1、Designation: F2903 11Standard Guide forTissue Engineered Medical Products (TEMPs) forReinforcement of Tendon and Ligament Surgical Repair1This standard is issued under the fixed designation F2903; 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 () indicates an editorial change since the last revision or reapproval.1. Scope1.1 This guide is intended as a resource for individuals andorganizations involved in the develo
3、pment, production, anddelivery of tissue engineered medical products (TEMPs) in-tended to provide a mechanical (functional) reinforcement ofthe surgical repair of tendons and ligaments.1.2 Surgical repair can include procedures that repair tendonto tendon, tendon to bone, tendon to muscle, ligament
4、toligament, and ligament to bone. In the context of this guide, atendon is a fibrous cord or band that connects a muscle to abone or other structure and consists of both dense collagenousfibers and rows of elongated tendon cells. In contrast, aligament is a band or sheet of fibrous tissue connecting
5、 two ormore bones, or cartilagenous structures.1.3 Examples of TEMPs for use in reinforcement of tendonor ligament repairs include extracellular matrices (includingallograft tissue, xenograft tissue, and tissue engineered extra-cellular matrix), polymeric matrices, membranes, or combina-tions of two
6、 or more of these, with or without cells and/ormolecular mediators, where the function is to reinforce thesurgical repair of tendon to tendon, tendon to bone, tendon tomuscle, ligament to ligament, or ligament to bone.1.4 The products may be rapidly degrading, slowly degrad-ing, or non-degrading.1.5
7、 The guide is not intended to apply to TEMPs that havea primary function to induce a biological repair through cell ormolecular action, although biologic activity may be a feature ofthe TEMPs. Examples of products or product concepts that arenot included are (a) growth factors or cytokines applied t
8、o abiologic or synthetic scaffold, and (b) platelet-enriched plasmaapplied to or within a biologic or polymeric scaffold, where theprimary function of the product is biologic.1.6 The guide is not intended to apply to TEMPs that havea primary function to induce a chemical repair. An example ofa produ
9、ct or product concept that would not be included wouldbe a polymeric matrix containing reagents that glue collag-enous tissues together.1.7 The guide is not intended to apply to TEMPs that aredesigned to be used to achieve primary surgical repair ofinjured tendons and ligaments.1.8 The guide is not
10、intended to apply to TEMPs that aredesigned to replace tendons or ligaments.1.9 The values stated in SI units are to be regarded asstandard. No other units of measurement are included in thisstandard.1.10 This standard does not purport to address all of thesafety concerns, if any, associated with it
11、s 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. Referenced Documents2.1 ASTM Standards:2D1004 Test Method for Tear Resistance (Graves Tear) ofPlastic Film and
12、SheetingD2990 Test Methods for Tensile, Compressive, and Flex-ural Creep and Creep-Rupture of PlasticsD3786 Test Method for Bursting Strength of TextileFabricsDiaphragm Bursting Strength Tester MethodD3787 Test Method for Bursting Strength of TextilesConstant-Rate-of-Traverse (CRT) Ball Burst TestD5
13、035 Test Method for Breaking Force and Elongation ofTextile Fabrics (Strip Method)E139 Test Methods for Conducting Creep, Creep-Rupture,and Stress-Rupture Tests of Metallic MaterialsF1635 Test Method for in vitro Degradation Testing ofHydrolytically Degradable Polymer Resins and FabricatedForms for
14、Surgical ImplantsF1978 Test Method for Measuring Abrasion Resistance ofMetallic Thermal Spray Coatings by Using the TaberAbraserF2150 Guide for Characterization and Testing of Biomate-rial Scaffolds Used in Tissue-Engineered Medical ProductsF2210 Guide for Processing Cells, Tissues, and Organs forUs
15、e in Tissue Engineered Medical Products1This guide is under the jurisdiction of ASTM Committee F04 on Medical andSurgical Materials and Devices and is the direct responsibility of SubcommitteeF04.44 on Assessment for TEMPs.Current edition approved March 1, 2011. Published April 2011. DOI: 10.1520/F2
16、90311.2For 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 website.1Copyright ASTM International, 100 Barr Harbor Drive, P
17、O Box C700, West Conshohocken, PA 19428-2959, United States.F2211 Classification for Tissue Engineered Medical Prod-ucts (TEMPs)F2212 Guide for Characterization of Type I Collagen asStarting Material for Surgical Implants and Substrates forTissue Engineered Medical Products (TEMPs)F2312 Terminology
18、Relating to Tissue Engineered MedicalProductsF2383 Guide for Assessment of Adventitious Agents inTissue Engineered Medical Products (TEMPs)F2739 Guide for Quantitating Cell Viability Within Bioma-terial Scaffolds2.2 ISO Documents:3ISO 10993 Biological Evaluation of Medical DevicesISO 111351 Steriliz
