Abstract
Purpose
This study aims to compare the compressive and tensile strengths of bone cement mixed with various concentrations of vancomycin, tobramycin, and combinations of the two.
Methods
12 mm × 6 mm antibiotic bone cement samples were created by vacuum mixing 0–4 g of vancomycin, tobramycin, and combinations of the two in 0.5 g increments per one pouch (40 g) of Palacos LV cement. An Instron 3369 Universal Testing System was used to determine the compressive and tensile strengths.
Results
Compressive and tensile strengths of the bone cement without antibiotics were 118 ± 4 MPa and 30.3 ± 12 MPa, respectively. 4 g of vancomycin alone decreased the compressive strength to 108 ± 4 MPa (p-value 0.001) and decreased the tensile strength beginning at 2 g which yielded a strength of 28.1 ± 12 MPa (p-value 0.016). Tobramycin alone decreased the tensile strength beginning at 1.5 g yielding a strength of 27.7 ± 7 MPa (p-value 0.003). Although it decreased compressive strength at 1 g to 117 ± 7 MPa (p-value 0.002), it demonstrated variable effects with increasing concentrations. A combination of vancomycin and tobramycin decreased both the compressive (111 ± 5 MPa, p-value 0.014) and tensile (27.9 ± 8 MPa, p-value 0.007) strengths beginning at 1 g each.
Conclusions
Various combinations of vancomycin and tobramycin affect the compressive and tensile strengths of bone cement. Clinicians should be diligent when mixing these antibiotics in bone cement to prevent possible failure of the constructs.
Keywords: Bone cement, Antibiotics, Biomechanics, Arthroplasty, Trauma
1. Introduction
Antibiotic bone cement is an integral component of several orthopedic surgery procedures. It was introduced in the 1970's for revision arthroplasty surgery due to infection and it continues to be a widely used and evolving technique.1 This technique is now commonly applied in various forms across all orthopedic specialties.
Previous research has explored the effects of antibiotics on the biomechanical properties of bone cement. Brock et al. demonstrated that the compressive strength of Palacos R was maintained above the international standard of 70 MPa when combined with 8 g of vancomycin2,3. Davies and Harris revealed no change in compressive or tensile strengths of Simplex P when combined with 1.2 g of tobramycin compared to controls.4 Slane et al. revealed that 40 g of Palacos R with either 3 g of tobramycin and 1 to 3 g of vancomycin or a combination of 2 g of tobramycin and 3 g of vancomycin led to a decrease in compressive strength below the international standard.5
Further information is required to fully understand the biomechanical properties and clinical applications of antibiotic bone cement. The purpose of this study is to assess the compressive and tensile strengths of Heraeus Palacos LV (Heraeus Medical GmbH, Wehrheim, Germany) bone cement mixed with various amounts of vancomycin, tobramycin, and combinations of the two. We aimed to determine the yield point for the compressive and tensile strengths of Palacos LV bone cement mixed with these antibiotics. The results of this study can be used to prevent failure of future antibiotic-loaded bone cement constructs.
2. Materials and Methods
To create the control bone cement samples without antibiotics, a ratio of one pouch of 40.0 g of Heraeus Palacos LV (Heraeus Medical GmbH, Wehrheim, Germany) bone cement powder was vacuum-mixed with one ampule of 20.0 mL of liquid polymer via manufacturer's protocol. The mixture was poured into a silicone mold with 12 mm × 6 mm holes. Samples of antibiotic bone cement were created by adding 0.5–4.0 g of vancomycin powder, tobramycin powder, or combinations of the two per one 40 g bag of bone cement powder prior to mixing with the liquid polymer. Twenty samples were created for each group yielding a total of 520 samples. The samples were allowed to dry for 24 hours prior to removing them from the silicone molds and measuring their dimensions with a micrometer.
An Instron 3369 Universal Testing System was utilized to evaluate the compressive strength of the bone cement samples. The samples were placed into the machine along their short axes and a modified ASTM F451 procedure was performed. The bone cement samples were stressed at a strain rate of 5 mm/min and the experiment continued until a displacement of 4 mm was reached. The peak of the stress versus strain curve determined the yield strength of the material. This displacement corresponded to either fracture or yielding behavior of the bone cement samples. The force, time, displacement, stress, and strain were measured for all 240 samples. These experimental groups were compared against the control compressive group using T-test comparisons.
