Bacterial infection of bone may result in bone destruction which is difficult to cure due to poor accessibility to bone of systemically-administrated antibiotic and poor performance of currently available local antibacterial treatments. PolyPid Ltd developed a novel local drug delivery system based on self-assembly of pharmaceutically approved lipids and polymers that encapsulate doxycycline (Doxy). The formulation is self-assembled lipid matrix via the interaction of the lipids (cholesterol and synthetic phospholipids) and biocompatible - biodegradable polymer (poly-lactic-co-glycolic).

The entrapped Doxy is located within the anhydrous environment and therefore fully protected from both enzymatic and long-term water-exposure-related degradation. The fine coating of the tri-calcium phosphate (TCP) bone filler by this Doxy-containing formulation (BonyPid™) is capable of releasing intact and active drug at zero-order kinetics for a predetermined period of up to 30 days. The coating of the TCP granules with the polymer-lipids-Doxy formula (BonyPid™) did not change the granules’ macroscopic shape, but altered its color from white to pale yellow, which resemble the color of the entrapped Doxy. The average sizes of the non-coated TCP granules and the coated granules BonyPid™ were similar, as determined by measuring the widest dimension of each granule (1135±241 µm and 1072±242 µm, respectively, P=0.16). The MIC for Doxy that was released from BonyPid™ at different time points was similar to the non-encapsulated Doxy, suggesting full bioavailability of the released drug. BonyPid™ formulation structure was characterised by different physical methods including wide angle X-ray analyses (WAXS), differential scanning calorimetric (DSC) and SEM. WAXS analyses of BonyPid™ samples show a strong signal in the range of 1.3–1.8 2θ°, suggesting that the polymer and lipid TCP coating is a highly organised nano-substructure.

The principle lipid in BonyPid™ formulation is phosphatidylcholine, which constitutes more than 85% of the overall lipid mass. It was found that the length of the acyl chains (14, 16 and 18 carbons, respectively) can significantly alter the release rate of Doxy during the prolonged (30 days), zero-order release phase, but did not alter the release profile. The anti-infection activity of BonyPid™ was tested in the rabbit tibia model contaminated with 5×10⁵S. aureus. Both acute and chronic infection models were tested. Only BonyPid™ treatment demonstrated a statistically significant reduced bone absorption over the infected group (P<0.04 for day 7, 14 and 21) and significantly lower bacterial bone concentration (p>0.05) on day 21 following the bone grafting and the bacterial inoculation. In addition it was found that BonyPid™ did not reduce the osteo-conductivity as compared to non-coated TCP bone-filler. The first-in-man study for the treatment of contaminated / infected severe open long-bone fractures of BonyPid™ completed its 6 months follow-up. The results demonstrated high safety profile and significant efficacy; early bone callus formation and 0% infections in the BonyPid™ target bone fracture.

Percutaneos radiofrequency (RF) ablation of osteoid osteoma has been proved as an effective treatment. However, there is limited data regarding other tumors. It also has been described in the treatment of other benign and malignant tumors like chondroblastoma and metastasis. In fact, one of the reported cases of chondroblastoma that were treated with RF was radiological small lesion erroneously diagnosed prior to treatment as osteoid osteomas. It was diagnosed as chondroblastoma only retrospectively. The aim of this study is to describe the success of RF as a definitive treatment and as an alternative to traditional surgery for the treatment of large chondroblastoma and chondromyxoid-fibroma which were diagnosed as such prior to ablation.

From April 2006 to April 2007, 3 patients with chondroblastoma and 1 patient with chondromyxoid-fibroma were treated with RF ablation using cool-tip probe. Three procedures were done in the CT suit and one in the operating room. There were 3 girls and 1 boy. Mean age was 12 y 9 m (range 11 y 6 m – 14 y 6 m). Clinical and radiological follow-up was performed to assess outcome. The mean follow-up was 23.25 months (range 20–32 months).

Three patients healed after single treatment and one needed repeated treatment. No immediate or delayed complications were observed. Follow up MRI showed no enhancement in the lesion and an extra-lesional sclerotic ream signifying RF effect beyond the lesion area. All patients returned to complete normal painless function.

In spite of the small number of patients, percutaneous RF ablation was shown to be an effective and safe minimally invasive procedure for the treatment of chondroblastoma and chondromyxoid-fibroma, avoiding the morbidity of commonly used wide excision surgeries.

Radiofrequency (RF) ablation carries success rate of 70–90% in the treatment of Osteoid Osteoma (OO). Failures are related to incomplete ablation which might be caused by the probe’s small heating radius (0.5–0.8 cm). Water cooled tips were developed in order to prevent charring of the tip and adjacent tissues and to allow for a larger, up to 3cm ablation diameter. To our knowledge safety and efficiency of this probe in the treatment of pediatric OO were never reported. Our goal was to examine if this technique, when added to conventional RF ablation, improves the clinical results and whether it carries any additional risks in the pediatric population.

Twenty two OO patients, 15 males and 7 females, 3 years and 6 months to 18 years old, were treated using the Cool-tip™ Tyco probe in a cooled mode followed immediately by conventional RF cycle under general anesthesia, in the CT suite. Fifteen of the lesions were in the femur, 2 in the tibia and the remainder lesions were located in the humerus, talus, calcaneus, 2nd metatarsus and sacrum. The OO was intraarticular in 5 patients: femur (3), calcaneus and Talus. Follow-up period averaged 38.5 months (range 16–66 months). All patients but one had their symptoms resolved immediately following a single treatment (95.5% success rate). One patient had partial relief and underwent second successful ablation. There were one recurrence after 18 months and one superficial infection. No fractures, neurovascular complications or growth disturbances were encountered.

We conclude that the addition of a Cool-tip cycle to conventional RF ablation in children is safe, efficient and reduces the risk of recurrence without adverse effects specific to this age group. We attribute this success to the larger diameter of heat distribution occurring due to cooling of the tip and the prevention of probe and tissue charring.