19、ation of Health Care ProductsEthylene OxidePart 1: Requirements for Development,Validation and Routine Control of a Sterilization Processfor Medical DevicesISO 111371 Sterilization of Health Care ProductsRadiationPart 1: Requirements for Development, Vali-dation and Routine Control of a Sterilizatio
20、n Process forMedical DevicesISO 224421 Medical Devices Utilizing Animal Tissuesand their DerivativesPart 1: Application of Risk Man-agement2.3 U.S. Regulations:421 CFR 610.12 Sterility21 CFR 1271 Human Cells, Tissues, and Cellular andTissue-Based Products2.4 ICH Document:5Q1A(R2) Stability Testing o
21、f New Drug Substances andProducts3. Terminology3.1 Unless provided otherwise in 3.2, terminology shall bein conformance with Terminology F2312.3.2 Definitions:3.2.1 function, vthe mechanism of producing the thera-peutic effect of a medical product.3.2.2 reinforcement, nthe process of strengthening t
22、hesurgical repair of tendon or ligament.4. Summary of Guide4.1 It is the intent of this guide to provide a compendium ofinformation that may be related to the functional characteristicsof the TEMPs used to reinforce surgical repair of injuredtendons and ligaments. TEMPs may be composed of thefollowi
23、ng individual components: biological products (forexample, cells, organs, tissues, derivatives, and processedbiologics), biomaterials (for example, substrates and scaffoldscomposed of natural and/or synthetic polymers), and activebiomolecules (for example, recombinant proteins) (see Termi-nology F23
24、12 for the complete definition). Examples ofTEMPs are listed in Classification F2211.4.2 Throughout this guide, the reader is referred to otherdocuments that may provide specific information that can beapplied in the manufacture and testing of TEMPs. Althoughmany of these documents were not written
25、with TEMPs inmind, parts are often applicable. Most of the potentiallyapplicable position papers and guidance documents from manyregions of the world can be accessed via the internet. Newdocuments are produced continually.4.3 The application of this guide does not guarantee clinicalsuccess of a fini
26、shed product but will help to ensure consis-tency in the properties and characterization of a given TEMPdeveloped for the purpose of mechanically reinforcing surgicalrepair of tendons and ligaments.4.4 This guide does not suggest that all the listed tests beconducted. The decision regarding applicab
27、ility or suitabilityof any particular test method remains the responsibility of thesupplier or user of the material based on applicable regulations,characterizations, and preclinical/clinical testing.5. Significance and Use5.1 Injuries to tendons or ligaments are frequently treated bysurgery to repa
28、ir the damaged tissues and facilitate the healingprocess. The potential of TEMPs to enhance the outcomes(including function, pain, anatomy) of the surgical repair hasbeen recognized.5.2 Examples of tissues that when injured may be appropri-ate for repair using TEMPs: rotator cuff with a partial or f
29、ulltear; Achilles tendon; Achilles tendon after harvesting foranterior cruciate ligament repair; patella tendon; patella tendonafter harvesting for anterior cruciate ligament repair; quadri-ceps tendon; posterior cruciate ligament; medial collateralligaments; lateral collateral ligaments; flexor ten
30、dons.5.3 TEMPs may be used with the intent to improve thesurgical outcome of tendon or ligament repair by (a) assumingsome of the mechanical load experienced at the repair site tostabilize the surgical repair, (b) improving the natural biologi-cal healing process, or (c) a combination of these mecha
31、nisms.5.4 TEMPs should improve clinical outcome. This may beaccomplished by reducing or eliminating pain, returning func-tion, shortening the recovery time following surgery, facilitat-ing early mobility, improving return of strength, improvingmobility, or other clinically relevant parameters.5.5 Th
32、e mechanism used by TEMPs to improve surgicalrepair should be understood and this conclusion should besupported by experimental results and should be supportive ofthe primary function of the TEMP.5.6 TEMPs with the primary function of mechanical rein-forcement may also have a secondary, biological f
33、unction.5.7 When the product is used to improve the bodys naturalbiological repair process of tendons or ligaments, the productshould allow cell attachment, migration, infiltration, extracel-lular matrix deposition and organization, formation of tendonor ligament repair tissue, integration with adja
34、cent tendon,ligament or bone, tendon-bone attachment, or more than one ofthese actions.3Available from American National Standards Institute (ANSI), 25 W. 43rd St.,4th Floor, New York, NY 10036, http:/www.ansi.org.4Available from U.S. Government Printing Office Superintendent of Documents,732 N. Cap
