Long-term in vivo degradation behaviour and biocompatibility of the magnesium alloy ZEK100 for use as a biodegradable bone implant.

Magnesium alloys are the focus of research as resorbable materials for osteosynthesis, as they provide sufficient stability and would make surgery to remove implants unnecessary. The new degradable magnesium alloy ZEK100 was developed to improve the stability and corrosion resistance by alloying with zinc, rare earth metals and zirconium. As the implants were degraded to only a limited extent after 6 months implantation in a previous in vivo study the present study was conducted to evaluate the long-term degradation behaviour and biocompatibility in the same animal model over 9 and 12 months. Five rabbits each with intramedullary tibia implants were examined over 9 and 12 months. Three legs were left without an implant to serve as negative controls. Numerous examinations were performed in the follow-up (clinical examinations, serum analysis, and radiographic and in vivo micro-CT investigations) and after death (ex vivo micro-CT, histology, and implant analysis) to assess the in vivo degradation and biocompatibility. It could be shown that favourable in vivo degradation behaviour is not necessarily associated with good biocompatibility. Although ZEK100 provided a very high initial stability and positive biodegradation, it must be excluded from further biomedical testing as it showed pathological effects on the host tissue following complete degradation.

[1]  Ke Yang,et al.  In vivo evaluation of biodegradable magnesium alloy bone implant in the first 6 months implantation. , 2009, Journal of biomedical materials research. Part A.

[2]  Yufeng Zheng,et al.  The development of binary Mg-Ca alloys for use as biodegradable materials within bone. , 2008, Biomaterials.

[3]  J. Reifenrath,et al.  Biocompatibility and degradation behaviour of degradable magnesium sponges coated with bioglass – method establishment within the framework of a pilot study , 2010 .

[4]  S. Stanzl-Tschegg,et al.  Bone-implant interface strength and osseointegration: Biodegradable magnesium alloy versus standard titanium control. , 2011, Acta biomaterialia.

[5]  Yang Song,et al.  Research on an Mg-Zn alloy as a degradable biomaterial. , 2010, Acta biomaterialia.

[6]  S. Perren,et al.  Galcein blue as a fluorescent label in bone , 1970, Experientia.

[7]  G. O. Hofmann,et al.  Biodegradable implants in traumatology: a review on the state-of-the-art , 2004, Archives of Orthopaedic and Trauma Surgery.

[8]  J. Jacobs,et al.  Biologic effects of implant debris. , 2009, Bulletin of the NYU hospital for joint diseases.

[9]  Jochem Nagels,et al.  Stress shielding and bone resorption in shoulder arthroplasty. , 2003, Journal of shoulder and elbow surgery.

[10]  Andrea Meyer-Lindenberg,et al.  Profound differences in the in‐vivo‐degradation and biocompatibility of two very similar rare‐earth containing Mg‐alloys in a rabbit model , 2010 .

[11]  Mitsuo Niinomi,et al.  Recent metallic materials for biomedical applications , 2002 .

[12]  Y. Mostafa,et al.  A simple and rapid method for osteoclast identification using a histochemical method for acid phosphatase , 1982, The Histochemical Journal.

[13]  J. Nellesen,et al.  Magnesium hydroxide temporarily enhancing osteoblast activity and decreasing the osteoclast number in peri-implant bone remodelling. , 2010, Acta biomaterialia.

[14]  Keith D K Luk,et al.  A biodegradable polymer-based coating to control the performance of magnesium alloy orthopaedic implants. , 2010, Biomaterials.

[15]  N. L. Fazzalari,et al.  Detecting early bone changes using in vivo micro-CT in ovariectomized, zoledronic acid-treated, and sham-operated rats , 2010, Osteoporosis International.

[16]  S. Virtanen,et al.  Time-dependent electrochemical characterization of the corrosion of a magnesium rare-earth alloy in simulated body fluids. , 2008, Journal of biomedical materials research. Part A.

[17]  Thomas A Einhorn,et al.  The biology of fracture healing. , 2011, Injury.

[18]  Y. Wan,et al.  Preparation and characterization of a new biomedical magnesium–calcium alloy , 2008 .

[19]  Henning Windhagen,et al.  Degradation behaviour and mechanical properties of magnesium implants in rabbit tibiae , 2010, Journal of Materials Science.

[20]  Wan Lee,et al.  The influence of alendronate on the healing of extraction sockets of ovariectomized rats assessed by in vivo micro-computed tomography. , 2010, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[21]  K. Donath,et al.  A method for the study of undecalcified bones and teeth with attached soft tissues. The Säge-Schliff (sawing and grinding) technique. , 1982, Journal of oral pathology.

[22]  Henning Windhagen,et al.  In Vivo Corrosion of Two Novel Magnesium Alloys ZEK100 and AX30 and Their Mechanical Suitability as Biodegradable Implants , 2011, Materials.

[23]  P. Uggowitzer,et al.  On the biodegradation performance of an Mg-Y-RE alloy with various surface conditions in simulated body fluid. , 2009, Acta biomaterialia.

[24]  Ke Yang,et al.  In vitro corrosion behaviour of Mg alloys in a phosphate buffered solution for bone implant application , 2008, Journal of materials science. Materials in medicine.

[25]  K. Donath,et al.  A method for the study of undecalcified bones and teeth with attached soft tissues. The sawing and grinding technique , 1982 .

[26]  R. Huiskes,et al.  Bone Degeneration and Recovery after Early and Late Bisphosphonate Treatment of Ovariectomized Wistar Rats Assessed by In Vivo Micro-Computed Tomography , 2008, Calcified Tissue International.

