Objectives

Thermal stability is a key property in determining the suitability of an antibiotic agent for local application in the treatment of orthopaedic infections. Despite the fact that long-term therapy is a stated goal of novel local delivery carriers, data describing thermal stability over a long period are scarce, and studies that avoid interference from specific carrier materials are absent from the orthopaedic literature.

Infections represent a devastating complication in orthopedic and traumatological surgery, with high rates of morbidity and mortality. An early intervention is essential, and it includes a radical surgical approach supported by targeted intravenous antimicrobial therapy. The availability of parenteral antibiotics at the site of infection is usually poor, so it is crucial to maximize local antibiotic concentration using local carriers. Our work aims to describe the uses of one of these systems, Stimulan®, for the management and prevention of infections at our Institution. Analysing the reported uses of Stimulan®, we identified two major groups: bone substitute and carrier material for local antibiotic therapy. The first group includes its application as a filler of dead spaces within bone or soft tissues resulting from traumatic events or previous surgery. The second group comprehends the use of Stimulan® for the treatment of osteomyelitis, post-traumatic septic events, periprosthetic joint infections, arthroplasty revision surgery, prevention in open fractures, surgery of the diabetic foot, oncological surgery and for all those patients susceptible to a high risk of infection. We used Stimulan® in several complex clinical situations: in PJIs, in DAPRI procedure and both during the first and the second stage of a 2-stage revision surgery; furthermore, we started to exploit this antibiotic carrier also in prophylaxis of surgical site infections, as it happens in open fractures, and when a surgical site remediation is required, like in osteomyelitis following ORIF. Stimulan® is an extremely versatile and polyhedric material, available in the form of beads or paste, and can be mixed to a very broad range of antibiotics to better adapt to different bacteria and their antibiograms, and to surgeon's needs. These properties make it a very useful adjuvant for the management of complex cases of infection, and for their prevention, as well

Orthopedic device-related bone infection is one of the most distressing complications of the surgical fixation of fractures. Despite best practice in medical and surgical interventions, the rate of infection remains stubbornly persistent, and current estimates indicate that treatment failure rates are also significant. As we approach the limit of the effectiveness of current anti-infective preventative and therapeutic strategies, novel approaches to infection management assume great importance. This presentation will describe our efforts to develop and test various hydrogels to serve as customized antibiotic delivery vehicles for infection prevention and treatment. Hydrogels offer solutions for many of the challenges faced by complex trauma wounds as they are not restricted spatially within a poorly defined surgical field, they often degrade rapidly with no compatibility issues, and releases 100% of the loaded antibiotic. The preliminary data set proving efficacy in preventing and treating infection in both rabbit and sheep studies will be described, including local antibiotic concentrations in the intramedullary canal over time, compared to that of the more conventional antibiotic loaded bone cement. These two technologies show potential for the prevention and treatment of infection in trauma patients, with a clear focus on optimized antibiotic delivery tailored for complex wounds

