Synthesis and Antimicrobial Activity of a Silver-Hydroxyapatite Nanocomposite

Hindawi Publishing Co po a ion Jou nal o Nanoma e ials Volume 2009, A icle ID 498505, 6pages doi:10.1155/2009/498505 Resea ch A icle Syn hesis and An imic obial Ac i i y o a Sil e -Hyd oxyapa i e Nanocomposi e Ma cos D´ ıaz,1Flo a Ba ba,2Mi iam Mi anda,3F ancisco Gui i´ an,4Ram´ on To ecillas,3 and Jos´ eS.Moya 1 1Depa men o Bioma e ials and Bioinspi ed Ma e ials, Ins i u o de Ciencia de Ma e iales de Mad id (ICMM-CSIC), Can oblanco, 28049, Mad id, Spain 2Depa men o Ce amic, Ins i u o de Ce ´ amica y Vid io (ICV-CSIC), Can oblanco, 28049, Mad id, Spain 3Depa men o Nanos uc u ed Ma e ials, Cen o de In es igaci´ on en Nanoma e iales y Nano ecnolog´ ıa (CINN-CSIC), F ancisco Pin ado Fe 26, 33011, O iedo, Spain 4Ins i u o de Ce ´ amica de Galicia, Uni e sidad de San iago de Compos ela, 15706, San iago de Compos ela, Spain Co espondence should be add essed o Ram´ on To ecillas, [email p o ec ed] Recei ed 21 Augus 2008; Re ised 14 Janua y 2009; Accep ed 13 Ma ch 2009 Recommended by Ma yam Tab izian A sil e -hyd oxyapa i e nanocomposi e has been ob ained by a colloidal chemical ou e and subsequen educ ion p ocess in H2/A a mosphe e a 350◦C. This ma e ial has been cha ac e ized by TEM, XRD, and UV-Visible spec oscopy, showing he sil e nanopa icles (∼65 nm) suppo ed on o he HA pa icles (∼130 nm) su ace wi hou a high deg ee o agglome a ion. The bac e icidal effec agains common G am-posi i e and G am-nega i e bac e ia has been also in es iga ed. The esul s indica ed a high an imic obial ac i i y o S aphylococcus au eus, Pneumococcus and Esche ichia coli, so his ma e ial can be a p omising an imic obial bioma e ial o implan and econs uc i e su ge y applica ions. Copy igh © 2009 Ma cos D´ ıaz e al. This is an open access a icle dis ibu ed unde he C ea i e Commons A ibu ion License, which pe mi s un es ic ed use, dis ibu ion, and ep oduc ion in any medium, p o ided he o iginal wo k is p ope ly ci ed. 1. In oduc ion Theoccu enceo bone ac u esdue o heg owingnumbe o affic acciden s, as well as he musculoskele al condi ions equi ing econs uc i e su ge y de i ed om he inc ease in he human li e expec ancy, has led o an inc easing numbe o people in he wo ld ha ing a leas one o hopedic o den al implan . In addi ion o he conside able impac on he heal h and quali y o li e ha hese ypes o su ge y ha e on he popula ion, hey impose an impo an bu den o he economy o coun ies. Only in he Uni ed S a es, he numbe o o hopedic p ocedu es pe o med each yea —including knee a h oplas y, o al and pa ial hip eplacemen , and spinal usion—inc eased by nea ly 25 pe cen be ween 1997 and 2005, climbing om 822000 o 1.3 million, acco ding o he la es News and Numbe s summa y om he Agency o Heal hca e Resea ch and Quali y [1]. The same epo inds also ha he cos s ela ed o hospi al s ays o o hopedic p ocedu es o alled $31.5 billion. I has also been es ima ed ha 2 million new den al implan s a e pe o med e e y yea [2]. The e o e he need o eliable and economically easible bioma e ials o healing ac u es o ea ing musculoskele al diseases has inc eased in he las yea s. Hyd oxyapa i e (HA, Ca10(PO4)6(OH)2) is he main mine al componen o bone, and i s syn he ic o m is one o he mos widely used bioma e ials o econs uc ion o he skele on due o he lack o local o sys emic oxici y oge he wi h i s os eoconduc i e p ope ies [3–5]. I is used as an implan ma e ial bo h in i s bulk mainly po ous o m, o illing in o econs uc ing bone