[27]  G. Song,et al.  Understanding Magnesium Corrosion—A Framework for Improved Alloy Performance , 2003 .

[28]  F. Beckmann,et al.  In vivo corrosion and corrosion protection of magnesium alloy LAE442. , 2010, Acta biomaterialia.

[29]  E. Mcbride,et al.  ABSORBABLE METAL IN BONE SURGERY: A FURTHER REPORT ON THE USE OF MAGNESIUM ALLOYS , 1938 .

[30]  C. R. Howlett,et al.  The Effect of Magnesium Ions on Bone Bonding to Hydroxyapatite Coating on Titanium Alloy Implants , 2003 .

[31]  R. Raman,et al.  In vitro degradation and mechanical integrity of calcium-containing magnesium alloys in modified-simulated body fluid. , 2008, Biomaterials.

[32]  M. Escudero,et al.  Corrosion behaviour of AZ31 magnesium alloy with different grain sizes in simulated biological fluids. , 2010, Acta biomaterialia.

[33]  M. Peuster,et al.  Are resorbable implants about to become a reality? , 2006, Cardiology in the Young.

[34]  C. Krettek,et al.  Effect of mechanical stability on fracture healing--an update. , 2007, Injury.

[35]  Guang-Ling Song,et al.  Control of biodegradation of biocompatable magnesium alloys , 2007 .

[36]  Rik Huiskes,et al.  Effects of mechanical forces on maintenance and adaptation of form in trabecular bone , 2000, Nature.

[37]  Andrea Meyer-Lindenberg,et al.  Evaluation of the soft tissue biocompatibility of MgCa0.8 and surgical steel 316L in vivo: a comparative study in rabbits , 2010, Biomedical engineering online.

[38]  B. Denkena,et al.  Influence of Different Surface Machining Treatments of Magnesium‐based Resorbable Implants on the Degradation Behavior in Rabbits , 2009 .

[39]  M. Störmer,et al.  Magnesium alloys as implant materials--principles of property design for Mg-RE alloys. , 2010, Acta biomaterialia.

[40]  G. Song Recent Progress in Corrosion and Protection of Magnesium Alloys , 2005 .

[41]  P. Erne,et al.  The Road to Bioabsorbable Stents: Reaching Clinical Reality? , 2006, CardioVascular and Interventional Radiology.

[42]  D. Pienkowski,et al.  Modified Tibial Nails for Treating Distal Tibia Fractures , 2002, Journal of orthopaedic trauma.

[43]  Frank Witte,et al.  Degradable biomaterials based on magnesium corrosion , 2008 .

[44]  B. Shaw Corrosion Resistance of Magnesium Alloys , 2003 .

[45]  Y. Shikinami,et al.  Bioresorbable devices made of forged composites of hydroxyapatite (HA) particles and poly-L-lactide (PLLA): Part I. Basic characteristics. , 1999, Biomaterials.

[46]  Thomas Hassel,et al.  Influence of a magnesium-fluoride coating of magnesium-based implants (MgCa0.8) on degradation in a rabbit model. , 2010, Journal of biomedical materials research. Part A.

[47]  O. Böstman,et al.  Polymeric debris from absorbable polyglycolide screws and pins. Intraosseous migration studied in rabbits. , 1992, Acta orthopaedica Scandinavica.

[48]  Yufeng Zheng,et al.  In vitro corrosion and biocompatibility of binary magnesium alloys. , 2009, Biomaterials.

[49]  H. Frost,et al.  The biology of fracture healing. An overview for clinicians. Part I. , 1989, Clinical orthopaedics and related research.

[50]  Alexis M Pietak,et al.  Magnesium and its alloys as orthopedic biomaterials: a review. , 2006, Biomaterials.

[51]  Fritz Thorey,et al.  Biomechanical testing and degradation analysis of MgCa0.8 alloy screws: a comparative in vivo study in rabbits. , 2011, Acta biomaterialia.

[52]  S. Perren,et al.  Xylenol orange, a fluorochrome useful in polychrome sequential labeling of calcifying tissues. , 1971, Stain technology.

[53]  B. Mckibbin,et al.  The biology of fracture healing in long bones. , 1978, The Journal of bone and joint surgery. British volume.

[54]  H. Haferkamp,et al.  In vivo corrosion of four magnesium alloys and the associated bone response. , 2005, Biomaterials.

[55]  Frank Witte,et al.  In vitro and in vivo corrosion measurements of magnesium alloys. , 2006, Biomaterials.

[56]  Mamoru Mabuchi,et al.  Processing of biocompatible porous Ti and Mg , 2001 .

[57]  Andrea Meyer-Lindenberg,et al.  Comparison of the resorbable magnesium . alloys LAE442 und MgCa0.8 concerning their mechanical properties, their progress of degradation and the bone‐implant‐contact after 12 months implantation duration in a rabbit model , 2009 .

[58]  Ke Yang,et al.  In vivo corrosion behavior of Mg-Mn-Zn alloy for bone implant application. , 2007, Journal of biomedical materials research. Part A.

[59]  K. Hartmann,et al.  Reference ranges for laboratory parameters in rabbits , 2003 .

[60]  P. Uggowitzer,et al.  MgZnCa glasses without clinically observable hydrogen evolution for biodegradable implants. , 2009, Nature materials.

[61]  Laurence Vico,et al.  Noninvasive In Vivo Monitoring of Bone Architecture Alterations in Hindlimb‐Unloaded Female Rats Using Novel Three‐Dimensional Microcomputed Tomography , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.