Skip to main content
Top
Published in: Clinical Oral Investigations 7/2017

01-09-2017 | Original Article

Osteogain® loaded onto an absorbable collagen sponge induces attachment and osteoblast differentiation of ST2 cells in vitro

Authors: Richard J. Miron, Masako Fujioka-Kobayashi, Yufeng Zhang, Anton Sculean, Benjamin Pippenger, Yoshinori Shirakata, Umadevi Kandalam, Maria Hernandez

Published in: Clinical Oral Investigations | Issue 7/2017

Login to get access

Abstract

Objectives

Dimensional changes of the alveolar bone following tooth extraction are a major challenge in daily dental practice. To limit bone loss, a variety of biomaterials including bone grafts, barrier membranes, and growth factors have been utilized either alone or in combination therapies to increase the speed and quality of new bone formation. The aim of the present in vitro study was to investigate the regenerative potential of Osteogain®, a new liquid carrier system of enamel matrix derivative (EMD) in combination with an absorbable collagen sponge (ACS) specifically designed for extraction socket healing.

Materials and methods

The potential of ACS was first investigated using ELISA to quantify total amelogenin adsorption and release from 0 to 10 days. Thereafter, the cellular effects of ST2 pre-osteoblasts were investigated for cellular attachment at 8 h and cell proliferation at 1, 3, and 5 days as well as osteoblast differentiation by real-time PCR and alizarin red staining for cells seeded on (1) tissue culture plastic, (2) ACS alone, and (3) ACS + Osteogain®.

Results

ACS efficiently loaded nearly 100% of the amelogenin proteins found in Osteogain® which were gradually released up to a 10-day period. Osteogain® also significantly induced a 1.5-fold increase in cell attachment and resulted in a 2–6-fold increase in mRNA levels of osteoblast differentiation markers including runt-related transcription factor 2 (Runx2), collagen1a2, alkaline phosphatase, and bone sialoprotein as well as induced alizarin red staining when combined with ACS.

Conclusions

In summary, these findings suggest that Osteogain® is capable of inducing osteoblast attachment and differentiation when combined with ACS. Future animal studies and randomized human clinical trials are necessary to further support these findings.

