Compromised Production of Extracellular Matrix in Mice Lacking Secreted Protein, Acidic and Rich in Cysteine (SPARC) Leads to a Reduced Foreign Body Reaction to Implanted Biomaterials

Am J Pathol. 2003 Feb;162(2):627-35. doi: 10.1016/S0002-9440(10)63856-4.

Abstract

SPARC (secreted protein, acidic and rich in cysteine), a matricellular glycoprotein, modulates the interaction of cells with the extracellular matrix (ECM). Recently, accelerated cutaneous wound closure and altered deposition of collagen were reported in SPARC-null mice. Herein we asked whether SPARC might influence the foreign body reaction to biomaterial implants. Polydimethylsiloxane (silicone rubber) disks and cellulose Millipore filters were implanted into wild-type and SPARC-null mice. In wild-type animals, significant levels of SPARC were observed in the cells and the ECM comprising the capsules around the implants. After 4 weeks, SPARC-null mice exhibited a significant decrease in the thickness of the foreign body capsule, as compared to that observed in wild-type mice. A significant reduction in capsular vascular density was also associated with the silicone implants in the SPARC-null animals. Electron microscopy revealed that collagen fibers in the capsules produced by SPARC-null mice were smaller and more uniform in size than those in wild-type animals. Furthermore, staining with picrosirius-red showed that the collagen fibers were less mature in SPARC-null than in wild-type mice. The altered ECM resulting in decreased capsular thickness, indicative of an altered foreign body reaction in SPARC-null mice, implicates SPARC as an important modulator of the encapsulation of implanted biomaterials.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bromodeoxyuridine
  • Cells, Cultured
  • Coated Materials, Biocompatible / adverse effects
  • Dimethylpolysiloxanes / adverse effects
  • Fibroblasts / pathology
  • Fibroblasts / ultrastructure
  • Foreign-Body Reaction / etiology
  • Foreign-Body Reaction / genetics*
  • Foreign-Body Reaction / pathology
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • Microscopy, Electron
  • Osteonectin / deficiency
  • Osteonectin / genetics*
  • Prostheses and Implants / adverse effects*
  • Silicones / adverse effects

Substances

  • Coated Materials, Biocompatible
  • Dimethylpolysiloxanes
  • Osteonectin
  • Silicones
  • baysilon
  • Bromodeoxyuridine