Skip to main content
Top
Published in: Clinical Oral Investigations 2/2014

01-03-2014 | Original Article

Effects of enamel matrix proteins in combination with a bovine-derived natural bone mineral for the repair of bone defects

Authors: Richard J. Miron, Lingfei Wei, Dieter D. Bosshardt, Daniel Buser, Anton Sculean, Yufeng Zhang

Published in: Clinical Oral Investigations | Issue 2/2014

Login to get access

Abstract

Objectives

Previously, the use of enamel matrix derivative (EMD) in combination with a natural bone mineral (NBM) was able to stimulate periodontal ligament cell and osteoblast proliferation and differentiation. Despite widespread use of EMD for periodontal applications, the effects of EMD on bone regeneration are not well understood. The aim of the present study was to test the ability of EMD on bone regeneration in a rat femur defect model in combination with NBM.

Materials and methods

Twenty-seven rats were treated with either NBM or NBM + EMD and assigned to histological analysis at 2, 4, and 8 weeks. Defect morphology and mineralized bone were assessed by μCT. For descriptive histology, hematoxylin and eosin staining and Safranin O staining were performed.

Results

Significantly more newly formed trabecular bone was observed at 4 weeks around the NBM particles precoated with EMD when compared with NBM particles alone. The drilled control group, in contrast, achieved minimal bone regeneration at all three time points (P < 0.05).

Conclusions

The present results may suggest that EMD has the ability to enhance the speed of new bone formation when combined with NBM particles in rat osseous defects.

