TODENTJ-25-03-2019_TODENTJ-10-347 1553506529 Bentham Open doi@benthamopen.net Bentham Open The Open Dentistry Journal TODENTJ 1874-2106 07 29 2016 10 1 Takehito Momose Hirofumi Miyaji Akihito Kato Kosuke Ogawa Takashi Yoshida Erika Nishida Syusuke Murakami Yuta Kosen Tsutomu Sugaya Masamitsu Kawanami Objective: Collagen hydrogel scaffold exhibits bio-safe properties and facilitates periodontal wound healing. However, regenerated tissue volume is insufficient. Fibroblast growth factor-2 (FGF2) up-regulates cell behaviors and subsequent wound healing. We evaluated whether periodontal wound healing is promoted by application of collagen hydrogel scaffold in combination with FGF2 in furcation defects in beagle dogs. Methods: Collagen hydrogel was fabricated from bovine type I collagen with an ascorbate-copper ion cross-linking system. Collagen hydrogel was mingled with FGF2 and injected into sponge-form collagen. Subsequently, FGF2 (50 µg)/collagen hydrogel scaffold and collagen hydrogel scaffold alone were implanted into class II furcation defects in dogs. In addition, no implantation was performed as a control. Histometric parameters were assessed at 10 days and 4 weeks after surgery. Result: FGF2 application to scaffold promoted considerable cell and tissue ingrowth containing numerous cells and blood vessel-like structure at day 10. At 4 weeks, reconstruction of alveolar bone was stimulated by implantation of scaffold loaded with FGF2. Furthermore, periodontal attachment, consisting of cementum-like tissue, periodontal ligament-like tissue and Sharpey’s fibers, was also repaired, indicating that FGF2-loaded scaffold guided self-assembly and then re-established the function of periodontal organs. Aberrant healing, such as ankylosis and root resorption, was not observed. Conclusion: FGF2-loaded collagen hydrogel scaffold possessed excellent biocompatibility and strongly promoted periodontal tissue engineering, including periodontal attachment re-organization. 07 29 2016 347 359 TODENTJ-10-347 1 10.2174/crossmark_policy opendentistryjournal.com benthamopen.com true Peer Reviewed Single blind Checked with iThenticate 2015-11-26 2016-6-13 2016-6-21 2016-07-29 https://creativecommons.org/licenses/by-nc/4.0/legalcode 10.2174/1874210601610010347 1553506529 https://opendentistryjournal.com/VOLUME/10/PAGE/347/ https://opendentistryjournal.com/contents/volumes/V10/TODENTJ-10-347/TODENTJ-10-347.pdf https://opendentistryjournal.com/contents/volumes/V10/TODENTJ-10-347/TODENTJ-10-347.pdf https://opendentistryjournal.com/contents/volumes/V10/TODENTJ-10-347/TODENTJ-10-347.pdf https://opendentistryjournal.com/contents/volumes/V10/TODENTJ-10-347/TODENTJ-10-347.pdf https://opendentistryjournal.com/contents/volumes/V10/TODENTJ-10-347/TODENTJ-10-347.pdf https://opendentistryjournal.com/contents/volumes/V10/TODENTJ-10-347/TODENTJ-10-347.pdf https://opendentistryjournal.com/contents/volumes/V10/TODENTJ-10-347/TODENTJ-10-347.pdf https://opendentistryjournal.com/contents/volumes/V10/TODENTJ-10-347/TODENTJ-10-347.xml J. Craniofac. Surg. Cicciù M. 25 860 2014 10.1097/SCS.0000000000000830 Cicciù M, Herford AS, Cicciù D, Tandon R, Maiorana C. Recombinant human bone morphogenetic protein-2 promote and stabilize hard and soft