Clinical relevance

The use of Osteogain® in combination with ACS may provide a valuable means to limit dimensional changes following tooth extraction.
Literature
1.
go back to reference Johnson K (1963) A study of the dimensional changes occurring in the maxilla after tooth extraction.—part I. Normal healing. Aust Dent J 8:428–433CrossRef Johnson K (1963) A study of the dimensional changes occurring in the maxilla after tooth extraction.—part I. Normal healing. Aust Dent J 8:428–433CrossRef
2.
go back to reference Araújo MG, Lindhe J (2005) Dimensional ridge alterations following tooth extraction. An experimental study in the dog. J Clin Periodontol 32:212–218CrossRefPubMed Araújo MG, Lindhe J (2005) Dimensional ridge alterations following tooth extraction. An experimental study in the dog. J Clin Periodontol 32:212–218CrossRefPubMed
4.
go back to reference Brkovic BM, Prasad HS, Konandreas G, Milan R, Antunovic D, Sandor GK, Rohrer MD (2008) Simple preservation of a maxillary extraction socket using beta-tricalcium phosphate with type I collagen: preliminary clinical and histomorphometric observations. J (Canadian Dental Association) 74:523–528 Brkovic BM, Prasad HS, Konandreas G, Milan R, Antunovic D, Sandor GK, Rohrer MD (2008) Simple preservation of a maxillary extraction socket using beta-tricalcium phosphate with type I collagen: preliminary clinical and histomorphometric observations. J (Canadian Dental Association) 74:523–528
5.
go back to reference Brkovic BM, Prasad HS, Rohrer MD, Konandreas G, Agrogiannis G, Antunovic D, Sandor GK (2012) Beta-tricalcium phosphate/type I collagen cones with or without a barrier membrane in human extraction socket healing: clinical, histologic, histomorphometric, and immunohistochemical evaluation. Clin Oral Invest 16:581–590. doi:10.1007/s00784-011-0531-1 CrossRef Brkovic BM, Prasad HS, Rohrer MD, Konandreas G, Agrogiannis G, Antunovic D, Sandor GK (2012) Beta-tricalcium phosphate/type I collagen cones with or without a barrier membrane in human extraction socket healing: clinical, histologic, histomorphometric, and immunohistochemical evaluation. Clin Oral Invest 16:581–590. doi:10.​1007/​s00784-011-0531-1 CrossRef
7.
go back to reference Wallace S (2015) Histomorphometric and 3D cone-beam computerized tomographic evaluation of socket preservation in molar extraction sites using human particulate mineralized cancellous allograft bone with a porcine collagen xenograft barrier: a case series. J Oral Implantol 41:291–297. doi:10.1563/aaid-joi-D-14-00078 CrossRefPubMed Wallace S (2015) Histomorphometric and 3D cone-beam computerized tomographic evaluation of socket preservation in molar extraction sites using human particulate mineralized cancellous allograft bone with a porcine collagen xenograft barrier: a case series. J Oral Implantol 41:291–297. doi:10.​1563/​aaid-joi-D-14-00078 CrossRefPubMed
8.
go back to reference Bayat M, Momen Heravi F, Mahmoudi M, Bahrami N (2015) Bone reconstruction following application of bone matrix gelatin to alveolar defects: a randomized clinical trial. Int J Organ Transplant Med 6:176–181PubMedPubMedCentral Bayat M, Momen Heravi F, Mahmoudi M, Bahrami N (2015) Bone reconstruction following application of bone matrix gelatin to alveolar defects: a randomized clinical trial. Int J Organ Transplant Med 6:176–181PubMedPubMedCentral
10.
go back to reference Coomes AM, Mealey BL, Huynh-Ba G, Barboza-Arguello C, Moore WS, Cochran DL (2014) Buccal bone formation after flapless extraction: a randomized, controlled clinical trial comparing recombinant human bone morphogenetic protein 2/absorbable collagen carrier and collagen sponge alone. J Periodontol 85:525–535. doi:10.1902/jop.2013.130207 CrossRefPubMed Coomes AM, Mealey BL, Huynh-Ba G, Barboza-Arguello C, Moore WS, Cochran DL (2014) Buccal bone formation after flapless extraction: a randomized, controlled clinical trial comparing recombinant human bone morphogenetic protein 2/absorbable collagen carrier and collagen sponge alone. J Periodontol 85:525–535. doi:10.​1902/​jop.​2013.​130207 CrossRefPubMed
11.
go back to reference Fiorellini JP, Howell TH, Cochran D, Malmquist J, Lilly LC, Spagnoli D, Toljanic J, Jones A, Nevins M (2005) Randomized study evaluating recombinant human bone morphogenetic protein-2 for extraction socket augmentation. J Periodontol 76:605–613. doi:10.1902/jop.2005.76.4.605 CrossRefPubMed Fiorellini JP, Howell TH, Cochran D, Malmquist J, Lilly LC, Spagnoli D, Toljanic J, Jones A, Nevins M (2005) Randomized study evaluating recombinant human bone morphogenetic protein-2 for extraction socket augmentation. J Periodontol 76:605–613. doi:10.​1902/​jop.​2005.​76.​4.​605 CrossRefPubMed
