Top

Published in:

01-04-2014 | Original Paper

Cellular reactions to biodegradable magnesium alloys on human growth plate chondrocytes and osteoblasts

Authors: Karin Pichler, Tanja Kraus, Elisabeth Martinelli, Patrick Sadoghi, Giuseppe Musumeci, Peter J. Uggowitzer, Annelie M. Weinberg

Published in: International Orthopaedics | Issue 4/2014

Abstract

Purpose

In recent decades operative fracture treatment using elastic stable intramedullary nails (ESINs) has mainly taken precedence over conservative alternatives in children. The development of biodegradable materials that could be used for ESINs would be a further step towards treatment improvement. Due to its mechanical and elastic properties, magnesium seems to be an ideal material for biodegradable implant application. The aim of this study was therefore to investigate the cellular reaction to biodegradable magnesium implants in vitro.

Methods

Primary human growth plate chondrocytes and MG63 osteoblasts were used for this study. Viability and metabolic activity in response to the eluate of a rapidly and a slower degrading magnesium alloy were investigated. Furthermore, changes in gene expression were assessed and live cell imaging was performed.

Results

A superior performance of the slower degrading WZ21 alloy’s eluate was detected regarding cell viability and metabolic activity, cell proliferation and morphology. However, the ZX50 alloy’s eluate induced a favourable up-regulation of osteogenic markers in MG63 osteoblasts.

Conclusions

This study showed that magnesium alloys for use in biodegradable implant application are well tolerated in both osteoblasts and growth plate chondrocytes respectively.

Available only for authorised users

Ligier JN, Metaizeau JP, Prévot J (1983) Closed flexible medullary nailing in pediatric traumatology. Chir Pediatr 24(6):383–385PubMed

Simanovsky N, Tair MA, Simanovsky N, Porat S (2006) Removal of flexible titanium nails in children. J Pediatr Orthop 26(2):188–192PubMed

Huan ZG, Leeflang MA, Zhou J, Fratila-Apachitei LE, Duszczyk J (2010) In vitro degradation behavior and cytocompatibility of Mg-Zn-Zr alloys. J Mater Sci Mater Med 21(9):2623–2635PubMedCentralPubMedCrossRef

Staiger MP, Pietak AM, Huadmai J, Dias G (2006) Magnesium and its alloys as orthopedic biomaterials: a review. Biomaterials 27(9):1728–1734PubMedCrossRef

Witte F, Hort N, Vogt C, Cohen S, Kainer KU, Willumeit R, Feyerabend F (2008) Degradable biomaterials based on magnesium corrosion. Curr Opin Solid State Mater Sci 12(5–6):63–72CrossRef

Claes LE (1992) Mechanical characterization of biodegradable implants. Clin Mater 10(1–2):41–46PubMedCrossRef

Hänzi AC, Gerber I, Schinhammer M, Löffler JF, Uggowitzer PJ (2010) On the in vitro and in vivo degradation performance and biological response of new biodegradable Mg-Y-Zn alloys. Acta Biomater 6(5):1824–1833PubMedCrossRef

Yu K, Chen L, Zhao J, Li S, Dai Y, Huang Q, Yu Z (2012) In vitro corrosion behavior and in vivo biodegradation of biomedical β-Ca3(PO4)2/Mg-Zn composites. Acta Biomater 8(7):2845–2855PubMedCrossRef

Krause A, Höh N, Bormann D, Krause C, Bach F-W, Windhagen H, Meyer-Lindenberg A (2010) Degradation behaviour and mechanical properties of magnesium implants in rabbit tibiae. J Mater Sci 45(3):624–632CrossRef

10.

Witte F, Kaese V, Haferkamp H, Switzer E, Meyer-Lindenberg A, Wirth CJ, Windhagen H (2005) In vivo corrosion of four magnesium alloys and the associated bone response. Biomaterials 26(17):3557–3563PubMedCrossRef

11.

Castellani C, Lindtner RA, Hausbrandt P, Tschegg E, Stanzl-Tschegg SE, Zanoni G, Beck S, Weinberg AM (2011) Bone-implant interface strength and osseointegration: biodegradable magnesium alloy versus standard titanium control. Acta Biomater 7(1):432–440PubMedCrossRef

12.

Pourbaix M (1974) Atlas of electrochemical equilibria in aqueous solutions. National Association of Corrosion Engineers, Houston

13.

Kraus T, Fischerauer SF, Hänzi AC, Uggowitzer PJ, Löffler JF, Weinberg AM (2012) Magnesium alloys for temporary implants in osteosynthesis: in vivo studies of their degradation and interaction with bone. Acta Biomater 8(3):1230–1238PubMedCrossRef

14.

