Inflammasome components Asc and caspase-1 mediate biomaterial-induced inflammation and foreign body response

Proc Natl Acad Sci U S A. 2011 Dec 13;108(50):20095-100. doi: 10.1073/pnas.1105152108. Epub 2011 Nov 22.


Implantation of biomaterials and devices into soft tissues leads to the development of the foreign body response (FBR), which can interfere with implant function and eventually lead to failure. The FBR consists of overlapping acute and persistent inflammatory phases coupled with collagenous encapsulation and currently there are no therapeutic options. Initiation of the FBR involves macrophage activation, proceeding to giant cell formation, fibroblast activation, and collagen matrix deposition. Despite the recognition of this sequence of events, the molecular pathways required for the FBR have not been elucidated. We have identified that the acute inflammatory response to biomaterials requires nucleotide-binding domain and leucine-rich repeat-containing 3 (Nlrp3), apoptosis-associated speck-like protein containing CARD (Asc), and caspase-1, as well as plasma membrane cholesterol, and Syk signaling. Full development of the FBR is dependent on Asc and caspase-1, but not Nlrp3. The common antiinflammatory drug aspirin can reduce inflammasome activation and significantly reduce the FBR. Taken together, these findings expand the role of the inflammasome from one of sensing damage associated molecular patterns (DAMPs) to sensing all particulate matter irrespective of size. In addition, implication of the inflammasome in biomaterial recognition identifies key pathways, which can be targeted to limit the FBR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Aspirin / administration & dosage
  • Aspirin / adverse effects
  • Biocompatible Materials / adverse effects*
  • CARD Signaling Adaptor Proteins
  • Calcium-Binding Proteins / metabolism
  • Carrier Proteins / metabolism
  • Caspase 1 / metabolism*
  • Cluster Analysis
  • Cytoskeletal Proteins / metabolism*
  • Foreign-Body Reaction / complications
  • Foreign-Body Reaction / enzymology
  • Foreign-Body Reaction / immunology
  • Foreign-Body Reaction / pathology*
  • Giant Cells / drug effects
  • Giant Cells / immunology
  • Giant Cells / pathology
  • Inflammasomes / metabolism*
  • Inflammation / complications
  • Inflammation / enzymology
  • Inflammation / immunology
  • Inflammation / pathology*
  • Interleukin-1beta / biosynthesis
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / pathology
  • Membrane Microdomains / drug effects
  • Membrane Microdomains / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microspheres
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Polymethyl Methacrylate / adverse effects


  • Apoptosis Regulatory Proteins
  • Biocompatible Materials
  • CARD Signaling Adaptor Proteins
  • Calcium-Binding Proteins
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Inflammasomes
  • Interleukin-1beta
  • Ipaf protein, mouse
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Pycard protein, mouse
  • Polymethyl Methacrylate
  • Caspase 1
  • Aspirin