1、Designation: F2883 11Standard Guide forCharacterization of Ceramic and Mineral Based Scaffoldsused for Tissue-Engineered Medical Products (TEMPs) andas Device for Surgical Implant Applications1This standard is issued under the fixed designation F2883; the number immediately following the designation
2、 indicates the year oforiginal adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. Asuperscript epsilon () indicates an editorial change since the last revision or reapproval.1. Scope1.1 This guidance document covers the che
3、mical, physical,biological, and mechanical characterization requirements forbiocompatible mineral- and ceramic-based scaffolds usedsolely as device or to manufacture tissue-engineered medicalproducts (TEMPs). In this guide, the pure device or the TEMPsproduct will be referred to as scaffold.1.2 The
4、test methods contained herein provide guidance onthe characterization of the bulk physical, chemical, mechani-cal, and surface properties of a scaffold construct. Theseproperties may be important for the performance of thescaffold, especially if they affect cell behavior, adhesion,proliferation and
5、differentiation. In addition, these propertiesmay affect the delivery of bioactive agents, the biocompatibil-ity and the bioactivity of the final product.1.3 This document may be used as guidance in the selectionof test methods for the comprehensive characterization of a rawmaterials, granules, pre-
6、shaped blocks, or an original equip-ment manufacture (OEM) specification. This guide may alsobe used to characterize the scaffold component of a finishedmedical product.1.4 While a variety of materials can be used to manufacturesuch scaffolds, the composition of the final scaffold shallcontain miner
7、al or ceramic components as its main ingredients.1.5 This guide assumes that the scaffold is homogeneous innature. Chemical or physical inhomogeneity or mechanicalanisotropy of the scaffold shall be declared in the manufactur-ers material and scaffold specification.1.6 This guide addresses neither t
8、he biocompatibility of thescaffold, nor the characterization or release profiles of anybiomolecules, cells, drugs, or bioactive agents that are used incombination with the scaffold.1.7 The values stated in SI units are to be regarded asstandard. No other units of measurement are included in thisstan
9、dard.1.8 This standard 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 and health practices and determine the applica-bility of regulatory limitations prior to use.2. Referen
10、ced Documents2.1 ASTM Standards:2C373 Test Method for Water Absorption, Bulk Density,Apparent Porosity, and Apparent Specific Gravity of FiredWhiteware ProductsC693 Test Method for Density of Glass by BuoyancyC729 Test Method for Density of Glass by the Sink-FloatComparatorC830 Test Methods for Appa
11、rent Porosity, Liquid Absorp-tion, Apparent Specific Gravity, and Bulk Density ofRefractory Shapes by Vacuum PressureC1198 Test Method for Dynamic Youngs Modulus, ShearModulus, and Poissons Ratio for Advanced Ceramics bySonic ResonanceC1274 Test Method forAdvanced Ceramic Specific SurfaceArea by Phy
12、sical AdsorptionC1424 Test Method for Monotonic Compressive Strengthof Advanced Ceramics at Ambient TemperatureD695 Test Method for Compressive Properties of RigidPlasticsD1621 Test Method for Compressive Properties of RigidCellular PlasticsD4404 Test Method for Determination of Pore Volume andPore
13、Volume Distribution of Soil and Rock by MercuryIntrusion PorosimetryD6226 Test Method for Open Cell Content of Rigid CellularPlasticsD6420 Test Method for Determination of Gaseous OrganicCompounds by Direct Interface Gas Chromatography-Mass Spectrometry1This guide is under the jurisdiction of ASTM C
14、ommittee F04 on Medical andSurgical Materials and Devices and is the direct responsibility of SubcommitteeF04.42 on Biomaterials and Biomolecules for TEMPs.Current edition approved Dec. 1, 2011. Published January 2012. DOI: 10.1520/F288311.2For referenced ASTM standards, visit the ASTM website, www.
