Osteosarcoma and other types of bone cancers often require bone resection, and backfill with cement. A novel silorane-based cement without PMMA's drawbacks, previously developed for dental applications, has been reformulated for orthopedic use. The aim of this study is to assess each cement's ability to elute doxorubicin, maintain its potency, and maintain suitable weight-bearing strength.

The silorane-based epoxy cement was synthesized using a platinum-based Lamoreaux's catalyst. Four groups of cement were prepared. Two PMMA groups, one without any additives, one with 200 mg of doxorubicin. Two silorane groups: one without any additive, one with doxorubicin, added so that the w% of drug into both cements were equal. Pellets 6 × 12 mm were used for testing (ASTM F451). n=10. Ten pellets from each group were kept dry. All others were placed into tubes containing 2.5 mL of PBS and stored at 37 °C. Elution from doxorubicin-containing groups were collected every day for 7 days, with daily PBS changeout. Antibiotic concentrations were determined via HPLC. Compressive strength and compressive modulus of all groups were determined for unsoaked specimens, and those soaked for 7 and 14 days. MTT assays were done using an MG63 osteosarcoma cell line.

Both cements were able to elute doxorubicin over 7 days in clinically-favorable quantities. For PMMA samples, the incorporation of doxorubicin was shown to significantly affect the compressive strength and modulus of the samples (p<0.01). Incorporation of doxorubicin into silorane had no significant effect on either (p>.05). MTT assays indicated that doxorubicin incorporated into the silorane cement maintained its effectiveness whereas that into PMMA did not. At the dosing used, both cements remained above the 70 MPa.

Both PMMA and silorane-based cements can deliver doxorubicin. Doxorubicin, however, interacts chemically with PMMA, inhibiting polymerization and lowering the chemotherapeutic's effectiveness.

We developed a novel silorane-based biomaterial (SBB) for use as an orthopedic cement. SBB is comprised of non-toxic silicon-based monomers, undergoes non-exothermic polymerization, and has weight-bearing strength required of orthopedic cements. We sought to compare the antibiotic release kinetics of this new cement to that of commercially available PMMA bone cement. We also evaluated each material's inherent propensity to support the attachment of bacteria under both static and dynamic conditions.

One gram of either rifampin or vancomycin was added to 40g batches of PMMA and SBB. Pellets were individually soaked in PBS. Eluate was collected and tested daily for 14 days using HPLC. Compressive strength and modulus were tested over 21 days. Bioassays were used to confirm the bioactivity of the antibiotics eluted.

We measured the growth and maturation of staphylococcus aureus (SA) biofilm on the surface of both PMMA and SBB disks over the course of 72 hours in a static well plate and in a dynamic biofilm reactor (CDC Biofilm Reactor). N=4 at 24, 48, and 72 hours. A luminescent strain of SA (Xen 29) was employed allowing imaging of bacteria on the discs.

SBB eluted higher concentrations of vancomycin than did PMMA over the course of 14 days (p<0.001). A significant 55.1% greater day 1 elution was observed from SBB. Silorane cement was able to deliver rifampin in clinically favorable concentrations over 14 days. On the contrary, PMMA was unable to deliver rifampin past day 1. The incorporation of rifampin into PMMA severely reduced its mechanical strength (p<0.001) and modulus (p<0.001).

Surface bacterial radiance of PMMA specimens was significantly greater than that of SBB specimens at all time points (p<0.05).

The novel silorane-based cement demonstrated superior antibiotic release and, even without antibiotic incorporation, demonstrated an innate inhabitation to bacterial attachment and biofilm.

Objectives

The objective of this study was to determine if combining variations in mixing technique of antibiotic-impregnated polymethylmethacrylate (PMMA) cement with low frequency ultrasound (LFUS) improves antibiotic elution during the initial high phase (Phase I) and subsequent low phase (Phase II) while not diminishing mechanical strength.

Summary Statement

A porcine model using Yucatan minipigs was found to be very promising for the investigation of healing around transcutaneous osseointegrated implants. Pigs demonstrated surprising agility and adaptability including the ability to ambulate on three legs during the immediate postoperative period.