title: Bioburden-responsive antimicrobial PLGA ultrafine fibers for wound healing.
abstract: Despite innovation in the design and functionalization of polymer nanofiber wound healing materials, information on their interaction with the biochemical wound environment is lacking. In an earlier study, we have reported the interaction of fusidic acid-loaded PLGA ultrafine fibers (UFs) with wound bacteria. Massive bacterial colonization and the formation of a dense biofilm throughout the mat were demonstrated. This was associated with a marked enhancement of initial drug release at concentrations allowing eradication of planktonic bacteria and considerable suppression of biofilm. The present study aimed at extending earlier findings to gain more mechanistic insights into the potential response of the fusidic acid-laden UFs under study to controlled microbial bioburden. Initial drug release enhancement was shown to involve surface erosion of the ultrafibrous mats likely mediated by microbial esterase activity determined in the study. Release data could be correlated with microbial bioburden over the inoculum size range 10³-10⁷ CFU/ml, suggesting a bioburden-triggered drug release enhancement mechanism. Moreover, the effectiveness of fusidic acid-laden UFs in the healing of either lightly contaminated or Staphylococcus aureus heavily infected wounds in a rat model suggested in-use relevant antimicrobial release patterns. Findings indicated active participation of polymer ultrafine wound dressings in a dynamic interaction with the wound milieu, which affects their structure-function relationship. Understanding such an interaction is fundamental to the characterization and performance assessment of wound materials under biorelevant conditions and the design of polymer-based infection-responsive biomaterials.
authors.affiliation: Department of Pharmaceutics, Alexandria University, Alexandria, Egypt.
authors.forename: Somiraa S
authors.initials: SS
authors.lastname: Said
authors.forename: Omar M
authors.initials: OM
authors.lastname: El-Halfawy
authors.forename: Hanan M
authors.initials: HM
authors.lastname: El-Gowelli
authors.forename: Affaf K
authors.initials: AK
authors.lastname: Aloufy
authors.forename: Nabila A
authors.initials: NA
authors.lastname: Boraei
authors.forename: Labiba K
authors.initials: LK
authors.lastname: El-Khordagui
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000008:administration & dosage; D018441:Biofilms / Q000187:drug effects; D060833:Cellular Microenvironment / Q000187:drug effects; D004950:Esterases / Q000378:metabolism; D005260:Female; D005672:Fusidic Acid / Q000494:pharmacology; D019344:Lactic Acid / Q000008:administration & dosage*; D057139:Nanofibers / Q000008:administration & dosage*; D052638:Particulate Matter; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012828:Silicones / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship; D014945:Wound Healing / Q000187:drug effects*; D014946:Wound Infection / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D052638:Particulate Matter; D011108:Polymers; D012828:Silicones; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005672:Fusidic Acid; D004950:Esterases