Abstract
The purpose of this project was to investigate the angiogenic mechanism of bioactive borate glass for soft tissue repair in a ‘hairless’ SKH1 mouse model. Subcutaneous microvascular responses to bioactive glass microfibers (45S5, 13-93B3, and 13-93B3Cu) and bioactive glass beads (13-93, 13-93B3, and 13-93B3Cu) were assessed via: noninvasive imaging of skin microvasculature; histomorphometry of microvascular densities; and quantitative PCR measurements of mRNA expression of VEGF and FGF-2 cytokines. Live imaging via dorsal skin windows showed the formation at twoweeks of a halo-like structure infused with microvessels surrounding implanted boratebased 13-93B3 and 13-93B3Cu glass beads, a response not observed with silicate-based 13-93 glass beads. Quantitative histomorphometry of tissues implanted with plugs of 45S5, 13-93B3, and 13-93B3Cu glass microfibers revealed microvascular densities that were 1.6-, 2.3-, and 2.7-times higher, respectively, than the sham control valueswhereas 13-93, 13-93B3, and 13-93B3Cu glass beads caused the microvascular density to increase 1.3-, 1.6-, and 2.5-fold, respectively, relative to sham controls. Quantitative PCR measurements indicate a marginally significant increased expression of VEGF mRNA in tissues with 13-93B3Cu glass beads, an outcome that supported the hypothesis that copper-doped borate glass could promote VEGF expression followed by angiogenesis for enhanced wound healing.
References
[1] Brown R., Watters R., Day D., Angiogenic Response of Bioactive Borate Glass Beads & Microfibers in “Hairless” Mice, The American Ceramic Society-Glass & Optical Materials Division and Deutsche Glastechnische Gesellschaft Joint Annual Meeting, Miami, FL, 17–21 May 2015. 10.1515/bglass-2015-0017Search in Google Scholar
[2] Chandan S., Gordillo M., Sashwati R., Kirsner R., Lambert L., Hunt T.K., et al., Human skin wounds: a major and snowballing threat to public health and the economy, Wound Repair Regen 2009, 17, 763–771. 10.1111/j.1524-475X.2009.00543.xSearch in Google Scholar
[3] Wu S., Driver V., Wrobel J., Armstrong D., Foot ulcers in the diabetic patient, prevention and treatment, Vasc Health Risk Manag 2007, 3, 65–76. Search in Google Scholar
[4] Caputo G., Cavanagh P., Ulbrecht J., Gibbons G., Karchmer A., Assessment and management of foot disease in patients with diabetes, New Engl J Med 1994, 13, 854-860. 10.1056/NEJM199409293311307Search in Google Scholar
[5] Keshaw H., Forbes A., Day R., Release of angiogenic growth factor from cells encapsulated in alginate beads with bioactive glass, Biomaterials 2005, 26, 4171–4179. 10.1016/j.biomaterials.2004.10.021Search in Google Scholar
[6] Barralet J., Gbureck U., Habibovic P., Vorndran E., Gerard C., Doillon C., Angiogenesis in calcium phosphate scaffolds by inorganic copper ion release, Tissue Eng 2009, 15, 1601–1608. 10.1089/ten.tea.2007.0370Search in Google Scholar
[7] Li J., Zhang Y., Kirsner R., Angiogenesis in wound repair: Angiogenic growth factors and the extracellular matrix, Microsc Res Tech 2003, 60, 107–114. 10.1002/jemt.10249Search in Google Scholar
[8] Cole R., Liu F., Herron B., Imaging of angiogenesis: past, present and future, In: A. Mendez – Vilas, J. Diaz (Eds.), Microscopy: Science, Technology, Applications and Education, Vol 3, Badajoz, Spain, 2010. Search in Google Scholar
[9] Folkman J., Shing Y., Angiogenesis, J Biol Chem 1992, 267, 10931–10934. 10.1016/S0021-9258(19)49853-0Search in Google Scholar
[10] Shih S., Robinson G., Perruzzi C., Calvo A., Desai K., Green J., et al., Molecular profiling of angiogenesis markers, Am J Pathol 2002, 161, 35–40. 10.1016/S0002-9440(10)64154-5Search in Google Scholar
[11] ClaytonW., Elasy T., A review of the pathophysiology, classification, and treatment of foot ulcers in diabetic patients, Clin Diabetes 2009, 27, 52–58. 10.2337/diaclin.27.2.52Search in Google Scholar
[12] Mohammad G., Pandey H., Tripathi K., Diabetic wound healing and its angiogenesis with special reference to nanoparticles, Dig J Nanomater Bios 2008, 3, 203–208. Search in Google Scholar
[13] Falanga V., Wound healing and its impairment in the diabetic foot, Lancet 2005, 366, 1736–43. 10.1016/S0140-6736(05)67700-8Search in Google Scholar
[14] Demidova-Rice T., Durham J., Herman I., Wound healing angiogenesis: innovations and challenges in acute and chronic wound healing, Adv Wound Care 2012, 1, 17–22. 10.1089/wound.2011.0308Search in Google Scholar
[15] Papanas N., Efstratios M., Becaplermin gel in the treatment of diabetic neuropathic foot ulcers, Clin Interv Aging, Jun 2008, 3(2), 233–240. 10.2147/CIA.S1106Search in Google Scholar
