title: Consequences of ineffective decellularization of biologic scaffolds on the host response.
abstract: Biologic scaffold materials composed of extracellular matrix (ECM) are routinely used for a variety of clinical applications. Despite known variations in tissue remodeling outcomes, quantitative criteria by which decellularization can be assessed were only recently described and as a result, the amount of retained cellular material varies widely among commercial products. The objective of this study was to evaluate the consequences of ineffective decellularization on the host response. Three different methods of decellularization were used to decellularize porcine small intestinal ECM (SIS-ECM). The amount of cell remnants was quantified by the amount and fragmentation of DNA within the scaffold materials. The M1/M2 phenotypic polarization profile of macrophages, activated in response to these ECM scaffolds, was assessed in vitro and in vivo using a rodent model of body wall repair. The results show that, in vitro, more aggressive decellularization is associated with a shift in macrophage phenotype predominance from M1 to M2. While this shift was not quantitatively apparent in vivo, notable differences were found in the distribution of M1 vs. M2 macrophages within the various scaffolds. A clear association between macrophage phenotype and remodeling outcome exists and effective decellularization remains an important component in the processing of ECM-based scaffolds.
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Keane
authors.forename: Ricardo
authors.initials: R
authors.lastname: Londono
authors.forename: Neill J
authors.initials: NJ
authors.lastname: Turner
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Badylak
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D004247:DNA / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D007107:Immune System; D007421:Intestine, Small / Q000166:cytology; D008264:Macrophages / Q000166:cytology; D008422:Materials Testing; D051379:Mice; D008954:Models, Biological; D010463:Peracetic Acid / Q000737:chemistry; D010641:Phenotype; D013552:Swine; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*; D014945:Wound Healing
chemical_list: D001672:Biocompatible Materials; D004247:DNA; D010463:Peracetic Acid