Adsorption of Enamel Matrix Derivative to Bone Grafts: Is the Devil in the Details
Over 15 years has now passed since enamel matrix derivative (EMD) was shown to facilitate periodontal regeneration by stimulating new cementum, alveolar bone and periodontal ligament formation [1-4]. The major component of EMD is a family of hydrophobic proteins, amelogenins, which account for more than 95% of the total protein content of the enamel matrix . Other proteins found in the enamel matrix include enamelin, ameloblastin (also called amelin or sheathlin), amelotin, apin, and various proteinases [6, 7]. Despite the ability for EMD to facilitate periodontal regeneration, many clinicians have combined EMD with various bone grafting materials in order to improve the outcomes by preventing a flap collapse and improving blood clot formation [8-14]. Recently, the effects of EMD in combination with a bone grafting material were investigated in a systematic review . It was found that while EMD was able to improve the regeneration with certain bone grafts, other types of materials have failed to improve clinical outcomes . Thus, direct evidence supporting the combination approach is still missing and further investigation is required.
Recently we have been highly interested in investigating the adsorption properties of EMD to various bone grafting materials (data not published yet). It was found that the adsorption of amelogenin proteins to the surface of grafting material varied substantially based on the bone grafting surface topography, material chemical composition, as well as the delivery-system utilized for delivering enamel matrix proteins to the material surface. Emdogain®, which is the trademark name of EMD and delivered in a propylene glycol alginate (PGA) carrier in gel-form adsorbed less protein to the surface of grafting particles, which easily dissociated from the graft surface following PBS rinsing. Emdogain® gel is formulated at a pH 5, and it is known that enamel matrix proteins aggregate and take their cellular effects more closely to pH 7 . For these reasons, much interest is derived to study the adsorption properties of EMD to grafting materials.Our most recent in vitro studies combining the use of a bone grafting material with EMD have delivered enamel matrix proteins in a carbonate buffer at pH 7.4 and these studies elicit a significant up regulation of osteoblast differentiation markers and increases cell proliferation [17-20]. Currently our laboratory is investigating a new formulation of enamel matrix derivative with better physico-chemical properties which will be utilized specifically for mixing with bone grafting materials. As the surface characteristics and material composition vary quite significantly between bone grafting materials, it becomes a challenge in order to provide a more efficient way to deliver enamel matrix proteins to bone grafting material surfaces for the clinicians who wish to utilize this combination.In retrospect, it has become more and more obvious that the clinical variability in outcomes that exists between EMD with bone grafting material is largely governed by the adsorption of enamel matrix proteins to the material surface. This has led us to ask ourselves the question ‘is the devil in the detail’ when it comes to why so much variability exists in clinical outcomes obtained between clinical trials that have investigated the use of EMD in combination with various bone grafting materials.
2.Aspriello SD, Ferrante L, Rubini C, Piemontese M. Comparative study of DFDBA in combination with enamel matrix derivative versus DFDBA alone for treatment of periodontal intrabony defects at 12 months post-surgery. Clinical oral investigations. 2011, 15(2): 225-232.
3.Pietruska M, Pietruski J, Nagy K, Brecx M, Arweiler NB et al. 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. 2012, 16(4): 1191-1197
4.Oortgiesen DA, Meijer GJ, Bronckers AL, Walboomers XF, Jansen JA. Regeneration of the periodontium using enamel matrix derivative in combination with an injectable bone cement. Clin Oral Investig. 2013, 17(2): 411-421.
8.Guida L, Annunziata M, Belardo S, Farina R, Scabbia A, et al. Effect of autogenous cortical bone particulate in conjunction with enamel matrix derivative in the treatment of periodontal intraosseous defects. J Periodontol. 2007, 78(2): 231-238.
10.Velasquez-Plata D, Scheyer ET, Mellonig JT , Brunsvold MA, Lasho DJ . 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. 2002, 73(4): 423-432.
11.Lekovic V, Camargo PM, Weinlaender M, Nedic M, Aleksic Z, et al. 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. 2000, 71(7): 1110-1116.
12.Zucchelli G, Amore C, Montebugnoli L, De Sanctis M. Enamel matrix proteins and bovine porous bone mineral in the treatment of intrabony defects: a comparative controlled clinical trial. J Periodontol. 2003, 74(12): 1725-1735.
13.Gurinsky BS, Mills MP, Mellonig JT .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. 2004, 75(10): 1309-1318.
17.Miron RJ, Bosshardt DD, Gemperli AC, Dard M, Buser D, et al. : In vitro characterization of a synthetic calcium phosphate bone graft on periodontal ligament cell and osteoblast behavior and its combination with an enamel matrix derivative. Clin Oral Investig 2014, 18(2): 443-451.
18.Miron RJ, Bosshardt DD, Hedbom E, Zhang Y, Haenni B, et al.: Adsorption of enamel matrix proteins to a bovine-derived bone grafting material and its regulation of cell adhesion, proliferation, and differentiation. J Periodontol2012, 83(7): 936-947.
19.Miron RJ, Bosshardt DD, Laugisch O, Dard M, Gemperli AC, et al. In vitro evaluation of demineralized freezedried bone allograft in combination with enamel matrix derivative. J Periodontol. 2013, 84(11): 1646-1654.
20.Miron RJ, Bosshardt DD, Zhang Y, Buser D, Sculean A. Gene array of primary human osteoblasts exposed to enamel matrix derivative in combination with a natural bone mineral. Clin Oral Investig. 2013, 17 (2): 405-410.