1、Designation: F 2150 02e1Standard 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 cas
2、e 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.e1NOTEThe designation, year date, and footnote 1 were editorially corrected in June 2002.1. Scope1.1 T
3、his guide is a resource of currently available testmethods for the characterization of biomaterial scaffolds usedto develop and manufacture tissue-engineered medical prod-ucts (TEMPs).1.2 The test methods contained herein guide characteriza-tion of the bulk physical, chemical, mechanical, and surfac
4、eproperties of a scaffold construct. Such properties 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 as guidanc
5、e in the selection ofappropriate test methods for the generation of a raw material ororiginal equipment manufacture (OEM) specification. Thisguide also may be used to characterize the scaffold componentof a finished medical product.1.4 This guide addresses natural, synthetic, or combinationscaffold
6、materials with or without bioactive agents or biologi-cal activity. This guide does not address the characterization orrelease profiles of any biomolecules, cells, drugs, or bioactiveagents that are used in combination with the scaffold.1.5 This standard does not purport to address all of thesafety
7、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 requirements prior to use.2. Referenced Documents2.1 ASTM Standards:D 412 Test Methods for Vulcanized R
8、ubber and Thermo-plastic Rubbers and Thermoplastic ElastomersTension2D 570 Test Method for Water Absorption of Plastics3D 638 Test Method for Tensile Properties of Plastics3D 648 Test Method for Deflection Temperature of PlasticsUnder Flexural Load in the Edgewise Position3D 671 Test Method for Flex
9、ural Fatigue of Plastics byConstant-Amplitude-of-Force3D 695 Test Method for Compressive Properties of RigidPlastics3D 747 Test Method for Apparent Bending Modulus ofPlastics by Means of a Cantilever Beam3D 790 Test Methods for Flexural Properties of Unreinforcedand Reinforced Plastics and Electrica
10、l Insulating Materi-als3D 792 Test Methods for Density and Specific Gravity (Rela-tive Density) of Plastics by Displacement3D 882 Test Method for Tensile Properties of Thin PlasticSheeting3D 1042 Test Method for Linear Dimensional Changes ofPlastics Under Accelerated Service Conditions3D 1238 Test M
11、ethod for Flow Rates of Thermoplastics byExtrusion Plastometer3D 1388 Test Method for Stiffness of Fabrics4D 1621 Test Method for Compressive Properties of RigidCellular Plastics3D 1623 Test Method for Tensile and Tensile AdhesionProperties of Rigid Cellular Plastics3D 1708 Test Method for Tensile P
12、roperties of Plastics byUse of Microtensile Specimens3D 1898 Practice for Sampling of Plastics5D 2857 Practice for Dilute Solution Viscosity of Polymers6D 2873 Test Method for Interior Porosity of Poly(VinylChloride) (PVC) Resins by Mercury Intrusion Porosim-etry6D 2990 Test Methods for Tensile, Com
13、pressive, and Flex-ural Creep and Creep-Rupture of Plastics6D 3016 Practice for Use of Liquid Exclusion Chromatogra-phy Terms and Relationships6D 3039/D 3039M Test Method for Tensile Properties of1This guide is under the jurisdiction of ASTM Committee F04 on Medical andSurgical Materials and Devices
14、 and is the direct responsibility of SubcommitteeF04.43 on Tissue Engineered Biomaterials.Current edition approved Jan. 10, 2002. Published January 2002.2Annual Book of ASTM Standards, Vol 09.01.3Annual Book of ASTM Standards, Vol 08.01.4Annual Book of ASTM Standards, Vol 07.01.5Discontinued 1998; s
15、ee 1997 Annual Book of ASTM Standards, Vol 08.01.6Annual Book of ASTM Standards, Vol 08.02.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.Polymer Matrix Composite Materials7D 3417 Test Method for Enthalpies of Fusion and Crystal-liz
16、ation of Polymers by Differential Scanning Calorimetry(DSC)6D 3418 Test Method for Transition Temperatures of Poly-mers by Differential Scanning Calorimetry6D 4001 Test Method for Determination of Weight-AverageMolecular Weight of Polymers by Light Scattering6D 4404 Test Method for Determination of
17、Pore Volume andPore Volume Distribution of Soil and Rock by MercuryIntrusion Porosimetry8D 4603 Test Method for Determining Inherent Viscosity ofPoly(Ethylene Terephthalate) (PET) by Glass CapillaryViscometer9D 5226 Practice for Dissolving Polymer Materials9D 5296 Test Method for Molecular Weight Av
18、erages andMolecular Weight Distribution of Polystyrene by HighPerformance Size-Exclusion Chromatography9D 5732 Test Method for Stiffness of Nonwoven FabricsUsing the Cantilever Test10D 6125 Test Method for Bending Resistance of Paper andPaperboard (Gurley Type Tester)11D 6420 Test Method for Determi