35、itol St., NW, Mail Stop: SDE, Washington, DC 20401, http:/www.access.gpo.gov.5Available from International Conference on Harmonisation of TechnicalRequirements for Registration of Pharmaceuticals for Human Use (ICH), ICHSecretariat, c/o IFPMA, 15 ch. Louis-Dunant, P.O. Box 195, 1211 Geneva 20,Switze
36、rland, http:/www.ich.org.F2903 1125.8 When the TEMP is used to provide a mechanicalsupport of the surgical repair of a tendon or ligament, theproduct may provide enhanced mechanical properties of therepaired construct immediately after the surgery. Ideally,TEMPs would have mechanical properties simi
37、lar to theuninjured native tissue being repaired.After surgery, the TEMPshould limit the amount of tendon/ligament separation from thebone, or separation of the fractured ends of the tendon orligament, or reduce the number of patients that have these asoutcomes of the surgery. The TEMP may allow fun
38、ctionality toreturn to the repaired tendon or ligament in a shorter time thanwithout the use of the product.6. Components of TEMPs for Tendon or LigamentSurgical Repair6.1 The following describes the components (polymers,matrices, cells, bioactive molecules) that may be used tomanufacture TEMPs, and
39、 if human cells or tissues are to beincluded, then 21 CFR 1271 may be used.6.2 Synthetically-Derived Matrices:6.2.1 Polymer TypesThe polymers used should allowmanufacture of a product that is biocompatible. The polymermay already be used in clinically marketed products, or mayrepresent an untested m
40、aterial.6.2.2 StructureThe material can be manufactured in sizesthat can be cut to size, or in a size appropriate for surgicalimplantation without alteration. The shape, size (includingthickness), and flexibility of the device should allow for easypositioning within the surgical site without requiri
41、ng perma-nent surgical anatomic modification, and preferentially allowdelivery to the surgical site using minimally invasive orarthroscopic surgery. The structure should allow for fixation ofthe product at the site such that the product will function asintended.6.2.3 DegradationThe material may be r
42、apidly degrading(for example, polyglycolic acid), slowly degrading (for ex-ample, poly L-lactic acid), or non-degrading (for example,polytetrafluoroethylene). The degradation features of the ma-terial should be selected for the particular tissue site andfunction of the implant, and the patient.6.2.4
43、 AnalysesPolymeric matrices in the manufacturedproduct may be tested for chemical composition, purity andcontaminants, porosity and void volume, mechanical proper-ties, degradation rate, stability, leachable compounds, as wellas residual solvents and crosslinking agents.6.3 Biologically-Derived Matr
44、ices:6.3.1 Native MatricesTissues derived from animal orhuman tissues may be used. These tissues are usually processedto remove cells, cell debris, and viral components. Addition-ally, the tissue may be crosslinked. They may contain a varietyof extracellular matrix proteins, glycoproteins, carbohydr
45、ates,lipids, as well as growth factors. It is likely that most productswill be predominantly composed of collagen.6.3.2 Other Naturally-Derived MatricesOther naturally-derived matrices used as a scaffold material in these TEMPsmay be derived from human, animal, or other biologic sources.They are usu
46、ally used in purified form, but may be used incombinations with other naturally-derived matrix components,or synthetic polymers. They may also be treated by crosslink-ing to provide additional mechanical properties and decreasedporosity, and may be combined with other extracellular pro-teins.6.3.3 C
47、ell Culture-Derived TEMPsThe extracellular ma-trix may be generated by culture of cells (most likely with ascaffold) in vitro. The culture conditions will often be opti-mized to allow rapid deposition of extracellular matrix. If thescaffold is degrading rapidly, then it acts as a support for matrixd
48、eposition; if it is degrading slowly or not at all, it can also addmechanical properties to the construct.6.3.4 AnalysesTests may include cell content, cell mem-brane content, biochemical composition, growth factors andother mediators, and other biological activities. Biologicallyoccurring matrices
49、may also be tested as is done for syntheticpolymers, for chemical composition, purity and contaminants,porosity and void volume, mechanical properties, degradationrate, and stability. Guide F2150 may be used for testingscaffolds for TEMPs, and Guide F2212 may be used when typeI collagen is used as a component of the TEMP.6.4 CellsCells may be included in the TEMP as a com-ponent of the product, secondary to the primary mechanism ofmechanical reinforcement. The considerations raised in thissection are general in nature, and more detailed characteriza-tion and
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