de ec s, and as a hin coa ing on me als, i anium and CoC Mo alloys, o hip, knee, and den al p os heses. Al hough success a es o hese kinds o implan s a e dependen on bone-implan os eoin eg a ion, he success and long- e m su i al o he implan s a e also dependen on he p e en ion o bac e ial in ec ion a e implan placemen . Despi e he use o pe iope a i e an imic obial p ophy- laxis and lamina low ope a ing ooms, he in ec ion a es associa ed wi h p os he ic join s ange be ween 1% and 9%, depending on he ype o implan [6]. Al hough he 2Jou nal o Nanoma e ials in ec ion-associa ed implan ailu es occu less equen ly han asep ic ones, hey a e he second eason o e ision su ge y in he case o o al hip eplacemen s [7]and ep esen he mos de as a ing complica ion wi h high mo bidi y and ele a ed medical cos . Mo eo e , in ec ion a es a e su ge y e ision a e 40% highe han a e p ima y eplacemen [8]. S udies on o hopaedic pa ien s e ealed ha he es ima ed a e age o al di ec cos associa ed wi h an in ec ed case anges be ween $15 000 and $30 000—an inc ease o app oxima ely 3 imes han he ini ial in e en ion—and shown ha he pa ien s spen on a e age 14 ex a days in he hospi al a e eadmission [9]. In he case o den al implan s, complica ions de i ed om an implan -associa ed in ec ion do no usually equi e pa ien hospi aliza ion, bu lead o a de imen in he pa ien quali y o li e and sa is ac ion because i is one o he easons o ea ly ailu es by lack o osseoin eg a ion and he majo cause o la e ailu es [10]. The e o e, efficien p e en ion o implan -associa ed in ec ions o a oid su gical e isions and expensi e and long hospi al s ays ha inc ease he pa ien mo bidi y is o pa amoun impo ance. One common and accep ed s a egy o ea and p e en in ec ions associa ed wi h o hopedic implan s is o deli e an ibio ics in a con olled manne a he si e o implan a ion in o de o adminis e high local doses wi hou exceeding he sys emic oxici y o hese d ugs [11– 13]. An ibio ic elease has been achie ed using a wide a ie y o biocompa ible ma e ials in he o m o coa ings o beads. Some o hese ma e ials a e polyme s (polyu e hane, poly- hyd oxylalkanoa es, polyme hylme hac yla e (PMMA), poly L-lac ic acid (PLA), poly(lac ic-co-glycolic) acid (PLGA), e c.), and syn he ic hyd oxyapa i e (HA) [14–16]. Al hough con olled d ug deli e y has been shown o nonbiodeg ad- ablepolyme s,suchasPMMA,i seffec i eness, howe e , is s ongly dependen on he an ibio ic elease p o ile om he polyme , which is a unc ion o he chemical simila i y be ween he d ug and he polyme , as well as o he physical p ope ies o he polyme i sel [14,15,17]. Mo eo e , he nonbiodeg adable polyme s do no eso b and equi e a subsequen ope a ion o emo al. The biodeg adable an ibio ic-loaded polyme coa ings, such as PLA o PLGA, a e able o eso b, so i o e comes his la e disad an age, bu i s high hyd ophobici y is ano he impo an d awback, since i places p ac ical cons ain s on o mula ing de ices wi h sufficien an ibio ic loading and dispe sion o eliable deli e y o an imic obials [14]. A good app oach o he local ea men o implan - associa ed in ec ions is he use o HA coa ings o an ibio ics deli e y, exploi ing he os eoconduc i e p ope ies o his ma e ial. Howe e , he loading and elease a e is s ongly dependen on he acidic o basic cha ac e o an ibio ics. Acidic an ibio ics a e inco po a ed wi h g ea e efficiency han basic an ibio ics because o he calcium-chela ing p op- e ies o he ca boxyla e g oups. Howe e , h ough calcium- ca boxyla e chela ing in e ac