Development and Evaluation of Porous Dental Implants in Miniature Swine

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Porous metallic and ceramic dental implantswere designed, fabricated, and implanted intofresh and healed alveolar sites of extractedmandibular premolar teeth in miniatureswine. Bone ingrowth securely anchoredthe implants; intraoral devices were later attachedto study the effects of stress on implantstability.

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    Journal of Dental Research

    http://jdr.sagepub.com/content/55/1/85The online version of this article can be found at:

    DOI: 10.1177/00220345760550013001 1976 55: 85J DENT RES

    M.T. Karagianes, R.E. Westerman, J.J. Rasmussen and A.M. LodmellDevelopment and Evaluation of Porous Dental Implants in Miniature Swine

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  • Development and Evaluation of Porous Dental Implants inMiniature Swine

    M. T. KARAGIANES, R. E. WESTERMAN, J. J. RASMUSSEN, andA. M. LODMELLBiology Department, Battelle Pacific Northwest Laboratories, Richland, Washington99352, USA, and Walla Walla, Washington 99362

    Porous metallic and ceramic dental implantswere designed, fabricated, and implanted in-to fresh and healed alveolar sites of ex-tracted mandibular premolar teeth in minia-ture swine. Bone ingrowth securely anchoredthe implants; intraoral devices were later at-tached to study the effects of stress on im-plant stability.

    The replacement of extracted teeth by en-dosteal implantation of prosthetic teeth isreceiving increased attention. The Journalof the American Dental Association has pub-lished an extensive review listing 274 refer-ences on the current status of such implants.'Basically, most techniques' used must beviewed as simply a penetration of bone by aforeign object, often followed by soft tissueencapsulation. However, we and others2-4have shown that bone will infiltrate suitableinert porous materials, yielding a good bone-prosthesis bond.

    This study has as its major long-term goalthe development of easily fabricated and im-plantable porous endosteal implants. Ourshort-term objectives included investigatingthe suitability of specific porous titaniumand ceramic materials for implant applica-tions, developing satisfactory designs andfabrication procedures for producing thesedevices, and defining bone-implant interfacebonding characteristics through in vivo ani-mal studies.

    Materials and MethodsThe principal metallic material studied is

    This investigation was supported by Contract No.NIH-71-2386 from the National Institute of Dental Re-search, National Institutes of Health, Bethesda, Md.

    Received for publication November 4, 1974.Accepted for publication July 28, 1975.

    void-metal composite (VMC), developed atthis laboratory. VMC consists of a Ti-6A1-4V alloy with interconnecting and controlledporosity achieved through special fabricationtechniques.5 The voids can be varied pre-cisely in shape (for example, spheres or cyl-inders) or orientation to alter the mechanicaland physical properties of the metal as wellas the structure of the metal-tissue interface.The ultimate compressive strength of 50%dense VMC (that is, a density of 0.5 timesthat of the solid alloy) is -30,000 psi. Themodulus of elasticity of the spherical-poreVMC is 5 (+ 1) X 105 psi, and that of thecylindrical-pore VMC is 9.5 ( 0.5) X 105psi. Dental implants having spherical-porediameters of 275 and 460 micrometers (/-cm)and cylindrical-pore diameters of 450 ,umwere fabricated from this alloy.

    Dental implants were also fabricated fromalumina porcelain ceramic composed of 95%aluminum oxide and 5% nepheline syenite.Material porosity is achieved by volatilizingvoid-forming cellulose particles within theceramic.6 The resulting pore size and inter-connectivity are not as controllable as withVMC, and pore diameters range from 200to 400 ttm. The modulus of rupture undertensile loading of 75% dense material is8,000 to 11,000 psi.

    Cylindrical implants of the two porousmaterials were surgically implanted intofresh and healed alveolar sites of extractedpremolars in the mandibles of miniatureswine. Typical implants, approximately 5mm in diameter and 18 mm in length, areshown in Figure 1. Note the solid top of theimplant that acts as a barrier to penetrationof the porous matrix by oral fluid and debris,the removable screw that keeps a threadedchannel in the implant clear during the

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  • J Dent Res January-February 1976

    12 13; f4FIG 1.-Left, cylindrical-pore VMC dental im-

    plants; and u-ight, porous ceramic implants withtrau-sgingival posts.

    hone ingrowtlh period, and the transgingivalpost tllat is secured to the implant six weeksafter implantation.

