title: Adding functionality with additive manufacturing: Fabrication of titanium-based antibiotic eluting implants.
abstract: Additive manufacturing technologies have been utilised in healthcare to create patient-specific implants. This study demonstrates the potential to add new implant functionality by further exploiting the design flexibility of these technologies. Selective laser melting was used to manufacture titanium-based (Ti-6Al-4V) implants containing a reservoir. Pore channels, connecting the implant surface to the reservoir, were incorporated to facilitate antibiotic delivery. An injectable brushite, calcium phosphate cement, was formulated as a carrier vehicle for gentamicin. Incorporation of the antibiotic significantly (p=0.01) improved the compressive strength (5.8±0.7MPa) of the cement compared to non-antibiotic samples. The controlled release of gentamicin sulphate from the calcium phosphate cement injected into the implant reservoir was demonstrated in short term elution studies using ultraviolet-visible spectroscopy. Orientation of the implant pore channels were shown, using micro-computed tomography, to impact design reproducibility and the back-pressure generated during cement injection which ultimately altered porosity. The amount of antibiotic released from all implant designs over a 6hour period (<28% of the total amount) were found to exceed the minimum inhibitory concentrations of Staphylococcus aureus (16μg/mL) and Staphylococcus epidermidis (1μg/mL); two bacterial species commonly associated with periprosthetic infections. Antibacterial efficacy was confirmed against both bacterial cultures using an agar diffusion assay. Interestingly, pore channel orientation was shown to influence the directionality of inhibition zones. Promisingly, this work demonstrates the potential to additively manufacture a titanium-based antibiotic eluting implant, which is an attractive alternative to current treatment strategies of periprosthetic infections.
authors.affiliation: School of Chemical Engineering, University of Birmingham, Edgbaston B15 2TT, UK.
authors.forename: Sophie C
authors.initials: SC
authors.lastname: Cox
authors.affiliation: School of Materials and Metallurgy, University of Birmingham, Edgbaston B15 2TT, UK.
authors.forename: Parastoo
authors.initials: P
authors.lastname: Jamshidi
authors.affiliation: School of Chemical Engineering, University of Birmingham, Edgbaston B15 2TT, UK; Royal Centre for Defence Medicine, Birmingham Research Park, Vincent Drive, Edgbaston B15 2SQ, UK.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Eisenstein
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston B15 2TT, UK.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Webber
authors.affiliation: School of Materials and Metallurgy, University of Birmingham, Edgbaston B15 2TT, UK; School of Mechanical and Automotive Engineering, Kingston University, London SW15 3DW, UK.
authors.forename: Hany
authors.initials: H
authors.lastname: Hassanin
authors.affiliation: School of Materials and Metallurgy, University of Birmingham, Edgbaston B15 2TT, UK.
authors.forename: Moataz M
authors.initials: MM
authors.lastname: Attallah
authors.affiliation: Department of Mechanical Engineering, School of Engineering, University of Birmingham, Edgbaston B15 2TT, UK.
authors.forename: Duncan E T
authors.initials: DET
authors.lastname: Shepherd
authors.affiliation: School of Dentistry, University of Birmingham, Edgbaston B15 2TT, UK.
authors.forename: Owen
authors.initials: O
authors.lastname: Addison
authors.affiliation: School of Chemical Engineering, University of Birmingham, Edgbaston B15 2TT, UK.
authors.forename: Liam M
authors.initials: LM
authors.lastname: Grover
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001843:Bone Cements / Q000737:chemistry / Q000494:pharmacology; D002130:Calcium Phosphates / Q000737:chemistry / Q000494:pharmacology; D004343:Drug Implants / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005839:Gentamicins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000254:growth & development*; D013212:Staphylococcus epidermidis / Q000254:growth & development*; D014025:Titanium / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001843:Bone Cements; D002130:Calcium Phosphates; D004343:Drug Implants; D005839:Gentamicins; C020243:calcium phosphate; D014025:Titanium
keywords: Additive manufacturing; Antibiotic; Calcium phosphate cement; Drug delivery; Implant; Selective laser melting; Titanium