FGF-2-loaded collagen scaffolds attract cells and blood vessels in rat oral mucosa.

J Oral Pathol Med. 2009 Mar 4; Jansen RG, van Kuppevelt TH, Daamen WF, Kuijpers-Jagtman AM, Von den Hoff JWJ Oral Pathol Med (2009)Background: Wound contraction and scar formation after cleft palate repair impair the growth of the maxilla. The implantation of a growth factor-loaded scaffold might solve these problems. Methods: The tissue response to fibroblast growth factor (FGF)-2 loaded collagen scaffolds was evaluated after implantation in the palate of rats. Scaffolds, with and without FGF-2, were implanted submucoperiosteally in the palate of 25 rats and evaluated after up to 16 weeks. On hematoxylin and eosin (H&E)-stained sections, the cell density and the number of giant cells within the scaffolds were quantified. Infiltration of inflammatory cells, myofibroblasts, and the number of blood vessels were quantified after immunohistochemistry. Results: The cell density was significantly higher in the FGF-2 group up to 4 weeks after implantation (102% at 2 weeks, P < 0.001). The number of blood vessels was also significantly higher in the FGF-2 group at 1 and 2 weeks (316% at 1 week, P = 0.003), but the myofibroblast score was lower (100% at 2 weeks, P = 0.008). A comparable mild and rapidly subsiding inflammatory response and foreign body reaction were found in both groups. Conclusion: FGF-2-loaded scaffolds displayed a faster influx of host cells, an increased rate of vascularization, and a reduced differentiation of myofibroblasts. These scaffolds might therefore be highly suitable for intra-oral reconstructions, such as cleft palate repair.

Inhibition of Vascular Endothelial Growth Factor Reduces Scar Formation after Glaucoma Filtration Surgery.

Invest Ophthalmol Vis Sci. 2009 May 27; Li Z, Van Bergen T, Van de Veire S, Van de Vel I, Moreau H, Dewerchin M, Maudgal P, Zeyen T, Spileers W, Moons L, Stalmans IPURPOSE: Filtration failure due to excessive post-operative scarring remains a major problem after glaucoma surgery. We have investigated whether glaucoma and filtration surgery are associated with increased levels of vascular endothelial growth factor (VEGF), and whether a humanized monoclonal antibody against VEGF, bevacizumab (AvastinTM, Genentech), can reduce post-operative scar formation and improve surgical outcome. METHODS: The levels of VEGF in samples of aqueous humour were measured by ELISA. The expression of the VEGF receptors Flt-1 and KDR was analysed in cultured Tenon fibroblasts by real-time RT-PCR and western blotting. The effect of VEGF and bevacizumab on Tenon fibroblasts in vitro was determined using a proliferation assay. The in vivo effect of the antibody was investigated in a rabbit model of trabeculectomy by measuring the intraocular pressure (IOP) and bleb area, and by immunohistological analysis of angiogenesis, inflammation, and fibrosis. RESULTS: VEGF levels were increased significantly in the aqueous humour of glaucoma patients and rabbits that had undergone surgery. Both VEGF receptors were expressed on Tenon fibroblasts. Fibroblast proliferation in vitro was stimulated by delivery of VEGF, and was inhibited by administration of bevacizumab. The antibody also reduced angiogenesis and collagen deposition significantly, and improved the outcome of glaucoma surgery in rabbits. CONCLUSIONS: VEGF was up-regulated in the aqueous humour of glaucoma patients and in the rabbit model, and it stimulated fibroblast proliferation in vitro. This suggests that it is involved in the scarring processs after filtration surgery. Bevacizumab reduced the proliferation of fibroblasts in vitro and improved surgical outcome.