Clinical relevance

These findings may provide additional clinical support for the combination of EMD with bone graft for the repair of osseous and periodontal intrabony defects.
Literature
1.
go back to reference Sculean A, Alessandri R, Miron R, Salvi G, Bosshard DD (2011) Enamel matrix proteins and periodontal wound healing and regeneration. Clin Adv Periodontics 1:101–117CrossRef Sculean A, Alessandri R, Miron R, Salvi G, Bosshard DD (2011) Enamel matrix proteins and periodontal wound healing and regeneration. Clin Adv Periodontics 1:101–117CrossRef
2.
go back to reference Aspriello SD, Ferrante L, Rubini C, Piemontese M (2011) Comparative study of DFDBA in combination with enamel matrix derivative versus DFDBA alone for treatment of periodontal intrabony defects at 12 months post-surgery. Clin Oral Investig 15:225–232PubMedCrossRef Aspriello SD, Ferrante L, Rubini C, Piemontese M (2011) Comparative study of DFDBA in combination with enamel matrix derivative versus DFDBA alone for treatment of periodontal intrabony defects at 12 months post-surgery. Clin Oral Investig 15:225–232PubMedCrossRef
3.
go back to reference Pietruska M, Pietruski J, Nagy K, Brecx M, Arweiler NB et al (2012) Four-year results following treatment of intrabony periodontal defects with an enamel matrix derivative alone or combined with a biphasic calcium phosphate. Clin Oral Investig 16:1191–1197PubMedCrossRef Pietruska M, Pietruski J, Nagy K, Brecx M, Arweiler NB et al (2012) Four-year results following treatment of intrabony periodontal defects with an enamel matrix derivative alone or combined with a biphasic calcium phosphate. Clin Oral Investig 16:1191–1197PubMedCrossRef
4.
go back to reference Oortgiesen DA, Meijer GJ, Bronckers AL, Walboomers XF, Jansen JA (2013) Regeneration of the periodontium using enamel matrix derivative in combination with an injectable bone cement. Clin Oral Investig 17:411–421PubMedCentralPubMedCrossRef Oortgiesen DA, Meijer GJ, Bronckers AL, Walboomers XF, Jansen JA (2013) Regeneration of the periodontium using enamel matrix derivative in combination with an injectable bone cement. Clin Oral Investig 17:411–421PubMedCentralPubMedCrossRef
5.
go back to reference Lyngstadaas SP, Wohlfahrt JC, Brookes SJ, Paine ML, Snead ML et al (2009) Enamel matrix proteins; old molecules for new applications. Orthod Craniofacial Res 12:243–253CrossRef Lyngstadaas SP, Wohlfahrt JC, Brookes SJ, Paine ML, Snead ML et al (2009) Enamel matrix proteins; old molecules for new applications. Orthod Craniofacial Res 12:243–253CrossRef
6.
go back to reference Margolis HC, Beniash E, Fowler CE (2006) Role of macromolecular assembly of enamel matrix proteins in enamel formation. J Dent Res 85:775–793PubMedCrossRef Margolis HC, Beniash E, Fowler CE (2006) Role of macromolecular assembly of enamel matrix proteins in enamel formation. J Dent Res 85:775–793PubMedCrossRef
7.
go back to reference Bartlett JD, Ganss B, Goldberg M, Moradian-Oldak J, Paine ML et al (2006) Protein–protein interactions of the developing enamel matrix. Curr Top Dev Biol 74:57–115, 3PubMedCrossRef Bartlett JD, Ganss B, Goldberg M, Moradian-Oldak J, Paine ML et al (2006) Protein–protein interactions of the developing enamel matrix. Curr Top Dev Biol 74:57–115, 3PubMedCrossRef
8.
go back to reference Guida L, Annunziata M, Belardo S, Farina R, Scabbia A et al (2007) Effect of autogenous cortical bone particulate in conjunction with enamel matrix derivative in the treatment of periodontal intraosseous defects. J Periodontol 78:231–238PubMedCrossRef Guida L, Annunziata M, Belardo S, Farina R, Scabbia A et al (2007) Effect of autogenous cortical bone particulate in conjunction with enamel matrix derivative in the treatment of periodontal intraosseous defects. J Periodontol 78:231–238PubMedCrossRef
9.
go back to reference Kuru B, Yilmaz S, Argin K, Noyan U (2006) Enamel matrix derivative alone or in combination with a bioactive glass in wide intrabony defects. Clin Oral Investig 10:227–234PubMedCrossRef Kuru B, Yilmaz S, Argin K, Noyan U (2006) Enamel matrix derivative alone or in combination with a bioactive glass in wide intrabony defects. Clin Oral Investig 10:227–234PubMedCrossRef
10.