    FIhe possible use of the nonocclusal trans-gingival posts (also made of Ti-6AUIValloy) for attaclhment of artificial crownsis olvious; lhowever, their primarhy purposein these experimenits was to stu(ly hone in-growth reaction to nonocclusal intraoralstresses transmitte(d to the implants and toinivestigate gingival tissue reaction suirotund-ing the post. In contrast to thle slend(ler cy-linclrical transgingival posts, several truLn-cated conical devices were also attachied toporous implants to investigate gingival re-sponse to this particular (lesign (Fig 2).

    In order to evaluate the effects of lhighlermasticatory stresses on hone ingrowth, ti-tanium alloy caps (Fig 2) were screwed onthreaded transgingival posts and placedl inocclusion with the opposing maxillary teeth.Free-standing gold crowns were attaclhed totwo VMC dental implants to more accuiratelyassess the effects of normal occlusion on thebone-implant union; hlowever, these pros-theses have not yet been fully evaluiated.

    Standardized and rapid techniques for oralimplan-t surgery in swine were developedlin thiis program. Dental implant surgery wasfollowed in six weeks by transgingival postor cap attachment to the implant or both.This two-phase operation is believed neces-sary in swine becatUse of the difficulty of pro-viding proper postoperative hygiene. Fesssurgical instiuments are needed for the pro-cedure and only one is specialized-a plutncllwiitl a recessed tip to prevent mutilating the

    removable screw when the implant is tappedinto place.

    Using the healed-site techniuLie, at leastthiree montlhs were allowed for hone healingafter tootlh extractioni. The gingiva overeli(lentLetlous areas (contralateral mandibildar1)1remolars 1, 2, and 3) was then incised andsuifficiently elevated from the mandibularci-est to allow space for surgical implantation.TIhe exposed hone was drilled using a stan-dard orthopedic intramedullary pin (irillwithl ai Jacobs-type chiuck and an appropri-ately sizedl twist (Irill hit. Using a hit 3 to

    CAP VENTSCREWDRIVER SLOT \ 61 ~~~~~~~~6.710O7.6 mm

    9.5 mmTYP

    oo 000 ooo000000

    M mm000000 00000000 0000 00000000 0000 000 00000 0000 00000000 00 00 000000

    00 0000 000000

    K4.8Bmm+- K4.8mm-TRUNCATED CONE ADJUSTABLE OCCLUSAL CAP

    Flm 2.-Diagraai of truncatedl cone and oc-clusal cap attachecd to VMC dental implants.

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  • POROUS IMPLANTS IN SWINE 87

    5% smaller in diameter than the implantresults in a tiglht interference fit l)etweenthe device and the bone. The site wasliberally flushed with sterile physiologicalsaline and the dental implant, autoclaved at135 C for 35 minutes at 15 psig in triply dis-tilled water, was then tapped snugly into thecavity. The gingiva was sutured over theimplant, the top of whiclhI lies 1 to 2 mml)elow the mandibular crest.

    In the fresh-site approach, implants wereimmediately placed in the freslh sites of extracted )remolar teetlh. Some alveolar boneremoval was necessary in order to accom-modate the cylindrical implant. All surgicaland postoperative procedures were oteierwiseidentical to those used witlh the lhealed-sitemethod.

    Th-e swine were kept indivi(lually inspaciouts, solid-walled pens to prevent self-mutilation- of the implanit sites. Thley werefed a soft diet for two weeks to allow gingivalhealing, and thien were retut nie(d to astandardl hard-pellet swine diet.The swine were anesthietizedl to attaclh

    transgingival posts or caps or both to theimplants six weeks after initial implant smr-gery. Tihis rapidl procetlutre coinis'ted ofincising and elevating tlhe gingiva fItom theimlplant site an(d burring away lone that lhaldgrowni over the tops of the implants. Thlcsmall implant screw was reThoved and re-

    placed by the transgingival post, aroundwhiclh the gingiva was approximated andsutured.No supplemental bracing was used to

    stabilize these devices. The six-week timeintersal before attaclling posts and caps al-lows tissue ingrowth and bone organizationto occur in the porous implants, giving suf-ficient strengthi and immobilization for re-tention.The experimental implants were evaluated

    by clinical and histological examination andmechalnical testing. Clinical examination it-ncluidedl inspection, pei-iodontal probe meas-uirements of the gingixval sulci, application offorce to determine implant mobility, andperiodic radiography to examine mandibularb)one response to the implants.