ions, he acidic an ibio ics a e e ained o a g ea e ex en ela i e o he basic an ibio ics [15]. This ac imposes ce ain limi a ions in cases ha equi e he use o acidic an ibio ics, o example amoxicillin. The capaci y o ce ain bac e ial s ains o de elop esis- ance agains an ibio ics has a oused an inc easing in e es o he con olled deli e y o o he an ibac e ial agen s wi h a b oade ac i i y and low incidence o esis ance, such me als like sil e o zinc, being an al e na i e s a egy o a oid he o ma ion o adhesi e bac e ial ilms [18]. The an ibac e ial p ope ies o sil e a low concen a ions o e a wide ange o pa hogens, including he common bac e ial s ains in ol ed in implan -associa ed in ec ions as well as he lack o oxici y o he mammalian cells, a e well known [19–24]. Mos sil e -con aining an imic obial bioma e ials consis o ei he elemen al sil e o Ag+(sil e sal s o sil e com- plexes) inco po a ed in o o ganic (polyme s) o ino ganic (bioglasses and HA) ma ices. While he in i o an imi- c obial ac i i y o sil e -con aining polyme s (polyamides, polyu e hane, and PMMA) and bioglasses has been ex en- si ely s udied [25–28], he bac e icide ac ion o Ag-HA ma e ials has been epo ed in less ex ension. Recen ly, Ag- loaded HA composi es ob ained by ion-exchange me hods (sol-gel o cop ecipi a ion) ha e been epo ed [29–32]. These ou es in ol e he sil e subs i u ion o calcium, esul ing in a Ca-de icien hyd oxyapa i e. The an imic obial esponse o hese ma e ials is good, bu hey ha e wo main d awbacks: (i) he deple ion o calcium could ha e nega i e effec s on he s uc u al s abili y o nano HA [31]aswell as on i s os eoconduc ion abili y [32]; (ii) a apid elease o sil e , depending on he pH, can ake place. These ac s ha e b ough ou an inc easing in e es on sil e nanopa icles as bac e icidal ese oi due o hei low solubili y in aqueous media. S udies on nanosil e -loaded polyme ilms e eal ha he du a ion o sil e elease is s ongly dependen on he o al amoun o sil e nanopa icles [19]. The biocide ac i i y o colloidal sil e nanopa icles is in luenced by hei size— he smalle he pa icles, he g ea e an imi- c obial effec [22]—howe e , he agg ega ion p oblems o nanopa icles a e well known. A common solu ion o a oid his disad an age is o suppo he nanopa icles on he su ace o diffe en subs a es. Despi e he po en ial clinical applica ions o nAg-HA composi es due o he combina ion o os eoconduc i e and bac e icide p ope ies, he e a e ew examples in he li e a u e o sil e nanopa icles suppo ed on o hyd oxyapa i e pa icles. These ma e ials ha e been ob ained by cospu e ing o sil e and hyd oxyapa i e o o m coa ings on i anium su aces [33], and by in si u educ ion o sil e ca ions on he su ace o HA pa icles [34]. In he p esen wo k, a simple and low-cos me hod o suppo sil e on he su ace o hyd oxyapa i e o ob ain a nano-nano hyb id composi e, con aining 1 w % o elemen al sil e , wi h an imic obial ac i i y is p esen ed. 2. Ma e ials and Me hods 2.1. P epa a ion. The p epa a ion me hod comp ises wo s eps: (i) syn hesis o HA nanopa icles by a sol-gel p o- cessing ou e, and (ii) p ecipi a ion o Ag2O nuclei om sil e ni a e aqueous solu ion and u he educ ion wi h an A /H2gas mix u e a low empe a u e o ob ain sil e nanopa icles a ached on o nano-HA. The p ecu so s employed in he HA nanopa icles we e ie hylphosphi e (98%, Ald ich) and calcium ni a e Jou nal o Nanoma e ials 3 (b) (a) In ensi y 0204060 2θ(deg ees) Figu e 1: XRD pa e ns co esponding o diffe en s ages o HA syn hesis: (a) amo phous d y