15、astm.org, orcontact ASTM Customer Service at serviceastm.org. For Annual Book of ASTMStandards volume information, refer to the standards Document Summary page onthe ASTM website.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.E128 T
16、est Method for Maximum Pore Diameter and Per-meability of Rigid Porous Filters for Laboratory UseE177 Practice for Use of the Terms Precision and Bias inASTM Test MethodsE456 Terminology Relating to Quality and StatisticsE691 Practice for Conducting an Interlaboratory Study toDetermine the Precision
17、 of a Test MethodE996 Practice for Reporting Data in Auger Electron Spec-troscopy and X-ray Photoelectron SpectroscopyE1078 Guide for Specimen Preparation and Mounting inSurface AnalysisE1131 Test Method for CompositionalAnalysis by Thermo-gravimetryE1252 Practice for General Techniques for Obtainin
18、g Infra-red Spectra for Qualitative AnalysisE1269 Test Method for Determining Specific Heat Capacityby Differential Scanning CalorimetryE1298 Guide for Determination of Purity, Impurities, andContaminants in Biological Drug ProductsE1504 Practice for Reporting Mass Spectral Data in Sec-ondary Ion Ma
19、ss Spectrometry (SIMS)E1635 Practice for Reporting Imaging Data in SecondaryIon Mass Spectrometry (SIMS)E1642 Practice for General Techniques of Gas Chromatog-raphy Infrared (GC/IR) AnalysisE1829 Guide for Handling Specimens Prior to SurfaceAnalysisE1876 Test Method for Dynamic Youngs Modulus, Shear
20、Modulus, and Poissons Ratio by Impulse Excitation ofVibrationE2070 Test Method for Kinetic Parameters by DifferentialScanning Calorimetry Using Isothermal MethodsE2253 Test Method for Enthalpy Measurement Validationof Differential Scanning CalorimetersF748 Practice for Selecting Generic Biological T
21、est Meth-ods for Materials and DevicesF981 Practice for Assessment of Compatibility of Biomate-rials for Surgical Implants with Respect to Effect ofMaterials on Muscle and BoneF1088 Specification for Beta-Tricalcium Phosphate for Sur-gical ImplantationF1185 Specification for Composition of Hydroxyla
22、patite forSurgical ImplantsF1634 Practice for In-Vitro Environmental Conditioning ofPolymer Matrix Composite Materials and Implant DevicesF1635 Test Method for in vitro Degradation Testing ofHydrolytically Degradable Polymer Resins and FabricatedForms for Surgical ImplantsF1983 Practice for Assessme
23、nt of Compatibility ofAbsorbable/Resorbable Biomaterials for Implant Applica-tionsF2024 Practice for X-ray Diffraction Determination ofPhase Content of Plasma-Sprayed Hydroxyapatite Coat-ingsF2150 Guide for Characterization and Testing of Biomate-rial Scaffolds Used in Tissue-Engineered Medical Prod
24、uctsF2450 Guide for Assessing Microstructure of PolymericScaffolds for Use in Tissue-Engineered Medical ProductsF2809 Terminology Relating to Medical and Surgical Ma-terials and Devices2.2 ISO Documents:3ISO 5016 Shaped Insulating Refractory ProductsDetermination of Bulk Density and True PorosityISO
25、 109931 Biological Evaluation of Medical DevicesPart 1: Evaluation and TestingISO 1099314 Biological Evaluation of Medical DevicesPart 14: Identification and Quantification of DegradationProducts from CeramicsISO 116071 Packaging for Terminally Sterilized MedicalDevicesPart 1: Requirements for Mater
26、ials, Sterile Bar-rier Systems and Packaging SystemsISO 116072 Packaging for Terminally Sterilized MedicalDevicesPart 2: Validation Requirements for Forming,Sealing and Assembly ProcessesISO 117371 Sterilization of Medical DevicesMicrobiological MethodsPart 1: Determination of aPopulation of Microor
27、ganisms on ProductsISO 12677 Chemical Analysis of Refractory Products byXRF-Fused Cast Bead MethodISO 159012 Pore Size Distribution and Porosity of SolidMaterials by Mercury Porosimetry and Gas AdsorptionPart 2: Analysis of Mesopores and Macropores by GasAdsorptionISO 9000 Quality Management Systems
28、Fundamentalsand VocabularyISO 9001 Quality Management SystemsRequirements2.3 United States Pharmacopeia (USP) Documents:4USP ArsenicUSP Heavy Metals Method 1USP LeadUSP Mercury2.4 Association for the Advancement of Medical Instrumen-tation (AAMI) Documents:5AAMI ST72 Bacterial endotoxinsTest methodo
29、logies,routine monitoring, and alternatives to batch testingAAMI STBK91 Sterilization-Part 1: Sterilization inHealth Care FacilitiesAAMI STBK92 Sterilization-Part 2: Sterilization Equip-mentAAMI STBK93 Sterilization-Part 3: Industrial ProcessControl2.5 Other References:FDA Guideline on Validation of
30、 the Limulus AmebocyteLysate Test as an End-Product Endotoxin Test for Humanand Animal Parenteral Drugs, Biological Products, andMedical Device, 198763Available from American National Standards Institute (ANSI), 25 W. 43rd St.,4th Floor, New York, NY 10036, http:/www.ansi.org.4Available from U.S. Ph
31、armacopeia (USP), 12601 Twinbrook Pkwy., Rockville,MD 20852-1790, http:/www.usp.org.5Available from Association for the Advancement of Medical Instrumentation(AAMI), 4301 N. Fairfax Dr., Suite 301, Arlington, VA 22203-1633, http:/www.aami.org.6Available from Food and Drug Administration (FDA), 10903
32、 New HampshireAve., Silver Spring, MD 20993-0002, http:/www.fda.gov.F2883 11221 CFR United States Code of Federal Regulations, Title2173. Terminology3.1 Unless provided otherwise in 3.2, terminology shall bein conformance with Terminology F28093.2 Definitions:3.2.1 bioactive agent, nany molecular co
