1、Designation: F 2150 07Standard Guide forCharacterization and Testing of Biomaterial Scaffolds Usedin Tissue-Engineered Medical Products1This standard is issued under the fixed designation F 2150; the number immediately following the designation indicates the year oforiginal adoption or, in the case
2、of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. Asuperscript epsilon (e) indicates an editorial change since the last revision or reapproval.1. Scope1.1 This guide is a resource of currently available testmethods for the characterization of the
3、compositional andstructural aspects of biomaterial scaffolds used to develop andmanufacture tissue-engineered medical products (TEMPs).1.2 The test methods contained herein guide characteriza-tion of the bulk physical, chemical, mechanical, and surfaceproperties of a scaffold construct. Such propert
4、ies may beimportant for the success of a TEMP, especially if they affectcell retention, activity and organization, the delivery of bioac-tive agents, or the biocompatibility and bioactivity within thefinal product.1.3 This guide may be used in the selection of appropriatetest methods for the generat
5、ion of an original equipmentmanufacture (OEM) specification. This guide also may be usedto characterize the scaffold component of a finished medicalproduct.1.4 This guide is intended to be utilized in conjunction withappropriate characterization(s) and evaluation(s) of any raw orstarting material(s)
6、 utilized in the fabrication of the scaffold,such as described in Guide F 2027.1.5 This guide addresses natural, synthetic, or combinationscaffold materials with or without bioactive agents or biologi-cal activity. This guide does not address the characterization orrelease profiles of any biomolecul
7、es, cells, drugs, or bioactiveagents that are used in combination with the scaffold. Adetermination of the suitability of a particular starting materialand/or finished scaffold structure to a specific cell type and/ortissue engineering application is essential, but will requireadditional in vitro an
8、d/or in vivo evaluations considered to beoutside the scope of this guide.1.6 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
9、the applica-bility of regulatory requirements prior to use.2. Referenced Documents2.1 ASTM Standards:2D 412 Test Methods for Vulcanized Rubber and Thermo-plastic ElastomersTensionD 570 Test Method for Water Absorption of PlasticsD 638 Test Method for Tensile Properties of PlasticsD 648 Test Method f
10、or Deflection Temperature of PlasticsUnder Flexural Load in the Edgewise PositionD 671 Test Method for Flexural Fatigue of Plastics byConstant-Amplitude-of-Force3D 695 Test Method for Compressive Properties of RigidPlasticsD 747 Test Method for Apparent Bending Modulus ofPlastics by Means of a Canti
11、lever BeamD 790 Test Methods for Flexural Properties of Unreinforcedand Reinforced Plastics and Electrical Insulating MaterialsD 792 Test Methods for Density and Specific Gravity (Rela-tive Density) of Plastics by DisplacementD 882 Test Method for Tensile Properties of Thin PlasticSheetingD 1042 Tes
12、t Method for Linear Dimensional Changes ofPlastics Under Accelerated Service ConditionsD 1238 Test Method for Melt Flow Rates of Thermoplasticsby Extrusion PlastometerD 1388 Test Method for Stiffness of FabricsD 1621 Test Method for Compressive Properties Of RigidCellular PlasticsD 1623 Test Method
13、for Tensile and Tensile AdhesionProperties of Rigid Cellular PlasticsD 1708 Test Method for Tensile Properties of Plastics byUse of Microtensile SpecimensD 2857 Practice for Dilute Solution Viscosity of PolymersD 2873 Test Method for Interior Porosity of Poly(VinylChloride) (PVC) Resins by Mercury I
14、ntrusion Porosim-etry31This guide is under the jurisdiction of ASTM Committee 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, 2007. Published January 2008. Originallyap
15、proved in 2002. Last previous edition approved in 2002 as F 2150 02e1.2For 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 page onthe ASTM
16、 website.3Withdrawn.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.D 2990 Test Methods for Tensile, Compressive, and Flex-ural Creep and Creep-Rupture of PlasticsD 3016 Practice for Use of Liquid Exclusion Chromatogra-phy Terms and
17、RelationshipsD 3039/D 3039M Test Method for Tensile Properties ofPolymer Matrix Composite MaterialsD 3417 Test Method for Enthalpies of Fusion and Crystal-lization of Polymers by Differential Scanning Calorimetry(DSC)3D 3418 Test Method for Transition Temperatures and En-thalpies of Fusion and Cryst
18、allization of Polymers byDifferential Scanning CalorimetryD 4001 Test Method for Determination of Weight-AverageMolecular Weight of Polymers By Light ScatteringD 4404 Test Method for Determination of Pore Volume andPore Volume Distribution of Soil and Rock by MercuryIntrusion PorosimetryD 4603 Test