gel; (b) c ys alliza ion a 550◦C. e ahyd a e (≥99%, Fluka). Aqueous solu ions 3 M we e p epa ed o eachp ecu so ino de oob aina inalCa/P mola a io o 1.67. The phospho ous solu ion was added d opwise o he calcium solu ion unde igo ous s i ing while main aining he empe a u e a 65◦C and pH =8. The pH was con olled by addi ion o NH4OH (28% w/w, Fluka) aqueous solu ion. The esul ing colloidal suspension was s i ed a 70◦C o wo hou s and hen aged a oom empe a u e o 24 hou s o ob ain whi e and iscous gel. The gel was d ied in a acuum chambe a 100◦C un il he sol en was comple ely emo ed. The d y powde was g ound and calcined a 550◦C o 2 hou s. A well-c ys allized HA powde was ob ained. In o de o p epa e he nAg-HA composi e 5g o he HA powde ob ained in he p e ious syn hesis we e suspended in 50.55 mL o dis illed wa e (9 w % o solids loading). Subsequen ly, he suspension pH was adjus ed o 5 by adding d opwise a 0.1 N HNO3aqueous solu ion unde s i ing a 60◦C.Then,10mLo a4.7×10−2MAgNO 3aqueous solu- ion we e added o ob ain an nAg-HA composi e con aining 1 w % o me allic sil e . Unde con inuous s i ing, he pH was adjus ed o 9 by adding d opwise a 1 M NaOH aqueous solu ion o p ecipi a e Ag+ca ionsasAg 2O, acco ding o he po en ial-pH diag am in aqueous solu ion o sil e [35]. The suspended whi e powde slowly u ned o g ay, indica ing he p esence o Ag2O p ecipi a ion nuclei. Finally, he suspension was il e ed and washed wice wi h dis illed wa e a 60◦C. The esul ing powde was d ied a 60◦Cand calcined a 350◦C o 2 hou s in a gas mix u e o A /H290/10 in o de o educe he sil e oxide o me allic sil e , yielding a pale b own powde . All s eps o his syn hesis we e ca ied ou in absence o ligh o a oid he spon aneous educ ion o sil e ca ions o elemen al sil e . 2.2. Cha ac e iza ion Techniques. X- ay powde diff ac ion (XRD) pa e ns we e egis e ed using a B uke D8 Ad ance diff ac ome e wi h a Cu Kα adia ion sou ce a a scan speed o 0.5◦/min and a s ep scan o 0.02◦. The powde pa icle size dis ibu ion was ca ied ou in a ins umen Coul e ?LS 13320 using lase adia ion (λ= 750 nm). T ansmission elec on mic oscopy images we e eco ded on a Jeol 2000 FXII ins umen ope a ing a 200 kV. 0 5 10 15 20 Numbe (%) 0.11 Pa icle diame e (μm) Figu e 2: Pa icle size dis ibu ion o hyd oxyapa i e powde . UV- is spec oscopy was pe o med using a Ca y 4000 u - is spec opho ome e . 2.3. An imic obial Ac i i y. To in es iga e he bac e icidal effec o he nAg-HA composi e, wo ypes o es s we e pe o med as ollows. (i) A quali a i e diffusion disk es using 105colony o ming uni s (CFUs) o he S aphylococcus au eus (Sa), Pneumococcus (Pn), and Esche ichia coli (Ec). They we e cul u ed on LB aga pla es. Pelle s o 0.05 g, 8 mm in diame e , p essed a 100 MPa o HA (as con ol) and o nAg-HA composi e we e loca ed a he cen e o he Pe i pla e. The pla es we e incuba ed o 24 hou s a 37◦C. The mic obial inhibi ion zone was obse ed unde op ical mic o- scope. The inhibi ion zone size a ound h ee pelle s co esponding o he nAg-HA sample and he con ol o he diffe en bac e ial cul u es was a e aged. (ii) A quan i a i e analysis using 105CFU o a G am- nega i e bac e ium Ec s ain B which we e cul u ed on LB aga pla es con aining diffe en concen a ions o composi e, 1, 5, and 10 mg/cm3, co esponding o 10, 50, and 100μg/cm3o sil e nanopa icles, espec i ely. Sil e - ee HA LB aga pla es cul u ed unde he same condi ions we e used as a con ol. Thepla eswe eincuba ed o 24hou sa 37 ◦C, and he numbe s o colonies we e coun ed. The coun s