Original Articles
 

By Dr. Charles Osier , Mr. William Pierce , Dr. Michael Huo , Mr. Robert Lindeman
Corresponding Author Dr. Charles Osier
University of Texas Southwestern Department of Orthopedic Surgery, 3610 Waldorf Dr - United States of America 75229
Submitting Author Dr. Charles J Osier
Other Authors Mr. William Pierce
TSRH Biomechanics Lab, Texas Scottish Rite Hospitaln2222 Welborn StnDallas, TXn - United States of America 75219

Dr. Michael Huo
UTSW Orthopedic Surgery, 1801 Inwood RdnWA 4.312nDallas, TX - United States of America 75390

Mr. Robert Lindeman
TSRH Biomechanics Lab, TSRHn2222 Welborn StnDallas, TX - United States of America 75219

BIOMEDICAL ENGINEERING

Porosity, Compression, PMMA, Elution, Poly-Methylmethacrylate

Osier C, Pierce W, Huo M, Lindeman R. Compression Failure Analysis of Porous Pmma - A Pilot Study. WebmedCentral BIOMEDICAL ENGINEERING 2012;3(1):WMC001092
doi: 10.9754/journal.wmc.2012.001092

This is an open-access article distributed under the terms of the Creative Commons Attribution License(CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
No
Submitted on: 31 Dec 2011 03:54:29 PM GMT
Published on: 01 Jan 2012 10:52:08 AM GMT

Abstract


We hypothesized that porous PMMA could maintain structural strength at porosities high enough to increase elution characteristics. Porous PMMA cylinders were formed and tested to failure in compression. Compositions of 11.1%, 20%, 27.3% and 33.7% sucrose by mass were tested and failure load compared to non-porous PMMA. Testing demonstrated a 2.19 MPa linear decrease (p < 0.0005) in compression strength per gram of sucrose added.  Analysis of strength as a function of time revealed an initial 7.9% decrease (p = 0.001) in compression strength followed by trend reversal and an ultimate 10.8% increase (p < 0.001) from minimum values over six weeks. Our failure analysis supports the hypothesis that adequate compression strength can be maintained while significantly increasing the porosity of PMMA to levels shown to improve elution characteristics.  

Introduction


Antibiotic-laden poly-methylmethacrylate (PMMA) has been used to treat peri-prosthetic infections both as a spacer in two-stage revision, or through direct exchange arthroplasty. Bucholz in 1973 successfully revised 78% of 263 infected total hip arthroplasties with gentamicin-laden PMMA using direct exchange protocol.1, 2 Current rates of peri-prosthetic infection are in the range of 0.5%-2%. This has been attributed to improved surgical technique, improved operating room environment, peri-operative antibiotics and the use of antibiotic-laden cement.3
Antibiotic-laden PMMA has been demonstrated to have poor elution characteristics, releasing only a small percentage of total antibiotic into the local tissue. This chemical release is initially rapid but then quickly decreases leaving local tissues with a low antibiotic concentration.4, 5 Soto-Hall et al measured the concentration of antibiotic in negative pressure dressing fluid after ten total hip revisions in which PMMA was laden with tobramycin. Antibiotic levels remained high for forty-eight hours and then rapidly declined to less than 25% of initial levels.5 Torholm et al measured urine concentrations of gentamicin after a series of ten total hip arthroplasties. Only 13% of the gentamicin was accounted for after sixty days, most of this during the first four days after which a rapid decline in drug level was measured.6
Research has also shown that local tissue antibiotic concentrations are either below the minimum inhibitory concentration (MIC) for many common bacteria or, was maintained above-threshold for only several days. In an in-vivo animal study, Escherichia coli was inoculated into the rabbit knees following hemi-arthroplasty fixed with gentamicin laden-PMMA. Joint aspirate data displayed gentamicin concentrations above the MIC for only three days. Only 8% of the antibiotic was accounted for after the first eight days, most in the first twenty-four hours.4
Efforts have been made at improving antibiotic-laden PMMA pharmaco-kinetics. Early research by Lautenschlager has shown that addition of excess antibiotic greatly altered the material properties of PMMA.7 In order to increase antibiotic delivery to local tissues without changing the chemical properties of PMMA, recent research has focused on increasing surface area by creating a porous network using the addition of soluble filler material.8-10 Glycine, sucrose, xylitol and erythritol have all been shown to increase fluid penetration and antibiotic elution from PMMA in recent studies.8 Mclaren et al demonstrated that elution rates of daptomycin from PMMA mixed with glycine were 2.67 times higher on day one and over twenty times higher on day seven when compared to PMMA without glycine.10
Current cement mixing techniques focus on large void reduction in order to increase the compression strength of PMMA. Porosity reduction sacrifices the ability of antibiotic-laden PMMA to deliver pharmacotherapy to the targeted tissues at clinically relevant concentrations over extended periods of time. McLaren et al demonstrated that PMMA with smaller pores had increased permeability, elution, interconnectivity and effective surface area compared to PMMA with large voids.9 Our study hypothesized that a critical porosity exists at which the compression strength of PMMA falls below the required 70 MPa standard to be used for fixation of orthopaedic bio-implants.