    Histological examination was performedoni nondecalcified sections (implant plusbone) that were delhydlratedl in graded al-colhols, infiltrated withl a low-viscosity em-bedding medlitum as described by Spunr,7 andstained uLsing techniques reported by Smithiand Karagianes.8 Soft tissue ancl decalcifiecdbone specimens were fixed in Formalin, em-bedded in paraffin, andl stained with hiema-toxylini and eosin (H&E).

    MeTliaciical testing was performed oni freshsectionis to letermine the slear strengthi ofthe hone-impllant interface. Thlie specimenswere produced by cutting transverse sections

    FIG 3.-Free-standing gold crowvn (attached to VMC implant) in full oc-clusion with maxillary teeth. Large distal embrasure promotes self-cleansing.

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  • J Dent Res January-February 1976

    (4 to 9 mm thick) from the central regionof the bone blocks containing the implants.The "pluLg" of implant material was thenpressed from the surrounding bone using atension-compression testing maclhinea antIthe peak loads recorded. Interface shearstrengths were calculated from specimenclimensions andl peak loads.A total of 76 poious VMAC and ces-amic

    dlental implants were suLrgically implantedin the freslh andl healed sites of extractedmandibular pl)emolar teethl in 16 miniatureswine. Twenty-three VMC and 12 ceramicimplants were implanted in freshi premolarextractioni sites; 23 VlMC and 18 ceramic im-plants were implanted in lhealed extractionsites. Th-e swine were killed at appioximately4, 5, 8, andl 12 monthis after implantation.

    ResultsTo date, 68 dental implants have been ex-

    amined. Nineteen were removed and ex-amined at approximately four montlis, 17at five monthis, 16 at eiglht monthis, and 19at 12 months after surgical implantation.Four (onie VMC and three ceramic) were re-moved before the swine were killed becauseof rejection that eventually resultedl in morethan 1-mm implant mobility when stressedmanually. Eight othler prostheses, incluidingtwo VAMC implants with gold crowns at-taclhed, remain to be evaluated at 17 months'postimplantation (Fig 3).

    Histological examination of nonldecalcifiedsections embedded in plastic showed boneingrowtlh into 39 of 41 VMC dental implants.One had a thin fibi-ous tissue attachmentand anotlher, as noted previously, was re-moved before the swine was killed. Nearlycomplete lhard tisstue invasion had occurredin several of the porous metallic implantsand all but three had good bone attachmentand ingrowtlh; tlhese tlhree had bone in-growth over less than 25%-O of the bone-im-plant interface and exhibited less than 500psi sheas- strength.No adverse celltular inflammatory response

    cotild be fouind around any portions of thedevices having intimate bone-implant ad-herence (Fig 4). T issuLe invasion and or-ganized calcificaton appeared to follow apattern of intramembranous ossificationi.Clusteis of osteoblasts were found sturround-

    a Instron Universal Testing Machine, model FCL,Instron Corp, Los Alamitos, Calif.

    ing bone trabeculae that penetrated the vosidsof the implants. Haversian systems were pres-ent in the invading bone. I hiin (lecalcifiedsections stained withl H&E (after implantpushioult tests) confirmed that normal bonewas also present arouind the implants.

    Histologically, no morplological differ-ences in the bone were observed in either thespherical or cylindrical poi-ous VATC im-plants he tween nonistressed, sliglhtly stressedl(transgingivxal posts) anid lhighily str-essed(occlusal caps) implants. No apparent dif-fesenices were noted between hone ingrowtliin implants from freslh or healed -sites, andlextenisis e tissuLe invasion anti calcificationihiad occurred in four-montll implants aswell as in those stutdlied for the longer timeperiods. Histological and mechanical testingresu-lts weie similar for 2715- and 450-4m poresize V7IC implants.

    Thlree of 27 ceramic (aluminla porcelain)

    Fic. 4.-Histological cross sections showing ex-tensive bone ingrowth into (top) 460-gm spher-ical-porec VMC implanit after fise months im-plantation (x50) and (bottom) 450-,1m cylin-duiical-pose VIMC implanit eight months aftel sur-gery (Alizarini red S and methylene blue stain;x20). Metal is black.