19、nation of Gaseous OrganicCompounds by Direct Interface Gas Chromatography-Mass Spectrometry12D 6474 Test Method for Determining Molecular WeightDistribution and Molecular Weight Averages of Polyole-fins by High Temperature Gel Permeation Chromatogra-phy9D 6539 Test Method for Measurement of Pneumati
20、c Perme-ability of Partially Saturated Porous Materials by FlowingAir13D 6579 Practice for Molecular Weight Averages and Mo-lecular Weight Distribution of Hydrocarbon and TerpeneResins by Size-Exclusion Chromatography14E 128 Test Method for Maximum Pore Diameter and Per-meability of Rigid Porous Fil
21、ters for Laboratory Use15E 177 Practice for Use of the Terms Precision and Bias inASTM Test Methods16E 456 Terminology for Relating to Quality and Statistics16E 473 Terminology Relating to Thermal Analysis16E 691 Practice for Conducting an Interlaboratory Study toDetermine the Precision of a Test Me
22、thod16E 793 Test Method for Enthalpies of Fusion and Crystalli-zation by Differential Scanning Calorimetry16E 794 Test Method for Melting and Crystallization Tem-peratures By Thermal Analysis16E 967 Practice for Temperature Calibration of DifferentialScanning Calorimeters and Differential Thermal An
23、alyz-ers16E 968 Practice for Heat Flow Calibration of DifferentialScanning Calorimeters16E 996 Practice for Reporting Data in Auger Electron Spec-troscopy and X-Ray Photoelectron Spectroscopy17E 1078 Guide for Procedures for Specimen Preparation andMounting in Surface Analysis17E 1142 Terminology Re
24、lating to Thermophysical Proper-ties16E 1294 Test Method for Pore Size Characteristics of Mem-brane Filters Using Automated Liquid Porosimeter18E 1298 Guide for Determination of Purity, Impurities, andContaminants in Biological Drug Products18E 1356 Test Method for Assignment of the Glass Transition
25、Temperatures by Differential Scanning Calorimetry orDifferential Thermal Analysis16E 1642 Practice for General Techniques of Gas Chromatog-raphy Infrared (GC/IR) Analysis17E 1829 Guide for Handling Specimens Prior to SurfaceAnalysis17F 151 Test Method for Residual Solvents in Flexible BarrierMateria
26、ls11F 316 Test Method for Pore Size Characteristics of Mem-brane Filters by Bubble Point and Mean Flow Pore Test19F 748 Practice for Selecting Generic Biological Test Meth-ods for Materials and Devices20F 1249 Test Method for Water Vapor Transmission RateThrough Plastic Film and Sheeting Using a Mod
27、ulatedInfrared Sensor11F 1251 Terminology Relating to Polymeric Biomaterials inMedical and Surgical Devices20F 1634 Practice for In-Vitro Environmental Conditioning ofPolymer Matrix Composite Materials and Implant De-vices20F 1635 Test Method for In Vitro Degradation Testing ofPoly (L-lactic Acid) R
28、esin and Fabricated Form for Surgi-cal Implants20F 1884 Test Method for Determining Residual Solvents inPackaging Materials11F 1980 Guide for Accelerated Aging of Sterile MedicalDevice Packages11F 1983 Practice for Assessment of Compatibility ofAbsorbable/Resorbable Biomaterials for Implant Applica-
29、tions11F 2025 Practice for Gravimetric Measurement of PolymericComponents for Wear Assessment20F 2027 Guide for Characterization and Testing of SubstrateMaterials for Tissue-Engineered Medical Products20G 120 Practice for Determination of Soluble Residual Con-tamination in Materials and Components b
30、y Soxhlet Ex-traction157Annual Book of ASTM Standards, Vol 15.03.8Annual Book of ASTM Standards, Vol 04.08.9Annual Book of ASTM Standards, Vol 08.03.10Annual Book of ASTM Standards, Vol 07.02.11Annual Book of ASTM Standards, Vol 15.09.12Annual Book of ASTM Standards, Vol 11.03.13Annual Book of ASTM
31、Standards, Vol 04.09.14Annual Book of ASTM Standards, Vol 06.03.15Annual Book of ASTM Standards, Vol 14.04.16Annual Book of ASTM Standards, Vol 14.02.17Annual Book of ASTM Standards, Vol 03.06.18Annual Book of ASTM Standards, Vol 11.05.19Discontinued 1995; see 1994 Annual Book of ASTM Standards, Vol
32、 11.02.20Annual Book of ASTM Standards, Vol 13.01.F215002e122.2 AAMI Standards:AAMI STBK9-1 SterilizationPart 1: Sterilization inHealth Care Facilities21AAMI STBK9-2 SterilizationPart 2: Sterilization Equip-ment21AAMI STBK9-3 SterilizationPart 3: Industrial ProcessControl212.3 ANSI Standards:ANSI/IS
33、O/ASQ Q9000-2000: Quality ManagementSystemsFundamentals and Vocabulary22ANSI/ISO/ASQ Q9001-2000: Quality Management Sys-tems: Requirements222.4 British Standards Institute:British StandardAnimal Tissues and Their DerivativesUtilized in the Manufacture of Medical DevicesPart 1:Analysis and Management
34、 of Risk (EN 12442-1)22British StandardAnimal Tissues and Their DerivativesUtilized in the Manufacture of Medical DevicesPart 2:Controls on Sourcing, Collection, and Handling (EN12442-2)22British StandardAnimal Tissues and Their DerivativesUtilized in the Manufacture of Medical DevicesPart 3:Validat
