title: Application of a dense gas technique for sterilizing soft biomaterials.
abstract: Sterilization of soft biomaterials such as hydrogels is challenging because existing methods such as gamma irradiation, steam sterilization, or ethylene oxide sterilization, while effective at achieving high sterility assurance levels (SAL), may compromise their physicochemical properties and biocompatibility. New methods that effectively sterilize soft biomaterials without compromising their properties are therefore required. In this report, a dense-carbon dioxide (CO(2) )-based technique was used to sterilize soft polyethylene glycol (PEG)-based hydrogels while retaining their structure and physicochemical properties. Conventional sterilization methods such as gamma irradiation and steam sterilization severely compromised the structure of the hydrogels. PEG hydrogels with high water content and low elastic shear modulus (a measure of stiffness) were deliberately inoculated with bacteria and spores and then subjected to dense CO(2) . The dense CO(2) -based methods effectively sterilized the hydrogels achieving a SAL of 10(-7) without compromising the viscoelastic properties, pH, water-content, and structure of the gels. Furthermore, dense CO(2) -treated gels were biocompatible and non-toxic when implanted subcutaneously in ferrets. The application of novel dense CO(2) -based methods to sterilize soft biomaterials has implications in developing safe sterilization methods for soft biomedical implants such as dermal fillers and viscosupplements.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. skarajanagi@partners.org
authors.forename: Sandeep S
authors.initials: SS
authors.lastname: Karajanagi
authors.forename: Roshan
authors.initials: R
authors.lastname: Yoganathan
authors.forename: Raffaella
authors.initials: R
authors.lastname: Mammucari
authors.forename: Hyoungshin
authors.initials: H
authors.lastname: Park
authors.forename: Julian
authors.initials: J
authors.lastname: Cox
authors.forename: Steven M
authors.initials: SM
authors.lastname: Zeitels
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Neil R
authors.initials: NR
authors.lastname: Foster
mesh_terms: D001419:Bacteria / Q000187:drug effects; D001672:Biocompatible Materials; D002245:Carbon Dioxide / Q000494:pharmacology*; D004202:Disinfectants / Q000494:pharmacology*; D005740:Gases / Q000494:pharmacology*; D020100:Hydrogels / Q000737:chemistry; D050296:Microbial Viability / Q000187:drug effects*; D011092:Polyethylene Glycols; D013171:Spores, Bacterial / Q000187:drug effects; D013242:Sterilization / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D004202:Disinfectants; D005740:Gases; D020100:Hydrogels; D002245:Carbon Dioxide; D011092:Polyethylene Glycols