tissue healing for large mandibular new bone reconstruction defects. J Craniofac Surg 2014; 25 (3) : 860-2. Biomed Res Int Petrauskaite O 2013 1 2013 Petrauskaite O, Gomes Pde S, Fernandes MH, et al. Biomimetic mineralization on a macroporous cellulose-based matrix for bone regeneration. Biomed Res Int 2013; 2013 : 1-9. (Article ID 452750) Open Dent. J. Maiorana C. 5 71 2011 10.2174/1874210601105010071 Maiorana C, Beretta M, Battista Grossi G, et al. Histomorphometric evaluation of anorganic bovine bone coverage to reduce autogenous grafts resorption: preliminary results. Open Dent J 2011; 5 : 71-8. Med. Oral Patol. Oral Cir. Bucal Park J.B. 16 e115 2011 10.4317/medoral.16.e115 Park JB. The use of hydrogels in bone-tissue engineering. Med Oral Patol Oral Cir Bucal 2011; 16 (1) : e115-8. J. Mater. Sci. Mater. Med. Barralet J.E. 16 515 2005 10.1007/s10856-005-0526-z Barralet JE, Wang L, Lawson M, Triffitt JT, Cooper PR, Shelton RM. Comparison of bone marrow cell growth on 2D and 3D alginate hydrogels. J Mater Sci Mater Med 2005; 16 (6) : 515-9. J. Mater. Sci. Mater. Med. Cui F.Z. 17 1393 2006 10.1007/s10856-006-0615-7 Cui FZ, Tian WM, Hou SP, Xu QY, Lee IS. Hyaluronic acid hydrogel immobilized with RGD peptides for brain tissue engineering. J Mater Sci Mater Med 2006; 17 (12) : 1393-401. J. Biomed. Mater. Res. A Hong Y. 79 913 2006 10.1002/jbm.a.30837 Hong Y, Mao Z, Wang H, Gao C, Shen J. Covalently crosslinked chitosan hydrogel formed at neutral pH and body temperature. J Biomed Mater Res A 2006; 79 (4) : 913-22. J. Biomed. Mater. Res. A Hesse E. 94 442 2010 Hesse E, Hefferan TE, Tarara JE, et al. Collagen type I hydrogel allows migration, proliferation, and osteogenic differentiation of rat bone marrow stromal cells. J Biomed Mater Res A 2010; 94 (2) : 442-9. Ann. Plast. Surg. Asamura S. 64 496 2010 10.1097/SAP.0b013e31819b6c52 Asamura S, Mochizuki Y, Yamamoto M, Tabata Y, Isogai N. Bone regeneration using a bone morphogenetic protein-2 saturated slow-release gelatin hydrogel sheet: evaluation in a canine orbital floor fracture model. Ann Plast Surg 2010; 64 (4) : 496-502. Jpn J Artif Organs Ishikawa K. 26 791 1997 Ishikawa K, Matsui R, Takano Y, Katakura T. Preparation of biodegradable hydrogel. Jpn J Artif Organs 1997; 26 : 791-7. Jpn J Artif Organs Matsui R. 26 772 1997 Matsui R, Ishikawa K, Takano Y, Katakura T. Application of collagen hydrogel material onto model delayed closing of full-thickness skin defect wound on guinea-pig. Jpn J Artif Organs 1997; 26 : 772-8. J. Periodontal Res. Kosen Y. 47 626 2012 10.1111/j.1600-0765.2012.01475.x Kosen Y, Miyaji H, Kato A, Sugaya T, Kawanami M. Application of collagen hydrogel/sponge scaffold facilitates periodontal wound healing in class II furcation defects in beagle dogs. J Periodontal Res 2012; 47 (5) : 626-34. Open Dent. J. Kato A. 9 52 2015 10.2174/1874210601509010052 Kato A, Miyaji H, Ishizuka R, et al. Combination of root surface modification with BMP-2 and collagen hydrogel scaffold implantation for periodontal healing in beagle dogs. Open Dent J 2015; 9 : 52-9. Bone Kodama N. 44 699 2009 10.1016/j.bone.2008.12.017 Kodama N, Nagata M, Tabata Y, Ozeki M, Ninomiya T, Takagi R. A local bone anabolic effect of rhFGF2-impregnated gelatin hydrogel