Methods


Our study was designed to evaluate the failure load of porous PMMA and to determine the critical porosity at which this material would no longer meet the 70 MPa required according to the ASTM standard.11 Five sucrose-polymer compositions (0%, 11.1%, 20%, 27.3%, 33.7% by mass sucrose) were hand-mixed in the manner described by Mclaren et al8, 9.  The PMMA compression testing samples were manufactured in the standard fashion per the ASTM F451-99a (2007) Standard Specification for Acrylic Bone Cement.11  Compression testing samples measuring 6 mm in diameter and 12 mm in height were formed using an aluminum mold.  Simplex P (Stryker, Mahwah, NJ) polymer and monomer were stored at 4o C in order to prolong curing time while manufacturing the samples.  Cement was mixed by hand according to the manufacturers instructions with the addition of sucrose (C&H Sugar Co, Crockett, CA).   Sucrose was sieved to less than 500 microns using an ASTM E-11 sieve.  The aluminum mold was coated with silicon spray and the cement was injected into the mold, which was capped and compressed with a C-clamp for twenty-five minutes.  After twenty-four hours of curing, samples were removed using a hand plunger and placed in normal saline at 37o C.  This environment was maintained by a furnace (Blue M, Blue Island, Illinois).  Test specimens with any visible molding defect were discarded and several cylinders from each group were fractured during removal from the molds resulting in minor variations in group number.  The test specimens were divided into eleven groups: Five groups with varied sucrose content by mass (0% n=27, 11.1% n=47, 20.0% n=46, 27.3% n=42, 33.7% n=40) were held in the bath at 37o C for six weeks and then tested to failure in compression. The next six groups were composed of 20% by mass sucrose-polymer PMMA (n= 33, 33, 33, 33, 33, 46).  This concentration was selected based on the results generated from the first five groups (Fig 1) as 20% sucrose by mass maintained compression strength above the required 70 MPa.  Every seven days, for six weeks a group was removed from the furnace and tested to failure in compression using the standard method outlined in the ASTM F451-99a (2007) with a universal testing machine (Bionix 858, MTS Inc, Minneapolis, MN).11  A reference group of pure PMMA (n=27) was cured in air at room temperature for twenty-four hours and then tested in compression.  Stress-strain curves were generated for each specimen and failure was determined as the load at 2.0% offset, upper yield point or at fracture, whichever occurred first.  Statistical analysis of mean failure load was conducted via an Analysis of Variance (Systat 8.0, Chicago, IL) test with Tukey’s test post hoc.