The Instron 3369 Universal Testing System was also used to evaluate the tensile strength of the bone cement samples. The samples were placed into the machine along their long axes and a modified ASTM D3967 procedure was performed. The samples were stressed at a strain rate of 5 mm/min until either the sample fractured or a displacement of 6 mm was reached. If the sample fractured, the maximum force at this point was used to calculate the tensile strength. If the sample did not fracture, the peak of the stress versus strain curve determined the yield strength of the material. The force, time, displacement, stress, and strain were measured for all 240 samples. These experimental groups were compared against the control tensile group using T-test comparisons.
3. Results
3.1. Controls
The Heraeus Palacos LV (Heraeus Medical GmbH, Wehrheim, Germany) bone cement without antibiotics revealed an average compressive strength of 118 ± 4 MPa and average tensile strength of 30.3 ± 12 MPa.
3.2. Compression
The vancomycin bone cement samples revealed no reduction in compressive strength compared to controls at concentrations of 0.5–3.5 g of vancomycin to 40 g of bone cement. A concentration of [4 g/40 g] decreased the compressive strength to 108 ± 4 MPa (p-value 0.001) (Table 1, Fig. 1).
Table 1.
Compressive strengths of control, vancomycin, tobramycin, and combined groups of bone cement.
| Antibiotic (g) | Compression Strength (MPa) | p-value |
|---|---|---|
| None | 118 ± 4 MPa | -- |
| Vancomycin 0.5 g | 113 ± 6 MPa | 0.105 |
| Vancomycin 1 g | 122 ± 6 MPa | 0.243 |
| Vancomycin 1.5 g | 123 ± 6 MPa | 0.187 |
| Vancomycin 2 g | 122 ± 8 MPa | 0.238 |
| Vancomycin 2.5 g | 114 ± 7 MPa | 0.172 |
| Vancomycin 3 g | 120 ± 8 MPa | 0.709 |
| Vancomycin 3.5 g | 115 ± 7 MPa | 0.298 |
| Vancomycin 4 g | 108 ± 4 MPa | 0.001 |
| Tobramycin 0.5 g | 117 ± 7 MPa | 0.789 |
| Tobramycin 1 g | 108 ± 5 MPa | 0.002 |
| Tobramycin 1.5 g | 120 ± 8 MPa | 0.693 |
| Tobramycin 2 g | 112 ± 5 MPa | 0.055 |
| Tobramycin 2.5 g | 103 ± 5 MPa | <0.001 |
| Tobramycin 3 g | 113 ± 5 MPa | 0.093 |
| Tobramycin 3.5 g | 109 ± 4 MPa | 0.002 |
| Tobramycin 4 g | 116 ± 3 MPa | 0.339 |
| Vancomycin 0.5 g + Tobramycin 0.5 g | 119 ± 6 MPa | 0.726 |
| Vancomycin 1 g + Tobramycin 1 g | 111 ± 5 MPa | 0.014 |
| Vancomycin 1.5 g + Tobramycin 1.5 g | 109 ± 7 MPa | 0.005 |
| Vancomycin 2 g + Tobramycin 2 g | 107 ± 5 MPa | <0.001 |
| Vancomycin 2.5 g + Tobramycin 2.5 g | 107 ± 6 MPa | 0.001 |
| Vancomycin 3 g + Tobramycin 3 g | 104 ± 6 MPa | <0.001 |
| Vancomycin 3.5 g + Tobramycin 3.5 g | 110 ± 5 MPa | 0.008 |
| Vancomycin 4 g + Tobramycin 4 g | 100 ± 6 MPa | <0.001 |
Fig. 1.
Compressive strengths of control, vancomycin, tobramycin, and combined groups of bone cement.
Tobramycin bone cement samples first demonstrated a decrease in compressive strength at a concentration of [1 g/40 g] to 108 ± 5 MPa (p-value 0.002). Concentrations of [2.5 g/40 g] and [3.5 g/40 g] also demonstrated significant decreases in compressive strength (Table 1, Fig. 1).
Combined vancomycin and tobramycin samples first demonstrated a decrease in compressive strength at a concentration of 1 g of each antibiotic to 40 g of bone cement to 111 ± 5 MPa (p-value 0.014). All increasing concentrations of the combined antibiotics revealed decreased compressive strength (Table 1, Fig. 1).
3.3. Tension
Vancomycin bone cement samples revealed no significant change in tensile strength compared to controls at concentrations up to [1.5 g/40 g]. A concentration of [2 g/40 g] demonstrated a decrease in tensile strength to 28.1 ± 12 MPa (p-value 0.016). All other increasing concentrations revealed decreases in tensile strength (Table 2, Fig. 2).