19、Method for Determining Inherent Viscosity ofPoly(Ethylene Terephthalate) (PET) by Glass CapillaryViscometerD 5226 Practice for Dissolving Polymer MaterialsD 5296 Test Method for Molecular Weight Averages andMolecular Weight Distribution of Polystyrene by HighPerformance Size-Exclusion Chromatography
20、D 5732 Test Method for Stiffness of Nonwoven FabricsUsing the Cantilever TestD 6125 Test Method for Bending Resistance of Paper andPaperboard (Gurley Type Tester)D 6420 Test Method for Determination of Gaseous OrganicCompounds by Direct Interface Gas Chromatography-Mass SpectrometryD 6474 Test Metho
21、d for Determining Molecular WeightDistribution and Molecular Weight Averages of Polyole-fins by High Temperature Gel Permeation Chromatogra-phyD 6539 Test Method for Measurement of Pneumatic Perme-ability of Partially Saturated Porous Materials by FlowingAirD 6579 Practice for Molecular Weight Avera
22、ges and Mo-lecular Weight Distribution of Hydrocarbon and TerpeneResins by Size-Exclusion ChromatographyE 128 Test Method for Maximum Pore Diameter and Per-meability of Rigid Porous Filters for Laboratory UseE 177 Practice for Use of the Terms Precision and Bias inASTM Test MethodsE 456 Terminology
23、Relating to Quality and StatisticsE 473 Terminology Relating to Thermal Analysis and Rhe-ologyE 691 Practice for Conducting an Interlaboratory Study toDetermine the Precision of a Test MethodE 793 Test Method for Enthalpies of Fusion and Crystalli-zation by Differential Scanning CalorimetryE 794 Tes
24、t Method for Melting And Crystallization Tem-peratures By Thermal AnalysisE 967 Test Method for Temperature Calibration of Differ-ential Scanning Calorimeters and Differential ThermalAnalyzersE 968 Practice for Heat Flow Calibration of DifferentialScanning CalorimetersE 996 Practice for Reporting Da
25、ta in Auger Electron Spec-troscopy and X-ray Photoelectron SpectroscopyE 1078 Guide for Specimen Preparation and Mounting inSurface AnalysisE 1142 Terminology Relating to Thermophysical PropertiesE 1294 Test Method for Pore Size Characteristics of Mem-brane Filters Using Automated Liquid Porosimeter
26、E 1298 Guide for Determination of Purity, Impurities, andContaminants in Biological Drug ProductsE 1356 Test Method for Assignment of the Glass TransitionTemperatures by Differential Scanning CalorimetryE 1642 Practice for General Techniques of Gas Chromatog-raphy Infrared (GC/IR) AnalysisE 1829 Gui
27、de for Handling Specimens Prior to SurfaceAnalysisE 1994 Practice for Use of Process Oriented AOQL andLTPD Sampling PlansF 151 Test Method for Residual Solvents in Flexible BarrierMaterials3F 316 Test Methods for Pore Size Characteristics of Mem-brane Filters by Bubble Point and Mean Flow Pore TestF
28、 748 Practice for Selecting Generic Biological Test Meth-ods for Materials and DevicesF 1249 Test Method for Water Vapor Transmission RateThrough Plastic Film and Sheeting Using a ModulatedInfrared SensorF 1251 Terminology Relating to Polymeric Biomaterials inMedical and Surgical DevicesF 1634 Pract
29、ice for In-Vitro Environmental Conditioning ofPolymer Matrix Composite Materials and Implant DevicesF 1635 Test Method for in vitro Degradation Testing ofHydrolytically Degradable Polymer Resins and FabricatedForms for Surgical ImplantsF 1884 Test Methods for Determining Residual Solvents inPackagin
30、g MaterialsF 1980 Guide for Accelerated Aging of Sterile BarrierSystems for Medical DevicesF 1983 Practice for Assessment of Compatibility ofAbsorbable/Resorbable Biomaterials for Implant Applica-tionsF 2025 Practice for Gravimetric Measurement of PolymericComponents for Wear AssessmentF 2027 Guide
31、for Characterization and Testing of SubstrateMaterials for Tissue-Engineered Medical ProductsF 2312 Terminology Relating to Tissue Engineered MedicalProductsF 2450 Guide for Assessing Microstructure of PolymericScaffolds for Use in Tissue Engineered Medical ProductsG 120 Practice for Determination o
32、f Soluble Residual Con-tamination by Soxhlet Extraction2.2 AAMI Standards:4AAMI STBK9-1 SterilizationPart 1: Sterilization inHealth Care Facilities4Available from the Association for the Advancement of Medical Instrumenta-tion, 1110 N. Glebe Rd., Suite 220, Arlington, VA 22201-4795.F2150072AAMI STBK
33、9-2 SterilizationPart 2: Sterilization Equip-mentAAMI STBK9-3 SterilizationPart 3: Industrial ProcessControl2.3 ANSI Standards:5ANSI/ISO/ASQ Q9000-2000: Quality ManagementSystemsFundamentals and VocabularyANSI/ISO/ASQ Q9001-2000: Quality Management Sys-tems: Requirements2.4 British Standards Institu
34、te:5EN 12441 British StandardAnimal Tissues and TheirDerivatives Utilized in the Manufacture of MedicalDevicesPart 1: Analysis and Management of RiskEN 124422 British StandardAnimal Tissues and TheirDerivatives Utilized in the Manufacture of MedicalDevicesPart 2: Controls on Sourcing, Collection, an
