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(American Journal of Pathology. 2003;162:627-635.)
© 2003 American Society for Investigative Pathology

Regular Articles

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

Pauli Puolakkainen^*, Amy D. Bradshaw^*, Themistoklis R. Kyriakides, May Reed, Rolf Brekken^*, Thomas Wight^*, Paul Bornstein, Buddy Ratner^¶ and E. Helene Sage^*

From the Department of Vascular Biology,^* The Hope Heart Institute, and the Departments of Medicine, Biochemistry, and Bioengineering,^¶ University of Washington, Seattle, Washington; and the Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland

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.

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