on he h ee pla es co esponding o each sample we e a e aged. 3. Resul s and Discussion The c ys alliza ion p ocess o he hyd oxyapa i e powde is shown in Figu e 1. The g anulome ic analysis (Figu e 2) e ealed a s e ch size dis ibu ion wi h an a e age size (d50) o 137 nm, in ag eemen wi h he TEM images o he powde shown in Figu e 3. The XRD pa e n o he esul ing HA-nAg powde is shown in Figu e 4. The e lec ions a 38.1◦and 44.3◦ co espond o me allic sil e . No o he phases bu HA we e 4Jou nal o Nanoma e ials 50nm Figu e 3: TEM image showing he size and mo phology o he HA nanopa icles syn hesized. 0 30 60 90 Rela i e in ensi y 10 20 30 40 50 60 70 2θ Figu e 4: XRD pa e n co esponding o he 1 w % Ag-con aining HA composi e a e educ ion ea men (Ag (0)). de ec ed, which indica es ha des abiliza ion o dissolu ion o hyd oxyapa i e has no aken place du ing he Ag nanopa - icles syn hesis. The a e age pa icle size o sil e , calcula ed om he Sche e o mula, was ound o be 65 nm. TEM images show in Figu e 5 a size dis ibu ion o globula -shape sil e pa icles ha ange be ween less han 20 nm and 100 nm. The majo i y o la ge sil e pa icles occu on o agg ega es o HA pa icles. This ac could be ela ed wi h a pa ial des abiliza ion o HA pa icles in aqueous suspension ha gi es ise o he o ma ion o agg ega es, whe e he g ow h o Ag2O nuclei could be a o ed. I is well known ha he size o he pa icles o med om a solu ion is in e sely p opo ional o he numbe o small p ecipi a ion nuclei, so he g ea e he numbe o hese, he smalle he pa icles ob ained [36]. The dec ease o he speci ic su ace o HA agg ega es can affec he dis ibu ion o he p ecipi a ion nuclei a hese si es, leading o he g ow h o he pa icles. On he o he hand, bigge Ag pa icles can also be o med by coalescence o smalle ones du ing he educ ion p ocess. 50 nm (a) 20 nm (b) Figu e 5: (a) TEM image showing he size dis ibu ion o Ag nanopa icles; (b) high magni ica ion TEM image showing n-Ag pa icles less han 20 nm a ached on he HA su ace. The pale b own colo o he Ag-HA powde is due o he exci a ion o su ace plasmon ib a ions o sil e nanopa icles on he HA su ace. The UV-VIS spec um is shown in Figu e 6.Theb oadbandcen e eda 450nmag ees wi h a size dis ibu ion due o he pa ial agg ega ion o sil e nanopa icles [34]. The colloidal sil e solu ions a e yellow when he nanopa icles a e well dispe sed. Howe e , i he pa icles a e close enough, he e is an o e lap o he su ace plasmon ib a ions be ween neighbo ing pa icles and esul s in changes in he op ical p ope ies. This can occu due o he agg ega ions o he sil e nanopa icles, leading o an effec i e dec ease in he a e age in e pa icle dis ance. The absence o highe -wa eleng h ea u es (see Figu e 6) indica es he lack o aniso opy o he sil e nanopa icles, in good ag eemen wi h he TEM images. Jou nal o Nanoma e ials 5 Abso bance (a.u.) 350 450 550 650 750 λ(nm) 450 nm Figu e 6: UV- is spec um o he Ag-HA powde showing he su ace plasmon band o sil e nanopa icles. 0 20 40 60 80 100 Numbe o E. coli colonies (%) HA Ag-HA 10 μg/cm3 50 μg/cm3 100 μg/cm3 Figu e 7: Numbe o E. coli colonies as a unc ion o he concen a ion o sil e nanopa icles exp essed as a pe cen age o he numbe o colonies g own on sil e - ee con ol pla es. The diffusion disk es s showed, in all he cases, a simila exclusion a ea ha appea s only a ound he nAg-HA composi e pelle s, as i is epo ed in Table 1. These esul s show ha a sil e concen a ion o 10000 ppm is ended up in oxici y o common G am-posi i e and G am-nega i e bac e ia. Figu