go back to reference Velasquez-Plata D, Scheyer ET, Mellonig JT (2002) Clinical comparison of an enamel matrix derivative used alone or in combination with a bovine-derived xenograft for the treatment of periodontal osseous defects in humans. J Periodontol 73:433–440PubMedCrossRef Velasquez-Plata D, Scheyer ET, Mellonig JT (2002) Clinical comparison of an enamel matrix derivative used alone or in combination with a bovine-derived xenograft for the treatment of periodontal osseous defects in humans. J Periodontol 73:433–440PubMedCrossRef
11.
go back to reference Lekovic V, Camargo PM, Weinlaender M, Nedic M, Aleksic Z et al (2000) A comparison between enamel matrix proteins used alone or in combination with bovine porous bone mineral in the treatment of intrabony periodontal defects in humans. J Periodontol 71:1110–1116PubMedCrossRef Lekovic V, Camargo PM, Weinlaender M, Nedic M, Aleksic Z et al (2000) A comparison between enamel matrix proteins used alone or in combination with bovine porous bone mineral in the treatment of intrabony periodontal defects in humans. J Periodontol 71:1110–1116PubMedCrossRef
12.
go back to reference Zucchelli G, Amore C, Montebugnoli L, De Sanctis M (2003) Enamel matrix proteins and bovine porous bone mineral in the treatment of intrabony defects: a comparative controlled clinical trial. J Periodontol 74:1725–1735PubMedCrossRef Zucchelli G, Amore C, Montebugnoli L, De Sanctis M (2003) Enamel matrix proteins and bovine porous bone mineral in the treatment of intrabony defects: a comparative controlled clinical trial. J Periodontol 74:1725–1735PubMedCrossRef
13.
go back to reference Gurinsky BS, Mills MP, Mellonig JT (2004) Clinical evaluation of demineralized freeze-dried bone allograft and enamel matrix derivative versus enamel matrix derivative alone for the treatment of periodontal osseous defects in humans. J Periodontol 75:1309–1318PubMedCrossRef Gurinsky BS, Mills MP, Mellonig JT (2004) Clinical evaluation of demineralized freeze-dried bone allograft and enamel matrix derivative versus enamel matrix derivative alone for the treatment of periodontal osseous defects in humans. J Periodontol 75:1309–1318PubMedCrossRef
14.
go back to reference Trombelli L, Farina R (2008) Clinical outcomes with bioactive agents alone or in combination with grafting or guided tissue regeneration. J Clin Periodontol 35:117–135PubMedCrossRef Trombelli L, Farina R (2008) Clinical outcomes with bioactive agents alone or in combination with grafting or guided tissue regeneration. J Clin Periodontol 35:117–135PubMedCrossRef
15.
go back to reference Miron RJ, Bosshardt DD, Hedbom E, Zhang Y, Haenni B et al (2012) Adsorption of enamel matrix proteins to a bovine-derived bone grafting material and its regulation of cell adhesion, proliferation, and differentiation. J Periodontol 83:936–947PubMedCrossRef Miron RJ, Bosshardt DD, Hedbom E, Zhang Y, Haenni B et al (2012) Adsorption of enamel matrix proteins to a bovine-derived bone grafting material and its regulation of cell adhesion, proliferation, and differentiation. J Periodontol 83:936–947PubMedCrossRef
16.
go back to reference Miron RJ, Bosshardt DD, Zhang Y, Buser D, Sculean A (2013) Gene array of primary human osteoblasts exposed to enamel matrix derivative in combination with a natural bone mineral. Clin Oral Investig 17:405–410PubMedCrossRef Miron RJ, Bosshardt DD, Zhang Y, Buser D, Sculean A (2013) Gene array of primary human osteoblasts exposed to enamel matrix derivative in combination with a natural bone mineral. Clin Oral Investig 17:405–410PubMedCrossRef
17.
go back to reference Zhang Y, Cheng N, Miron R, Shi B, Cheng X (2012) Delivery of PDGF-B and BMP-7 by mesoporous bioglass/silk fibrin scaffolds for the repair of osteoporotic defects. Biomaterials 33:6698–6708PubMedCrossRef Zhang Y, Cheng N, Miron R, Shi B, Cheng X (2012) Delivery of PDGF-B and BMP-7 by mesoporous bioglass/silk fibrin scaffolds for the repair of osteoporotic defects. Biomaterials 33:6698–6708PubMedCrossRef
18.
go back to reference Zhang Y, Wu C, Luo T, Li S, Cheng X et al (2012) Synthesis and inflammatory response of a novel silk fibroin scaffold containing BMP7 adenovirus for bone regeneration. Bone 51:704–713PubMedCrossRef Zhang Y, Wu C, Luo T, Li S, Cheng X et al (2012) Synthesis and inflammatory response of a novel silk fibroin scaffold containing BMP7 adenovirus for bone regeneration. Bone 51:704–713PubMedCrossRef