Gu X, Zheng Y, Zhong S, Xi T, Wang J, Wang W (2010) Corrosion of, and cellular responses to Mg-Zn-Ca bulk metallic glasses. Biomaterials 31(6):1093–1103PubMedCrossRef

15.

Lu P, Cao L, Liu Y, Xu X, Wu X (2011) Evaluation of magnesium ions release, biocorrosion, and hemocompatibility of MAO/PLLA-modified magnesium alloy WE42. J Biomed Mater Res B Appl Biomater 96(1):101–109PubMedCrossRef

16.

Chung R, Foster BK, Xian CJ (2011) Injury responses and repair mechanisms of the injured growth plate. Front Biosci (Schol Ed) 3:117–125CrossRef

17.

Davies JH, Evans BA, Jenney ME, Gregory JW (2002) In vitro effects of chemotherapeutic agents on human osteoblast-like cells. Calcif Tissue Int 70(5):408–415PubMedCrossRef

18.

Pichler K, Schmidt B, Fischerauer EE, Rinner B, Dohr G, Leithner A, Weinberg AM (2012) Behaviour of human physeal chondro-progenitorcells in early growth plate injury response in vitro. Int Orthop 36(9):1961–1966PubMedCentralPubMedCrossRef

19.

Lefebvre V, Peeters-Joris C, Vaes G (1990) Production of collagens, collagenase and collagenase inhibitor during the dedifferentiation of articular chondrocytes by serial subcultures. Biochim Biophys Acta 1051(3):266–275PubMedCrossRef

20.

Chacko S, Abbott J, Holtzer S, Holtzer H (1969) The loss of phenotypic traits by differentiated cells. VI. Behavior of the progeny of a single chondrocyte. J Exp Med 130(2):417–442PubMedCentralPubMedCrossRef

21.

Coon HG (1966) Clonal stability and phenotypic expression of chick cartilage cells in vitro. Proc Natl Acad Sci U S A 55(1):66–73PubMedCentralPubMedCrossRef

22.

Lefebvre V, Smits P (2005) Transcriptional control of chondrocyte fate and differentiation. Birth Defects Res C Embryo Today 75(3):200–212PubMedCrossRef

23.

Gerstenfeld LC, Shapiro FD (1996) Expression of bone-specific genes by hypertrophic chondrocytes: implication of the complex functions of the hypertrophic chondrocyte during endochondral bone development. J Cell Biochem 62(1):1–9PubMedCrossRef

24.

Gu XN, Xie XH, Li N, Zheng YF, Qin L (2012) In vitro and in vivo studies on a Mg-Sr binary alloy system developed as a new kind of biodegradable metal. Acta Biomater 8(6):2360–2374PubMedCrossRef

25.

Zhou WR, Zheng YF, Leeflang MA, Zhou J (2013) Mechanical property, biocorrosion and in vitro biocompatibility evaluations of Mg-Li-(Al)-(RE) alloys for future cardiovascular stent application. Acta Biomater 9(10):8488–8498

26.

Del Gaudio C, Bagalà P, Venturini M, Grandi C, Parnigotto PP, Bianco A, Montesperelli G (2012) Assessment of in vitro temporal corrosion and cytotoxicity of AZ91D alloy. J Mater Sci Mater Med 23(10):2553–2562PubMedCrossRef

27.

Cipriano AF, Zhao T, Johnson I, Guan RG, Garcia S, Liu H (2013) In vitro degradation of four magnesium-zinc-strontium alloys and their cytocompatibility with human embryonic stem cells. J Mater Sci Mater Med 24(4):989–1003PubMedCrossRef

28.

Feyerabend F, Witte F, Kammal M, Willumeit R (2006) Unphysiologically high magnesium concentrations support chondrocyte proliferation and redifferentiation. Tissue Eng 12(12):3545–3556PubMedCrossRef

29.

Feser K, Kietzmann M, Bäumer W, Krause C, Bach FW (2011) Effects of degradable Mg-Ca alloys on dendritic cell function. J Biomater Appl 25(7):685–697PubMedCrossRef

30.

Feyerabend F, Fischer J, Holtz J, Witte F, Willumeit R, Drücker H, Vogt C, Hort N (2010) Evaluation of short-term effects of rare earth and other elements used in magnesium alloys on primary cells and cell lines. Acta Biomater 6(5):1834–1842PubMedCrossRef

31.

Li J, Song Y, Zhang S, Zhao C, Zhang F, Zhang X, Cao L, Fan Q, Tang T (2010) In vitro responses of human bone marrow stromal cells to a fluoridated hydroxyapatite coated biodegradable Mg-Zn alloy. Biomaterials 31(22):5782–5788PubMedCrossRef

32.

