title: Interactions of Staphylococcus aureus with ultrasoft hydrogel biomaterials.
abstract: Ultrasoft biomaterials-polymers, gels, and human soft tissues with an elastic modulus less than ∼100 kPa-are increasingly used in medical devices. While bacterial interactions (adhesion and biofilm formation) have been extensively studied on stiffer materials, little is known about how bacteria colonize ultrasoft materials as a nidus for infection. The goal of this work was to determine how material properties of ultrasoft hydrogels used for dermal fillers might affect pathogenesis of associated infections. We first synthesized a range of polyacrylamide hydrogels (PAAm) with moduli similar to clinically used dermal fillers and characterized the rheological, morphological and porous properties. We then developed a novel microfabricated insert to contain the PAAm in a flow system for quantification of bacterial adhesion and biofilm formation. The rate of adhesion and numbers of adherent Staphylococcus aureus on the surface of PAAm both decreased as the modulus increased. Adhesion was reduced by 3 logs (from 93 × 10(4)/cm(2) to 0.083 × 10(4)/cm(2)) with increasing modulus (from 17 Pa to 654 Pa). However, the number of bacteria in the bulk was the highest within the stiffest gels. This trend was further amplified in subsequent biofilm studies, where interfacial coverage of biofilm decreased as the modulus increased, while the fraction of biofilm in the bulk was the highest within the stiffest gel. The results show significant differences in bacterial colonization of PAAm based on material properties, and reveal how the injection process may unexpectedly create discontinuities that provide a microenvironmental niche for bacterial colonization.
authors.affiliation: United States Food and Drug Administration, Office of Medical Products and Tobacco, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Biology, Chemistry and Materials Science, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, The George Washington University, Science and Engineering Hall, 800 22nd Street NW, Washington, DC, 20052, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Guan
authors.affiliation: United States Food and Drug Administration, Office of Medical Products and Tobacco, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Biology, Chemistry and Materials Science, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA.
authors.forename: Irada
authors.initials: I
authors.lastname: Isayeva
authors.affiliation: United States Food and Drug Administration, Office of Medical Products and Tobacco, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Biology, Chemistry and Materials Science, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Vorvolakos
authors.affiliation: United States Food and Drug Administration, Office of Medical Products and Tobacco, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Biology, Chemistry and Materials Science, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA.
authors.forename: Srilekha
authors.initials: S
authors.lastname: Das
authors.affiliation: Department of Biomedical Engineering, The George Washington University, Science and Engineering Hall, 800 22nd Street NW, Washington, DC, 20052, USA.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: United States Food and Drug Administration, Office of Medical Products and Tobacco, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Biology, Chemistry and Materials Science, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA. Electronic address: kenneth.phillips@fda.hhs.gov.
authors.forename: K Scott
authors.initials: KS
authors.lastname: Phillips
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D018441:Biofilms / Q000187:drug effects; D055119:Elastic Modulus; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D020100:Hydrogels; D016062:Porosity; D012038:Regeneration; D012212:Rheology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D013499:Surface Properties
chemical_list: D000180:Acrylic Resins; D020100:Hydrogels; C016680:polyacrylamide gels; D049452:Green Fluorescent Proteins
keywords: Bacteria; Biofilm; Hydrogel; Infection; Medical device; Plastic surgery