Results


Our testing data demonstrated a decrease in compression strength with increasing sucrose concentrations.  Trend line analysis (Fig 1) revealed a 2.2 MPa decrease in strength for each gram of sucrose added (p < 0.0005).  Based on this slope we estimated that a critical porosity is achieved at 24.2% by mass of sucrose when mixed with 40 grams of PMMA polymer.  At levels below this, porous PMMA samples ultimately maintained greater than the required 70 MPa biomechanical standard.  When compression strength of control PMMA cured for twenty-four hours in room air was compared to non-porous PMMA held in saline at 37o C, we found a 6.8% increase (p = 0.00003) in compression strength (Fig 2).   Analysis of time as a variable in the compression strength of porous PMMA (20% sucrose) revealed an early, 7.9% decrease in strength (p = 0.001) followed by trend reversal at week four and a late, 10.8% (p < 0.001) increase in strength above minimum values by week six (Fig 3).  There was no statistically significant difference in compression strength between the groups incubated for six weeks versus one week (p = 0.26).

Discussion


This study was designed to define the mechanical properties of porous PMMA. Specifically, our goal was to determine the critical degree of induced porosity at which the compression strength of PMMA would fall below the required 70 MPa standard.
PMMA porosity has been successfully decreased through centrifuge and vacuum-mixing techniques. Research on these low-porosity cement specimens has demonstrated the inverse relationship between porosity and mechanical strength. Burke et al proved a 24% increase in PMMA ultimate tensile strength after only thirty seconds of centrifuge mixing.12 However, our results support that a significant degree of porosity may be induced while still maintaining adequate compression strength. Mclaren et al demonstrated that porous PMMA, made with 41% sucrose by mass and granule diameter of less than 500 microns achieved prolonged and increased elution of phenolphthalein compared to non-porous PMMA.9 Our testing data demonstrated compression strengths of 39 MPa in comparable PMMA specimens. This level of porosity was too high to meet the standards required for implant fixation.
Our data demonstrated that the mechanical properties of sucrose-laden PMMA were altered through a time-dependant process. Mclaren et al demonstrated that fluid penetrated to the center of 7 mm diameter porous-PMMA beads by day fifteen of exposure to 0.1% NaOH.9 As a porous network is formed over time, the compression strength decreases due to the reduced surface area secondary to voids in the macrostructure of the cement (Fig 3). However, both exposure to water and elevated curing temperatures have been shown to effect the mechanical properties of PMMA.7, 13, 14 This theory could account for the increase in the compression strength over six weeks in porous PMMA incubated in normal saline as compared to that in room air (Fig 2). Nejatiant et al demonstrated that PMMA cured in tap water at 37o C had significantly higher biaxial flexural strength than specimens cured in a dry environment.13 After testing the mechanical properties of PMMA cured in water at 60o C, Soderholm and Calvert showed an initial decrease in Young’s modulus and compressive yield strength at six days followed by an increase in both by day thirty. In addition, Young’s modulus after thirty days exposure to water was 10% greater than initial values.14 Exposure to elevated temperatures has been suggested to increase compression strength. Lautenschlager et al demonstrated a 25% increase in compression strength of PMMA cured for forty days in normal saline at 37o C compared to cement cured in air at room temperature for twenty-four hours.7 In our study, these interactions could have accounted for the net increase in compression strength returning to initial values by week six although the minimum strength achieved was below the required 70 MPa threshold at week four (Fig 3).
There were several limitations in our study. Prior to the mixing of our cement composites, it was necessary to store the PMMA at 4o C in order to prolong the polymerization time. Both mechanical deformation and increased ambient temperature will decrease the polymerization time of PMMA. In order to mold uniform cement specimens it was necessary to keep the PMMA in a liquid state for as long as possible. The PMMA cylinders were removed from the molds via a punch press. Although silicon spray was used to coat the cylinder surface, this punch could have induced significant mechanical stress on the cement. It is unknown how this mechanical stress could have influenced the failure load when the specimens were compressed. This study only generated compression data on the porous cement after six weeks of exposure to normal saline. The initial decrease and subsequent increase in compression strength after week four requires further evaluation. It is possible that a six-week period is insufficient to achieve a steady state with respect to not only cement solidification but porous macrostructure formation as well.
Lautenschlager demonstrated no appreciable decrease in the mechanical properties when small amounts of antibiotics were added to PMMA. This study did not address the issue of additional antibiotics in the porous cement.7 Future mechanical testing of porous PMMA should include the addition of various antibiotics. Future studies should also more clearly define the effects of saline and curing temperature on the mechanical properties of these composite PMMA specimens. Moreover, we plan to use the same study model to evaluate the mechanical properties, specifically the fatigue strength of particle-loaded cement mixed with porosity reduction mixing techniques.

