1、Designation: F 2027 08Standard Guide forCharacterization and Testing of Raw or StartingBiomaterials for Tissue-Engineered Medical Products1This standard is issued under the fixed designation F 2027; the number immediately following the designation indicates the year oforiginal adoption or, in the ca
2、se 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 document provides guidance on writing a materialsspecification for raw or starting bi
3、omaterials intended for use intissue engineering scaffolds for growth, support, or delivery ofcells and/or biomolecules. This guide does not apply tobiomaterials that are already in a scaffold form or are finishedtissue-engineered medical products.1.2 The purpose of this guide is to provide a compen
4、dium ofrelevant existing standards and test methods for biomaterialsalready commonly used within medical products and to pro-vide characterization guidance for interim use of raw bioma-terials for which a standard does not exist.1.3 This guide covers specifications and characterizations ofall the ma
5、jor classes of materials including polymers, ceramics,metals, composites, and natural tissues of human, animal, orplant origin. This guide does not apply to pharmaceuticals.1.4 This guide is focused on specification of chemical,physical, and mechanical properties of the raw or startingmaterial. It d
6、oes not include safety and biocompatibilityrequirements since safety and biocompatibility testing is typi-cally done on materials fabricated into a final form to includeall possible effects of fabrication and sterilization techniques.1.5 Compliance with materials specifications developed inaccordanc
7、e with this standard may not necessarily result in amaterial suitable for its intended purpose. Additional testingspecific to the intend use may be required.2. Referenced Documents2.1 ASTM Standards:2D 1763 Specification for Epoxy ResinsD 1898 Practice for Sampling of Plastics3E 1298 Guide for Deter
8、mination of Purity, Impurities, andContaminants in Biological Drug ProductsF67 Specification for Unalloyed Titanium, for SurgicalImplant Applications (UNS R50250, UNS R50400, UNSR50550, UNS R50700)F75 Specification for Cobalt-28 Chromium-6 MolybdenumAlloy Castings and Casting Alloy for Surgical Impl
9、ants(UNS R30075)F90 Specification for Wrought Cobalt-20Chromium-15Tungsten-10Nickel Alloy for Surgical Implant Applica-tions (UNS R30605)F 136 Specification for Wrought Titanium-6Aluminum-4Vanadium ELI (Extra Low Interstitial) Alloy for SurgicalImplant Applications (UNS R56401)F 138 Specification fo
10、r Wrought 18Chromium-14Nickel-2.5Molybdenum Stainless Steel Bar and Wire for SurgicalImplants (UNS S31673)F 139 Specification for Wrought 18Chromium-14Nickel-2.5Molybdenum Stainless Steel Sheet and Strip for Surgi-cal Implants (UNS S31673)F 451 Specification for Acrylic Bone CementF 560 Specificatio
11、n for Unalloyed Tantalum for SurgicalImplant Applications (UNS R05200, UNS R05400)F 562 Specification for Wrought 35Cobalt-35Nickel-20Chromium-10Molybdenum Alloy for Surgical ImplantApplications (UNS R30035)F 563 Specification for Wrought Cobalt-20Nickel-20Chromium-3.5Molybdenum-3.5Tungsten-5Iron Al
12、loyfor Surgical Implant Applications (UNS R30563)3F 602 Criteria for Implantable Thermoset Epoxy PlasticsF 603 Specification for High-Purity Dense Aluminum Ox-ide for Medical ApplicationF 604 Specification for Silicone Elastomers Used in Medi-cal Applications3F 619 Practice for Extraction of Medical
13、 PlasticsF 624 Guide for Evaluation of Thermoplastic PolyurethaneSolids and Solutions for Biomedical ApplicationsF 639 Specification for Polyethylene Plastics for MedicalApplicationsF 641 Specification for Implantable Epoxy Electronic En-capsulants1This guide is under the jurisdiction of ASTM Commit
14、tee F04 on Medical andSurgical Materials and Devices and is the direct responsibility of SubcommitteeF04.42 on Biomaterials and Biomolecules for TEMPs.Current edition approved May 1, 2008. Published June 2008. Originallyapproved in 2000. Last previous edition approved in 2000 as F 2027 001.2For refe
15、renced 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 website.3Withdrawn.1Copyright ASTM International, 100 Barr Harbor Drive, PO Bo
16、x C700, West Conshohocken, PA 19428-2959, United States.F 648 Specification for Ultra-High-Molecular-Weight Poly-ethylene Powder and Fabricated Form for Surgical Im-plantsF 665 Classification for Vinyl Chloride Plastics Used inBiomedical ApplicationF 702 Specification for Polysulfone Resin for Medic
17、al Ap-plicationsF 755 Specification for Selection of Porous Polyethylenefor Use in Surgical ImplantsF 755 Specification for Selection of Porous Polyethylenefor Use in Surgical ImplantsF 997 Specification for Polycarbonate Resin for MedicalApplicationsF 1088 Specification for Beta-Tricalcium Phosphat