35、dHandlingEN 124423 British StandardAnimal Tissues and TheirDerivatives Utilized in the Manufacture of MedicalDevicesPart 3: Validation of the Elimination and/orInactivation of Viruses and Transmissible Agents2.5 ISO Standards:5ISO 31-8 Physical Chemistry and Molecular PhysicsPart8: Quantities and Un
36、itsISO 1133 Determination of the Melt-Mass Flow Rate(MFR) and the Melt Volume-Flow Rate (MVR) of Ther-moplasticsISO 10993-9 Biological Evaluation of Medical DevicesPart 9: Degradation of Materials Related to BiologicalTestingISO 10993-13 Biological Evaluation of Medical DevicesPart 13: Identificatio
37、n and Quantification of DegradationProducts from PolymersISO 10993-14 Biological Evaluation of Medical DevicesPart 14: Identification and Quantification of DegradationProducts from CeramicsISO 10993-15 Biological Evaluation of Medical DevicesPart 15: Identification and Quantification of DegradationP
38、roducts from Coated and Uncoated Metals and AlloysISO 11357-1 PlasticsDifferential Scanning Calorimetry(DSC)Part 1: General PrinciplesISO 11357-2 PlasticsDifferential Scanning Calorimetry(DSC)Part 2: Determination of Glass Transition Tem-perature2.6 U.S. Code of Federal Regulations:621 CFR Part 58 T
39、itle 21Food And Drug Administration,Part 58Good Laboratory Practice For Nonclinical Labo-ratory Studies21 CFR Part 820 Title 21Food and Drugs Services, Part820Quality System Regulation2.7 U.S. Pharmacopeia (USP) Standards:7Source: General Tests and AssaysUSP30/NF25, May 1,20072.8 NIST Document:8NIST
40、 SP811 Special Publication SP811: Guide for the Useof the International System of Units (SI)2.9 Other Documents/Web Sites:U.S. Food Final.5.4.3 FDA-CDRH Premarket Approval (PMA) Database:5.4.3.1 http:/www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm5.4.4 FDA-CDRH 510(k) (Premarket Notificati
41、on) Data-base:5.4.4.1 http:/www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm6. Chemical Properties and TestsNOTE 1Chemical properties are the chemical composition character-istics of a compound. Chemical tests provide information about theidentity or nature of the chemical components of a sc
42、affold. Chemical testsinclude those that provide information about the nature or size ofconstituent molecules, the products purity, and/or the chemical nature ofthe scaffold surface.6.1 Identification of Impurities:6.1.1 Chemical impurities are expected and unexpectedmaterials that are not part of t
43、he intended design of thescaffold. Acceptable levels are a function of the nature of theimpurity and the scaffolds intended in vitro or in vivoapplication, and may be evaluated by appropriate qualificationstudies. A more precise definition of both contaminants andimpurities and guidance regarding th
44、eir significance may befound in Guide E 1298.6.1.2 Expected impurities of potential biological signifi-cance should be monitored through appropriate analytic means.Impurities can occur in both synthetic and natural basedmaterials (for example, proteins, such as collagen and elastin;polysaccharides,
45、such as cellulose, alginate, hyaluronan, andchitin based derivatives) and may include, but are not limitedto processing aids or solvents, unreacted cross-linking agents,residual monomers, endotoxins, sterilization residuals, andresidual solutions that, by their chemical nature or relativeconcentrati
46、ons, carry potential for influencing cell or tissueresponse.6.1.3 Impurities may be identified or quantitatively deter-mined by infrared (IR) spectroscopy, nuclear magnetic reso-nance (NMR), combined gas chromatography/mass spectrom-etry (GC/MS), or other analytic methods as appropriate.Polyacrylami
47、de gel electrophoresis is a possible method forassessing the presence of impurities in biologically derivedscaffold materials (for example, collagen, hyaluronic acid).13The boldface numbers in parentheses refer to the list of references at the endof this standard.F2150074Impurities separated within
48、such gels can be detected withCoomassie Blue (as a general protein stain) or silver (as ageneral protein and carbohydrate stain), and characterizedfurther by immunonblot analysis and/or protein sequencing toidentify specific impurities that may possess critical biologicalactivities (for example, ela
49、stin immunogenicity, cytokines andgrowth factors). Once characterized, such impurities can beassessed by other robust and sensitive methods well suited to amanufacturing environment (for example, ELISA for specificsubstances identified by immunoblot analysis or protein se-quencing.)6.1.4 Generally, impurities are isolated more readily whenthe scaffold in its entirety can be solvated along with possiblecontaminants. If the scaffold cannot be dissolved, exhaustiveextraction with one or more solvents appropriate to thesuspected impurity is necessary.6.1.
