Blood monocyte-derived macrophages (a class of phagocytic leukocytes) play a critical role in directing inflammation and foreign body reaction to biomaterials. However, the processes leading to macrophage adhesion and activation on materials are complex and not yet fully understood. Hence, our interest in macrophage interaction with material macrophage adhesion and activation. Second, we would like to exploit that knowledge in the design of materials and fundamental understanding of the interplay between macrophage-active proteins and receptors on the cell membranes must be obtained. Oligopeptides will be designed based on the known structural structure of modulating inflammation. These protein mimetic peptides will be utilized to probe the molecular mechanisms required for ligand-receptor recognition and the induction of cellular functions. In term, the bioactive peptides production. Heterofunctionalized polymeric materials will be developed and optimized to enhanced the physicochemical properties and bioavailability of macrophage-active oligopeptides in vitro and in vivo. This research plan offers a systematic method in the study of protein-receptor interaction and the development of material constructs designed to modulate the release of selected cytokines and growth factors produced by endogenous inflammatory cells. The controlled release of these bioactive factors may have therapeutic values in the fundamental processes of inflammation, biocompatibility, and tissue healing.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL063686-02
Application #
6351578
Study Section
Surgery and Bioengineering Study Section (SB)
Program Officer
Kelley, Christine A
Project Start
2000-02-01
Project End
2004-01-31
Budget Start
2001-02-01
Budget End
2002-01-31
Support Year
2
Fiscal Year
2001
Total Cost
$141,889
Indirect Cost
Name
University of Wisconsin Madison
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Burmania, Jeanine A; Martinez-Diaz, Gabriel J; Kao, Weiyuan John (2003) Synthesis and physicochemical analysis of interpenetrating networks containing modified gelatin and poly(ethylene glycol) diacrylate. J Biomed Mater Res A 67:224-34
Kao, Weiyuan John; Liu, Yiping (2003) Intracellular protein tyrosine phosphorylation of adherent human macrophages on adsorbed fibronectin. Biomaterials 24:1183-91
Einerson, Nicole J; Stevens, Kelly R; Kao, Weiyuan John (2003) Synthesis and physicochemical analysis of gelatin-based hydrogels for drug carrier matrices. Biomaterials 24:509-23
Burmania, Jeanine A; Stevens, Kelly R; Kao, Weiyuan John (2003) Cell interaction with protein-loaded interpenetrating networks containing modified gelatin and poly(ethylene glycol) diacrylate. Biomaterials 24:3921-30
Liu, Yiping; Kao, Weiyuan John (2002) Human macrophage adhesion on fibronectin: the role of substratum and intracellular signalling kinases. Cell Signal 14:145-52
Kao, Weiyuan John; Liu, Yiping; Gundloori, Rathna et al. (2002) Engineering endogenous inflammatory cells as delivery vehicles. J Control Release 78:219-33
Kao, Weiyuan John; Liu, Yiping (2002) Intracellular signaling involved in macrophage adhesion and FBGC formation as mediated by ligand-substrate interaction. J Biomed Mater Res 62:478-87
Stevens, Kelly R; Einerson, Nicole J; Burmania, Jeanine A et al. (2002) In vivo biocompatibility of gelatin-based hydrogels and interpenetrating networks. J Biomater Sci Polym Ed 13:1353-66
Kao, W J; Lee, D; Schense, J C et al. (2001) Fibronectin modulates macrophage adhesion and FBGC formation: the role of RGD, PHSRN, and PRRARV domains. J Biomed Mater Res 55:79-88
Kao, W J; Liu, Y (2001) Utilizing biomimetic oligopeptides to probe fibronectin-integrin binding and signaling in regulating macrophage function in vitro and in vivo. Front Biosci 6:D992-9

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