12.
go back to reference Misch CM (2010) The use of recombinant human bone morphogenetic protein-2 for the repair of extraction socket defects: a technical modification and case series report. Int J Oral Maxillofac Implants 25:1246–1252PubMed Misch CM (2010) The use of recombinant human bone morphogenetic protein-2 for the repair of extraction socket defects: a technical modification and case series report. Int J Oral Maxillofac Implants 25:1246–1252PubMed
13.
go back to reference Wallace SC, Pikos MA, Prasad H (2014) De novo bone regeneration in human extraction sites using recombinant human bone morphogenetic protein-2/ACS: a clinical, histomorphometric, densitometric, and 3-dimensional cone-beam computerized tomographic scan evaluation. Implant Dent 23:132–137. doi:10.1097/id.0000000000000035 CrossRefPubMed Wallace SC, Pikos MA, Prasad H (2014) De novo bone regeneration in human extraction sites using recombinant human bone morphogenetic protein-2/ACS: a clinical, histomorphometric, densitometric, and 3-dimensional cone-beam computerized tomographic scan evaluation. Implant Dent 23:132–137. doi:10.​1097/​id.​0000000000000035​ CrossRefPubMed
14.
go back to reference De Risi V, Clementini M, Vittorini G, Mannocci A, De Sanctis M (2015) Alveolar ridge preservation techniques: a systematic review and meta-analysis of histological and histomorphometrical data. Clin Oral Implants Res 26:50–68. doi:10.1111/clr.12288 CrossRefPubMed De Risi V, Clementini M, Vittorini G, Mannocci A, De Sanctis M (2015) Alveolar ridge preservation techniques: a systematic review and meta-analysis of histological and histomorphometrical data. Clin Oral Implants Res 26:50–68. doi:10.​1111/​clr.​12288 CrossRefPubMed
20.
go back to reference De Sarkar A, Singhvi N, Shetty JN, Ramakrishna T, Shetye O, Islam M, Keerthy H (2015) The local effect of alendronate with intra-alveolar collagen sponges on post extraction alveolar ridge resorption: a clinical trial. J Maxillofac Oral Surg 14:344–356. doi:10.1007/s12663-014-0633-9 CrossRefPubMed De Sarkar A, Singhvi N, Shetty JN, Ramakrishna T, Shetye O, Islam M, Keerthy H (2015) The local effect of alendronate with intra-alveolar collagen sponges on post extraction alveolar ridge resorption: a clinical trial. J Maxillofac Oral Surg 14:344–356. doi:10.​1007/​s12663-014-0633-9 CrossRefPubMed
21.
go back to reference Zhang Y, Yang S, Zhou W, Fu H, Qian L, Miron RJ (2015) Addition of a synthetically fabricated osteoinductive biphasic calcium phosphate bone graft to BMP2 improves new bone formation. Clin Implant Dent Relat Res. doi:10.1111/cid.12384 Zhang Y, Yang S, Zhou W, Fu H, Qian L, Miron RJ (2015) Addition of a synthetically fabricated osteoinductive biphasic calcium phosphate bone graft to BMP2 improves new bone formation. Clin Implant Dent Relat Res. doi:10.​1111/​cid.​12384
22.
go back to reference Miron RJ, Bosshardt DD, Buser D, Zhang Y, Tugulu S, Gemperli A, Dard M, Caluseru OM, Chandad F, Sculean A (2015) Comparison of the capacity of enamel matrix derivative gel and enamel matrix derivative in liquid formulation to adsorb to bone grafting materials. J Periodontol 86:578–587. doi:10.1902/jop.2015.140538 CrossRefPubMed Miron RJ, Bosshardt DD, Buser D, Zhang Y, Tugulu S, Gemperli A, Dard M, Caluseru OM, Chandad F, Sculean A (2015) Comparison of the capacity of enamel matrix derivative gel and enamel matrix derivative in liquid formulation to adsorb to bone grafting materials. J Periodontol 86:578–587. doi:10.​1902/​jop.​2015.​140538 CrossRefPubMed
23.
go back to reference Miron RJ, Chandad F, Buser D, Sculean A, Cochran DL, Zhang Y (2016) Effect of enamel matrix derivative liquid on osteoblast and periodontal ligament cell proliferation and differentiation. J Periodontol 87:91–99. doi:10.1902/jop.2015.150389 CrossRefPubMed Miron RJ, Chandad F, Buser D, Sculean A, Cochran DL, Zhang Y (2016) Effect of enamel matrix derivative liquid on osteoblast and periodontal ligament cell proliferation and differentiation. J Periodontol 87:91–99. doi:10.​1902/​jop.​2015.​150389 CrossRefPubMed
24.
go back to reference Zhang Y, Jing D, Buser D, Sculean A, Chandad F, Miron RJ (2016) Bone grafting material in combination with Osteogain for bone repair: a rat histomorphometric study. Clin Oral Invest 20:589–595. doi:10.1007/s00784-015-1532-2 CrossRef Zhang Y, Jing D, Buser D, Sculean A, Chandad F, Miron RJ (2016) Bone grafting material in combination with Osteogain for bone repair: a rat histomorphometric study. Clin Oral Invest 20:589–595. doi:10.​1007/​s00784-015-1532-2 CrossRef
25.
