Prosthesis with antibiotic-eluting nanofibrous (NF) coating represents coating alternative to prevent periprosthetic joint infection (PJI). In this study, four formulas of erythromycin (EM)-embedded both in core and sheath components of coaxial PCL/PLGA-PVA NF coatings were developed: EM 0 (no EM), EM 100 (100 μg/mL), EM500 (500 μg/mL) and EM1000 (1000 μg/mL). EM doping altered the physicochemical and structural properties of NFs to some extent, including the increase of NF porosity and surface wettability. A sustained EM release from EM-NFs for >4 weeks was observed. Eluents collected from EM-NFs showed strong zone of inhibition (ZOI) to Staphylococcus aureus growth and the sizes of ZOI positively related to the amount of EM released. EM-NFs were nontoxic to rat bone marrow stem cells (rBMSCs). Cell growth was significantly enhanced when comparing rBMSCs cultured on EM-NFs (EM0 and EM 100) to those cultured on NF-free control. Cell differentiation (ALP activity) was notably enhanced by EM100, compared to control and EM0. Eluents from EM-NFs on rBMSCs were also investigated. The presence of 10% EM-NF eluents inhibited the growth of rBMSCs, which was proportional to the amount of EM doped. The ALP activity was notably enhanced by eluents from EM-NFs with the highest activity in EM100 compared to control and EM0. Our data indicate that EM-doped PCL/PLGA-PVA coaxial NF coatings have a great potential to be applied as a new implant coating matrices. Further in vivo testing in animal models is currently planned that should represent the first step in predicting the clinical outcomes of EM-eluting NF coating approach.
KurtzSMOngKLLauE, et al.Prosthetic joint infection risk after TKA in the Medicare population. Clin Orthop Relat Res2010; 468(1): 52–56.
2.
BozicKJKurtzSMLauE, et al.The epidemiology of revision total hip arthroplasty in the United States. J Bone Jt Surg. Am2009; 91(1): 128–133.
3.
BozicKJKurtzSMLauE, et al.The epidemiology of revision total knee arthroplasty in the United States. Clin Orthop Relat Res2010; 468(1): 45–51.
4.
SimchiATamjidEPishbinF, et al.Recent progress in inorganic and composite coatings with bactericidal capability for orthopaedic applications. Nanomedicine: Nanotechnology, Biol Med2011; 7(1): 22–39.
5.
HinarejosPGuirroPLealJ, et al.The use of erythromycin and colistin-loaded cement in total knee arthroplasty does not reduce the incidence of infection: a prospective randomized study in 3000 knees. J Bone Jt Surg. Am2013; 95(9): 769–774.
6.
ZhangBGMyersDEWallaceGG, et al.Bioactive coatings for orthopaedic implants-recent trends in development of implant coatings. Int J Mol Sci2014; 15(7): 11878–11921.
7.
RafiqIGambhirAKWroblewskiBM, et al.The microbiology of infected hip arthroplasty. Int Orthop2006; 30(6): 532–535.
8.
Giamarellos-BourboulisEJ. Macrolides beyond the conventional antimicrobials: a class of potent immunomodulators. Int J Antimicrob Agents2008; 31(1): 12–20.
9.
ShahabooeiMRazaviSMMinaiyanM, et al.A histomorphometric study of the effect of doxycycline and erythromycin on bone formation in dental alveolar socket of rat. Adv Biomedical Research2015; 4(1): 71.
10.
RenWMarkelDC. Emerging Ideas: Can Erythromycin Reduce the Risk of Aseptic Loosening?Clin Orthop Relat Res2011; 469(8): 2399–2403.
11.
BosnjakovicAMishraMKRenW, et al.Poly(amidoamine) dendrimer-erythromycin conjugates for drug delivery to macrophages involved in periprosthetic inflammation. Nanomedicine2011; 7(3): 284–294.
12.
SongWYuXWangS, et al.Cyclodextrin-erythromycin complexes as a drug delivery device for orthopedic application. Int J Nanomedicine2011; 6: 3173–3186.
13.
RenWPSongWEsquivelAO, et al.Effect of erythromycin-doped calcium polyphosphate scaffold composite in a mouse pouch infection model. J Biomed Mater Res B Appl Biomater2014; 102(6): 1140–1147.
14.
BakerBMHandorfAMIonescuLC, et al.New directions in nanofibrous scaffolds for soft tissue engineering and regeneration. Expert Rev Med Devices2009; 6(5): 515–532.
15.
GluckJMRahgozarPIngleNP, et al.Hybrid coaxial electrospun nanofibrous scaffolds with limited immunological response created for tissue engineering. J Biomed Mater Res B: Appl Biomater2011; 99B(1): 180–190.
16.
SzentivanyiAChakradeoTZernetschH, et al.Electrospun cellular microenvironments: Understanding controlled release and scaffold structure. Adv Drug Deliv Rev2011; 63(4–5): 209–220.
17.
