengineered 6mer-HNP1 protein demonstrated inhibitory effects against microbial pathogens. Silk-based films with 6mer-HNP1 and different contents of silk fibroin (SF) significantly reduced bacterial adhesion and biofilm formation, whereas higher bacterial counts were found on the films prepared with 6mer or SF alone. The silk-based films showed no cytotoxic effects on human foreskin fibroblasts. The positive cellular response, together with structural and antimicrobial properties, highlight the potential of these multifunctional silk-based films as new materials for preventing SSI. CI - (c) 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Franco, Albina R AU - Franco AR AUID- ORCID: 0000-0001-8974-8354 AD - 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimaraes, Portugal. AD - ICVS/3B's - PT Government Associate Laboratory, 4805 Braga/Guimaraes, Portugal. FAU - Palma Kimmerling, Erica AU - Palma Kimmerling E AD - Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA. FAU - Silva, Carla AU - Silva C AUID- ORCID: 0000-0001-6252-8693 AD - 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimaraes, Portugal. AD - ICVS/3B's - PT Government Associate Laboratory, 4805 Braga/Guimaraes, Portugal. FAU - Rodrigues, Fernando J AU - Rodrigues FJ AD - ICVS/3B's - PT Government Associate Laboratory, 4805 Braga/Guimaraes, Portugal. AD - Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, 4805 Braga, Portugal. FAU - Leonor, Isabel B AU - Leonor IB AUID- ORCID: 0000-0002-4319-4883 AD - 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimaraes, Portugal. AD - ICVS/3B's - PT Government Associate Laboratory, 4805 Braga/Guimaraes, Portugal. FAU - Reis, Rui L AU - Reis RL AD - 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimaraes, Portugal. AD - ICVS/3B's - PT Government Associate Laboratory, 4805 Braga/Guimaraes, Portugal. AD - The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, 4805-017, Barco, Guimaraes, Portugal. FAU - Kaplan, David L AU - Kaplan DL AD - Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181108 PL - Germany TA - Macromol Biosci JT - Macromolecular bioscience JID - 101135941 RN - 0 (Anti-Infective Agents) RN - 0 (Biocompatible Materials) RN - 0 (Hepcidins) RN - 0 (Recombinant Fusion Proteins) RN - 0 (alpha-Defensins) RN - 0 (human neutrophil peptide 1) RN - 9007-76-5 (Fibroins) MH - Animals MH - Anti-Infective Agents/*chemistry/metabolism/pharmacology MH - Bacterial Adhesion/drug effects MH - Biocompatible Materials/*chemistry/metabolism/pharmacology MH - Biofilms/drug effects/growth & development MH - Candida albicans/drug effects/growth & development MH - Cell Line MH - Cell Survival MH - Fibroblasts/cytology/drug effects MH - Fibroins/biosynthesis/*chemistry/genetics/pharmacology MH - Gene Expression MH - Gram-Negative Bacteria/drug effects/growth & development MH - Gram-Positive Bacteria/drug effects/growth & development MH - Hepcidins/*biosynthesis/genetics/pharmacology MH - Humans MH - Microbial Viability/drug effects MH - Plasmids/chemistry/metabolism MH - Polymerization MH - Protein Conformation, beta-Strand MH - Recombinant Fusion Proteins/biosynthesis/*chemistry/genetics/pharmacology MH - Spiders/physiology MH - Surgical Wound Infection/prevention & control MH - Sutures/microbiology MH - alpha-Defensins/*biosynthesis/genetics/pharmacology OTO - NOTNLM OT - antimicrobial peptides OT - bacterial adhesion OT - biocompatibility OT - bioengineered silk proteins OT - drug-free polymers EDAT- 2018/11/09 06:00 MHDA- 2019/08/21 06:00 CRDT- 2018/11/09 06:00 PHST- 2018/07/11 00:00 [received] PHST- 2018/10/03 00:00 [revised] PHST- 2018/11/09 06:00 [pubmed] PHST- 2019/08/21 06:00 [medline] PHST- 2018/11/09 06:00 [entrez] AID - 10.1002/mabi.201800262 [doi] PST - ppublish SO - Macromol Biosci. 2018 Dec;18(12):e1800262. doi: 10.1002/mabi.201800262. Epub 2018 Nov 8.