Table 2.
Tensile strengths of control, vancomycin, tobramycin, and combined groups of bone cement.
| Antibiotic (g) | Tension Strength (MPa) | p-value |
|---|---|---|
| None | 30.3 ± 1.2 MPa | -- |
| Vancomycin 0.5 g | 28.8 ± 1.5 MPa | 0.110 |
| Vancomycin 1 g | 29.8 ± 1.3 MPa | 0.555 |
| Vancomycin 1.5 g | 29.7 ± 0.9 MPa | 0.444 |
| Vancomycin 2 g | 28.1 ± 1.2 MPa | 0.016 |
| Vancomycin 2.5 g | 27.9 ± 0.9 MPa | 0.006 |
| Vancomycin 3 g | 28.3 ± 0.4 MPa | 0.003 |
| Vancomycin 3.5 g | 28.1 ± 1.2 MPa | 0.018 |
| Vancomycin 4 g | 26.5 ± 0.8 MPa | <0.001 |
| Tobramycin 0.5 g | 29.6 ± 0.7 MPa | 0.412 |
| Tobramycin 1 g | 29.8 ± 0.9 MPa | 0.519 |
| Tobramycin 1.5 g | 27.7 ± 0.7 MPa | 0.003 |
| Tobramycin 2 g | 27.6 ± 1.0 MPa | 0.003 |
| Tobramycin 2.5 g | 28.6 ± 1.1 MPa | 0.047 |
| Tobramycin 3 g | 28.2 ± 0.6 MPa | 0.015 |
| Tobramycin 3.5 g | 27.6 ± 0.8 MPa | 0.003 |
| Tobramycin 4 g | 27.1 ± 1.1 MPa | <0.001 |
| Vancomycin 0.5 g + Tobramycin 0.5 g | 30.2 ± 0.8 MPa | 0.900 |
| Vancomycin 1 g + Tobramycin 1 g | 27.9 ± 0.8 MPa | 0.007 |
| Vancomycin 1.5 g + Tobramycin 1.5 g | 28.0 ± 0.7 MPa | 0.008 |
| Vancomycin 2 g + Tobramycin 2 g | 26.4 ± 0.9 MPa | <0.001 |
| Vancomycin 2.5 g + Tobramycin 2.5 g | 25.2 ± 0.9 MPa | <0.001 |
| Vancomycin 3 g + Tobramycin 3 g | 25.6 ± 0.8 MPa | <0.001 |
| Vancomycin 3.5 g + Tobramycin 3.5 g | 24.9 ± 0.7 MPa | <0.001 |
| Vancomycin 4 g + Tobramycin 4 g | 23.7 ± 0.9 MPa | <0.001 |
Fig. 2.
Tensile strengths of control, vancomycin, tobramycin, and combined groups of bone cement.
Tobramycin bone cement samples first demonstrated a decrease in tensile strength at a concentration of [1.5 g/40 g] to 27.7 ± 7 MPa (p-value 0.003). All other increasing concentrations revealed decreases in tensile strength (Table 2, Fig. 2).
Combined vancomycin and tobramycin samples first demonstrated a significant decrease in tensile strength at a concentration of 1 g of each antibiotic to 40 g of bone cement to 27.9 ± 8 MPa (p-value 0.006). All increasing concentrations of the combined antibiotics revealed decreased tensile strength (Table 2, Fig. 2).
4. Discussion
Antibiotic bone cement has become an important aspect of various orthopedic surgery procedures. Previous research has demonstrated the effects of antibiotics on the biomechanical properties of bone cement. This study was performed to evaluate changes in compressive and tensile strengths of Palacos LV bone cement mixed with various amounts of antibiotics including vancomycin, tobramycin, and combinations of the two.
