title: Macrophage polarization in response to ECM coated polypropylene mesh.
abstract: The host response to implanted biomaterials is a highly regulated process that influences device functionality and clinical outcome. Non-degradable biomaterials, such as knitted polypropylene mesh, frequently elicit a chronic foreign body reaction with resultant fibrosis. Previous studies have shown that an extracellular matrix (ECM) hydrogel coating of polypropylene mesh reduces the intensity of the foreign body reaction, though the mode of action is unknown. Macrophage participation plays a key role in the development of the foreign body reaction to biomaterials, and therefore the present study investigated macrophage polarization following mesh implantation. Spatiotemporal analysis of macrophage polarization was conducted in response to uncoated polypropylene mesh and mesh coated with hydrated and dry forms of ECM hydrogels derived from either dermis or urinary bladder. Pro-inflammatory M1 macrophages (CD86+/CD68+), alternatively activated M2 macrophages (CD206+/CD68+), and foreign body giant cells were quantified between 3 and 35 days. Uncoated polypropylene mesh elicited a dominant M1 response at the mesh fiber surface, which was decreased by each ECM coating type beginning at 7 days. The diminished M1 response was accompanied by a reduction in the number of foreign body giant cells at 14 and 35 days, though there was a minimal effect upon the number of M2 macrophages at any time. These results show that ECM coatings attenuate the M1 macrophage response and increase the M2/M1 ratio to polypropylene mesh in vivo.
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Wolf
authors.affiliation: Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Dearth
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Ranallo
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Samuel T
authors.initials: ST
authors.lastname: LoPresti
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Carey
authors.affiliation: Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Daly
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Bryan N
authors.initials: BN
authors.lastname: Brown
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: badylaks@upmc.edu.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Badylak
mesh_terms: D000818:Animals; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D005109:Extracellular Matrix / Q000737:chemistry*; D005260:Female; D005355:Fibrosis / Q000473:pathology; D005549:Foreign-Body Reaction; D020100:Hydrogels / Q000737:chemistry; D007113:Immunity, Innate / Q000187:drug effects; D008264:Macrophages / Q000737:chemistry*; D008422:Materials Testing; D011126:Polypropylenes / Q000737:chemistry*; D019736:Prostheses and Implants; D051381:Rats; D017207:Rats, Sprague-Dawley; D013526:Surgical Mesh
chemical_list: D020099:Coated Materials, Biocompatible; D020100:Hydrogels; D011126:Polypropylenes
keywords: ECM (extracellular matrix); Hydrogel; Macrophage; Polypropylene; Surgical mesh; Ventral hernia