Perioperative steroid administration inhibits angiogenic host tissue response to porous polyethylene (medpor®) implants

Abstract

Porous polyethylene (Medpor ® ) is an alloplastic biomaterial, which is commonly used in plastic and reconstructive surgery. In the present study, we analyzed the effect of perioperative steroid administration on the inflammatory and angiogenic host tissue response to implanted Medpor ® . For this purpose, Medpor ® was implanted into the dorsal skinfold chamber of prednisolonetreated and vehicle-treated (control) balb/c mice and analyzed by means of intravital fluorescence microscopy over a 14-day period. Incorporation of the implants was evaluated by histology. An aortic ring assay and Western blot analyses were performed to determine in vitro the effect of prednisolone on angiogenesis. Implantation of Medpor ® did not induce a leukocytic inflammatory host tissue response. However, in prednisolone-treated and control animals giant cells could be detected at the interface between the implants and the surrounding granulation tissue as a typical indicator for a chronic foreign body reaction. Interestingly, perioperative prednisolone administration inhibited vascularisation of the implants, as indicated by a significantly decreased functional density of newly developing capillary blood vessels. Accordingly, prednisolone suppressed in vitro endothelial sprouting and tube formation in the aortic ring assay and reduced proliferating cell nuclear antigen (PCNA), Tie2, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 expression of murine endothelioma cells. In conclusion, prednisolone treatment inhibits the early vascularisation of Medpor ® implants due to direct inhibition of distinct angiogenic mechanisms. Therefore, perioperative steroid therapy should be avoided in case of Medpor ® implantation to achieve a rapid incorporation of the biomaterial at the implantation site.

Inhibition of protein kinase CK2 suppresses tumor necrosis factor (TNF)-α-induced leukocyte–endothelial cell interaction

“…Accordingly, inhibition of CK2 by quinalizarin or CX-4945 markedly decreased the number of bound MNC in our leukocyte adhesion assay. To confirm these in vitro results in vivo, we used the dorsal skinfold chamber, which has been proven to be a suitable model for the analysis of leukocyte-endothelial cell interaction under physiological and inflammatory conditions by means of intravital fluorescence microscopy [27,28,64]. For this purpose, we repetitively assessed the number of rolling and adherent leukocytes in postcapillary and collecting venules of TNF-α-treated chambers.…”

Protein kinase CK2 is a regulator of angiogenesis in endometriotic lesions

“…To analyze in vitro the anti-angiogenic activity of different doses of the CK2 inhibitor quinalizarin, an aortic ring assay was performed with aortic rings of 3 male Sprague-Dawley rats (250-300 g body weight), as described previously [20]. Matrigel-embedded rings were overlaid with 800 lL of Dulbecco's modified Eagle's medium (DMEM, 10% fetal calf serum (FCS), 100 U/mL penicillin, 0.1 mg/mL streptomycin; PAA, Cölbe, Germany) supplemented with 10, 25 and 50 lM quinalizarin (Labotest, Niederschöna, Germany) or vehicle (DMSO; Sigma-Aldrich, Taufkirchen, Germany), respectively, and maintained at 37°C and 5% CO 2 for 6 days with medium change at day 3.…”

Prednisolone treatment reduces endometrial spiral artery development in women with recurrent miscarriage

“…In addition, the percentage of airways immunostained positive for vascular endothelial growth factor (VEGF)-A was also reduced, although immunostaining for VEGF-R1, VEGF-R2 and Ang-1 did not alter [28]. More recently, Ehrmantraut et al [29] demonstrated reduced angiogenesis associated with porous polyethylene (MEDPOR Ò ) implants in vivo after prednisolone administration as well as reduced outgrowth from an in vitro aortic ring culture model after culture with prednisolone. In addition, murine endothelial cells cultured with prednisolone had reduced Tie-2, VEGF-A and matrix metalloproteinase (MMP)-9 protein levels as determined by Western Blot analysis [29].…”

“…We have, however, demonstrated that prednisolone treatment reduces the percentage of non-pregnant mid-luteal phase endometrial blood vessels that are completely surrounded by VSMCs. The degree of maturation of the vasculature was not studied in these previous studies [26][27][28][29].…”

“…More recently, Ehrmantraut et al [29] demonstrated reduced angiogenesis associated with porous polyethylene (MEDPOR Ò ) implants in vivo after prednisolone administration as well as reduced outgrowth from an in vitro aortic ring culture model after culture with prednisolone. In addition, murine endothelial cells cultured with prednisolone had reduced Tie-2, VEGF-A and matrix metalloproteinase (MMP)-9 protein levels as determined by Western Blot analysis [29]. In contrast, in the current study administration of prednisolone did not alter the total number of blood vessels in non-pregnant mid-luteal phase endometrium as assessed by the total number of either EC or VSMC marker positive vessel profiles.…”