e 7 shows he numbe o bac e ial colonies g own on LB pla es con aining 1, 5, and 10mg/cm3o nAg- HA composi e and pu e HA as con ol, when app oxima ely 105CFU we e cul u ed in he pla es. A e 24 hou s, he p esence o sil e nanopa icles a a concen a ion o 10 and 50 μg/cm3inhibi ed he bac e ial g ow h by 62% and 88%, espec i ely, while a concen a ion o 100 μg/cm3caused 100% inhibi ion o bac e ial g ow h. These esul s show a s ong bac e icidal effec agains Sa, Pn, and Ec. In he pa icula case o G am-nega i e bac e ium E. coli, i is sligh ly lowe han colloidal sil e nanopa icles sys ems [20] wi h an a e age pa icle size be ween 10 and 20 nm. Howe e , he nanocomposi e powde posseses an in e es ing ad an age: i can be easily handled and shaped in o pelle s o sponges wi hou special ca e Table 1: Diffusion disk es o HA-nAg pelle s, con aining 10000 ppm o Ag, agains S aphylococcus au eus,Pneumococcus,and Esche ichia coli a e 24 hou s a 37◦C. S. au eus Pneumococcus E. coli Inhibi ion zone 17 17.5 18 diame e (±0.5 mm) o a oid he ypical agglome a ion p oblems ela ed o he colloidal sys ems o nanopa icles. 4. Conclusions In summa y, we ha e desc ibed a simple and low-cos me hod o ob ain a HA-Ag nanocomposi e powde wi h bac e icidal p ope ies. TEM, XRD, and UV- is echniques ha e showed he p esence o sil e nanopa icles (∼65 nm) a ached on he hyd oxyapa i e pa icles su ace wi hou a high deg ee o agglome a ion. The bac e icidal ac i i y esul s show ha his nanocomposi e is s ongly ac i e agains some o he mos common G am-posi i e and G am- nega i e bac e ial s ains, so i can be conside ed as an an imic obial bioma e ial ha can be used in implan and econs uc i e su ge y applica ions. Acknowledgmen s This wo k was suppo ed by Bioke Resea ch S.L. and by he Spanish Minis y o Educa ion and Science unde P ojec CENIT-INTELIMPLANT ( e .: 20071210). M. D´ ıaz has been suppo ed by Spanish Minis y o Educa ion and Science and CSIC unde I3P P og am inanced by Eu opean Social Fund. The au ho s hank Raul Pina o he echnical suppo in he TEM s udy. Re e ences [1] “O hopedic P ocedu es Inc ease D ama ically in Se en Yea s,” Agency o Heal hca e Resea ch and Quali y (AHRQ News and Numbe s), Rock ille, Md, USA, 2007, h p://www.ah q.go /news/nn/nn071807.h m. [2]E.E.MacH ei,D.Mahle ,O.Oe inge -Ba ak,O.Zuabi,and J. Ho wi z, “Den al implan s placed in p e iously ailed si es: su i al a e and ac o s affec ing he ou come,” Clinical O al Implan s Resea ch, ol. 19, no. 3, pp. 259–264, 2008. [3] M. Ja cho, “Re ospec i e analysis o hyd oxyapa i e de elop- men o o al implan applica ions,” Den al Clinics o No h Ame ica, ol. 36, no. 1, pp. 19–26, 1992. [4] M. Ti ell, E. Kokkoli, and M. Biesalski, “The ole o su ace science in bioenginee ed ma e ials,” Su ace Science, ol. 500, no. 1–3, pp. 61–83, 2002. [5] L. L. Hench, “Bioce amics,” Jou nal o he Ame ican Ce amic Socie y, ol. 81, no. 7, pp. 1705–1728, 1998. [6] W. Zimme li, A. T ampuz, and P. E. Ochsne , “Cu en con- cep s: p os he ic-join in ec ions,” The New England Jou nal o Medicine, ol. 351, no. 16, pp. 1645–1654, 2004. [7] H. Malchau, G. Ga elick, and P. He be s, “The e idence om he Swedish hip egis e ,” in The Well-Cemen ed To al Hip A h oplas y: Theo y and P ac ice, S. B eusch and H. Malchau, Eds., pp. 291–301, Sp inge , Be lin, Ge many, 2006. 