1、Designation: F3268 18Standard Guide forin vitro Degradation Testing of Absorbable Metals1This standard is issued under the fixed designation F3268; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revision, the year of last revision. A number
2、 in parentheses indicates the year of last reapproval. Asuperscript epsilon () indicates an editorial change since the last revision or reapproval.1. Scope1.1 The purpose of this standard is to outline appropriateexperimental approaches for conducting an initial evaluation ofthe in vitro degradation
3、 properties of a device or test samplefabricated from an absorbable metal or alloy.1.2 The described experimental approaches are intended tocontrol the corrosion test environment through standardizationof conditions and utilization of physiologically relevant elec-trolyte fluids. Evaluation of a sta
4、ndardized degradation controlmaterial is also incorporated to facilitate comparison andnormalization of results across laboratories.1.3 The obtained test results may be used to screen materialsand/or constructs prior to evaluation of a more refined fabri-cated device. The described tests may also be
5、 utilized to definea devices performance threshold prior to more extensive invitro performance evaluations (e.g. fatigue testing) or in vivoevaluations.1.4 This standard is considered to be applicable to allabsorbable metals, including magnesium, iron, and zinc-basedmetals and alloys.1.5 The describ
6、ed tests are not considered to be representa-tive of in vivo conditions and could potentially provide a morerapid or slower degradation rate than an absorbable metalsactual in vivo corrosion rate. The herein described test methodsare to be used for material comparison purposes only and arenot to act
7、 as either a predictor or substitute for evaluation of thein vivo degradation properties of a device.1.6 This standard only provides guidance regarding the invitro degradation of absorbable metals and does not addressany aspect regarding either in vivo or biocompatibility evalu-ations.1.7 This stand
8、ard does not purport to address all of thesafety concerns, if any, associated with its use. It is theresponsibility of the user of this standard to establish appro-priate safety, health, and environmental practices and deter-mine the applicability of regulatory limitations prior to use.1.8 This inte
9、rnational standard was developed in accor-dance with internationally recognized principles on standard-ization established in the Decision on Principles for theDevelopment of International Standards, Guides and Recom-mendations issued by the World Trade Organization TechnicalBarriers to Trade (TBT)
10、Committee.2. Referenced Documents2.1 ASTM Standards:2B943 Specification for Zinc and Tin Alloy Wire Used inThermal Spraying for Electronic ApplicationsB954 Test Method for Analysis of Magnesium and Magne-sium Alloys by Atomic Emission SpectrometryE2375 Practice for Ultrasonic Testing of Wrought Prod
11、uctsF1854 Test Method for Stereological Evaluation of PorousCoatings on Medical ImplantsF2129 Test Method for Conducting Cyclic PotentiodynamicPolarization Measurements to Determine the CorrosionSusceptibility of Small Implant DevicesF2739 Guide for Quantifying Cell Viability within Bioma-terial Sca
12、ffoldsF3160 Guide for Metallurgical Characterization of Absorb-able Metallic Materials for Medical ImplantsG1 Practice for Preparing, Cleaning, and Evaluating Corro-sion Test SpecimensG3 Practice for Conventions Applicable to ElectrochemicalMeasurements in Corrosion TestingG4 Guide for Conducting Co
13、rrosion Tests in Field Applica-tionsG16 Guide for Applying Statistics to Analysis of CorrosionDataG31 Guide for Laboratory Immersion Corrosion Testing ofMetalsG46 Guide for Examination and Evaluation of Pitting Cor-rosionG59 Test Method for Conducting Potentiodynamic Polariza-tion Resistance Measure
14、mentsG102 Practice for Calculation of Corrosion Rates and Re-lated Information from Electrochemical Measurements1This guide is under the jurisdiction of ASTM Committee F04 on Medical andSurgical Materials and Devices and is the direct responsibility of SubcommitteeF04.15 on Material Test Methods.Cur
15、rent edition approved April 1, 2018. Published May 2018. DOI: 10.1520/F3268-18.vb h2For referenced ASTM standards, visit the ASTM website, www.astm.org, orcontact ASTM Customer Service at serviceastm.org. For Annual Book of ASTMStandards volume information, refer to the standards Document Summary pa
16、ge onthe ASTM website.Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United StatesThis international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for t
17、heDevelopment of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.1G106 Practice for Verification of Algorithm and Equipmentfor Electrochemical Impedance Measurements2.2 DIN Standards:3DIN 50918 Elektrochemische Ko
