Gentamicin-Loaded Hydraulic Calcium Phosphate Bone Cement as Antibiotic Delivery System

Bohner, Marc; Lemaître, Jonathan; Landuyt, P. Van; Zambelli, Pierre‐Yves; Merkle, Hans P.; Gander, Bruno

doi:10.1021/js960405a

Cited by 144 publications

(121 citation statements)

References 23 publications

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“…[38] where a β-TCP/phosphoric cement was investigated, a similar temperature dependence for the formation of brushite or monetite was reported; at 37°C the main phase after reaction was brushite and at 55°C the main phase was monetite. Furthermore, studies have reported dehydration of brushite, forming monetite, at 37°C in PBS [15,39,40]. In the present study it was shown that brushite, in fact, can be formed also in the premixed system, but only at lower temperatures than in the water mixed system.…”

Section: Citationsupporting

confidence: 59%

Setting Mechanisms of an Acidic Premixed Calcium Phosphate Cement

Åberg¹,

Unosson

Engqvist³

2013

Bioceram Dev Appl

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Premixed calcium phosphate cements (pCPC), where glycerol is used instead of water as mixing liquid, present better handling characteristics than water-based cements. However, the setting mechanisms of pCPC have not been described thoroughly. The aim of this paper is to increase the understanding of the setting mechanism of pCPC. The investigated cement starts to set when glycerol is exchanged with water via diffusion of glycerol out to the surrounding body fluid and water into the material. To better understand the water-glycerol exchange a method was developed where the setting depth of the cement was measured over time. Thermo gravimetric analysis (TGA) was used to determine the liquid exchange rate during setting. To study the influence of temperature on the crystalline end product, pCPC and water-mixed calcium phosphate cement (wCPC) were set at different temperatures and analyzed with X-ray diffraction (XRD). The setting depth measurements showed that the set layer of the pCPC grew with a speed proportional to t 0.51 at 37°C. TGA results furthermore showed that less than 10% of the glycerol remained after 16 hours. Setting of pCPC at different temperatures showed that mainly brushite was formed at 5°C, a mixture of brushite and monetite at 21°C and mainly monetite at 37°C. It furthermore showed that brushite was the main phase after setting of wCPC, but some monetite was present in these cements. The study presents a new method for evaluation of pCPC that increases the understanding of their setting mechanism. Furthermore, the XRD results indicate that storage at 5°C could improve the shelf life of acidic pCPC.

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Section: Citationsupporting

confidence: 59%

Setting Mechanisms of an Acidic Premixed Calcium Phosphate Cement

Åberg¹,

Unosson

Engqvist³

2013

Bioceram Dev Appl

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“…Since the microstructure of cast and injected samples without gentamicin was not obviously different it may be assumed that the positive influence of residual β-TCP dominates the effect of porosity changes for these samples. Interestingly, Bohner et al noted an improvement in tensile strength of brushite cements as a result of gentamicin addition [36]. This was ascribed to the decrease in size and thickness of DCPD particles due to the presence of sulphate ions in gentamicin (35 ± 2%).…”

Section: 1mentioning

confidence: 99%

Adding functionality with additive manufacturing: Fabrication of titanium-based antibiotic eluting implants

Cox

Jamshidi

Eisenstein

et al. 2016

Materials Science and Engineering: C

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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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“…Moreover, in several studies [18][19][20][21][22] the conditions used were not indicated. Hence, most studies in the literature disregard the fact that the release pattern may change depending on the time the cement was set for; only Canal et al compared the drug release patterns of cements set for different times (1 h vs 7 days), but this was done on apatitic cements only [10].…”

Section: Introductionmentioning

confidence: 99%

Changes in the drug release pattern of fresh and set simvastatin-loaded brushite cement

Mestres

Kugiejko

Pastorino

et al. 2016

Materials Science and Engineering: C

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Calcium phosphate cements are synthetic bone graft substitutes able to set at physiological conditions. They can be applied by minimally invasive surgery and can also be used as drug delivery systems.Consequently, the drug release pattern from the cement paste (fresh cement) is of high clinical interest.However, previous studies have commonly evaluated the drug release using pre-set cements only.Therefore, the aim of this work was to determine if the time elapsed from cement preparation until immersion in the solution (3 min for fresh cements, and 1 h and 15 h for pre-set cements) had an influence on its physical properties, and correlating these to the drug release profile. Simvastatin was selected as a model drug, while brushite cement was used as drug carrier. This study quantified how the setting of a material reduces the accessibility of the release media to the material, thus preventing drug release. A shift in the drug release pattern was observed, from a burst-release for fresh cements to a sustained release for pre-set cements.

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Gentamicin-Loaded Hydraulic Calcium Phosphate Bone Cement as Antibiotic Delivery System

Cited by 144 publications

References 23 publications

Setting Mechanisms of an Acidic Premixed Calcium Phosphate Cement

Setting Mechanisms of an Acidic Premixed Calcium Phosphate Cement

Adding functionality with additive manufacturing: Fabrication of titanium-based antibiotic eluting implants

Changes in the drug release pattern of fresh and set simvastatin-loaded brushite cement

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