18、e forSurgical ImplantationF 1185 Specification for Composition of Hydroxylapatitefor Surgical ImplantsF 1251 Terminology Relating to Polymeric Biomaterials inMedical and Surgical DevicesF 1472 Specification for Wrought Titanium-6Aluminum-4Vanadium Alloy for Surgical Implant Applications (UNSR56400)F
19、 1537 Specification for Wrought Cobalt-28Chromium-6MolybdenumAlloys for Surgical Implants (UNS R31537,UNS R31538, and UNS R31539)F 1538 Specification for Glass and Glass Ceramic Bioma-terials for ImplantationF 1579 Specification for Polyaryletherketone (PAEK) Poly-mers for Surgical Implant Applicati
20、onsF 1581 Specification for Composition of Anorganic Bonefor Surgical ImplantsF 1634 Practice 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 FabricatedF
21、orms for Surgical ImplantsF 1713 Specification for Wrought Titanium-13Niobium-13Zirconium Alloy for Surgical Implant Applications(UNS R58130)F 1855 Specification for Polyoxymethylene (Acetal) forMedical ApplicationsF 1873 Specification for High-Purity Dense Yttria Tetrago-nal Zirconium Oxide Polycry
22、stal (Y-TZP) for SurgicalImplant Applications3F 1876 Specification for Polyetherketoneetherketoneketone(PEKEKK) Resins for Surgical Implant ApplicationsF 1877 Practice for Characterization of ParticlesF 1925 Specification for Virgin Poly(L-Lactic Acid) Resinfor Surgical ImplantsF 1926 Test Method fo
23、r Evaluation of the EnvironmentalStability of Calcium Phosphate CoatingsF 2064 Guide for Characterization and Testing of Alginatesas Starting Materials Intended for Use in Biomedical andTissue-Engineered Medical Products ApplicationF 2103 Guide for Characterization and Testing of ChitosanSalts as St
24、arting Materials Intended for Use in Biomedicaland Tissue-Engineered Medical Product ApplicationsF 2150 Guide for Characterization and Testing of Biomate-rial Scaffolds Used in Tissue-Engineered Medical ProductsF 2212 Guide for Characterization of Type I Collagen asStarting Material for Surgical Imp
25、lants and Substrates forTissue Engineered Medical Products (TEMPs)F 2259 Test Method for Determining the Chemical Compo-sition and Sequence in Alginate by Proton Nuclear Mag-netic Resonance (1H NMR) SpectroscopyF 2260 Test Method for Determining Degree of Deacetyla-tion in Chitosan Salts by Proton N
26、uclear Magnetic Reso-nance (1H NMR) SpectroscopyF 2347 Guide for Characterization and Testing of Hyaluro-nan as Starting Materials Intended for Use in Biomedicaland Tissue Engineered Medical Product Applications2.2 Other Document:U.S. Pharmacopeia, Edition XXX or current edition42.3 ISO and CEN Stan
27、dards:5ISO 6474 Implants for SurgeryCeramic Materials Basedon AluminaISO/IEC 17025 General Requirements for the Competenceof Testing and Calibration LaboratoriesISO 10993-1 Biological Evaluation of Medical DevicesPart 1: Evaluation and TestingISO 10993-9Part 9: Framework for Identification andQuanti
28、fication of Potential Degradation ProductsISO 10993-12Part 12: Sample Preparation and ReferenceMaterialsISO 10993-13Part 13: Identification and Quantificationof Potential Degradation Products from Polymeric Medi-cal DevicesISO 10993-14Part 14: Identification and Quantificationof Potential Degradatio
29、n Products from CeramicsISO 10993-15Part 15: Identification and Quantificationof Potential Degradation Products from Metals andAlloysISO 10993-17Part 17: Methods for the Establishment ofAllowable Limits for Leachable Substances using Health-Based Risk AssessmentISO/CD 10993-18Part 18: Chemical Chara
30、cterization ofMaterialsISO/NWI 10993-19Part 19: Physico-chemical, Mechani-cal and Morphological Characterization of MaterialsBSI BS EN 12442-1 Animal Tissues and Their DerivativesUtilized in the Manufacture of Medical DevicesPart 1:Analysis and Management of RiskBSI BS EN 12442-2Part 2: Controls on
31、Sourcing, Col-lection and HandlingBSI BS EN 12442-3Part 3: Validation of the Eliminationand/or Inactivation of Virus and Transmissible AgentsISO 111607 Product Packaging2.4 Food and Drug Administration Documents:6, 721 CFR Part 610 General Biological Products Standards4Available from U.S. Pharmacope
32、ia (USP), 12601 Twinbrook Pkwy., Rockville,MD 20852-1790, http:/www.usp.org.5Available from American National Standards Institute (ANSI), 25 W. 43rd St.,4th Floor, New York, NY 10036, http:/www.ansi.org.6Available from Food and Drug Administration (FDA), 5600 Fishers Ln.,Rockville, MD 20857, http:/w
33、ww.fda.gov. Additional titles (Parts 11499) can befound at http:/www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm.F202708221 CFR Part 820 Quality System Regulation21 CFR Part 1270 Human Tissue Intended for Transplanta-tion21 CFR Part 1271 Human Cells, Tissues, and Cellular andTissue Ba
34、sed Products3. Summary of Guide3.1 Novel materials that do not yet have standards associ-ated with them are being created for use in tissue engineeringapplications. The lack of standardized specifications for thephysical and chemical properties of these new materials maylead to variation between lot