18、rrosionsuntersuchungen.Deutsche Normen. Berlin: Beuth Verlag; 1978. p. 1-62.3 ISO Standards:4ISO 10993-15 Biological evaluation of medical devices Part15: Identification and quantification of degradation prod-ucts from metals and alloysISO 13485 Medical devices Quality management systems Requirement
19、s for regulatory purposes3. Terminology3.1 Definitions:3.1.1 absorbable, adjin the body, referring to an initiallydistinct foreign material or substance that either directly orthrough intended degradation can be excreted, metabolized orassimilated by cells and/or tissue.3.1.2 surface roughness, RA,n
20、the arithmetic average de-viation of the surface profile from the centerline, normallyreported in micrometers.3.2 Definitions of Terms Specific to This Standard:3.2.1 degradation, nthe breakdown of a metallic testmaterial or metallic device principally due to corrosion in anelectrolyte solution rele
21、vant to physiologic conditions.3.2.2 degradation control material, nmultiple batches of adefined metallic compositon with sufficiently uniform corro-sion properties to verify an experimental setup and to comparerelative intra-laboratory and/or inter-laboratory corrosion rates.4. Summary of Guide4.1
22、Guidance is given on in vitro evaluation of thecorrosion/degradation properties of absorbable metal materialsand devices fabricated from absorbable metals. Considerationsspecific to the application of corrosion testing methods toabsorbable metal materials are outlined for both immersion andelectroch
23、emical methods.4.1.1 Electrolyte composition is a critical factor in corrosionexperiments. Several electrolytes are commonly used to mimicin vivo conditions. Electrolyte selection may also take intoconsideration the alloy being tested.4.1.2 Control of the experimental conditions (i.e.,temperature, p
24、H and fluid movement around the test piece(s)can markedly affect the corrosion rates and experimentaloutcomes. Controlling and documenting these factors areimportant with regard to generating consistent, reproducibleresults. Experimental conditions may be altered, depending onthe intent of the exper
25、iment.4.1.3 The surrounding atmosphere may interact with theelectrolyte solution (liquid-gas interface), depending on elec-trolyte composition, particularly if the electrolyte contains acarbonate buffer or if oxygen in the electrolyte is consumedduring the corrosion process, as with iron-based alloy
26、s. Mea-surement and control of the atmospheric composition may beimportant, depending on the specific circumstances of theexperiment.4.1.4 Measurements of corrosion may include weight lossof the sample, accumulation of corrosion products in theexperiment, generation of H2gas, and changes to physical
27、 andmechanical properties.4.2 Electrochemical methods, Polarization Resistance, andElectrochemical Impedance Spectroscopy also can be used tomeasure relative corrosion rates and generate additional insightinto the corrosion process. The electrolyte used in thesemethods may not be relevant to in vivo
28、 conditions and may notmimic the process in vivo. It is important to fully documentrelevant experimental conditions (e.g. electrolyte composition,current, current density and atmosphere), so that their impacton the test results can be understood.4.3 Use of a degradation control material to monitor t
29、heconsistency of the experimental system is recommended, butnot mandatory. See Annex A1 for details.5. Significance and Use5.1 This standard provides an itemization of potential invitro test methods to evaluate the degradation of absorbablemetals. The provided approach defers to the user of thisstan
30、dard to pick most appropriate method(s) based on thespecific requirements of the intended application. However, aminimum of at least two different corrosion evaluation meth-ods is considered necessary for basic profiling of the materialor device, with additional methods potentially needed for anadeq
31、uate characterization. However, in some instances theremay be only one method that correlates to in vivo degradationresults.5.2 It is recognized that not all test methods will bemeaningful for every situation. In addition, some methodscarry different potential than others regarding their relativeapp
32、roximation to the in vivo conditions within which actual useis to occur. As a result, some discussion and ranking of therelevance of the described methods is provided by this guid-ance.5.3 It should be noted that degradation of absorbable metalsis not linear. Thus, precautions should be taken that e
33、valuationsof the degradation profile of a metal or metal device areappropriately adapted to reflect the varying stages and rates ofdegradation. Relevant factors can include the amount orpercentage (%) of tissue coverage of the implanted device andthe metabolic rate of surrounding tissue, which is no
34、t neces-sarily accompanied by a high perfusion rate.5.4 It is recognized that in vivo environments will impartspecialized considerations that can directly affect the corrosionrate, even when compared with other in vivo locations. Thus, abasic understanding of the biochemistry and physiology of thesp