6Jou nal o Nanoma e ials [8] A. T ampuz and W. Zimme li, “P os he ic join in ec ions: upda e in diagnosis and ea men ,” Swiss Medical Weekly, ol. 135, no. 17-18, pp. 243–251, 2005. [9] R. O. Da ouiche, “T ea men o in ec ions associa ed wi h su gical implan s,” The New England Jou nal o Medicine, ol. 350, no. 14, pp. 1422–1429, 2004. [10] S. Chen and I. Da by, “Den al implan s: main enance, ca e and ea men o pe i-implan in ec ion,” Aus alian Den al Jou nal, ol. 48, no. 4, pp. 212–220, 2003. [11] W. J. Leach and N. I. L. Wilson, “T ends in in ec ion p ophylaxis in o hopaedics,” Jou nal o he Royal College o Su geons o Edinbu gh, ol. 37, no. 4, pp. 265–266, 1992. [12] J. Calhoun, G. Cie ny III, P. Hol om, J. Made , and C. L. Nelson, “Symposium: cu en concep s in he managemen o os eomyeli is,” Con empo a y O hopaedics, ol.28,no.2,pp. 157–185, 1994. [13] T.N.Ge ha ,R.D.Roux,P.A.Hanff,G.L.Ho owi z,A.A. Renshaw, and W. C. Hayes, “An ibio ic-loaded biodeg adable bone cemen o p ophylaxis and ea men o expe imen al os eomyeli is in a s,” Jou nal o O hopaedic Resea ch, ol. 11, no. 2, pp. 250–255, 1993. [14] P. Wu and D. W. G ainge , “D ug/de ice combina ions o local d ug he apies and in ec ion p ophylaxis,” Bioma e ials, ol. 27, no. 11, pp. 2450–2467, 2006. [15] E. M. He ick and M. H. Schoen isch, “Reducing implan - ela ed in ec ions: ac i e elease s a egies,” Chemical Socie y Re iews, ol. 35, no. 9, pp. 780–789, 2006. [16] A. Sudo, M. Hasegawa, A. Fukuda, and A. Uchida, “T ea men o in ec ed hip a h oplas y wi h an ibio ic-imp egna ed cal- cium hyd oxyapa i e,” The Jou nal o A h oplas y, ol. 23, no. 1, pp. 145–150, 2008. [17] J. S. P ice, A. F. Tence , D. M. A m, and G. A. Bohach, “Con olled elease o an ibio ics om coa ed o hopedic implan s,” Jou nal o Biomedical Ma e ials Resea ch, ol. 30, no. 3, pp. 281–286, 1996. [18] S. L. Pe ci al, P. G. Bowle , and D. Russell, “Bac e ial esis ance o sil e in wound ca e,” Jou nal o Hospi al In ec ion, ol. 60, no. 1, pp. 1–7, 2005. [19] D. Lee, R. E. Cohen, and M. F. Rubne , “An ibac e ial p op- e ies o Ag nanopa icle loaded mul ilaye s and o ma ion o magne ically di ec ed an ibac e ial mic opa icles,” Langmui , ol. 21, no. 21, pp. 9651–9659, 2005. [20] I. Sondi and B. Salopek-Sondi, “Sil e nanopa icles as an imi- c obial agen : a case s udy on E. coli as a model o G am- nega i e bac e ia,” Jou nal o Colloid and In e ace Science, ol. 275, no. 1, pp. 177–182, 2004. [21] A. R. Shah e di, A. F. Pha m, H. R. Shah e di, and S. Minaian, “Syn hesis and effec o sil e nanopa icles on he an ibac- e ial ac i i y o diffe en an ibio ics agains S aphylococcus au eus and Esche ichia coli,” Nanomedicine: Nano echnology, Biology and Medicine, ol. 3, no. 2, pp. 168–171, 2007. [22] A. Pan´ aˇ cek, L. K ´ ı ek, R. P ucek, e al., “Sil e colloid nanopa icles: syn hesis, cha ac e iza ion, and hei an ibac e- ial ac i i y,” Jou nal o Physical Chemis y B, ol. 110, no. 33, pp. 16248–16253, 2006. [23] K. Dunn and V. Edwa ds-Jones, Eds., “The ole o Ac icoa TM wi h nanoc ys alline sil e in he managemen o bu ns,” Bu ns, ol. 30, supplemen 1, pp. S1–S9, 2004. [24] K.-H. Cho, J.-E. Pa k, T. Osaka, and S.-G. Pa k, “The s udy o an imic obial ac i i y and p ese a i e effec s o nanosil e ing edien ,” Elec ochimica Ac a, ol. 51, no. 5, pp. 956–960, 2005. [25] R. Kuma and H. M¨ uns ed , “Sil e ion elease om an imi- c obial polyamide/sil e composi es,” Bioma e ials, ol. 26, no. 14, pp. 2081–2088, 2005. [26] M. Bellan one, H. D. Williams, and L. L. Hench, “B oad- spec um bac e icidal ac i i y o Ag2O-doped bioac i e glass,” An imic obial Agen s and Chemo he apy, ol.46,no.6,pp. 1940–1945, 2002. [27] V. Al , T. Beche , P. S ein ¨ ucke, e al., “An in i o