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In vivo leukocyte cytokine mRNA responses to biomaterials are dependent on surface chemistry.pdf

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In vivo leukocyte cytokine mRNA responses to biomaterials are dependent on surface chemistry

In vivo leukocyte cytokine mRNA responses to biomaterials are dependent on surface chemistry William G. Brodbeck,1 Gabriela Voskerician,2 Nicholas P. Ziats,1,2 Yasuhide Nakayama,3 Takehisa Matsuda,4 James M. Anderson1,2 1Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106 2Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106 3Department of Bioengineering, National Cardiovascular Center, Osaka, Japan 4Department of Biomedical Engineering, Kyushu University, Fukuoka, Japan Received 8 March 2002; revised 13 May 2002; accepted 16 May 2002 Abstract: An in vivo mouse cage implant system was used to determine whether leukocyte cytokine mRNA responses to implanted biomaterials were dependent on surface chem- istry. Surfaces displaying various chemistries (hydrophobic, hydrophilic, anionic, and cationic) were placed into stainless steel cages and implanted subcutaneously. Semiquantitative RT-PCR analyses revealed that hydrophilic surfaces showed a decreased expression of proinflammatory cytokines, IL-6 and IL-8, and pro-wound healing cytokines, IL-10 and TGF- by adherent cells, and mRNA levels of the proinflam- matory cytokine, IL-1, and the pro-wound healing cytokine IL-13 were decreased in surrounding, exudate cells. Cyto- kine responses by adherent and exudate cells to hydropho- bic, anionic and cationic surfaces were similar and indicative of a strong inflammatory response at the earliest time point followed by a wound healing response at later time points. However, no differences in the types or levels of exudate cells for any of the surfaces or the empty cage at each of the respective time points were observed, indicating their re- spective biocompatibility. These studies identify hydrophilic surface chemistries as having significant effects on leukocyte cytokine responses in vivo by decreasing the expression of inflammatory and wound healing cytokines by inflamma- tory cells adherent to the biomater