35、ion of the Elimination and/or Inactivation of Vi-ruses and Transmissible Agents (EN 12442-3)222.5 ISO Standards:ISO 1133-1991 Determination of the Melt-Mass Flow Rate(MFR) and the Melt Volume-Flow Rate (MVR) of Ther-moplastics22ISO 10993-9 Biological Evaluation of Medical DevicesPart 9: Degradation
36、of Materials Related to BiologicalTesting22ISO 10993-13 Biological Evaluation of Medical DevicesPart 13: Identification and Quantification of DegradationProducts from Polymers22ISO 10993-14 Biological Evaluation of Medical DevicesPart 14: Identification and Quantification of DegradationProducts from
37、 Ceramics22ISO 10993-15 Biological Evaluation of Medical DevicesPart 15: Identification and Quantification of DegradationProducts from Coated and Uncoated Metals and Alloys22ISO 11357-1 PlasticsDifferential Scanning Calorimetry(DSC)Part 1: General Principles22ISO 11357-2 PlasticsDifferential Scannin
38、g Calorimetry(DSC)Part 2: Determination of Glass Transition Tem-perature222.6 U.S. Code of Federal Regulations:Title 21Food and Drugs Services, Part 820QualitySystem Regulation (21 CFR Part 820)232.7 U.S. Pharmacopeia (USP) Standards:Source: General Tests and AssaysUSP24/NF19, Jan. 1,2000243. Termin
39、ology3.1 Unless provided otherwise in 3.2, terminology shall bein conformance with Terminology F 1251.3.2 Definitions:3.2.1 bioactive agents, nany molecular component in, on,or with the interstices of a device that is intended to elicit adesired tissue or cell response. Growth factors, antibiotics,
40、andantimicrobials are typical examples of bioactive agents. Devicestructural components or degradation byproducts that evokelimited localized bioactivity are not included.3.2.2 pores, nan inherent or induced network of channelsand open spaces within an otherwise solid structure.3.2.3 porometry, nthe
41、 determination of the distribution ofpore diameters relative to direction of fluid flow by thedisplacement of a wetting liquid as a function of pressure.3.2.4 porosimetry, nthe determination of pore volume andpore size distribution through the use of a nonwetting liquid(typically mercury) intrusion
42、into a porous material as afunction of pressure.3.2.5 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) volume of a porous material and iscommonly expressed as a p
43、ercentage.3.2.6 scaffold, na support, delivery vehicle, or matrix forfacilitating the migration, binding, or transport of cells orbioactive molecules used to replace, repair, or regeneratetissues.3.2.6.1 DiscussionASTM Committee F04 is continuing torefine definitions for the terms tissue engineering
44、, tissue-engineered medical products (TEMPs), and scaffold. Finaldefinitions will be from consideration of Committee F04 andother resources such as The Williams Dictionary of Biomate-rials (9) and will be balloted at a later date.4. Summary of Guide4.1 The physicochemical and three-dimensional chara
45、cter-istics of the scaffold material are expected to influence theproperties of TEMPs. It is the intent of this guide to provide acompendium of materials characterization techniques for prop-erties that may be related directly to the functionality ofscaffolds for TEMPs.4.2 Numerous general areas of
46、characterization also shouldbe considered when developing a scaffold for TEMPs. Amongthese are compositional identity, physical and chemical prop-erties or characteristics, viable sterilization techniques,degradability/resorbability, and mechanical properties.4.3 Application of the test methods cont
47、ained within thisguide do not guarantee clinical success of a finished productbut will help to ensure consistency in the properties andcharacterization of a given scaffold material.21Available from the Association for the Advancement of Medical Instrumen-tation, 1110 N. Glebe Rd., Suite 220, Arlingt
48、on, VA 22201-4795.22Available from American National Standards Institute, 25 W. 43rd St., 4thFloor, New York, NY 10036.23Available from the Superintendent of Documents, U.S. Government PrintingOffice, Washington, DC 20593.24Available from U.S. Pharmacopeia, 12601 Twinbrook Pkwy., Rockville, MD20852.
49、 The standards will be listed by appropriate USP citation number. SucceedingUSP editions alternately may be referenced.F215002e134.4 This guide does not suggest that all of the listed tests beconducted. The decision regarding applicability or suitabilityof any particular test method remains the responsibility of thesupplier, user, or regulator of the scaffold material based onapplicable regulations, characterizations, and preclinical/clinical testing.5. Significance and Use5.1 Scaffolds potentially may be metallic, ceramic, poly-meric, natural, or composite