by promoting cell proliferation and coordinating osteoblastic differentiation. Bone 2009; 44 (4) : 699-707. J Tissue Eng Yun YR 1 1 2010 Yun YR, Won JE, Jeon E, et al. Fibroblast growth factors: biology, function, and application for tissue regeneration. J Tissue Eng 2010; 1 : 1-18. (Article ID 218142) N. Engl. J. Med. Singer A.J. 341 738 1999 10.1056/NEJM199909023411006 Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med 1999; 341 (10) : 738-46. Endocrinology Martin I. 138 4456 1997 Martin I, Muraglia A, Campanile G, Cancedda R, Quarto R. Fibroblast growth factor-2 supports ex vivo expansion and maintenance of osteogenic precursors from human bone marrow. Endocrinology 1997; 138 (10) : 4456-62. Bone Zellin G. 26 161 2000 10.1016/S8756-3282(99)00252-5 Zellin G, Linde A. Effects of recombinant human fibroblast growth factor-2 on osteogenic cell populations during orthopic osteogenesis in vivo.. Bone 2000; 26 (2) : 161-8. J Periodont Res Murakami S 38 97 2003 Murakami S, Takayama S, Kitamura M, et al. Recombinant human basic fibroblast growth factor (bFGF) stimulates periodontal regeneration in class II furcation defects created in beagle dogs. J Periodont Res 2003; 38 : 97-103. J. Dent. Res. Takayama S. 80 2075 2001 10.1177/00220345010800121001 Takayama S, Murakami S, Shimabukuro Y, Kitamura M, Okada H. Periodontal regeneration by FGF-2 (bFGF) in primate models. J Dent Res 2001; 80 (12) : 2075-9. J Nanomater Ibara A 2013 1 2013 Ibara A, Miyaji H, Fugetsu B, et al. Osteoconductivity and biodegradability of collagen scaffold coated with nano-β-TCP and fibroblast growth factor 2. J Nanomater 2013; 2013 : 1-11. (Article ID 639502) J. Periodontol. Kim Y.T. 84 812 2013 10.1902/jop.2012.120307 Kim YT, Wikesjö UM, Jung UW, Lee JS, Kim TG, Kim CK. Comparison between a β-tricalcium phosphate and an absorbable collagen sponge carrier technology for rhGDF-5-stimulated periodontal wound healing/regeneration. J Periodontol 2013; 84 (6) : 812-20. Nature Gospodarowicz D. 249 123 1974 10.1038/249123a0 Gospodarowicz D. Localisation of a fibroblast growth factor and its effect alone and with hydrocortisone on 3T3 cell growth. Nature 1974; 249 (453) : 123-7. Kidney Int. Strutz F. 57 1521 2000 10.1046/j.1523-1755.2000.00997.x Strutz F, Zeisberg M, Hemmerlein B, et al. Basic fibroblast growth factor expression is increased in human renal fibrogenesis and may mediate autocrine fibroblast proliferation. Kidney Int 2000; 57 (4) : 1521-38. J. Bone Miner. Res. Debiais F. 13 645 1998 10.1359/jbmr.1998.13.4.645 Debiais F, Hott M, Graulet AM, Marie PJ. The effects of fibroblast growth factor-2 on human neonatal calvaria osteoblastic cells are differentiation stage specific. J Bone Miner Res 1998; 13 (4) : 645-54. Arch. Oral Biol. Donzelli E. 52 64 2007 10.1016/j.archoralbio.2006.07.007 Donzelli E, Salvadè A, Mimo P, et al. Mesenchymal stem cells cultured on a collagen scaffold: In vitro osteogenic differentiation. Arch Oral Biol 2007; 52 (1) : 64-73. Cell. Dev. Biol. Anim. Talley-Ronsholdt D.J. 31 274 1995 10.1007/BF02634001 Talley-Ronsholdt DJ, Lajiness E, Nagodawithana K. Transforming growth factor-beta inhibition of mineralization by neonatal rat osteoblasts in monolayer and collagen gel culture. In Vitro Cell Dev Biol Anim 1995; 31 (4) : 274-82. Annu. Rev. Physiol. Klagsbrun M. 53 217 1991 10.1146/annurev.ph.53.030191.001245 Klagsbrun M, D’Amore PA. Regulators of angiogenesis. Annu Rev Physiol 1991; 53 : 217-39. J. Dent. Res. Yanagita M. 93 89 2014 10.1177/0022034513511640 Yanagita M, Kojima Y, Kubota M, et al. Cooperative effects of FGF-2 and VEGF-A in periodontal ligament cells. J Dent Res 2014; 93 (1) : 89-95. Periodontol. 