Previous studies showed that a fast-resorbable antibacterial hydrogel coating (DAC®, Novagenit Srl, Mezzolombardo, TN, Italy) composed of covalently linked hyaluronan and poly-D, L-lactide, is able to reduce early post-surgical infection both after joint replacement and osteosynthesis. Aim of the present report is to investigate medium-term safety and efficacy of the coating in patients undergoing primary and revision cementless total hip replacement (THR).

We designed a two-phases study. In both phases, DAC was prepared according to manufacturer's instructions. In brief, the syringe prefilled with 300 mg of sterile DAC powder was mixed, at the time of surgery, with a solution of 5 mL of sterile water and with the tailored antibiotics, at a concentration ranging from 25 mg/mL to 50 mg/mL. The resulting antibacterial hydrogel was then spread on the outer surface of the prosthesis just before implantation.

In the first phase, safety was assessed. Forty-six patients (13 primary and 33 revision THR) were treated with DAC between 2013 and 2015 and evaluated at a 2.8 ± 0.7 years follow up (FU). Antibiotics used for DAC reconstruction were Vancomycin in 33 cases, Vancomycin + Meropenem in 10, Vancomycin + Rifampicin, Teicoplanin or Ceftazidime in 1 case, respectively. Patients were evaluated at 3, 6, 12 months and yearly after with a clinical and radiographic FU. No evidence of infection and no failure/loosening of the prosthesis were observed. No adverse events were reported.

The second phase was designed to evaluate efficacy of DAC in preventing infection recurrences after a two stage revision for infected THR. Twenty-seven patients, treated with DAC coating, were compared with a control group of 32, treated in the same time period, without the coating. Demographics, host type and and identified bacteria were similar in the two groups (18.6% of MRSA in DAC group vs 18.5% MRSA in no-DAC group). Patients were evaluated clinically and radiographically at 3, 6, 12 months and yearly thereafter. At a minimum 2 years FU (mean 2.7), we observed 1 dislocation in each group and 2 cases of loosening in the no-DAC group. 4 cases (11%) of recurrence of infection in the no-DAC group (1 MRSA and 3 St. Epidermidis) and no infection recurrences in the DAC group. Due to the small cohort of patients this difference is not statistically significant (Fisher's exact test, p=0.18).

This is, to our knowledge, the longest observation concerning the safety and efficacy of the DAC antibacterial coating, applied to hip replacement. The results are in line with those previously reported and point out the absence of side effects of the antibacterial coating in this application and the tendency to reduce re-infection in second stage. This finding needs to be confirmed by a larger dataset.

Aim

The treatment of osteomyelitis often requires extensive surgical debridement and removal of all infected tissues and foreign bodies. Resulting bone loss can then eventually be managed with antibacterial bone substitutes, that may also serve as a regenerative scaffold. Aim of the present study is to report the clinical results of a continuous series of patients, treated at our centre with an antibacterial bioglass*.

Development of antibacterial surfaces or coatings to prevent bacterial adhesion and hence colonization of implants and biofilm formation is an attractive option, in order to reduce the tremendous impact of implant-related infections associated with modern surgery. To overcome the lack of in vivo and clinical models, able to evaluate the performance of anti-adhesive coatings, we designed an in vitro experimental setting that allows to quantitatively evaluate the ability of a coating to reduce bacterial adhesion on a given surface; this model may efficiently serve as a surrogate endpoint to validate anti-adhesive medical devices and compounds. Here we report the results the evaluation of the anti-adhesive properties of a patented, fast-resorbable hydrogel coating, (“Defensive Antibacterial Coating”, DAC).

