ASTM F763-2004 Standard Practice for Short-Term Screening of Implant Materials《植入材料的短期屏蔽的标准规程》.pdf

1、Designation: F 763 04Standard Practice forShort-Term Screening of Implant Materials1This standard is issued under the fixed designation F 763; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revision, the year of last revision. A number in p

2、arentheses indicates the year of last reapproval. Asuperscript epsilon (e) indicates an editorial change since the last revision or reapproval.1. Scope1.1 This practice provides guidelines for short-term testingor screening of candidate materials, both porous and dense, asto the effects of the mater

3、ial on animal tissue in which it isimplanted. This is a rapid screening prodedure for determiningacceptability of candidate materials.1.2 This practice, along with other appropriate biologicaltests (including other appropriate ASTM tests) may be used inthe biocompatibility assessment of the candidat

4、e materials foruse in the fabrication of devices for clinical application.1.3 This experimental protocol is not designed to provide acomprehensive assessment of the systemic toxicity, carcinoge-nicity, teratogenicity, or mutagenicity of the material sinceother standards deal with these issues.1.4 Th

5、is practice is one of several developed for theassessment of the biocompatibility of materials. Practice F 748provides guidance for the selection of appropriate methods fortesting materials for a specific application.2. Referenced Documents2.1 ASTM Standards:2F 75 Specification for Cobalt-28Chromium

6、-6MolybdenumAlloy Castings and Casting Alloy for Surgical Implants(UNS R30075)F 86 Practice for Surface Preparation and Marking of Me-tallic Surgical ImplantsF 90 Specification for Wrought Cobalt-20Chromium-15Tungsten-10Nickel Alloy for Surgical Implant Applica-tions (UNS R30605)F 136 Specification

7、for Wrought Titanium-6Aluminum-4Vanadium 4V ELI (Extra Low Interstiitial) Alloy forSurgical Implant Applications (UNS R56401)F 138 Specification for Wrought 18Chromium-14Nickel-2.5Molybdenum Stainless Steel Bar and Wire for SurgicalImplants (UNS S31673)F 562 Specification for Wrought Cobalt-35Nickel

8、-20Chromium10Molybdenum Alloy for Surgical ImplantApplications (UNS R30035)F 563 Specification for Wrought Cobalt-20Nickel-20Chromium-3.5Molybdenum-3.5Tungsten-5Iron Alloyfor Surgical Implant Applications (UNS R30563)F 603 Specification for High-Purity Dense Aluminum Ox-ide for Surgical Implant Appl

9、icationF 648 Specification for Ultra-High-Molecular-Weight Poly-ethlene Powder and Fabricated Form for Surgical ImplantsF 748 Practice for Selecting Generic Biological Test Meth-ods for Materials and DevicesF 981 Practice for Assessment of Compatibility of Bioma-terials for Surgical Implants with Re

10、spect to Effect ofMaterials on Muscle and Bone3. Terminology3.1 Description of a Term Specific to this Standard:3.1.1 biocompatibility assaya comparison of the tissueresponse produced through the close association of the im-planted candidate material to its implant site within the hostanimal to that

11、 tissue response recognized and established assuitable with control materials.4. Summary of Practice4.1 Under aseptic conditions, test specimens of the candi-date material and of controls are inserted into a muscle orgroup of muscles of the animal host. After a period of time theanimals are euthaniz

12、ed. The tissue reactions to implants of thecandidate material during the acute to subchronic time periodof healing are compared with tissue reactions to controlmaterials which have a well characterized response. Theimplants are not subject to major stress while in situ.5. Significance and Use5.1 The

13、 use of in vivo implantation techniques for charac-terizing the biocompatibility of materials to be utilized invarious medical applications provides a unique assessment ofsuch materials not achieved by other procedures. Physicalcharacteristics (that is, form, density, hardness, surface finish)can in

14、fluence the character of the tissue response to the testmaterials.1This practice is under the jurisdiction of ASTM Committee F04 on Medical andSurgical Materials and Devices and is the direct responsibility of SubcommitteeF04.16 on Biocompatibility Test Methods.Current edition approved May 1, 2004.

