ASTM F1904-1998(2008) Standard Practice for Testing the Biological Responses to Particles in vivo《测试活体中粒子生物反应的标准规范》.pdf

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1、Designation: F 1904 98 (Reapproved 2008)Standard Practice forTesting the Biological Responses to Particles in vivo1This standard is issued under the fixed designation F 1904; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revision, the year

2、 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 practice covers the production of wear debris anddegradation products from implanted materials that may lead

3、toa cascade of biological responses resulting in damage toadjacent and remote tissues. In order to ascertain the role ofparticles in stimulating such responses, the nature of theresponses, and the consequences of the responses, establishedprotocols are needed. This is an emerging, rapidly developing

4、area and the information gained from standard protocols isnecessary to interpret responses. Some of the procedures listedhere may, on further testing, not prove to be predictive ofclinical responses to particulate debris. However, only the useof standard protocols will establish which are useful tec

5、h-niques. Since there are many possible and established ways ofdetermining responses, a single standard protocol is not stated.However, this recommended practice indicates which neces-sary information should be supplied with test results. Forlaboratories without established protocols, recommendation

6、sare given and indicated with an *.1.2 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 the applica-bility of regulatory limit

7、ations prior to use.2. Referenced Documents2.1 ASTM Standards:2F 561 Practice for Retrieval and Analysis of Medical De-vices, and Associated Tissues and FluidsF 619 Practice for Extraction of Medical PlasticsF 748 Practice for Selecting Generic Biological Test Meth-ods for Materials and DevicesF 187

8、7 Practice for Characterization of Particles3. Summary of Practice3.1 Biological responses to particles testing may be doneusing specimens from animals being tested according to thePractice F 748 matrix for irritation and sensitivity, or forimplantation. Blood, organs, or tissues from the animals ma

9、ybe used. Procedures according to F 561 may be used to assessthe cellular response.3.2 Biological responses to particles may be tested usingmaterials or extracts according to Practice F 619. These mate-rials or extracts may be used in in vivo tests or for the in vitrotests. Particles generated by ot

10、her methods may also be used.The method of generation must be described.4. Significance and Use4.1 This practice is to be used to help assess the biocom-patibility of materials used in medical devices. It is designed totest the effect of particles from the materials on the host tissues.4.2 The appro

11、priateness of the methods should be carefullyconsidered by the user since not all materials or applicationsneed be tested by this practice. The validity of these studies inpredicting the human response is not known at this time andstudies such as described here are needed.4.3 Abbreviation Used:4.3.1

12、 LPSLipopolysaccharide (endotoxin).4.3.2 LALLimulus amebocyte lysate.4.3.3 PCRPolymerase chain reaction.4.3.4 CDCluster differentiation.4.3.5 HLAHuman leukocyte antigens.5. Responses from In Vivo Systems5.1 ParticlesDefine the nature of the particles used:5.1.1 Source,5.1.2 Chemistry,5.1.3 Size (mea

13、n and range),5.1.4 Shape,5.1.5 Surface charge (if known),5.1.6 Method of sterilization,5.1.7 If the presence of bacterial lipopolysaccharide (LPS)was determined, specify how this was done and the sensitivityof the method. (LAL testing with a sensitivity of at least 0.06EU is recommended),1This pract

14、ice is under the jurisdiction ofASTM Committee F04 on Medical andSurgical Materials and Devices and is the direct responsibility of SubcommitteeF04.16 on Biocompatibility Test Methods.Current edition approved Aug. 1, 2008. Published August 2008. Originallyapproved in 1998. Last previous edition appr

15、oved in 2003 as F 1904 98 (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 standards Document Summary page onthe ASTM website.1Copyright ASTM Internationa

16、l, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.5.1.8 Concentration of particles used as weight, or number,or surface area/implant, and5.1.9 Polystyrene particles, spherical, 1 to 5 m in sizeshould be used as a reference particle.5.2 Biological SystemOne or mor

17、e of these sites shouldbe used:5.2.1 Air Pouch Model This is an emerging model tosimulate synovial tissue. The volume of air and the timeallowed before introduction of the particles should be speci-fied. This model needs to be validated for length of time ofimplantation and relevance to other in viv

18、o systems.5.2.2 CagesCages made of porous materials such asstainless steel mesh or porous teflon can be implanted with atest material inside the cage. These may be implanted subcu-taneously or intraperitoneally. The material and the implantlocation chosen should be specified. The fluid accumulating

19、inthe cage can be sampled at various time intervals. The timeintervals must be specified. The cage and contained material isremoved at the termination of the experiment (specify timechosen) and evaluated for cell adhesion, cell type, and prod-ucts. Fluid containing large number of red blood cells sh

20、ouldbe discarded since it represents blood, not cage fluid.5.2.3 Bone Implant ChamberThis is a modification of thecage system and allows determination of the effect of particlesand the resulting biological response on bone remodeling5.2.4 Direct Injection Intraperitoneal, intravenous, intra-muscular

21、, subcutaneous are the favored routes. The end useapplication should govern the route of injection and the organor tissue utilized in this test. Inhalation may be suitable forsome end use applications.5.2.5 Examination of tissue at implant retrieval from animalmodels or clinical conditions is dealt