Introduction and Objective. Management of bone loss associated with bone contamination or infection represents a double biological and clinical challenge frequent in traumatology. The advent of new biomaterials can allow a different approach in the treatment of bone gap. The purpose of this study was to evaluate the prophylactic and therapeutic effectiveness of addition of a new absorbable bone substitute (BS) eluting different antibiotics in reconstruction of bone defects after infections and fractures with soft tissue damage. Materials and Methods. We conducted a review of patients with contaminated or infected bone defects treated using a new biomaterial, a porous composite of collagen matrices and Beta tricalcium phosphate (β TCP), able to provide a long-term release of different antibiotics. We have included treatment of osteomyelitis and osteosynthesis of exposed fracture (Gustilo Anderson 1–3b) or fractures with soft tissue damage and high risk of contamination. Surgical technique included debridement filling bone defect with BS eluting antibiotics, osteosynthesis (plate, nail, external fixator, kirschner wire), soft tissue coverage, and systemic antibiotic therapy. Radiographic and clinical data including complications (wound dehiscence, superficial or deep infection, osteomyelitis) were collected. Results. We treated 25 patients (21 male, 4 female) with mean age 47 yrs. (range 21–83). The locations treated (for incidence) was: 9 femurs (7 plates, 2 nail), 7 calcanei (one bilateral), 3 tibias, 2 forearms, 2 metatarsi, 2 hands, 1 elbow. 6 patients had large bone loss. 7 patients had bone infections (4 were Cierny Madern 4); 8 patients had osteosynthesis of exposed fractures Gustilo Anderson 1–3b (9 plate, one bilateral calcaneus). 8 patients had treatment for pseudoarthrosis of exposed fractures (6 femurs, 1 forearm, 1 metatarsus) and 3 patients a prophylactic treatment for calcaneal fractures with soft tissue damage. 4 deep infection were treated with multiple surgical debridement and new filling bone defect with BS eluting antibiotic with infection eradication. We have used a combination of vancomycin and gentamicin on 15 cases, vancomycin alone on 4 cases, combination of vancomycin and amikacin on 1 case and amikacin and Linezolid in a targeted multi drug resistance. At final follow-up functional outcome was good in all cases with bone healing. Conclusions. Extensive debridement is a fundamental requisite for eradication of bone infections and contamination. Filling of the bone void with loaded bio-composite eluting diversifiable local antibiotics with synergistic anti-biofilm activity is desirable. Treatment of this bone defects are advantaged when combining his reconstruction with BS and the possibility of release high antibiotic concentration at least for 10 days. This is an important complementing prophylactic and therapeutic antimicrobial option with adjuvant role to systemic therapy that enlarges the success rate

There has been a significant increase in the demand of polymeric scaffolds with promising affects in bone regeneration. However, inflammation is still a problem in transplantations to overcome with local antibiotic therapy. In this study, it is aimed to develop a functional POSS nanocage reinforced chitosan scaffold (CS/POSS) coated with drug loaded chitosan composite nanospheres to provide a controlled antibianyiotic delivery at the defect site. Gentamicin and vancomycin were selected as model antibiotic drugs. Drug loaded nanospheres were fabricated with electrospray method and characterized in terms of morphology, hydrodynamic size, surface charge, FT-IR, in vitro drug release, antimicrobial activity and cytotoxicity. CS/POSS scaffolds were fabricated via lyophilisation and characterized with mechanic, swelling test, SEM and micro CT analyses. Positively charged nanospheres with uniform morphology were obtained. High drug encapsulation efficiency (80–95%) and sustained release profile up to 25 days were achieved with a cumulative release of 80–90%. In addition, the release media of the nanospheres (in 6 hours, 24 hours and 25 days of incubation period) showed a strong antimicrobial activity against S.aureus and E.coli, and did not show any cytotoxic effect to 3T3 and SaOS-2 cell lines. CS/POSS scaffolds were obtained with high porosity (89%) and 223.3±55.2μm average pore size. POSS reinforcement increased the compression modulus from 755.7 to 846.1Pa for 10 % POSS addition. In vitro studies of nanosphere coated bilayer scaffolds have showed high cell viability. Besides ALP activity results showed that POSS incorporation significantly increased the ALP activity of Saos-2 cells cultured on the scaffold. In conclusion, these composites can be considered as a potential candidate in view of its enhanced physico-chemical properties as well as biological activities for infection preventive bone tissue engineering applications

