title: The effect of terminal sterilization on the material properties and in vivo remodeling of a porcine dermal biologic scaffold.
abstract: Biologic scaffolds composed of extracellular matrix are commonly used in a variety of surgical procedures. The Food and Drug Administration typically regulates biologic scaffolds as medical devices, thus requiring terminal sterilization prior to clinical use. However, to date, no consensus exists for the most effective yet minimally destructive sterilization protocol for biologic scaffold materials. The objective of the present study was to characterize the effect of ethylene oxide, gamma irradiation and electron beam (e-beam) irradiation on the material properties and the elicited in vivo remodeling response of a porcine dermal biologic scaffold. Outcome measures included biochemical, structural, and mechanical properties as well as cytocompatibility in vitro. In vivo evaluation utilized a rodent model to examine the host response to the materials following 7, 14, and 35 days. The host response to each experimental group was determined by quantitative histologic methods and by immunolabeling for macrophage polarization (M1/M2). In vitro results show that increasing irradiation dosage resulted in a dose dependent decrease in mechanical properties compared to untreated controls. Ethylene oxide-treated porcine dermal ECM resulted in decreased DNA content, extractable total protein, and bFGF content compared to untreated controls. All ETO treated, gamma irradiated, and e-beam irradiated samples had similar cytocompatibility scores in vitro. However, in vivo results showed that increasing dosages of e-beam and gamma irradiation elicited an increased rate of degradation of the biologic scaffold material following 35 days.
  
  
  CONCLUSIONS
  The FDA typically regulates biologic scaffolds derived from mammalian tissues as medical devices, thus requiring terminal sterilization prior to clinical use. However, there is little data and no consensus for the most effective yet minimally destructive sterilization protocol for such materials. The present study characterized the effect of common sterilization methods: ethylene oxide, gamma irradiation and electron beam irradiation on the material properties and the elicited in vivo remodeling response of a porcine dermal biologic scaffold. The results of the study will aid in the meaningful selection of sterilization methods for biologic scaffold materials.
authors.affiliation: McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15219, United States; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, United States; DoD-VA Extremity Trauma & Amputation Center of Excellence, Walter Reed National Military Medical Center, Bethesda, MD 20889, United States.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Dearth
authors.affiliation: McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15219, United States; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15213, United States.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Keane
authors.affiliation: McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15219, United States; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15213, United States.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Carruthers
authors.affiliation: McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15219, United States.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Reing
authors.affiliation: McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15219, United States.
authors.forename: Luai
authors.initials: L
authors.lastname: Huleihel
authors.affiliation: McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15219, United States.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Ranallo
authors.affiliation: McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15219, United States.
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Kollar
authors.affiliation: McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15219, United States; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, United States; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15213, United States. Electronic address: badylaks@upmc.edu.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Badylak
mesh_terms: D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D020405:Dermis / Q000502:physiology* / Q000648:ultrastructure; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D006801:Humans; D008264:Macrophages / Q000166:cytology; D008422:Materials Testing / Q000379:methods*; D055806:Microvessels / Q000166:cytology; D010641:Phenotype; D016062:Porosity; D017207:Rats, Sprague-Dawley; D013242:Sterilization; D034421:Sus scrofa; D054457:Tissue Scaffolds / Q000737:chemistry*
keywords: Extracelluar matrix; Terminal sterilization