2000 Aukhil I. 22 44 2000 10.1034/j.1600-0757.2000.2220104.x Aukhil I. Biology of wound healing. Periodontol 2000 2000; 22 (22) : 44-50. Br. J. Oral Maxillofac. Surg. Fujimura K. 39 294 2001 10.1054/bjom.2001.0647 Fujimura K, Bessho K, Kusumoto K, Konishi Y, Ogawa Y, Iizuka T. Experimental osteoinduction by recombinant human bone morphogeneticprotein 2 in tissue with low blood flow: a study in rats. Br J Oral Maxillofac Surg 2001; 39 (4) : 294-300. Arch. Oral Biol. Hidaka T. 57 830 2012 10.1016/j.archoralbio.2011.12.003 Hidaka T, Nagasawa T, Shirai K, Kado T, Furuichi Y. FGF-2 induces proliferation of human periodontal ligament cells and maintains differentiation potentials of STRO-1(+)/CD146(+) periodontal ligament cells. Arch Oral Biol 2012; 57 (6) : 830-40. J. Craniofac. Surg. Herford A.S. 24 1383 2013 10.1097/SCS.0b013e318292c2ce Herford AS, Tandon R, Stevens TW, Stoffella E, Cicciu M. Immediate distraction osteogenesis: the sandwich technique in combination with rhBMP-2 for anterior maxillary and mandibular defects. J Craniofac Surg 2013; 24 (4) : 1383-7. J. Craniofac. Surg. Cicciù M. 23 784 2012 10.1097/SCS.0b013e31824dbdd4 Cicciù M, Herford AS, Juodžbalys G, Stoffella E. Recombinant human bone morphogenetic protein type 2 application for a possible treatment of bisphosphonates-related osteonecrosis of the jaw. J Craniofac Surg 2012; 23 (3) : 784-8. J. Craniofac. Surg. Herford A.S. 21 1970 2010 10.1097/SCS.0b013e3181f502fa Herford AS, Cicciù M. Recombinant human bone morphogenetic protein type 2 jaw reconstruction in patients affected by giant cell tumor. J Craniofac Surg 2010; 21 (6) : 1970-5. J. Biochem. Kano Y. 102 839 1987 Kano Y, Sakano Y, Fujimoto D. Cross-linking of collagen by ascorbate-copper ion systems. J Biochem 1987; 102 (4) : 839-42. Br. J. Plast. Surg. Suzuki S. 53 659 2000 10.1054/bjps.2000.3426 Suzuki S, Kawai K, Ashoori F, Morimoto N, Nishimura Y, Ikada Y. Long-term follow-up study of artificial dermis composed of outer silicone layer and inner collagen sponge. Br J Plast Surg 2000; 53 (8) : 659-66. Br. J. Plast. Surg. Abramo A.C. 45 117 1992 10.1016/0007-1226(92)90170-3 Abramo AC, Viola JC. Heterologous collagen matrix sponge: histologic and clinical response to its implantation in third-degree burn injuries. Br J Plast Surg 1992; 45 (2) : 117-22. J. Clin. Diagn. Res. D’lima J.P. 8 ZC52 2014 D’lima JP, Paul J, Palathingal P, Varma B, Bhat M, Mohanty M. Histological and histometrical evaluation of two synthetic hydroxyapatite based biomaterials in the experimental periodontal defects in dogs. J Clin Diagn Res 2014; 8 (9) : ZC52-5. Biomaterials Matsui R. 17 995 1996 10.1016/0142-9612(96)84674-6 Matsui R, Okura N, Osaki K, Konishi J, Ikegami K, Koide M. Histological evaluation of skin reconstruction using artificial dermis. Biomaterials 1996; 17 (10) : 995-1000.