TY - JOUR
T1 - 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
AU - Puolakkainen, Pauli
AU - Bradshaw, Amy D.
AU - Kyriakides, Themistoklis R.
AU - Reed, May
AU - Brekken, Rolf
AU - Wight, Thomas
AU - Bornstein, Paul
AU - Ratner, Buddy
AU - Sage, E. Helene
PY - 2003/2/1
Y1 - 2003/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037331246&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037331246&partnerID=8YFLogxK
U2 - 10.1016/S0002-9440(10)63856-4
DO - 10.1016/S0002-9440(10)63856-4
M3 - Article
C2 - 12547720
AN - SCOPUS:0037331246
SN - 0002-9440
VL - 162
SP - 627
EP - 635
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 2
ER -