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  • POROUS IMPLANTS IN SWINE 89

    Fi. 5.-Histological cross sectioni of alumina poicelain implant showingbone-ceramic interfacc after five months implantationi. Lack of initercoinnect-itig poiosity in material is exident (Alizarin red S and methylene blue stain;X20) .

    implants failed and were removedl before theswinie were killedl. Histological examinationwas performed on nonidecalcified sectionis of24 ceiamic implants removed at the (liffereiitstLudy intervals. Seven hlad an excellent bone-implatnt interface uinion (Fig 5), also suh-stantiated byIihiglh mechanical shear sts-engthtests. Anotlher implant, not mechanicallytested, also showed good bone invasion inltothe pores of the ceramic. Bone reslonrse tothese eighit implants was similar to thatfounid witlh tthe VNIlC implants; hiowever,thete was a smaller amouLnt of lhardl tissueinfiltration as a restult of the lack of adeqlutateinterconnecting porosity in this material.Againi, n-o apparent differences in bonemorplhology were noted in freslh vs lhealedsites, time periods investigated, or varyingstress conditions placecd on these implants.The i-emaining 16 ceramic implants

    slhowedl zero to minimal bone ingrowthi andwere characterized by a soft tissue interfaceunion. Tlils fibrouis tissue rangedl from 100to 500 Mm in tllickness and in most instancesentirely sui roundled the implant. These hlis-tological observations were fturther sub-stantiatedl 1y the low shear strengtlhs (O to300 psi) of 13 of these implants. It slhouildbe noted, hlowever, that these implants, aswell as those anclhored by bone ingrowth.

    weie (luite firmly immobilized (less than 0.5mm in)ovement) in the manidible and lackedany inif-lammatory responise indicative of imPl)anit iejection.

    Mechanical (pusliout) tests of the po0ousrlental iml)lants shlowedI a widle range ofshiear strengths. Samples from some swineslhowed high interface shear strength valuesequixvalent to a total load-bearing capacityof ulp to 1,000 11). It was evident from his-tological examination that the samples ex-hibiting low slhear strenigth valuies eithler lhadfibrous tissuie suirroun(ling the implant sec-tion or only spai-se bone infiltration over thesuirf ace of the implant. Specimens slhowinlghiigh shear strengtlh values demonstrated theexpected complete incorporation of the im-plant section into mandibular bone, withextensive organized bone ingrowthi and ab-sence of fibrous tissue. Figure 6 shows thebone-imlj1ant interface strengths of sectionsof 50 of the porouis implants puslhed ou-t onthe tension-compression testing machine.Twenty-seven of the 30 VMIC implants

    tested had hiigh shiear strengths (rangingfrom 500 to 2,500 psi) inldicative of goodl)one-implant interface union. In contrast,strengthls of 1.3 of 20 porotus ceramic im-plants were less than 500 psi (most less than100 psi) as a result of little or no bone in-

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    4 4

    2 2 2

    0 500 1000 1500 2000 2500 3000BONEIIMPLANT INTERFACE SHEAR STRENGTH, psi

    FtcG 6.-Mechanical test data for SO implantssloio'ing unumber ill each 500-psi shiear stressi}icremen t.

    growtl. Tlhis listological resullts were coim-patilble witlh these findinigs, as the majotityof ceramic im)lants xsere stii-rouLd(led x softtissule s-lather than hone.

    1'lhe attaclhment of ttransgingival plosts.tt uncatcd coIes, atndl occlusal capt)s (placingthe implants uinder varying stress conlitionis)made it possible to investigate ginlgval te-action to the titatiitm alloy deevices. How-evex, the rapidl accumulation of calculus onmany of these exten-sions (ft-om lack of post-operative liygiene), as seen- in Figure 7, in-

    terfered with a true evaluation of thegingiva-metal interface response.The extent of gingival tissue recession and

    inflammationi appeared to correlate directlywith the amount of calculus on thle intraoralextensions. Generally, transgingival postsand occlusal caps lhadl tolerable amounts ofcalculus, and the gingiva-metal interface re-action was acceptablle, showing moderateepitlhelial liyperplasia and inflammatory re-sponse in the immediate area (Fig 8). Plasmacells macle up the majority of the inflam-matory cells in these sites; some neutrophilsand lymplhocytes were also present.Truncated-cone posts typically accumu-

    lated large calctulus deposits up to 1.5 mmin thickness. This cone-shaped design alsoappeared to dlirect the calculus in an apicaldix ection, causing extensive gingival inflam-mation that itesuilted in excessive alveolarbone resorption (up to 2 mm in depth) insix of ten implants witlh these devices. Incontrast, radiographic examinations plusm1(easuirements after the swine were killedlshiowecd alveolar bone resorption aiouind thetops of the majority of otlher implants torange from near zero to 0.5 mm. In twoof the ssine dturing a one-year period, 1 2im)lants witlh cylindrical transginlgival postsshlowed only zei-o to ap)roximately 0.2 mmhone loss (Fig 9)