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

Background. The different biodegradable local antibiotic delivery systems are widely used in recent years. The aim of this study was to evaluate the bactericidal activity antibiotic loaded PerOssal pellet in vitro and its effectiveness in the treatment of Staphylococcus aureus induced chronic osteomyelitis. Material and methods. MALDI-TOF have been applied to microbiological diagnosis in patient with osteomyelitis. In most cases, Staphylococcus aureus was isolated. In vitro Ceftriaxone-Loaded PerOssal pellet were placed in middle agar plate containing a stock strain of Staphylococcus aureus. Plates were incubated at 37ºC for 24 hours. The zones of bacterial inhibition were recorded after 24, 48 and 72 hours of incubation. In vivo evaluation was performed by prospectively studying of 21 patients with a clinically and bacteriologically diagnosed Staphylococcus aureus induced osteomyelitis. Mean age was 38±4,2(26 to 53)). After radical surgical debridement and ultrasound cavitation, the bone cavity was full filled with Perosal pellets loaded with different antibiotics depending from the antibiotic sensitivity test. Endpoints were the absence of clinical manifestation of infection or disease recurrence, no need for further surgery. Results. In vitro showed after 24 hrs inhibition zone was 4,2 х 4,9 cm, after 72 hrs the inhibition zone was increased till 7,6 х 8,4 cm. During the subsequent time, there were no changes. Results of the clinical study evidenced no signs of infection in 18 patients (86% (CI 69,8;100)) (p<0,05) at the follow up, while 3 (14%(CI 0;30,2)) (p<0,05) subjects showed infection recurrence at 6 months from operation and 2 of them needed further surgical procedures. Conclusion. PerOssal as an antibiotic carrier stabilizes the action of the antibiotic. This antibiotic carrier system allows to choose an antibiotic individually for each patient according to the antibiotic sensitivity test and can be successfully used in clinical cases of osteomyelitis

Introduction. Prosthetic joint infections (PJI) occur infrequently, but due to its increased clinical use represent the most devastating complication with high morbidity and substantial cost. Staphylococcus aureus and coagulase-negative staphylococci are the most common infecting agents associated with PJI. A possible therapeutic approach could be the local antibiotic by fluoride-TiO2 nanostructured anodic layers in order to prevent surface colonisation during the early moments after surgery. Here we describe the first results of this model using two common antibiotics. Methods. Fluoride-TiO2 nanostructured anodic layers on Ti6Al4V alloy were produced as described previously by Arenas et al (2013). Discs shaped pieces of Ti6Al4V alloy were loaded with a solution of 150 mg antibiotic (vancomycin or gentamicin)/20 ml sterile distilled water. Samples were immersed in this solution during 24 hours at room temperature with agitation, and then were dried during 48 hours at 20°C. Antibiotic release was studied by introducing both discs in sterile PBS and samples were taken at different times. Samples were then frozen at −80°C until HPLC measurements and biological activity tests using Bacillus subtilis ATCC 6051 (vancomycin) and Escherichia coli ATCC 25922 (gentamicin) were performed. Results. Release kinetic constant was not be obtained by HPLC-UV due to chemical degradation, therefore it was needed to prove biological activity. According to biological activity test, vancomycin and gentamicin estimated concentration mean and standard deviation were 2.9±0.61 and 2.71±0.64 mg/L over time respectively. Conclusions. Fluoride-TiO2 nanostructured anodic layers on Ti6Al4V alloy could be considered as promising vector of antibiotics for the prevention of PJI during early moments after surgery

We describe a case series using calcium sulphate bio composite with antibiotics (Cerament/Stimulan) in treating infected metalwork in the lower limb. Eight patients aged 22–74 (7 males, 1 female) presented with clinical evidence of infected limb metal work from previous orthopaedic surgery. Metal work removal with application of either cerement in 5 cases (10–20ml including 175mg–350mg gentamycin) or stimulan in 3 cases (10–20ml including either 1g vancomycin or clindamycin 1.2g or 100mg tigecycline) into the site was performed. Supplemental systemic antibiotic therapy (oral/intravenous) was instituted based on intraoperative tissue culture and sensitivity. Four patients had infected ankle metalwork, 2 patients infected distal tibial metalwork and 2 had infected external fixators. Metal work was removed in all cases. The mean pre operative CRP was 15.8mg/l (range 1–56mg/l). The mean postoperative CRP at 1 month was 20.5mg/l (range 2–98mg/l). The mean pre op WCC was 7.9×10. 9. (range 4.7–10.5 ×10. 9. ). Mean post op WCC at 1 month was 7.1×10. 9. (range 5.0–9.2×10. 9. ). The organisms cultured included enterobacter, staphylococcus aureus, staphylococcus epidermidis, staphylococcus cohnii, stenotrophomonas, acinetobacter, group B streptococcus, enterococcus and escherichia coli. No additional procedures were required in any case. All surgical wounds went on to heal uneventfully. Infection control and union was achieved both clinically and radiologically in all cases. Our results support the use of a calcium sulphate bio composite with antibiotic as an adjuvant for effective local infection control in cases with implant related bone sepsis. The technique is well tolerated with no systemic or local side effects. We believe that implant removal, debridement and local antibiotic delivery can minimise the need for prolonged systemic antibiotic therapy in such cases