Conclusion(s)


The formation and mechanical properties of sucrose-laden PMMA depend on multiple variables.  In order to define compression strength behavior, the mechanical properties of porous PMMA must be established during the formation of the composite as well as after a steady state has been reached.  Once steady state has been reached our research suggests that compression strength may be maintained.  By maintaining porosity below the critical value, it is possible to increase antibiotic elution and retain mechanical strength.  Critical porosity can be defined only after the relationship between strength and each independent variable are understood.  If the mechanical properties of porous PMMA can be maintained over time, our results support the theory that this technology may be implicated for use in permanent implant fixation.

Acknowledgement(s)


The Authors wish to thank the Stryker Corporation for the donation of Simplex P PMMA.  This project was funded internally via the UTSW Orthopaedic Surgery Hoffman fund.

 

Reference(s)


1.Bucholz HE, H. Uber die Depotwirkung einiger Antibiotica bei Vermischung mit dem Kunstharz Palacos. Chirurg. 1970;41:511-5.
2.Bucholz K. Tiefe Infektionen nach alloplasticchem Huftgelenkersatz. Chirurg. 1973;334:547-53.
3.Josefsson G, Lindberg L, Wiklander B. Systemic antibiotics and gentamicin-containing bone cement in the prophylaxis of postoperative infections in total hip arthroplasty. Clin Orthop Relat Res. 1981 Sep(159):194-200.
4.Schurman DJ, Trindade C, Hirshman HP, Moser K, Kajiyama G, Stevens P. Antibiotic-acrylic bone cement composites. Studies of gentamicin and Palacos. J Bone Joint Surg Am. 1978 Oct;60(7):978-84.
5.Soto-Hall R, Saenz L, Tavernetti R, Cabaud HE, Cochran TP. Tobramycin in bone cement. An in-depth analysis of wound, serum, and urine concentrations in patients undergoing total hip revision arthroplasty. Clin Orthop Relat Res. 1983 May(175):60-4.
6.Torholm C, Lidgren L, Lindberg L, Kahlmeter G. Total hip joint arthroplasty with gentamicin-impregnated cement. A clinical study of gentamicin excretion kinetics. Clin Orthop Relat Res. 1983 Dec(181):99-106.
7.Lautenschlager EP, Marshall GW, Marks KE, Schwartz J, Nelson CL. Mechanical strength of acrylic bone cements impregnated with antibiotics. J Biomed Mater Res. 1976 Nov;10(6):837-45.
8.McLaren AC, McLaren SG, Hickmon MK. Sucrose, xylitol, and erythritol increase PMMA permeability for depot antibiotics. Clin Orthop Relat Res. 2007 Aug;461:60-3.
9.McLaren AC, McLaren SG, McLemore R, Vernon BL. Particle size of fillers affects permeability of polymethylmethacrylate. Clin Orthop Relat Res. 2007 Aug;461:64-7.
10.McLaren AC, McLaren SG, Smeltzer M. Xylitol and glycine fillers increase permeability of PMMA to enhance elution of daptomycin. Clin Orthop Relat Res. 2006 Oct;451:25-8.
11.451-99a ASF. Standard Specification for Acrylic Bone Cement. In: International A, editor. West Conshohocken, PA2007.
12.Burke DW, Gates EI, Harris WH. Centrifugation as a method of improving tensile and fatigue properties of acrylic bone cement. J Bone Joint Surg Am. 1984 Oct;66(8):1265-73.
13.Nejatiant TVN, J. Reinforcement fo Denture Base Resins. Iranian Journal of Public Health. 2005;34 (sup):9-10.
14.Soderholm KC, P. Effects of water on glass-filled methacrylate resins. Journal of Materials Science. 1983;18:2957-62.

Source(s) of Funding


Department of Orthopedic Surgery - University of Texas Southwestern resident research Hoffman Fund

Competing Interests


none

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