    Epithelial invagirnation around the deviceswxas a prxolem only isitlh the trunticated cones;the mucosal epithlelium was foiund to extendlah)ically to the tops of the implants. Thosewitlh slendclei cxlindrical posts an(d occlusalcasl)5 hl(I periodontal probe measurementsranging from 1.5 to 3.0 mm. (Gingival sulcimeasurements taken at six points on a num-

    F1ic 7.-Intraosal attaclhmenits (triuncatedI conie, occlusal cap, antI traizsginigival post) eightiniouths aftei implanitatioin. Note heaxy calculus deposits (left) Aftei calculus removal, oh-servedI weise gingival inflammiiiationi ant(I ecession aroundtoxic, excellent tissute t-esponise to capand(I mild reactioni to small post (right) .

    13

    Q CERAMIC

    [19 V

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  • POROUS IMPLANTS IN SWINE 91

    FIG 8.-Histological sectioII of ginigiva at tissue-transgingiral post interface(arrow) slhowing epitlhelial inxagiiiation andl iniflammatory cell responlse(H&E staini; X140).

    hei of pr1erniolar teetlh in control swine irangedfi-om 1.0 to 2.5 mm.) A healthy und(lerlyingsoft tissUe-metal adheience impeded epi-thllelial migrationi, at leatst utp to the timeperiodls insvestigated.

    DiscussionPeihaps the most signiificant aspects of

    tills reseatrclh ai-e the encout aging resuilts te-lating to the possihility of long-term reteni-tioii of enclosteal implants by an intimatehone-implant un1ioIn. hriere was no appartentrliffeietice in hone teactionls wlietlei- the im-

    llants wsiee untler slighit stress or uniicler theliglh stiesses of occlusal contact.

    Ilie intent of mechanical testitig was to(leteimiite the hone-implant inteitface shieat-strengtlh and compat e and correlate thesedlata, wlitlh histological observatioItis. The i-levasace of liglh shlear strengtlh values andtlteit relationshlip to load-bearing capalili tyand long-term retention of hone-ingrowniml)lants lhave not heen demonstrated; liow-exet, it is significant that implnts iunlethiighi stress (occlusal contact) slhowedl inter-face strengths similar to tlhose uLndlet- slighit

    FiG 9.-Radiographs showin-g (left) three VMC implanits immedliately after transgingixval postsurgery. Radiolucenit ate-as around tops of implaiits aie due to bon-e removal for post attachi-menit. Righit, just hefoie (leath, show-ing miiiimal ahecolar hone resorption aftei one-searimplantation. (Dimensioiial distortions are caused by anigle of radiography.)

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  • J Dent Res January-February 1976

    stress. For example, four VMC implantswith occlusal caps, two at five and two ateight months after implantation, lhad shlearstrengtlhs of 760, 1,700, 1,900, and 1,700psi, respectively. These results, in conjunc-tion witlh the histological findings, suggestthat bone ingrowth is conducive to endostealimplant retention under masticatory con-ditions.The initial stability of porous devices im-

    planted in bone is critical; however, it isnot known what degree of movement pro-hiibits osteogenesis and initiates soft tissueencapsulation. Bracing devices were notused in thiese experiments, therefore initialstability was achieved at the time of surgerytlhrough a tight bone-implant interference fit.The hiiglh strength of the VMC material per-mitted this type of surgical fit and, withthe high porosity of the material, resulted inorganized bone ingrowth that securely an-chored the implants in the mandible. Thefailure to obtain similar results with porousaltumina porcelain implants appeared to berelated to material porosity and strength.Increasing ceramic porosity (for improvedbone ingrowth) resulted in decreased ma-terial strengthi and implant fracture when aninterference fit was attempted. If implantedmore loosely, initial stability was reducedand soft tissue encapsulation without boneinvasion resulted.One might assume that bone ingrowth

    was initially present in some of the ceramicimplants, with bone resorption occurringafter the attachment of stress-producing in-traoral devices; however, as bone was presentin all but one VMC implant, the deductionwas that hard tissue ingrowth did not occurat all in these ceramic implants. This isfurther supported by the fact that eight im-plants (three VMC and five ceramic withtransgingival posts) in two of the swine dur-ing a one-year period had zero mobility butdifferent pushout results. The three VMCprostheses had shear strengths of 2,300, 1,400,and 2,300 psi, respectively, whereas the shearstrengths of all ceramic implants were lessthan 300 psi. Histological examinationshowed a soft tissue attachment to the ce-ramic implants in contrast to the bony at-tachment to VMC.