19.
go back to reference Wang L, Fan H, Zhang ZY, Lou AJ, Pei GX et al (2010) Osteogenesis and angiogenesis of tissue-engineered bone constructed by prevascularized β-tricalcium phosphate scaffold and mesenchymal stem cells. Biomaterials 31:9452–9461PubMedCrossRef Wang L, Fan H, Zhang ZY, Lou AJ, Pei GX et al (2010) Osteogenesis and angiogenesis of tissue-engineered bone constructed by prevascularized β-tricalcium phosphate scaffold and mesenchymal stem cells. Biomaterials 31:9452–9461PubMedCrossRef
20.
go back to reference Wang CJ, Zhou ZG, Holmqvist A, Zhang H, Li Y et al (2009) Survivin expression quantified by Image Pro-Plus compared with visual assessment. Appl Immunohistochem Mol Morphol 17:530–535PubMedCrossRef Wang CJ, Zhou ZG, Holmqvist A, Zhang H, Li Y et al (2009) Survivin expression quantified by Image Pro-Plus compared with visual assessment. Appl Immunohistochem Mol Morphol 17:530–535PubMedCrossRef
21.
go back to reference Bosshardt DD (2008) Biological mediators and periodontal regeneration: a review of enamel matrix proteins at the cellular and molecular levels. J Clin Periodontol 35:87–105PubMedCrossRef Bosshardt DD (2008) Biological mediators and periodontal regeneration: a review of enamel matrix proteins at the cellular and molecular levels. J Clin Periodontol 35:87–105PubMedCrossRef
22.
go back to reference Kasaj A, Willershausen B, Junker R, Stratul SI, Schmidt M (2012) Human periodontal ligament fibroblasts stimulated by nanocrystalline hydroxyapatite paste or enamel matrix derivative. An in vitro assessment of PDL attachment, migration, and proliferation. Clin Oral Investig 16:745–754PubMedCrossRef Kasaj A, Willershausen B, Junker R, Stratul SI, Schmidt M (2012) Human periodontal ligament fibroblasts stimulated by nanocrystalline hydroxyapatite paste or enamel matrix derivative. An in vitro assessment of PDL attachment, migration, and proliferation. Clin Oral Investig 16:745–754PubMedCrossRef
23.
go back to reference Mrozik KM, Gronthos S, Menicanin D, Marino V, Bartold PM (2012) Effect of coating Straumann bone ceramic with Emdogain on mesenchymal stromal cell hard tissue formation. Clin Oral Investig 16:867–878PubMedCrossRef Mrozik KM, Gronthos S, Menicanin D, Marino V, Bartold PM (2012) Effect of coating Straumann bone ceramic with Emdogain on mesenchymal stromal cell hard tissue formation. Clin Oral Investig 16:867–878PubMedCrossRef
24.
go back to reference Nokhbehsaim M, Deschner B, Winter J, Bourauel C, Jager A et al (2012) Anti-inflammatory effects of EMD in the presence of biomechanical loading and interleukin-1β in vitro. Clin Oral Investig 16:275–283PubMedCrossRef Nokhbehsaim M, Deschner B, Winter J, Bourauel C, Jager A et al (2012) Anti-inflammatory effects of EMD in the presence of biomechanical loading and interleukin-1β in vitro. Clin Oral Investig 16:275–283PubMedCrossRef
25.
go back to reference Miron RJ, Hedbom E, Ruggiero S, Bosshardt DD, Zhang Y et al (2011) Premature osteoblast clustering by enamel matrix proteins induces osteoblast differentiation through up-regulation of connexin 43 and N-cadherin. PLoS One 6:e23375PubMedCentralPubMedCrossRef Miron RJ, Hedbom E, Ruggiero S, Bosshardt DD, Zhang Y et al (2011) Premature osteoblast clustering by enamel matrix proteins induces osteoblast differentiation through up-regulation of connexin 43 and N-cadherin. PLoS One 6:e23375PubMedCentralPubMedCrossRef
26.
go back to reference Kawana F, Sawae Y, Sahara T, Tanaka S, Debari K et al (2001) Porcine enamel matrix derivative enhances trabecular bone regeneration during wound healing of injured rat femur. Anat Rec 264:438–446PubMedCrossRef Kawana F, Sawae Y, Sahara T, Tanaka S, Debari K et al (2001) Porcine enamel matrix derivative enhances trabecular bone regeneration during wound healing of injured rat femur. Anat Rec 264:438–446PubMedCrossRef
27.