15、Published June 2004. Originallyapproved in 1982. Last previous edition approved in 2003 as F 763 99 (2003).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 stand

16、ards Document Summary page onthe ASTM website.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.5.2 This practice is intended as a rapid screening procedurefor determining the acceptability of candidate materials. Itwould be invoked pr

17、ior to using the long-term tests describedin Practice F 981. It is understood that for some applicationsadditional tests, including long-term implantation studies, maybe required to assess the final suitability of the candidatematerials.5.3 This practice may not be appropriate for all types ofimplan

18、t applications. The user is cautioned to consider theappropriateness of the method in view of the materials beingtested, their potential applications, and the recommendationscontained in Practice F 748.6. Test Preparation6.1 Rabbits, rats, or other animals may be used as test hosts.The following pro

19、cedure is written for New Zealand whiterabbits, a commonly used test host but the procedure can beadapted with few alterations to other test hosts.6.2 Test Hosts and Sites:6.2.1 Choose healthy adult rabbits that weigh more than 2.5kg and whose paravertebral muscles are sufficiently large toallow for

20、 implantation of the test specimens.6.2.2 The paravertebral muscle shall serve as the test site forimplants. (The gluteal muscles of rats have been used as testsites by some investigators.)6.2.3 Preparation of RabbitsOn the day of the implanta-tion or up to 20 h before implantation, clip the fur of

21、theanimals on both sides of the spinal column. Remove loose hair.6.3 Selection of Control Materials:6.3.1 Selection of control material(s) should be based ontheir prior acceptable use in medical applications similar tothose proposed for the candidate test material and is notrestricted to those liste

22、d in 6.3.2.6.3.2 Metallic control materials, which have been demon-strated to elicit minimal tissue reactions, are the metal alloys,such as in Specifications F 75, F 90, F 136, F 138, F 562, orF 563, or a ceramic, such as, alumina F 603. A suitablepolymeric control material is found in polyethylene

23、Specifica-tion F 648.NOTE 1There are times when use of a positive control can help toclarify the character of the tissue response to the candidate test sample.6.3.3 If the most appropriate control material is expected toelicit a tissue response greater than that normally observed withNegative Contro

24、l Plastic or the alloys cited above, samples ofthese latter materials may be implanted as controls on thesurgical technique.7. Test Specimens7.1 FabricationEach implant shall be fabricated, finished,and its surface cleaned in a manner appropriate for its projectedapplication in humans. Dense metal i

25、mplants should be fin-ished in accordance with Practice F 86. The size, shape, andsurface of test and control implants shall be as similar as ispractically possible.7.2 Implant sizes are left to the discretion of the investigator.Implants in the size range 1 by 10 mm (0.04 by 0.4 in.) to 3.2by 12 mm

26、 (0.125 by 0.5 in.) have often been used. They maybe of circular or square cross section. The edges of thespecimens should be as smooth as possible to avoid additionalmechanical trauma upon implantation.7.3 Implantation Period:7.3.1 The insertion of all implants into any one animal shallbe done at t

27、he same surgical session.7.3.2 Implant evaluation should be performed at 7 and 30 dso that an accurate characterization of both the test and controlmaterials can be made during the acute and subchronic stagesof the healing tissue response. Three animals will be used foreach sample period, that is, 3

28、 at 7 d, and 3 at 30 d.NOTE 2Some investigators have found that extending the test toinclude a third group of animals maintained for 90 d can provideadditional data on the host response to the implant material.38. Procedure8.1 Implantation:8.1.1 The recommended method of implantation is byhypodermic

29、 needle or tube and trochar. For larger diametersamples, an incision of appropriate size will be required topermit passage of the larger diameter tube. If this technique isnot convenient, however, other equivalent implantation tech-niques judged appropriate may be used. These should bereported as in

30、 9.1. The implantation must be done using asepticprocedures.8.1.2 Preparation of Test SpecimensThe specimensshould be fabricated as described in 7.1 and prepared forimplantation following the procedure in either 8.1.2.1 or8.1.2.2.8.1.2.1 Sterilize each specimen as appropriate for finalapplication an

31、d, using aseptic technique, insert it into a sterileneedle or tube; or,8.1.2.2 Insert the specimen into a needle or tube, protect theends with an appropriate cover, and sterilize the assemblies inan appropriate manner.NOTE 3Allow for proper degassing if sterilizing agents such asethylene oxide are u

32、sed.NOTE 4If the materials to be tested are harder than the materials fromwhich the handling instruments are made, there is the danger of surfacecontamination of the test specimens by wear from the instruments whichcan disturb the results (for example, ceramic test specimens implantedwith metal inst

33、ruments). If such test specimens must be handled, softtextile or plastic should be used between the implants and the instruments.Of course, care must be taken that none of these auxiliary protectingmaterials remain in the implantation wound.8.1.3 The animals should be anesthetized with a commonlyuse