    Gingival reaction to the intraoral deviceswas not great, except with the truncated-cone design, and it was thought that muchof the reaction reflected the poor postop-

    erative dental hygiene of the pig. Compar-ison of control swine gingivae with those atthe implant sites showed that the inflam-matory response of the latter is merely anexaggeration of that seen in the "normal"pig gingiva and couldl be classified, in mostinstances, as a moderate gingivitis.

    ConclusionsOrganized bone ingrowth in endosteal

    porous implants fabricated from VMC tita-nium alloy and surgically implanted with atight interference fit, securely anchored theimplants in fresh and healed mandibular pre-molar sites of miniature swine. This bone-implant union retained its integrity underhigh as well as slight masticatory stresses upto one-year after implantation. Bone inva-sion of the alumina porcelain implants wasimpeded by the lack of adequate intercon-necting porosity; when the porosity was in-creased, insufficient ceramic strength pro-hibited a tight initial bone-implant fit. Asa consequence, inadequate initial implantstability resulted in a soft tissue encapsula-tion of the majority of the ceramic implants.

    Histological examination and mechanicaltesting results were similar for bone-ingrownimplants exposed to different experimentalstresses for 4, 5, 8, and 12 months. Bone in-growth and interface shear strengths werealso similar in the different VMC pore sizesand shapes investigated.The design of intraoral attachments ap-

    peared critical, at least in swine where nopostoperative treatment was administered.Gingival inflammation and alveolar boneresorption caused by calculus were severearound truncated cone-shaped devices. Slen-der transgingival posts, occlusal caps, andcrown restorations were less susceptible tocalculus accumulation, resulting in a moresatisfactory gingival and subgingival re-sponse.

    Excessive epithelial invagination was aproblem only in implants with transgingivaltruncated cones. Good adherence of soft tis-sue to metal under the gingival mucosa pre-vented epithelial migration around implantswith other transgingival devices.

    Alveolar bone resorption around the topsof bone-ingrown implants was minimal atthe time intervals examined (up to oneyear); however, a definite conclusion shouldbe delayed until longer-term implants underfull occlusion are evaluated.

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    References1. NATIELLA, J.R.; ARMITAGE, J.E.; GREENE,

    G.W., JR.; and MEENAGHAN, M.A.: CurrentEvaluation of Dental Implants, JADA 84:1358-1372, 1972.

    2. GALANTE, J.; ROSTOKER, W.; LUECK, R.; andRAY, R.D.: Sintered Fiber Metal Compositesas a Basis for Attachment of Implants toBone, J Bone Joint Surg 53A: 101-114, 1971.

    3. HULBERT, S. F; YOUNG, F.A.; MATTHEWS, R.S.;KLAWITTER, J.J.; TALBERT, C.D.; and STEL-LING, F.H.: Potential of Ceramic Materialsas Permanently Implantable Skeletal Pros-theses, J Biomed Mater Res 4: 433-456, 1970.

    4. KARAGIANES, M.T.: Porous Metals as a HardTissue Substitute: I. Biomedical Aspects,Biomater Med Devices Artif Organs 1: 171-181, 1973.

    5. WHEELER, K.R.; MARSHALL, R.P., and SUMP,

    K.R.: Porous Metals as a Hard Tissue Sub-stitute: II. Porous Metal Properties, Bio-mater Med Devices Artif Organs 1: 337-348,1973.

    6. MARSHALL, R.P.; KARAGIANES, M.T.; RAS-MUSSEN, J.J.; and WESTERMAN, R.E.: Devel-opment and Evaluation of Artificial DentalAnchors of Non-Natural Design Implantedin Miniature Swine, in First and SecondYear Report to National Institute of DentalResearch, June, 1971 to June, 1973, Con-tract No. 211B-00402, Richlarid, Wash: Bat-telle, Pacific Northwest Laboratories.

    7. SPURR, A.R.: A Low-Viscosity Epoxy ResinEmbedding Medium for Electron Micro-scopy, J Ultrastruct Res 26: 31-43, 1969.

    8. SMITH, L.G., and KARAGIANES, M.T.: Histo-logical Preparation of Bone to Study In-growth into Implanted Materials, Calif Tis-sue Res 14: 333-337, 1974.

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