assessmen o he an ibac e ial p ope ies and cy o oxici y o nanopa ic- ula e sil e bone cemen ,” Bioma e ials, ol. 25, no. 18, pp. 4383–4391, 2004. [28] V. Sambhy, M. M. MacB ide, B. R. Pe e son, and A. Sen, “Sil e b omide nanopa icle/polyme composi es: dual ac ion unable an imic obial ma e ials,” Jou nalo heAme ican Chemical Socie y, ol. 128, no. 30, pp. 9798–9808, 2006. [29] W. Chen, S. Oh, A. P. Ong, e al., “An ibac e ial and os eogenic p ope ies o sil e -con aining hyd oxyapa i e coa ings p o- duced using a sol gel p ocess,” Jou nal o Biomedical Ma e ials Resea ch Pa A, ol. 82, no. 4, pp. 899–906, 2007. [30] R.-J. Chung, M.-F. Hsieh, K.-C. Huang, L.-H. Pe ng, F.- I. Chou, and T.-S. Chin, “An i-mic obial hyd oxyapa i e pa icles syn hesized by a sol-gel ou e,” Jou nal o Sol-Gel Science and Technology, ol. 33, no. 2, pp. 229–239, 2005. [31] N. Rameshbabu, T. S. Sampa h Kuma , T. G. P abhaka , V. S. Sas y, K. V. G. K. Mu y, and K. P asad Rao, “An ibac e ial nanosized sil e subs i u ed hyd oxyapa i e: syn hesis and cha ac e iza ion,” Jou nal o Biomedical Ma e ials Resea ch Pa A, ol. 80, no. 3, pp. 581–591, 2007. [32] I.-H. Han, I.-S. Lee, J.-H. Song, e al., “Cha ac e iza ion o a sil e -inco po a ed calcium phospha e ilm by RBS and i s an imic obial effec s,” Biomedical Ma e ials, ol.2,no.3,pp. S91–S94, 2007. [33] W.Chen,Y.Liu,H.S.Cou ney,e al.,“In i oan i-bac e ial and biological p ope ies o magne on co-spu e ed sil e - con aining hyd oxyapa i e coa ing,” Bioma e ials, ol. 27, no. 32, pp. 5512–5517, 2006. [34] S. K. A umugam, T. P. Sas y, B. S eedha , and A. B. Mandal, “One s ep syn hesis o sil e nano ods by au o educ ion o aqueous sil e ions wi h hyd oxyapa i e: an ino ganic- ino ganic hyb id nanocomposi e,” Jou nal o Biomedical Ma e- ials Resea ch Pa A, ol. 80, no. 2, pp. 391–398, 2007. [35] M. Pou baix, A las o Elec ochemical Equilib ia in Aqueous Solu ions, Na ional Associa ion o Co osion Enginee s, Hous- on, Tex, USA, 1974. [36] B. L. Cushing, V. L. Kolesnichenko, and C. J. O’Conno , “Recen ad ances in he liquid-phase syn heses o ino ganic nanopa icles,” Chemical Re iews, ol. 104, no. 9, pp. 3893– 3946, 2004. Submi you manusc ip s a h p://www.hindawi.com Scien i ica Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 Co osion In e na ional Jou nal o Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 Polyme Science In e na ional Jou nal o Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 Ce amics Jou nal o Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 Composi es Jou nal o Nanopa icles Jou nal o Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 In e na ional Jou nal o Bioma e ials Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 Nanoscience Jou nal o Tex iles Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 Jou nal o Nano echnology Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 Jou nal o C ys allog aphy Jou nal o Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 The Scien i ic Wo ld Jou nal Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 Coa ings Jou nal o Ad ances in Ma e ials Science and Enginee ing Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 Sma Ma e ials Resea ch Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 Me allu gy Jou nal o Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 BioMed Resea ch In e na ional Ma e ials Jou nal o Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 Nanoma e ials Hindawi Publishing Co po a ion h p://www.hindawi.com Volume 2014 Jou nal o Nanoma e ials