The vancomycin experimental groups were more resilient to compressive strain than tensile strain with increasing concentrations of antibiotics. The compressive strength of the vancomycin group was significantly decreased compared to controls only at the maximum concentration of [4 g/40 g]. All samples maintained compressive strength above the international standard of 70 MPa and a Palacos LV compressive strength of 93.28 MPa reported by Wang et al.3,6 However, it demonstrated a significant decrease in tensile strength at [2 g/40 g] and all increasing concentrations. The tensile strengths of all vancomycin samples were less than CMW-1, Simplex P, and Zimmer LVC bone cements with 47 ± 8 MPa, 46 ± 4 MPa, and 44 ± 6 MPa, respectively.7 Brock et al. revealed that vacuum mixing 8 g of vancomycin to 40 g of Simplex P bone cement decreased compressive strength to below international standard. However, all samples including up to 8 g of vancomycin to 40 g of Palacos R bone cement maintained compressive strength above the international standard.2 One study by Lilikakis and Sutcliffe showed that Palamed, Palamed G, and Copal bone cements mixed with vancomycin up to [4 g/40 g] also maintained compressive strength above the international standard.8 Pelletier et al. revealed that Simplex P and VersaBond bone cement mixed with 3 g of vancomycin and 3 g of flucloxacillin had similar compressive strength compared to low dose and cement only groups at 24 hours. However, the high strength Simplex P group demonstrated decreased compressive strength to below international standard at four weeks. Authors stipulated that this was possibly related to increased porosity and clumping as seen on microcomputer tomography.9
The majority of tobramycin experimental groups demonstrated decreased compressive and tensile strengths compared to controls. Concentrations as little as [1 g/40 g] and up to [4 g/40 g] revealed a significant decrease in compressive strength. The overall trend in compressive strength was inconsistent with increasing concentrations of antibiotic. However, all samples maintained compressive strength above the international standard of 70 MPa and a reported Palacos LV compressive strength of 93.28 MPa.3,6 In addition, Gates et al. performed a biomechanical study that suggested that failure of cement is determined primarily by tensile strain rather than compressive strain10. Tobramycin samples at or above [1.5 g/40 g] demonstrated a significant decrease in tensile strength compared to controls. All tobramycin samples demonstrated decreased tensile strengths compared to CMW-1, Simplex P, and Zimmer LVC bone cements.7 Davies and Harris revealed no change in compressive or tensile strengths of 40 g of Simplex P bone cement with the addition of 1.2 g of tobramycin compared to controls.4 Deluise and Scott revealed that 40 g of commercially prepared Simplex P with 1 g of tobramycin revealed equivalent tensile strengths to controls. However, the addition of 1.2 g of tobramycin led to a 36% decrease in tensile strength compared to the other groups.11 All samples in this study were prepared under manufacturer's protocol including vacuum-mixing the cement with nitrogen gas. One study revealed that 40 g of Simplex P with 1 g of gentamicin and 60 g of Zimmer LVC with 1.5 g or 3 g of gentamicin revealed decreased compressive and tensile strengths compared to their controls at all time points up to 35 days.12 He et al. revealed that the addition of greater than 2 g of gentamicin to 40 g of Palacos R bone cement decreased compressive strength compared to controls.13 Lautenschlager revealed that the addition of greater than 2 g of gentamicin to 40 g Simplex P resulted in a significant decrease in both the compressive and tensile strengths compared to 40 g of Simplex P controls.14
The compressive and tensile strengths of the combined vancomycin and tobramycin samples were significantly decreased at low concentrations of each antibiotic. Any combination of the two antibiotics at or above 1 g of each antibiotic to 40 g of bone cement revealed decreased compressive and tensile strengths. Slane et al. revealed that 40 g of Palacos R with 3 g of tobramycin and 1 to 3 g of vancomycin or a combination of 2 g of tobramycin and 3 g of vancomycin decreased the compressive strength below the international standard of 70 MPa.5 This may suggest that higher concentrations of combined antibiotics may have a significant impact on the compressive and tensile strengths of antibiotic bone cement.
There are several limitations to this study. Only the compressive and tensile strengths of bone cement samples were evaluated. Other biomechanical properties such as bending, shear, and fatigue strengths were not evaluated. In addition, limited concentrations of only two different antibiotics were utilized. Future studies should investigate the effect of other types of antibiotic bone cement on these properties. Another limitation is that only one brand of bone cement (Palacos, Heraeus, Hanau, Germany) was included in the study. Various bone cement brands have different properties and may react differently to the same antibiotics. Future studies should evaluate these biomechanical properties using different brands of bone cement mixed with other types and concentrations of antibiotics.
Various combinations of vancomycin and tobramycin affect the compressive and tensile strengths of bone cement. Clinicians should be diligent when mixing these antibiotics in bone cement to prevent possible failure of the constructs. More studies are required to further investigate the biomechanical and clinical effects of various types and concentrations of antibiotic bone cement.
Ethics
IRB approval was not required for this study and ethical principles as they relate to human subjects were not applicable.
Consent statement
This study did not involve human subjects and therefore consent was not required.