34、d anesthetic agent to a degree deep enough to preventmuscular movement, such as twitching. Properly scrub theclipped skin surface of the animal.8.1.4 Implant four specimens of the sample into the paraver-tebral muscle on one side of the spine of each rabbit, about 2.5cm from the mid-line and paralle

35、l to the spinal columns, andabout 2.5 cm apart from each other. In a similar fashion,implant four specimens of the control material in the corre-sponding muscle on the opposite side of the spine of eachanimal.3Turner, E., Lawrence, W. H., and Autian, J., “Subacute Toxicity Testing ofBiomaterials Usi

36、ng Histopathological Evaluation of Rabbit Muscle Tissue,” Journalof Biomedical Materials Research, Vol 7, 1973, pp. 3958.F7630428.1.5 In cases where the negative control is other thanspecified in 6.3.2 and may be expected to elicit more than aminimal response, use only two test specimens of this neg

37、ativecontrol. Implant these two control specimens in a location thatwill not interfere with the test samples.8.1.6 When using a sterile needle for insertion, insert asterile stylet into the needle to hold the test specimen in thetissue while withdrawing the needle. With trocar implantation,insert th

38、e test specimen after withdrawing the central point anduse a stylet to hold the sample while withdrawing the cannula.8.1.7 If excessive bleeding is observed after implantation ofa test specimen, place a duplicate test specimen at another site.Close the incision after implantation is complete, if app

39、licable.If a test host other than the rabbit is chosen, use as manyanimals as are necessary to permit the implantation of 12 testspecimens and 12 controls for each sacrifice interval.8.2 Postoperative Care:8.2.1 All animal studies must be done, in a facility approvedby a nationally-recognized organi

40、zation and in accordance withall appropriate regulations.8.2.2 Carefully observe each animal during the period ofassay and report any abnormal findings.8.2.3 If an animal dies prior to the expected date of sacrifice,perform a necropsy to determine the cause of death. Include theanimal in the assay o

41、f data if the cause of death is related to theprocedure or test material.8.2.4 A successful test is one in which eight test specimensand eight controls for each test period are available forhistologic evaluation.8.2.5 Should infection or injury of the test implant siteinvalidate the results, replace

42、 the animal with another ifnecessary as described in 8.2.4.8.3 Sacrifice and Implant Retrieval:8.3.1 Sacrifice animals at the intervals suggested in 7.3.2.8.3.2 At sacrifice, record any gross abnormalities of color orconsistency observed in the tissue surrounding the implant.Documentation of finding

43、s using photography for a permanentrecord is highly recommended.8.4 Gross Observations, Acute Test (7 d) and SubchronicTest (30 d):8.4.1 Macroscopically examine the area of the tissue sur-rounding the center portion of each implanted test specimen.Use a magnifying glass, if necessary.8.4.2 The requi

44、rements of the test are met if, in each rabbit,the reaction to three of four sample test specimens is notsignificantly greater than that of the reaction to the correspond-ing negative control. In situations in which two types ofnegative controls are included, these criteria apply to the tissuesurrou

45、nding specimens of the minimally reactive material.8.5 Histopathological Observation, Acute Test (7 d), andSubchronic Test (30 d):8.5.1 Tissue Sample Preparation:8.5.1.1 Remove each implant with an intact envelope ofsurrounding tissue. The tissue sample should include a 4-mmthick layer of tissue sur

46、rounding the implants. If less than 4mm of tissue is removed, report in accordance with 9.1.Process the excised tissue block containing either a test implantor control implant for histopathological and such other studiesas are appropriate. Cut the tissue sample into appropriatespecimens for each stu

47、dy. Record the gross appearance of theimplant and the tissue immediately adjacent to the implant asto consistency and color, as seen by the naked eye, and with ahand lens or stereomicroscope (see 9.2).8.5.1.2 If possible, process the specimen with the implant inplace. This allows easy identification

48、 of the implant site andminimizes distortion during fixation. After fixation, the implantmaterial can be removed if necessary, and the tissue specimensprocessed for sectioning using standard laboratory practice forembedding and staining. If an implant is removed from itstissue bed, report the amount

49、 of tissue removed with theimplant as required in 9.1.8.5.1.3 Histological sections can be prepared using conven-tional microtomy section, or grinding of plastic embeddedspecimens as appropriate.8.5.1.4 For porous implant materials, the quality and quan-tity of tissue ingrowth may also be examined using theappropriate prepared sections.8.5.2 Histopathological Schedule:8.5.2.1 Process at least two tissue microscope slides fromeach sample of control and test implant, including the tissueenvelope surrounding the implant so as to obtain adequatehistopathological assessment of ti