Li L, Gao J, Wang Y (2004) Evaluation of cyto-toxicity and corrosion behavior of alkali-heat-treated magnesium in simulated body fluid. Surf Coat Technol 185(1):92–98CrossRef

33.

Pietak A, Mahoney P, Dias GJ, Staiger MP (2007) Bone-like matrix formation on magnesium and magnesium alloys. J Mater Sci Mater Med 19(1):407–415PubMedCrossRef

34.

Witte F, Feyerabend F, Maier P, Fischer J, Störmer M, Blawert C, Dietzel W, Hort N (2007) Biodegradable magnesium-hydroxyapatite metal matrix composites. Biomaterials 28(13):2163–2174PubMedCrossRef

35.

Yang C, Yuan G, Zhang J, Tang Z, Zhang X, Dai K (2010) Effects of magnesium alloys extracts on adult human bone marrow-derived stromal cell viability and osteogenic differentiation. Biomed Mater 5(4):045005PubMedCrossRef

36.

Zhang S, Li J, Song Y, Zhao C, Zhang X, Xie C, Zhang Y, Tao H, He Y, Jiang Y, Bian Y (2009) In vitro degradation, hemolysis and MC3T3-E1 cell adhesion of biodegradable Mg–Zn alloy. Mater Sci Eng C 29(6):1907–1912CrossRef

37.

Zreiqat H, Howlett CR, Zannettino A, Evans P, Schulze-Tanzil G, Knabe C, Shakibaei M (2002) Mechanisms of magnesium-stimulated adhesion of osteoblastic cells to commonly used orthopaedic implants. J Biomed Mater Res 62(2):175–184PubMedCrossRef

38.

Zreiqat H, Valenzuela SM, Nissan BB, Roest R, Knabe C, Radlanski RJ, Renz H, Evans PJ (2005) The effect of surface chemistry modification of titanium alloy on signalling pathways in human osteoblasts. Biomaterials 26(36):7579–7586PubMedCrossRef

39.

Coleman JE (1992) Structure and mechanism of alkaline phosphatase. Annu Rev Biophys Biomol Struct 21:441–483PubMedCrossRef

40.

Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z et al (2007) Endocrine regulation of energy metabolism by the skeleton. Cell 130(3):456–469PubMedCentralPubMedCrossRef

41.

Gu XN, Li N, Zhou WR, Zheng YF, Zhao X, Cai QZ, Ruan L (2011) Corrosion resistance and surface biocompatibility of a microarc oxidation coating on a Mg-Ca alloy. Acta Biomater 7(4):1880–1889PubMedCrossRef

42.

Michalke B, Halbach S, Nischwitz V (2009) JEM spotlight: metal speciation related to neurotoxicity in humans. J Environ Monit 11(5):939–954PubMedCrossRef

43.

Drynda A, Deinet N, Braun N, Peuster M (2009) Rare earth metals used in biodegradable magnesium-based stents do not interfere with proliferation of smooth muscle cells but do induce the upregulation of inflammatory genes. J Biomed Mater Res A 91(2):360–369PubMedCrossRef

44.

Hirano S, Suzuki KT (1996) Exposure, metabolism, and toxicity of rare earths and related compounds. Environ Health Perspect 104(Suppl 1):85–95PubMedCentralPubMedCrossRef

45.

Wells WH Jr, Wells VL (2012) The lanthanides, rare earth metals. In: Bingham E, Cohrssen B (eds) Patty’s toxicology. Wiley, Hoboken

Title: Cellular reactions to biodegradable magnesium alloys on human growth plate chondrocytes and osteoblasts
Authors: Karin Pichler
Tanja Kraus
Elisabeth Martinelli
Patrick Sadoghi
Giuseppe Musumeci
Peter J. Uggowitzer
Annelie M. Weinberg
Publication date: 01-04-2014
Publisher: Springer Berlin Heidelberg
Published in: International Orthopaedics / Issue 4/2014
Print ISSN: 0341-2695
Electronic ISSN: 1432-5195
DOI: https://doi.org/10.1007/s00264-013-2163-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Cellular reactions to biodegradable magnesium alloys on human growth plate chondrocytes and osteoblasts

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2014

Systematic review on outcomes of acetabular revisions with highly-porous metals

Clinical outcomes of Kyocera Modular Limb Salvage system after resection of bone sarcoma of the distal part of the femur: the Japanese Musculoskeletal Oncology Group study

Mono- versus polyaxial locking plates in distal femur fractures: a prospective randomized multicentre clinical trial

Wound infections following open reduction and internal fixation of calcaneal fractures with an extended lateral approach

Total knee arthroplasty in elderly patients with severe Kashin-Beck disease of the knee

Comparison of minimally invasive versus open transforaminal lumbar interbody fusion in two-level degenerative lumbar disease