SongWMarkelDCWangS, et al.Electrospun polyvinyl alcohol-collagen-hydroxyapatite nanofibers: a biomimetic extracellular matrix for osteoblastic cells. Nanotechnology2012; 23(11): 115101.
18.
SongWSetaJChenL, et al.Doxycycline-loaded coaxial nanofiber coating of titanium implants enhances osseointegration and inhibits Staphylococcus aureus infection. Biomed Materials (Bristol)2017; 12(4): 045008.
19.
ChenLMazehHGuardiaA, et al.Sustained release of strontium (Sr2+) from polycaprolactone/poly (D,L-lactide-co-glycolide)-polyvinyl alcohol coaxial nanofibers enhances osteoblastic differentiation. J Biomater Appl2019; 34(4): 533–545.
20.
DawesGFratila-ApachiteiLNeculaB, et al.Release of PLGA-encapsulated dexamethasone from microsphere loaded porous surfaces. J Mater Sci Mater Med2010; 21(1): 215–221.
21.
ChenLAl-ShawkAReaC, et al.Preparation of electrospun nanofibers with desired microstructures using a programmed three-dimensional (3D) nanofiber collector. Mater Sci Eng C2020; 106: 110188.
22.
NatuMVGasparMNRibeiroCA, et al.A poly(epsilon-caprolactone) device for sustained release of an anti-glaucoma drug. Biomed Mater2011; 6(2): 025003.
23.
MakadiaHKSiegelSJ. Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Polymers2011; 3(3): 1377–1397.
24.
LuLPeterSJLymanMD, et al.In vitro and in vivo degradation of porous poly (DL-lactic-co-glycolic acid) foams. Biomaterials2000; 21(18): 1837–1845.
25.
FuSZMengXHFanJ, et al.In vitro and in vivo degradation behavior of n-HA/PCL-Pluronic-PCL polyurethane composites. J Biomed Mater Res A2014; 102(2): 479–486.
26.
SongWYuXMarkelDC, et al.Coaxial PCL/PVA electrospun nanofibers: osseointegration enhancer and controlled drug release device. Biofabrication2013; 5(3): 035006.
27.
BaruaRDaly-SeilerCSChenreghanianzabiY, et al.Comparing the physicochemical properties of dicalcium phosphate dihydrate (DCPD) and polymeric DCPD (P-DCPD) cement particles. J Biomed Mater Res Part B: Appl Biomater2021; n/a(n/a): 1–12.
28.
GuardiaAShiTBou-AklT, et al.Properties of erythromycin-loaded polymeric dicalcium phosphate dehydrate bone graft substitute. J Orthopaedic Res2021; 39: 1–9, n/a(n/a).
29.
UygunBEStojsihSEMatthewHW. Effects of immobilized glycosaminoglycans on the proliferation and differentiation of mesenchymal stem cells. Tissue Eng A2009; 15(11): 3499–3512.
30.
ShahiAParviziJ. Prevention of Periprosthetic Joint Infection. Arch Bone Joint Surgery2015; 3(2): 72–81.
31.
LewisG. Properties of antibiotic-loaded acrylic bone cements for use in cemented arthroplasties: a state-of-the-art review. J Biomed Mater Res B Appl Biomater2009; 89B(2): 558–574.
32.
RosenthalALRovellJMGirardAE. Polyacrylic Bone Cement Containing Erythromycin and Colistin I. In vitro Bacteriological Activity and Diffusion Properties of Erythromycin, Colistin and Erythromycin/Colistin Combination. J International Medical Research1976; 4(5): 296–304.
33.
ArcosDVallet-RegisM. Bioceramics for drug delivery. Acta Materialia2013; 61(3): 890–911.
34.
RenWZhangRHawkinsM, et al.Efficacy of periprosthetic erythromycin delivery for wear debris-induced inflammation and osteolysis. Inflamm Res2010; 59(12): 1091–1097.
35.
AlkhraisatMHRuedaCCabrejos-AzamaJ, et al.Loading and release of doxycycline hyclate from strontium-substituted calcium phosphate cement. Acta Biomater2010; 6(4): 1522–1528.
36.
HofmannMPMohammedARPerrieY, et al.High-strength resorbable brushite bone cement with controlled drug-releasing capabilities. Acta Biomater2009; 5(1): 43–49.
37.
SongWRenWWanC, et al.A novel strontium-doped calcium polyphosphate/erythromycin/poly(vinyl alcohol) composite for bone tissue engineering. J Biomed Mater Res A2011; 98(3): 359–371.
38.
RathboneCRCrossJDBrownKV, et al.Effect of various concentrations of antibiotics on osteogenic cell viability and activity. J Orthopaedic Res2011; 29(7): 1070–1074.
39.
ShenYWangWLiX, et al.Mitigative effect of erythromycin on PMMA challenged preosteoblastic MC3T3-E1 cells. ScientificWorldJournal2014; 2014: 107196–107197.
