Background/Purpose: Polymethylmethacrylate (PMMA) and calcium phosphate (Ca-P) cements are widely used for arthroplasty surgery and augmentation of bone defects. However, aseptic implant loosening in absence of wear-induced osteolysis indicates an unfavourable interaction between the cement surface and human osteoblasts. Our underlying hypothesis is that cement surfaces directly modify cell viability, proliferation rate, and cell differentiation. Methods: To test this hypothesis, we examined primary human osteoblasts harvested from six individuals. These cells were pooled and subsequently seeded directly on cement pellets prepared from Palacos® R, Palacos® R+G, and Norian® Drillable cements. After incubation for 24 and 72 h, cell viability, proliferation rate, apoptosis rate, and cell differentiation were analysed. Results: Upon cultivation of human osteoblasts on cement surfaces, we observed a significantly reduced cell viability and DNA content compared to the control. Analysis of the apoptosis rate revealed an increase for cells on Palacos R and Norian Drillable, but a significant decrease on Palacos R+G compared to the control. Regarding osteogenic differentiation, significantly lower values of alkaline phosphatase enzyme activity were identified for all cement surfaces after 24 and 72 h compared to cultivation on tissue culture plastic, serving as control. Conclusions: In summary, these data suggest a limited biocompatibility of both PMMA and Ca-P cements, necessitating further research to reduce unfavourable cell-cement interactions and consequently extend implant survival.

Jakob M, Saxer F, Scotti C, Schreiner S, Studer P, Scherberich A, Heberer M, Martin I: Perspective on the evolution of cell-based bone tissue engineering strategies. Eur Surg Res 2012;49:1-7.
Lobenhoffer P, Gerich T, Witte F, Tscherne H: Use of an injectable calcium phosphate bone cement in the treatment of tibial plateau fractures: a prospective study of twenty-six cases with twenty-month mean follow-up. J Orthop Trauma 2002;16:143-149.
Zimmermann G, Moghaddam A: Allograft bone matrix versus synthetic bone graft substitutes. Injury 2011;42(suppl 2):S16-S21.
Everts PA, Jakimowicz JJ, van Beek M, Schonberger JP, Devilee RJ, Overdevest EP, Knape JT, van Zundert A: Reviewing the structural features of autologous platelet-leukocyte gel and suggestions for use in surgery. Eur Surg Res 2007;39:199-207.
Rueger JM: Bone substitution materials. Current status and prospects (in German). Orthopade 1998;27:72-79.
Arrington ED, Smith WJ, Chambers HG, Bucknell AL, Davino NA: Complications of iliac crest bone graft harvesting. Clin Orthop Relat Res 1996;329:300-309.
Banwart JC, Asher MA, Hassanein RS: Iliac crest bone graft harvest donor site morbidity. A statistical evaluation. Spine (Phila Pa 1976) 1995;20:1055-1060.
Silber JS, Anderson DG, Daffner SD, Brislin BT, Leland JM, Hilibrand AS, Vaccaro AR, Albert TJ: Donor site morbidity after anterior iliac crest bone harvest for single-level anterior cervical discectomy and fusion. Spine (Phila Pa 1976) 2003;28:134-139.
Summers BN, Eisenstein SM: Donor site pain from the ilium. A complication of lumbar spine fusion. J Bone Joint Surg Br 1989;71:677-680.
Henkel KO, Gerber T, Dorfling P, Hartel J, Jonas L, Gundlach KK, Bienengraber V: Stimulating regeneration of bone defects by implantation of bioceramics and autologous osteoblast transplantation (in German). Mund Kiefer Gesichtschir 2002;6:59-65.
Zhang J, Liu W, Schnitzler V, Tancret F, Bouler JM: Calcium phosphate cements for bone substitution: chemistry, handling and mechanical properties. Acta Biomater 2014;10:1035-1049.
Brown TE, Harper BL, Bjorgul K: Comparison of cemented and uncemented fixation in total knee arthroplasty. Orthopedics 2013;36:380-387.
Becker S, Meissner J, Bartl R, Bretschneider W, Ogon M: Preliminary results with modified techniques of balloon kyphoplasty for vertebra plana, traumatic fractures and neoplasms. Acta Orthop Belg 2006;72:187-193.
Blattert TR, Jestaedt L, Weckbach A: Suitability of a calcium phosphate cement in osteoporotic vertebral body fracture augmentation: a controlled, randomized, clinical trial of balloon kyphoplasty comparing calcium phosphate versus polymethylmethacrylate. Spine (Phila Pa 1976) 2009;34:108-114.
Postl LK, Ahrens P, Beirer M, Cronlein M, Imhoff AB, Foehr P, Burgkart R, Braun C, Kirchhoff C: Pull-out stability of anchors for rotator cuff repair is also increased by bio-absorbable augmentation: a cadaver study. Arch Orthop Trauma Surg 2016;136:1153-1158.
Moreau MF, Chappard D, Lesourd M, Montheard JP, Basle MF: Free radicals and side products released during methylmethacrylate polymerization are cytotoxic for osteoblastic cells. J Biomed Mater Res 1998;40:124-131.