35、ecific targeted implant location (e.g. hard tissue; soft tissue;high, low or zero perfusion areas/tissue; high, low or zeroloading environments) is needed to optimize in vitro and invivo evaluations.3Available from Deutsches Institut fr Normung e.V.(DIN), Am DIN-Platz,Burggrafenstrasse 6, 10787 Berl
36、in, Germany, http:/www.din.de.4Available from International Organization for Standardization (ISO), ISOCentral Secretariat, BIBC II, Chemin de Blandonnet 8, CP 401, 1214 Vernier,Geneva, Switzerland, http:/www.iso.org.F3268 1825.5 Within the evaluation of absorbable metals, rate unifor-mity is consid
37、ered to be the principle concern and design goal.The recognized primary value for the herein described in vitrotesting under static (i.e. not dynamic) conditions is to monitorand screen materials and/or devices for their corrosion consis-tency. Such an evaluation may provide a practical understand-i
38、ng of the uniformity of the device prior to any subsequent invivo testing - where device consistency is considered to becritical for optimizing the quality of the obtained observations.5.6 Once a suitable level of device corrosion consistencyhas been established (either directly or historically), st
39、aticand/or dynamic fatigue testing can then be undertaken, ifneeded, to further enhance the understanding of the corrosionprocess within the context of the devices overall design and itsintended application/use.5.7 Depending on the intended application, appropriatelevels of implant loading may range
40、 from minimal to severe.Thus, this standard does NOT directly address the appropriatelevel of loading of absorbable metallic devices, guidance forwhich may be found in documents specific to the intendedimplant application and the design requirements for the prod-uct.5.8 This standard does NOT direct
41、ly address dynamicfatigue testing of absorbable metallic devices.6. Material/Metallurgical Characterization6.1 A full understanding of the compositional and morpho-logical features of the material or device to be tested is neededprior to conducting any in vitro degradation evaluation. Lack ofcontrol
42、 of critical material features (e.g. elementalcomposition, contamination, grain size, etc.) may lead toinconsistent results both in vitro and/or in vivo. Characteriza-tion of the test material should be undertaken in accordancewith ASTM F3160.6.2 Depending on the goals of the experiment, selectedmec
43、hanical tests may be repeated at various intervals duringthe corrosion experiment. In most cases, it would be appropri-ate to retire mechanically tested samples.7. General Testing Conditions7.1 The intention of the following listing of general consid-erations is to provide a fundamental overview of
44、the criticalfactors involved with generating consistent in vitro corrosioncharacterization results.7.2 Fluid Composition:7.2.1 For all in vitro test systems, fluid composition is acritical factor that requires both control and disclosure.Additionally, pH (which can be influenced by degradationproduc
45、t composition and generation rate), fluid flow, andsolution buffer capacity are significant variables that can affectan absorbable metals corrosion rate. While it is desirable tomaintain an in vitro pH at a level that is representative of thein vivo condition, it is important to note that the compos
46、ition ofa buffers anions can significantly affect the corrosion rate.Critical electrolytes and biomolecules that are known todirectly affect the corrosion rate of Mg alloys includephosphate, carbonate, chloride, calcium, serum proteins, andlipids see references (1-7). As a result, solutions with aph
47、ysiologically relevant combination of electrolytes should beused.NOTE 1If the intention of the experiment is to provide an in vitroapproximation to an in vivo system, the use of a well-controlled, simplerelectrolyte system that has been correlated to in vivo data may bepreferable to a more complex,
48、less stable system.7.2.2 Numerous formulations exist for simulated body flu-ids (SBFs) or buffering solutions that are intended to mimic thein vivo condition. Hanks Solution, which is phosphate-basedand designed to buffer in a normal atmosphere, provides anapproximation of the electrolyte compositio
49、n found in thebody. However, while it does provide a reasonable approxima-tion of inorganic moieties, it does NOT provide the bodysbuffer capacity (as enhanced through carbonate equilibria5)orthe presence of a myriad of organic molecules many ofwhich, particularly proteins, can be expected to adsorb to theimplant surface and further affect the degradation rate. Table 1defines the main ions in several common SBF solutions.7.2.3 Additional factors to consider in electrolyte solutionsare the levels of dissolved O2and CO2, which, depending on aparticular metals com