go back to reference Miron RJ, Sculean A, Cochran DL, Froum S, Zucchelli G, Nemcovsky C, Donos N, Lyngstadaas SP, Deschner J, Dard M, Stavropoulos A, Zhang Y, Trombelli L, Kasaj A, Shirakata Y, Cortellini P, Tonetti M, Rasperini G, Jepsen S, Bosshardt DD (2016) 20 years of enamel matrix derivative: the past, the present and the future. J Clin Periodontol. doi:10.1111/jcpe.12546 PubMed Miron RJ, Sculean A, Cochran DL, Froum S, Zucchelli G, Nemcovsky C, Donos N, Lyngstadaas SP, Deschner J, Dard M, Stavropoulos A, Zhang Y, Trombelli L, Kasaj A, Shirakata Y, Cortellini P, Tonetti M, Rasperini G, Jepsen S, Bosshardt DD (2016) 20 years of enamel matrix derivative: the past, the present and the future. J Clin Periodontol. doi:10.​1111/​jcpe.​12546 PubMed
26.
go back to reference Boyan BD, Weesner TC, Lohmann CH, Andreacchio D, Carnes DL, Dean DD, Cochran DL, Schwartz Z (2000) Porcine fetal enamel matrix derivative enhances bone formation induced by demineralized freeze dried bone allograft in vivo. J Periodontol 71:1278–1286. doi:10.1902/jop.2000.71.8.1278 CrossRefPubMed Boyan BD, Weesner TC, Lohmann CH, Andreacchio D, Carnes DL, Dean DD, Cochran DL, Schwartz Z (2000) Porcine fetal enamel matrix derivative enhances bone formation induced by demineralized freeze dried bone allograft in vivo. J Periodontol 71:1278–1286. doi:10.​1902/​jop.​2000.​71.​8.​1278 CrossRefPubMed
31.
32.
go back to reference Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative CT method. Nat Protoc 3:1101–1108CrossRefPubMed Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative CT method. Nat Protoc 3:1101–1108CrossRefPubMed
33.
go back to reference Hoang AM, Klebe RJ, Steffensen B, Ryu OH, Simmer JP, Cochran DL (2002) Amelogenin is a cell adhesion protein. J Dent Res 81:497–500CrossRefPubMed Hoang AM, Klebe RJ, Steffensen B, Ryu OH, Simmer JP, Cochran DL (2002) Amelogenin is a cell adhesion protein. J Dent Res 81:497–500CrossRefPubMed
34.
go back to reference Quarles LD, Yohay DA, Lever LW, Caton R, Wenstrup RJ (1992) Distinct proliferative and differentiated stages of murine MC3T3-E1 cells in culture: an in vitro model of osteoblast development. J Bone Miner Res 7:683–692. doi:10.1002/jbmr.5650070613 CrossRefPubMed Quarles LD, Yohay DA, Lever LW, Caton R, Wenstrup RJ (1992) Distinct proliferative and differentiated stages of murine MC3T3-E1 cells in culture: an in vitro model of osteoblast development. J Bone Miner Res 7:683–692. doi:10.​1002/​jbmr.​5650070613 CrossRefPubMed
35.
go back to reference Miron RJ, Bosshardt DD, Hedbom E, Zhang Y, Haenni B, Buser D, Sculean A (2012) Adsorption of enamel matrix proteins to a bovine-derived bone grafting material and its regulation of cell adhesion, proliferation, and differentiation. J Periodontol 83:936–947. doi:10.1902/jop.2011.110480 CrossRefPubMed Miron RJ, Bosshardt DD, Hedbom E, Zhang Y, Haenni B, Buser D, Sculean A (2012) Adsorption of enamel matrix proteins to a bovine-derived bone grafting material and its regulation of cell adhesion, proliferation, and differentiation. J Periodontol 83:936–947. doi:10.​1902/​jop.​2011.​110480 CrossRefPubMed
36.
go back to reference Miron RJ, Caluseru OM, Guillemette V, Zhang Y, Buser D, Chandad F, Sculean A (2015) Effect of bone graft density on in vitro cell behavior with enamel matrix derivative. Clin Oral Invest 19:1643–1651. doi:10.1007/s00784-014-1388-x CrossRef Miron RJ, Caluseru OM, Guillemette V, Zhang Y, Buser D, Chandad F, Sculean A (2015) Effect of bone graft density on in vitro cell behavior with enamel matrix derivative. Clin Oral Invest 19:1643–1651. doi:10.​1007/​s00784-014-1388-x CrossRef
37.
go back to reference Miron RJ, Fujioka-Kobayashi M, Zhang Y, Caballe-Serrano J, Shirakata Y, Bosshardt DD, Buser D, Sculean A (2016) Osteogain improves osteoblast adhesion, proliferation and differentiation on a bovine-derived natural bone mineral. Clin Oral Implants Res. doi:10.1111/clr.12802 Miron RJ, Fujioka-Kobayashi M, Zhang Y, Caballe-Serrano J, Shirakata Y, Bosshardt DD, Buser D, Sculean A (2016) Osteogain improves osteoblast adhesion, proliferation and differentiation on a bovine-derived natural bone mineral. Clin Oral Implants Res. doi:10.​1111/​clr.​12802
Metadata
Title
Osteogain® loaded onto an absorbable collagen sponge induces attachment and osteoblast differentiation of ST2 cells in vitro
Authors
Richard J. Miron
Masako Fujioka-Kobayashi
Yufeng Zhang
Anton Sculean
Benjamin Pippenger
Yoshinori Shirakata
Umadevi Kandalam
Maria Hernandez
Publication date
01-09-2017
Publisher
Springer Berlin Heidelberg
Published in
Clinical Oral Investigations / Issue 7/2017
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-016-2019-5

Other articles of this Issue 7/2017

Clinical Oral Investigations 7/2017 Go to the issue