Vale FM, Castro M, Monteiro J, Couto FS, Pinto R, Giao Toscano Rico JM: Acrylic bone cement induces the production of free radicals by cultured human fibroblasts. Biomaterials 1997;18:1133-1135.
Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983;65:55-63.
Liu D, Li C, Chen Y, Burnett C, Liu XY, Downs S, Collins RD, Hawiger J: Nuclear import of proinflammatory transcription factors is required for massive liver apoptosis induced by bacterial lipopolysaccharide. J Biol Chem 2004;279:48434-48442.
Aubin JE, Liu F, Malaval L, Gupta AK: Osteoblast and chondroblast differentiation. Bone 1995;17(2 suppl):77S-83S.
Isama K, Tsuchiya T: Enhancing effect of poly(L-lactide) on the differentiation of mouse osteoblast-like MC3T3-E1 cells. Biomaterials 2003;24:3303-3309.
Pauksch L, Hartmann S, Szalay G, Alt V, Lips KS: In vitro assessment of nanosilver-functionalized PMMA bone cement on primary human mesenchymal stem cells and osteoblasts. PLoS One 2014;9:e114740.
Palmer I, Nelson J, Schatton W, Dunne NJ, Buchanan FJ, Clarke SA: Biocompatibility of calcium phosphate bone cement with optimized mechanical properties. J Biomed Mater Res B Appl Biomater 2016;104:308-315.
Chang Y, Goldberg VM, Caplan AI: Toxic effects of gentamicin on marrow-derived human mesenchymal stem cells. Clin Orthop Relat Res 2006;452:242-249.
Ince A, Schutze N, Karl N, Lohr JF, Eulert J: Gentamicin negatively influenced osteogenic function in vitro. Int Orthop 2007;31:223-228.
Rathbone CR, Cross JD, Brown KV, Murray CK, Wenke JC: Effect of various concentrations of antibiotics on osteogenic cell viability and activity. J Orthop Res 2011;29:1070-1074.
von Stechow D, Rauschmann MA: Effectiveness of combination use of antibiotic-loaded perossal with spinal surgery in patients with spondylodiscitis. Eur Surg Res 2009;43:298-305.
Hajnoczky G, Csordas G, Das S, Garcia-Perez C, Saotome M, Sinha Roy S, Yi M: Mitochondrial calcium signalling and cell death: approaches for assessing the role of mitochondrial Ca2+ uptake in apoptosis. Cell Calcium 2006;40:553-560.
Schwertz DW, Kreisberg JI, Venkatachalam MA: Gentamicin-induced alterations in pig kidney epithelial (LLC-PK1) cells in culture. J Pharmacol Exp Ther 1986;236:254-262.
Rustenbeck I, Eggers G, Reiter H, Munster W, Lenzen S: Polyamine modulation of mitochondrial calcium transport. I. Stimulatory and inhibitory effects of aliphatic polyamines, aminoglucosides and other polyamine analogues on mitochondrial calcium uptake. Biochem Pharmacol 1998;56:977-985.
Somermeyer MG, Knauss TC, Weinberg JM, Humes HD: Characterization of Ca2+ transport in rat renal brush-border membranes and its modulation by phosphatidic acid. Biochem J 1983;214:37-46.
Sastrasinh M, Weinberg JM, Humes HD: The effect of gentamicin on calcium uptake by renal mitochondria. Life Sci 1982;30:2309-2315.
Jiang Y, Jia T, Gong W, Wooley PH, Yang SY: Effects of Ti, PMMA, UHMWPE, and Co-Cr wear particles on differentiation and functions of bone marrow stromal cells. J Biomed Mater Res A 2013;101:2817-2825.
Abu-Amer Y, Darwech I, Clohisy JC: Aseptic loosening of total joint replacements: mechanisms underlying osteolysis and potential therapies. Arthritis Res Ther 2007;9(suppl 1):S6.
Elder S, Frankenburg E, Goulet J, Yetkinler D, Poser R, Goldstein S: Biomechanical evaluation of calcium phosphate cement-augmented fixation of unstable intertrochanteric fractures. J Orthop Trauma 2000;14:386-393.
Gong T, Wang Z, Zhang Y, Zhang Y, Hou M, Liu X, Wang Y, Zhao L, Ruse ND, Troczynski T, Hafeli UO: A comprehensive study of osteogenic calcium phosphate silicate cement: material characterization and in vitro/in vivo testing. Adv Healthc Mater 2016;5:457-466.
Goodman SB, Bauer TW, Carter D, Casteleyn PP, Goldstein SA, Kyle RF, Larsson S, Stankewich CJ, Swiontkowski MF, Tencer AF, Yetkinler DN, Poser RD: Norian SRS cement augmentation in hip fracture treatment. Laboratory and initial clinical results. Clin Orthop Relat Res 1998;348:42-50.
Yetkinler DN, Ladd AL, Poser RD, Constantz BR, Carter D: Biomechanical evaluation of fixation of intra-articular fractures of the distal part of the radius in cadavera: Kirschner wires compared with calcium-phosphate bone cement. J Bone Joint Surg Am 1999;81:391-399.
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