go back to reference Potijanyakul P, Sattayasansakul W, Pongpanich S, Leepong N, Kintarak S (2010) Effects of enamel matrix derivative on bioactive glass in rat calvarium defects. J Oral Implantol 36:195–204PubMedCrossRef Potijanyakul P, Sattayasansakul W, Pongpanich S, Leepong N, Kintarak S (2010) Effects of enamel matrix derivative on bioactive glass in rat calvarium defects. J Oral Implantol 36:195–204PubMedCrossRef
28.
go back to reference Donos N, Lang NP, Karoussis IK, Bosshardt D, Tonetti M et al (2004) Effect of GBR in combination with deproteinized bovine bone mineral and/or enamel matrix proteins on the healing of critical-size defects. Clin Oral Implants Res 15:101–111PubMedCrossRef Donos N, Lang NP, Karoussis IK, Bosshardt D, Tonetti M et al (2004) Effect of GBR in combination with deproteinized bovine bone mineral and/or enamel matrix proteins on the healing of critical-size defects. Clin Oral Implants Res 15:101–111PubMedCrossRef
29.
go back to reference Intini G, Andreana S, Buhite RJ, Bobek LA (2008) A comparative analysis of bone formation induced by human demineralized freeze-dried bone and enamel matrix derivative in rat calvaria critical-size bone defects. J Periodontol 79:1217–1224PubMedCrossRef Intini G, Andreana S, Buhite RJ, Bobek LA (2008) A comparative analysis of bone formation induced by human demineralized freeze-dried bone and enamel matrix derivative in rat calvaria critical-size bone defects. J Periodontol 79:1217–1224PubMedCrossRef
30.
go back to reference Cornelini R, Scarano A, Piattelli M, Andreana S, Covani U et al (2004) Effect of enamel matrix derivative (Emdogain) on bone defects in rabbit tibias. J Oral Implantol 30:69–73PubMedCrossRef Cornelini R, Scarano A, Piattelli M, Andreana S, Covani U et al (2004) Effect of enamel matrix derivative (Emdogain) on bone defects in rabbit tibias. J Oral Implantol 30:69–73PubMedCrossRef
31.
go back to reference Casati MZ, Sallum EA, Nociti FH Jr, Caffesse RG, Sallum AW (2002) Enamel matrix derivative and bone healing after guided bone regeneration in dehiscence-type defects around implants. A histomorphometric study in dogs. J Periodontol 73:789–796PubMedCrossRef Casati MZ, Sallum EA, Nociti FH Jr, Caffesse RG, Sallum AW (2002) Enamel matrix derivative and bone healing after guided bone regeneration in dehiscence-type defects around implants. A histomorphometric study in dogs. J Periodontol 73:789–796PubMedCrossRef
32.
go back to reference Amin HD, Olsen I, Knowles JC, Dard M, Donos N (2013) Effects of enamel matrix proteins on multi-lineage differentiation of periodontal ligament cells in vitro. Acta Biomater 9:4796–4805PubMedCrossRef Amin HD, Olsen I, Knowles JC, Dard M, Donos N (2013) Effects of enamel matrix proteins on multi-lineage differentiation of periodontal ligament cells in vitro. Acta Biomater 9:4796–4805PubMedCrossRef
33.
go back to reference Boyan BD, Weesner TC, Lohmann CH, Andreacchio D, Carnes DL et al (2000) Porcine fetal enamel matrix derivative enhances bone formation induced by demineralized freeze dried bone allograft in vivo. J Periodontol 71:1278–1286PubMedCrossRef Boyan BD, Weesner TC, Lohmann CH, Andreacchio D, Carnes DL et al (2000) Porcine fetal enamel matrix derivative enhances bone formation induced by demineralized freeze dried bone allograft in vivo. J Periodontol 71:1278–1286PubMedCrossRef
34.
go back to reference Dean DD, Lohmann CH, Sylvia VL, Cochran DL, Liu Y et al (2002) Effect of porcine fetal enamel matrix derivative on chondrocyte proliferation, differentiation, and local factor production is dependent on cell maturation state. Cells Tissues Organs 171:117–127PubMedCrossRef Dean DD, Lohmann CH, Sylvia VL, Cochran DL, Liu Y et al (2002) Effect of porcine fetal enamel matrix derivative on chondrocyte proliferation, differentiation, and local factor production is dependent on cell maturation state. Cells Tissues Organs 171:117–127PubMedCrossRef
Metadata
Title
Effects of enamel matrix proteins in combination with a bovine-derived natural bone mineral for the repair of bone defects
Authors
Richard J. Miron
Lingfei Wei
Dieter D. Bosshardt
Daniel Buser
Anton Sculean
Yufeng Zhang
Publication date
01-03-2014
Publisher
Springer Berlin Heidelberg
Published in
Clinical Oral Investigations / Issue 2/2014
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-013-0992-5

Other articles of this Issue 2/2014

Clinical Oral Investigations 2/2014 Go to the issue