[16] Giavazzi R., Sennino B., Coltrini D., Garofalo A., Dossi R., Ronca R., et al., Distinct role of fibroblast growth factor-2 and vascular endothelial growth factor on tumor growth and angiogenesis, Am J Pathol, Jun 2003, 162, 1913–1926. 10.1016/S0002-9440(10)64325-8Search in Google Scholar
[17] Witkowski J., Parish L., Rational approach to wound care, Int J Dermatol 1992, 31, 27–28. 10.1111/j.1365-4362.1992.tb03514.xSearch in Google Scholar PubMed
[18] Fang R., Galiano R., A review of becaplermin gel in the treatment of diabetic neuropathic foot ulcers, Biologics, 2008, 2, 1–12. 10.2147/BTT.S1338Search in Google Scholar PubMed PubMed Central
[19] Hoppe A., Mouriñob V., Boccaccini A., Therapeutic inorganic ions in bioactive glasses to enhance bone formation and beyond, Biomater Sci 2013, 1, 254–256. 10.1039/C2BM00116KSearch in Google Scholar PubMed
[20] Chen Q., Zhu C., Thouas G., Progress and challenges in biomaterials used for bone tissue engineering: bioactive glasses and elastomeric composites, Prog Biomater 2012, 1(1), 2. 10.1186/2194-0517-1-2Search in Google Scholar PubMed PubMed Central
[21] Haro Durand L.A., Gongora A., Porto-Lopez J.M., Boccaccini A.R., Zago M.P., Baldi A., et al., In vitro endothelial cell response to ionic dissolution products from a boron-doped bioactive glass in the SiO2–CaO–P2O5–Na2O system, J Mater Chem B 2014, 2, 7620–7630. 10.1039/C4TB01043DSearch in Google Scholar
[22] Haro Durand L.A., Vargas G.E., Romero N.M., Vera-Mesones R., Porto-Lopez J.M., Boccaccini A.R., et al., Angiogenic effects of ionic dissolution products released from a boron-doped 45S5 bioactive glass, J Mater Chem B 2015, 3, 1142–1148. 10.1039/C4TB01840KSearch in Google Scholar
[23] Jung S., Borate Based Bioactive Glass Scaffolds for Hard and Soft Tissue Engineering, Ph.D Dissertation, Missouri University of Science and Technology, Rolla, MO, 2010. Search in Google Scholar
[24] Taylor P., personal communication, Phelps County Regional Medical Center, Rolla, MO. 2012. Search in Google Scholar
[25] Lin Y., Brown R., Jung S., Day D., Angiogenic effects of borate glass microfibers in a rodent model, J Biomed Mat Res A 2014, 102(12), 4491–4499. 10.1002/jbm.a.35120Search in Google Scholar PubMed
[26] Eliza M., Ben I., Reuven B., Histopathological periodic acid– schiff stains of nail clippings as a second-line diagnostic tool in onychomycosis, Am J Dermatopath 2012, 34, 270–273. 10.1097/DAD.0b013e318234cc49Search in Google Scholar
[27] Chomczynski P., Sacchi N., Single-step method of RNA isolation by acid guanidiniumthiocyanate-phenol-chloroform extraction, Anal Biochem 1987, 162, 156–9. 10.1016/0003-2697(87)90021-2Search in Google Scholar
[28] Chomczynski P., Sacchi N., The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: twenty-something years on, Nat Protoc 2006, 1, 581– 585. 10.1038/nprot.2006.83Search in Google Scholar
[29] Wong M., Medrano J., Real-time PCR for mRNA quantitation, BioTechniques 2005, 39, 75–85. 10.2144/05391RV01Search in Google Scholar
[30] Livak K., Schmittgen T., Analysis of relative gene expression data using real-time quantitative PCR and the 2-Search in Google Scholar
[Delta]Search in Google Scholar
[Delta]Ct method, Methods 2001, 25, 402–408. 10.1006/meth.2001.1262Search in Google Scholar
[31] Liu D., Handbook of Nucleic Acid Purification, CLC press, Boca Raton, FL. 2009. 10.1201/9781420070972Search in Google Scholar
[32] Zhao S., Li L., Wang H., Zhang Y., Cheng X., Zhou N., et al., Wound dressings composed of copper-doped borate bioactive glass microfibers stimulate angiogenesis and heal fullthickness skin defects in a rodent model, Biomaterials 2015, 53, 379–391. 10.1016/j.biomaterials.2015.02.112Search in Google Scholar
[33] Kucan J., Robson M., Heggers J., Ko F., Comparison of silver sulfadiazine, povidone-iodine and physiologic saline in the treatment of chronic pressure ulcers, J Am Geriatr Soc 1981, 29, 232– 235. 10.1111/j.1532-5415.1981.tb01773.xSearch in Google Scholar
[34] Harris E., A requirement for copper in angiogenesis, Nutr Rev 2004, 62, 60–64. 10.1111/j.1753-4887.2004.tb00025.xSearch in Google Scholar
[35] Hu G., Copper stimulates proliferation of human endothelial cells under culture, J Cellular Biochem 1998, 69, 326–335. 10.1002/(SICI)1097-4644(19980601)69:3<326::AID-JCB10>3.0.CO;2-ASearch in Google Scholar
[36] Sen C.K., Copper-induced vascular endothelial growth factor expression and wound healing, Am J Physiol 2002, 282, H1821– H1827. 10.1152/ajpheart.01015.2001Search in Google Scholar PubMed
[37] Emanueli C., Madeddu P., Angiogenesis gene therapy to rescue ischemic tissues: achievements and future directions, Brit J Pharmacol 2001, 133, 951–958. 10.1038/sj.bjp.0704155Search in Google Scholar PubMed PubMed Central
© 2015 R. J. Watters et al.
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.