Sterile sandblasted titanium discs of approximately 5cm² surface area were used as substrates for bacterial adhesion. The gel was prepared as follows: syringes prefilled with 300 mg of DAC powder (Novagenit Srl) were reconstituted with 5 ml of sterile water to obtain a hydrogel with a DAC concentration of 6%. Two experiments were conducted. In the first, 200 mg of hydrogel were homogenously spread on the surface of titanium disc, with the spreading device provided by the manufacturer. Both coated and uncoated substrates (controls) were overlaid with a standardized inoculum (10⁸ CFU/ml) of a wild methicillin-resistant Staphylococcus aureus strain, previously isolated from a peri-prosthetic joint infection, for 15, 30, 60 and 120 minutes. Afterwards, non-adherent bacteria were removed by rinsing with sterile saline. The remaining adhered cells were seeded on agar plates for CFU count. In the second experiment, the discs were first inoculated with bacterial cells followed by a treatment with the hydrogel and bacterial count as described above. Ten discs were used for each condition and each time interval (total 160 discs).

The adhesion density of S. aureus on titanium discs pre-treated with DAC was significantly lower than that observed on untreated controls at each time point. In particular, the average number of adherent bacteria at 15, 30, 60 and 120 minutes of incubation, was respectively reduced by 86.8%, 80.4%, 74.6% and 66.7%, compared to controls (p<0.001). DAC treatment of discs with previously adhered S. aureus reduced bacterial adhesion, at 15, 30, 60 and 120 minutes of incubation, by, respectively, 84.0% (p<0.05), 72.8%, 72.3% and 64.3% (p<0.001), compared to untreated controls.

Our results shows that DAC, “Defensive Antibacterial Coating”, has anti-adhesive properties that allow to reduce bacterial adhesion on a sanded titanium surface by more than 80%, even in the presence of remarkably high bacterial loads (10⁸ CFU/ml), of multi-resistant bacteria (MRSA) and even in the case of previous contamination. Providing anti-adhesive properties to a surface with a fast-resorbable coating may be a safe option to protect inorganic and organic surfaces and biomaterials. Those observation could be the pre-requisite for its in vivo application.

The treatment of chronic osteomyelitis often includes surgical debridement and filling the resultant void with antibiotic-loaded polymethylmethacrylate cement, bone grafts or bone substitutes. Recently, the use of bioactive glass to treat bone defects in infections has been reported in a limited series of patients. However, no direct comparison between this biomaterial and antibiotic-loaded bone substitute has been performed.

In this retrospective study, we compared the safety and efficacy of surgical debridement and local application of the bioactive glass S53P4 in a series of 27 patients affected by chronic osteomyelitis of the long bones (Group A) with two other series, treated respectively with an antibiotic-loaded hydroxyapatite and calcium sulphate compound (Group B; n = 27) or a mixture of tricalcium phosphate and an antibiotic-loaded demineralised bone matrix (Group C; n = 22). Systemic antibiotics were also used in all groups.

After comparable periods of follow-up, the control of infection was similar in the three groups. In particular, 25 out of 27 (92.6%) patients of Group A, 24 out of 27 (88.9%) in Group B and 19 out of 22 (86.3%) in Group C showed no infection recurrence at means of 21.8 (12 to 36), 22.1 (12 to 36) and 21.5 (12 to 36) months follow-up, respectively, while Group A showed a reduced wound complication rate.

Our results show that patients treated with a bioactive glass without local antibiotics achieved similar eradication of infection and less drainage than those treated with two different antibiotic-loaded calcium-based bone substitutes.

Cite this article: Bone Joint J 2014; 96-B:845–50.

Introduction: In 1995 we started using, at the G. Pini Orthopaedic Istitute of Milano, a system for bone healing stimulation based on low intensity pulsed ultrasound. Advantages of the method are: home therapy (20 minutes per day); no side effects, even in the presence of metallic devices or infection; ease of use. Indications of low intensità pulsed ultrasound are bone healing after fresh frarctures, in which a significant bone healing accelation can be observed, delayed and non-unions. We share our experience in a challenging field of application: septic non-unions.

Materials and methods: We retrospectively evaluated 30 patients, treated from 1996 to 2003, affected by septic non-unions (a fracture that, in the presence of infection, did not show any significant increase in callus formation at 8 months from the time of fracture). The patients had a mean 1.7 ± 2 previous failed intervention. Patients were treated, in the absence of other medical or surgical treatment (excluding antibiotic therapy), with low intensity pulsed ultrasound (EXOGEN S.A.F.H.S. or, since year 2002, IGEA F.A.S.T.). The treatment was applied, after the necessary instructions, directly from the patient, at home, 20 minutes per day. Failures of the treatment were considered need for further surgery to stimulate bone healing, persistence of non-union at follow-up. Exclusion criteria included: evident instability of the synthesis, soft tissue loss and bone exposure, wide bone loss (> 2 cm).