CRediT authorship contribution statement
Ernesto S. Quinto: Conceptualization, Data curation, Formal analysis, Writing – original draft. Nathan P. Reyes: Conceptualization, Writing – original draft. Brenden M. Cutter: Conceptualization, Writing – original draft. Noah D. Paisner: Writing – original draft, All authors reviewed the results and approved the final version of the manuscript. Joshua P. Steimel: Data curation, Formal analysis, Writing – original draft. JuEun Lee: Data curation, Formal analysis, Writing – original draft. Eric G. Huish: Conceptualization, Writing – original draft. William Holmes: Conceptualization.
Declaration of competing interest
None.
Acknowledgements
This work was supported by Heraeus Medical who supplied Palacos LV bone cement and mixing supplies. No other funds, grants or other support were received during the preparation of this manuscript.
References
- 1.Buchholz H.W., Elson R.A., Heiner K. Antibiotic-loaded acrylic cement: current concepts. Clin Orthop Relat Res. 1984;190:96–108. 1984. [PubMed] [Google Scholar]
- 2.Brock H.S., Moodie P.G., Hendricks K.J., McIff T.E. Compression strength and porosity of single-antibiotic cement vacuum-mixed with vancomycin. J Arthroplasty. 2010;25:990–997. doi: 10.1016/j.arth.2009.06.027. [DOI] [PubMed] [Google Scholar]
- 3.International Standards Organization Technical Committee ISO/TC 150 . 2002. ISO Standard 5833:2002 Implants for Surgery—Acrylic Resin Cements. [Google Scholar]
- 4.Davies J.P., Harris W.H. Effect of hand mixing tobramycin on the fatigue strength of Simplex P. J Biomed Mater Res. 1991;25:1409–1414. doi: 10.1002/jbm.820251108. [DOI] [PubMed] [Google Scholar]
- 5.Slane J., Gietman B., Squire M. Antibiotic elution from acrylic bone cement loaded with high doses of tobramycin and vancomycin. J Orthop Res. 2018;36:1078–1085. doi: 10.1002/jor.23722. [DOI] [PubMed] [Google Scholar]
- 6.Wang L.H., Feng Y.D., Zhang X.W., Jin L., Zhou F., Xu G. Elution and biomechanical properties of meropenem-loaded bone Cement. Orthop Surg. 2021;13:2417–2422. doi: 10.1111/os.13139. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Kindt-Larsen T., Smith D.B., Jensen J.S. Innovations in acrylic bone cement and application equipment. J Appl Biomater. 1995;6:75–83. doi: 10.1002/jab.770060111. [DOI] [PubMed] [Google Scholar]
- 8.Lilikakis A., Sutcliffe M.P. The effect of vancomycin addition to the compression strength of antibiotic-loaded bone cements. Int Orthop. 2009;33:815–819. doi: 10.1007/s00264-008-0521-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Pelletier M.H., Malisano L., Smitham P.J., Okamoto K., Walsh W.R. The compressive properties of bone cements containing large doses of antibiotics. J Arthroplasty. 2009;24:454–460. doi: 10.1016/j.arth.2007.10.023. [DOI] [PubMed] [Google Scholar]
- 10.Gates E.I., Carter D.R., Harris W.H. Tensile fatigue failure of acrylic bone cement. J Biomech Eng. 1983;105:393–397. doi: 10.1115/1.3138438. [DOI] [PubMed] [Google Scholar]
- 11.DeLuise M., Scott C.P. Addition of hand-blended generic tobramycin in bone cement: effect on mechanical strength. Orthopaedics. 2004;27:1289–1291. doi: 10.3928/0147-7447-20041201-19. [DOI] [PubMed] [Google Scholar]
- 12.Krause W.R., Hofmann A.A. Antibiotic impregnated acrylic bone cements: a comparative study of the mechanical properties. J Bioact Compat Polym. 1989;4:345–361. [Google Scholar]
- 13.He Y., Trotignon J.P., Loty B., Tcharkhtchi A., Verdu J. Effect of antibiotics on the properties of poly(methylmethacrylate)-based bone cement. J Biomed Mater Res. 2002;63:800–806. doi: 10.1002/jbm.10405. [DOI] [PubMed] [Google Scholar]
- 14.Lautenschlager E.P., Jacobs J.J., Marshall G.W., Meyer Jr P.R. Mechanical properties of bone cements containing large doses of antibiotic powders. J Biomed Mater Res. 1976;10:929–938. doi: 10.1002/jbm.820100610. [DOI] [PubMed] [Google Scholar]