title: 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.
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.
authors.affiliation: Department of Vascular Biology, The Hope Heart Institute, University of Washington, Seattle, Washington 98104, USA. hsage@hopeheart.org
authors.forename: Pauli
authors.initials: P
authors.lastname: Puolakkainen
authors.forename: Amy D
authors.initials: AD
authors.lastname: Bradshaw
authors.forename: Themistoklis R
authors.initials: TR
authors.lastname: Kyriakides
authors.forename: May
authors.initials: M
authors.lastname: Reed
authors.forename: Rolf
authors.initials: R
authors.lastname: Brekken
authors.forename: Thomas
authors.initials: T
authors.lastname: Wight
authors.forename: Paul
authors.initials: P
authors.lastname: Bornstein
authors.forename: Buddy
authors.initials: B
authors.lastname: Ratner
authors.forename: E Helene
authors.initials: EH
authors.lastname: Sage
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000009:adverse effects; D004129:Dimethylpolysiloxanes / Q000009:adverse effects; D005347:Fibroblasts / Q000473:pathology / Q000648:ultrastructure; D005549:Foreign-Body Reaction / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D015676:Osteonectin / Q000172:deficiency / Q000235:genetics*; D019736:Prostheses and Implants / Q000009:adverse effects*; D012828:Silicones / Q000009:adverse effects
chemical_list: D020099:Coated Materials, Biocompatible; D004129:Dimethylpolysiloxanes; D015676:Osteonectin; D012828:Silicones; C013830:baysilon; D001973:Bromodeoxyuridine