Results: 24 bone healing (86 %), 4 failures (need for surgery), 2 treatment discontinuation. Mean treatment duration: 123 ± 43 days (minimum 90, maximum 240 days). No side effects local or general were observed. In 18 cases a bone debridment and/or hardware removal intervention had been performed after bone healing. At follow-up, 28 patients are free from infection, while two showed infection recurrence.

Conclusions: Low intensity pulsed ultrasound is an effective options in the treatment of septic non-unions, without side effects. An accurate indication and patient selection provide an advantageous cost/benefit ratio.

Bone loss, either due to a septic process or to surgical débridements, is frequently associated with bone infections. Bone loss may be present in septic non-unions, osteomyelitis or septic joint prosthesis. In each of these conditions the use of bone or bone substitutes may be indicated. However, the risk of septic recurrence makes the choice of the right implant in these patients particularly difficult.

Clinical cases are presented to show the different choices available. Attention is focussed on: (1) when, in the presence of bone loss, a bone graft can be avoided and with which suitable procedures good results can be obtained; (2) when and how autologous bone grafts should be used; (3) when homologous bone grafts or bone substitutes are indicated; (4) how bone grafts should be protected against bacterial adesion and proliferation; and (5) the role of new technologies, such as bone growth factors. In this regard the clinical results are presented of the use of platelet-rich plasma (PRP) added to autologous or homologous bone after bone débridement in six patients treated with two-stage non-cemented revision of septic hip prosthesis and in two patients with septic non-union of the femur. At a minimum follow-up of 6 months (max. 1 year), we did not observe any infection recurrence, while bone remodelling and clinical outcome were favourable.

The use of bone growth factors such as PRP possibly added to autologous or homologous bone appears to be a promising technique to achieve bone reconstruction in débrided bone infections. However, with the limited numbers of patients and the short-term follow-up conclusions cannot be drawn and the use of growth factors with this indication should be limited to selected cases: patients with wide bone loss and with no signs of active infections.

No international guidelines are available concerning bone reconstruction in infections. Clinical experience shows that different surgical procedures are effective and the choice should take into considerations the type and site of bone defect, the host type and the pathogenesis of the bone loss. Growth factors may be a useful tool in these conditions and further studies are indicated.

A modular neck allows to choose the offset of the femoral head and the degree of anti-retroversion, lateralization and varus-valgus intraoperatively. At the G. Pini Institute we have been using modular necks in custom prostheses since 1989. Excellent results in this application did open the way to a larger use in off-the-shelf prostheses. Modular necks can be now coupled with different stems, leaving the surgeon free to use the preferred prosthetic stem design. Modular necks have been implanted in more than 50,000 in the world. Medium term results in custom prosthesis and the experience in off-the-shelf non-cemented stems are presented, together with further improvements of this technology under study.

From 1989 to December 1999, 481 custom stems have been implanted. All patients but ten received modular necks. The prostheses were made of a titanium alloy and HA coated. 61 % of patients had dysplastic oxarthrosis. 372 implants performed between 1989 and 1996 were retrospectively evaluated. Data from off-the-shelf prosthesis, at a shorter follow-up, are also reported. Laboratory data showed that the use of an elliptical Morse cone of the neck reduced wear debris production to less than 1 mg/year. In custom implants, (mean follow-up: 7 years), we did not observe any thigh pain or radiological signs of osteolysis or fretting. Mean leg-length discrepancy was 2.8 cm pre-op and 0.3 cm post-operatively. Off-the-shelf implants also showed good clinical and radiological results. New design modular necks will increase the possible range of motion and provide more solutions for positioning the center of rotation. Modular neck is a safe and reliable solution to obtain the correct position of the center of rotation intra-operatively, without side effects. Applications in off-the-shelf prostheses allow to reduce costs while maintaining the advantages of this technology.