22、with in Practice F 1877.Some of the procedures defined here are also applicable tothese tissues.5.2.6 All sites used in these studies should be carefullyevaluated for infection at the termination of the study. Thepresence of infection will have a major impact on the outcomesince it stimulates many r

23、esponses.5.3 Biological Response DeterminedOne or more of thefollowing:5.3.1 Cell accumulation at the site of the particles should beevaluated for relative number and type of cells. Standardparaffin or plastic embedded sections are usually sufficient toidentify acute inflammatory cells, lymphocytes,

24、 macrophages,foreign body giant cells, osteoclasts, osteoblasts, osteocytes,eosinophils, etc. But in some cases special histological proce-dures, or immunohistochemical stains such as those describedin Practice F 561, or flow cytometry may be needed to confirmthe identity of lymphocytes and macropha

25、ges. An evaluationscale of 0 to 5 with 0 being no cell response, 1 beingaccumulation of a few cells, 2 being a mild response with somecell accumulation, 3 being a moderate response, 4 being a largeresponse, and 5 being a severe response is recommended. Itshould also be noted whether the response is

26、focal or diffuse.5.3.1.1 Transport of particles to relevant draining organsand histologic responses in these organs should be determined,especially when direct injection is used. The relevant organswould be spleen, liver, kidney, and some cases the lung. Thedraining nodes should be harvested if iden

27、tifiable. Some typesof debris are distinctive (for example, carbon fibers), but lymphnodes and lung commonly contain particles and bits ofbirefringent stuff that may be confused with particles used inthe experiment. Light microscopy with and without polarizedlight can be suggestive of particle migra

28、tion, but other meth-ods, (for example, EDAX, may be necessary to confirm thecomposition of the migrating particles. Organs from controlanimals should also be evaluated.5.3.2 Soluble Cell Products ElaboratedThis is a rapidlyemerging area of technology. Histochemical and immunohis-tochemical techniqu

29、es can be used to great advantage in thesestudies. Reliable reagents, kits, or hybridization protocols areavailable to detect the following products IL- 1b, IL-2, IL-4,IL-6, IL-10, PGE2, TNFa, immunoglobulins, as well as thelymphocyte CD markers and some HLA markers. It is notnecessary to measure al

30、l of these and the selection should bebased on whether there is emphasis on the macrophageresponse or the specific immune response.5.3.3 Where other products from the cellular response arebeing detected, they should be specified and the method usedspecified.5.4 Effects of the particles on other syst

31、ems such as boneremodeling, chondrocyte function, cartilage repair, and syn-ovial tissue function and repair are also important studies. Themethods used should be fully described.6. Report Section and Data Analysis6.1 The histologic response should be compared to that ofnormal tissues with no partic

32、les and to that of tissues receivingthe polystyrene reference particle. This may be done bycounting, by digitization, by cell analyzer, or by estimation inthe field of view. In some circumstances presence or absence ofmarker or response will suffice. In some circumstances quan-titation of the respon

33、se may be obtained with data on responsessuch as Ca+ released, enyzyme levels. DNA or RNA levels,etc.7. Keywords7.1 biocompatibility; biological response; in vivo; interleu-kins; particlesF 1904 98 (2008)2APPENDIX(Nonmandatory Information)X1. RATIONALEX1.1 The primary purpose of this practice is to

34、describemethodologies to determine the biological response to particlesusing in vivo responses.X1.2 It is well recognized that the biological responses toparticles could be different from those to solid materials. Theinteraction of the particles with cells in the tissue, notablymacrophages and other

35、 phagocytic cells, is a key to the finalbiological response.X1.3 The interaction of particles with host tissue has beenan active research area for many years. Many investigatorshave developed procedures for doing these studies. Thispractice is intended to delineate the information necessary forinter

36、pretation of the results from these various studies and todescribe methodology appropriate for those investigators de-veloping such studies.X1.4 The interaction of the biological system with particleswill lead to the accumulation of various cells which mayproduce soluble mediators which influence th

37、e progression ofthe biological response and the immune response. It is un-known at this time which of these responses are favorable andwhich are unfavorable to the host. Studies such as the onesdescribed here are needed to determine the importance of theseresponses in biocompatibility and biocompati

38、bility testing ofmaterials.ASTM International takes no position respecting the validity of any patent rights asserted in connection with any item mentionedin this standard. Users of this standard are expressly advised that determination of the validity of any such patent rights, and the riskof infri

39、ngement of such rights, are entirely their own responsibility.This standard is subject to revision at any time by the responsible technical committee and must be reviewed every five years andif not revised, either reapproved or withdrawn. Your comments are invited either for revision of this standar

40、d or for additional standardsand should be addressed to ASTM International Headquarters. Your comments will receive careful consideration at a meeting of theresponsible technical committee, which you may attend. If you feel that your comments have not received a fair hearing you shouldmake your view

41、s known to the ASTM Committee on Standards, at the address shown below.This standard is copyrighted by ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959,United States. Individual reprints (single or multiple copies) of this standard may be obtained by contacting ASTM at the aboveaddress or at 610-832-9585 (phone), 610-832-9555 (fax), or serviceastm.org (e-mail); or through the ASTM website(www.astm.org).F 1904 98 (2008)3