33、mponent in, on,or within the interstices of a scaffold that is intended to elicit adesired tissue or cell response. Growth factors, antibiotics, andantimicrobials are examples of bioactive agents. Scaffoldstructural components or degradation byproducts that evokelimited localized bioactivity are not
34、 considered bioactiveagents.3.2.2 interconnectivity, nthe degree of connections be-tween pores via necks. The overall interconnectivity of ascaffold is expressed as the percentage of interconnected poresdivided by the total number of pores (see also Guide F2450).3.2.3 macropore, nin life sciences, a
35、 pore with dimen-sions exceeding 100 micrometers. Tissue Level. (See alsoGuide F2450.)3.2.4 micropore, nin life sciences, a pore with dimensionsbetween 100 nanometers and 100 micrometers. Cell Level.(See also Guide F2450.)3.2.5 nanopore, n in life sciences, a pore with dimensionsbetween 2 and 100 na
36、nometers. Molecular Level. (See alsoGuide F2450.)3.2.6 permeability, nmeasure of fluid, particle, or gasflow through an open pore structure.3.2.7 pores, nan inherent or induced network of channelsand open spaces within an otherwise solid structure. Pores maybe open (interconnected), blind-end (open
37、at one end) or closed(blind).3.2.8 porometry, nthe determination of the distribution ofpore diameters relative to the direction of fluid flow by thedisplacement of a wetting liquid as a function of pressure.3.2.9 porosimetry, nthe determination of pore volume andpore size distribution through the us
38、e of a non-wetting liquid(typically mercury) intrusion into a porous material as afunction of pressure.3.2.10 porosity, nproperty of a solid which contains aninherent or induced network of channels and open spaces.Porosity can be measured by the ratio of pore (void) volume tothe apparent (total or b
39、ulk) volume and is commonly expressedas a percentage.3.2.11 pure device, nA scaffold with no additional cells,genes, proteins or other biological agents that may causeantigenicity.3.2.12 scaffold, na support, delivery vehicle, or matrix forfacilitating the migration, binding, or transport of cells o
40、rbioactive molecules used to replace, repair, or regeneratetissues.3.2.13 specific surface area, nthe sum of external andinternal accessible surfaces of voids, cracks, open porosity andfissures of a solid or powder in relation to its mass.4. Summary of Guide4.1 The physicochemical characteristics an
41、d three-dimensional structure of scaffolds influence the biologicalresponse of cells. The intent of this guide is to provide aselection of test methods that are required for comprehensivecharacterization of chemical, physical, and mechanical prop-erties of a scaffold influencing consequently the bio
42、logicalperformance.4.2 Aportfolio of characteristics should be considered whendeveloping a mineral- or ceramic-based scaffold for TEMPs oras bone void filler for surgical implantation. Among these areidentification of the following characteristics: scaffold compo-sition, physical, chemical, and mech
43、anical properties; viablesterilization techniques; and degradation/resorption behavior.4.3 Application of the test methods contained within thisguide does not guarantee clinical or regulatory success of afinished scaffold or product but will help to ensure consistencyin the properties of a given sca
44、ffold material.5. Significance and Use5.1 Scaffolds may be composed of purely mineral or ce-ramic materials, or they may be composed of a compositematerial with its main phase being a mineral or ceramic.Scaffolds may be porous or non-porous, mechanically rigid orcompliant, and degradable or non-degr
45、adable. The scaffoldmay or may not have undergone a surface treatment.6. Chemical Properties and TestsNOTE 1Chemical properties are the chemical composition character-istics of a bulk compound. Chemical tests provide information about theidentity or nature of the chemical components of a scaffold. C
46、hemical testsinclude those that provide information about the nature or size ofconstituent molecules, the products purity, and the chemical nature of thescaffold surface. If possible, all constituents used for manufacturing themineral scaffolds should be pharmaceutical or medical grade or the finalp
47、roduct should comply with the requirements for medical scaffolds. If theconstituents are not of medical grade, the manufacturer of the device orTEMP shall demonstrate their quality and biocompatibility using appro-priate standard test methods.6.1 Chemical Composition:6.1.1 There are several methods
48、that can be used to deter-mine the elemental composition of the material including, butnot limited to, X-ray fluorescence analysis (XRF), atomicabsorption analysis (AAS), and infrared spectrometry (IR).Guidelines are found in ISO 12677 or in Practice E1252. X-raydiffraction (XRD) can also be used to
49、 determine the chemicalcomposition as an indirect method. Its use requires special careas it is an indirect method that requires identification of thecrystal lattice. It does not produce accurate information whenisoforms occur or amorphous and organic fractions are present.6.1.2 The elemental composition of the bulk material shallbe determined with a standard uncertainty of at least 0.5 %.6.2 Determination of the Total Organic Fraction:6.2.1 The total organic fraction includes synthetic andnatural organic compounds. The total organic
