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, calciumphosphate cement, was formulated as a carrier vehicle for gentamicin. Incorporation of the antibiotic significantly (p=0.01) improved the compressive strength (5.8± 0.7 MPa) 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 6 hour period (b28% of the total amount) were found to exceed the minimum inhibitory concentrations of Staphylococcus aureus (16 μg/mL) and Staphylococcus epidermidis (1 μg/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.
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Additive manufacturing (AM) technologies enable greater geometrical design freedom compared with subtractive processes. This flexibility has been used to manufacture patient-matched implants. Although the advantages of AM are clear, the optimization at each process stage is often understated. Here we demonstrate that surface finishing of selective laser melted (SLM) implants significantly alters topography, which has implications for cellular and biofilm adhesion. Hot isostatic pressing of as-fabricated Ti-6Al-4V implants was shown to reduce porosity (1.04 to 0.02%) and surface roughness (34 ± 8 to 22 ± 3 μm). Despite these surface changes, preosteoblasts exhibited a similar viability and proliferation after 7 days of culture. Contrastingly, sandblasting and polishing significantly reduced cellular activity and increased cytotoxicity. Bacterial specimens (Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa) adhered more homogeneously to sandblasted implants compared with other treatments. This suggests that sandblasting may place the implant at risk of infection and reduce the strength of interaction with the surrounding soft tissues. The ability to tune the adhesion of cells to additively manufactured Ti-6Al-4V implants using postprocessing methods was demonstrated. Because the degree of tissue integration required of implants is application specific, these methods may be useful to tailor osseointegration. However, surface competition between mammalian and bacterial cells remains a challenge.
Inorganic cements have found utility in tissue replacement since the late nineteenth century, one of the first examples being calcium sulphates in the augmentation of bone defects. In the intervening period of time countless formulations of calcium phosphate, sulphate and silicate cement have been researched and as a result, many are now commercially available for a variety of biomedical applications. This review summarises the applications, formulations, advantages and drawbacks of such inorganic cements, suggesting future work that will drive progress in this area into the future of biomaterials research.
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