35、s, which could create variation inobserved biological performance of the final product. It is theintent of this guide to provide a compendium of existingmedical product materials specifications and test methods toserve as a guide for specifying the important chemical andphysical properties of new ra
36、w or starting materials. Tables ofcommonly specified chemical, physical, and mechanical re-quirements are provided for each type of material (for example,ceramic, metal, polymer, composite, natural product) to assistwith the development of a specification for a new biomaterialto be utilized for tiss
37、ue engineering.3.2 This guide is focused on providing a characterizationtemplate for raw or starting materials prior to their fabricationinto a scaffold or tissue-engineered medical product. Guidancefor the characterization and testing of biomaterials after theyhave been formulated into three-dimens
38、ional scaffolds can befound in Guide F 2150.4. Significance and Use4.1 The physico-chemical characteristics of the raw orstarting biomaterial used in regenerative medicine scaffoldscarries significant potential to affect product performance byinfluencing cell behavior and/or the release of bioactive
39、 mol-ecules or drugs. This guide describes recommended specifica-tions or characterizations of raw or starting biomaterials toensure reproducibility prior to their fabrication into implant-able tissue engineering scaffolds and/or controlled releasematrices.5. Classification of Biomaterials5.1 The pr
40、operties of a biomaterial are a function of whichtype of material they are made from. All materials can beclassified according to their atomic content and bonding aseither a ceramic, polymer, metal, or composite. Ceramicsconsist of ionically or covalently bonded metallic and non-metallic elements su
41、ch as calcium phosphate or aluminumphosphate and include minerals and glasses, sintered or unsin-tered. Polymers consist of a repeating backbone structure.Metals are made of metallic elements bonded together bymetallic bonds. Composites are blends of any of the three maintypes of materials. Even mat
42、erials derived from natural sourcessuch as anorganic bone or chitosan fall into one of these basictypes; anorganic bone is a ceramic and chitosan is a polymer.5.2 To use this guide, first classify the material into one ofthe types above. Important properties that should be specifiedare listed and ta
43、bulated according to material type in Table 1and Table 2.6. Chemical Requirements6.1 Chemical Requirements for CeramicsThe raw orstarting material shall have specifications for relevant chemicalproperties such as, but not limited to, those listed within Table1, Col. 1. This includes, for ceramics: c
44、hemical formula orcomposition, requirements for the major and minor elementalconstituents, phase content, and processing aids.6.2 Chemical Requirements for MetalsThe raw or startingmaterial shall have specifications for relevant chemical prop-erties such as, but not limited to, those listed within T
45、able 1,7FDA guidance documents searchable through this website, (http:/www.fda.gov/opacom/morechoices/industry/guidedc.htm). Selected GuidanceDocuments Applicable to Combination Products may be found at this website,(http:/www.fda.gov/oc/combination/guidance.html).TABLE 1 Typically Specified Chemica
46、l Requirements for Each Type of MaterialNOTENatural materials made of proteins, nucleic acids, or polysaccharides are classified as polymers, so the chemical requirements listed forpolymers apply. Anorganic bone and other naturally occurring inorganic substances are classified as ceramics, so the ch
47、emical requirements listed forceramics apply.Ceramics Metals Polymers CompositesChemical formula or composition Chemical formula or composition Chemical formula or composition Chemical formula or compositionPhase content Phase content Unreacted monomer content Phase contentPurity Purity Synthesis me
48、thod Characterization of the bonding processbetween phasesMajor and minor elemental constituents Major and minor elemental constituents Source, if naturally harvested Chemical content at the interfaceProcessing aids (dispersing agents,binders)Corrosion susceptibility Viscosity (molar mass) All other
49、 properties listed in this tablethat may apply based onthe type of materialsused in the compositematerial.Allowable % of foreign materialcontaminantsSurface modification Additives, fillers, contaminantsCuring agents, catalysts, initiators,acceleratorsCo-polymer ratio, if appropriateExtractablesDegradation products, mechanism andkineticsResidual moisture or solvent contentContact anglesurface tensionF2027083Col. 2. The composition, trace elements analysis, phase con-tent, and any surface modification (for example, pickled,ground, polished, acid-etched) should