The aim of this study was to determine the effectiveness of antibiotic-impregnated implants in the prevention of bone infection. We used a model of contaminated fracture in goats to evaluate four treatment groups: no treatment, hand-made tobramycin-impregnated polymethylmethacrylate beads, commercially-available tobramycin-impregnated calcium sulphate pellets and commercially-available tobramycin-impregnated polymethylmethacrylate beads. Three weeks after intraosseous inoculation with streptomycin-resistant Staphylococcus aureus tissue cultures showed no evidence of infection in any of the antibiotic-treated groups. All of the cultures were positive in the untreated group. These results show that effective local antibiotic delivery can be obtained with both commercially-available products and with hand-made polymethylmethacrylate beads. The calcium sulphate pellets have the advantage of being bioabsorbable, thereby obviating the need for a second procedure to remove them

Bone infection occurring after fractures or orthopedic surgery can progress to the chronic stage and lead to poor results of treatment. Optimal treatment of chronic osteomyelitis are stabilization the fracture, biological recovery of bone defects and destroy bacterial infection. Traditional methods of treatment are systemic administration of antibiotics and surgical treatment of active infection focus. Systemic antibiotics are part of the standard therapy after surgical treatment of infected bone, but their effectiveness is limited due to malnutrition and low absorption at the site of infection. Moreover, long-term treatment and higher doses are associated with serious side effects. The aim of this investigation was to study the results of the complex treatment of patients with chronic osteomyelitis using biodegradable nanomaterials “PerOssal” as antibiotic delivery system. The study was performed at Regional center traumatology and orthopedics, Karaganda, Kazakhstan. A total 20 patient with post-traumatic/post-operative osteomyelitis were included in this open-label, prospective study. Bacteriological examination was taken with the determination of culture and sensitivity test preoperatively, during and postoperatively. After radical surgical debridement and ultrasound cavitation, the bone cavity was full filled with Perosal which can be loaded with different antibiotics depending from the antibiotic sensitivity test. Postoperative wound is completely was sutured. Systemic antibiotic treatment are allowed. The course of infection was monitored by determination leukocyte count and blood sedimentation rate; blood samples were taken befor, 24 hours after surgery, and on days 3, 7, 10, 14. Wound healing was assessed on days 2, 3, 7, 10, and at the time of removal of sutures. Resorption of implanted beads and bone reconstruction were evaluated by X-ray at after operation and at approximately one, three and six months after implantation. A total of 20 patients (mean age 38,1 (26 to 53), 14 male, 6 female) were treated with Perossal pellets (AAP, Germany) from October 2013 to April 2015. Mean leukocyte counts and blood sedimentation rate were within the normal laboratory range and did not indicate infectious complications during the first 21 days after surgery. Primary wound healing occurred in 18 patients and secondary wound healing in two patients. There were two cases of re-infection during the course of the study, one of them related to an incomplete eradication of infected tissue and multidrug-resistant strain occurring during the course of the study, the other is occurred that patient non-compliance. Radiographic analysis six months after surgery showed progressive resorption of the implanted pellets, but only 10 cases have decreasing size of defects on X-ray. This study in adult patients with chronic post-traumatic/post-operative osteomyelitis demonstrated that these biodegradable bone filler pellets which can be loaded with different antibiotics are a clinically useful local antibiotic delivery system and bone substitute which can be used as an alternative to other anti-infective implants. The implantation of the pellets was safety and well tolerated in all patients. This composite can provide adequate protection against bacterial infection during the first weeks after implantation and to support the bone healing process

To prevent infections after orthopedic surgery, intravenous antibiotics are administered perioperatively. Cefazolin is widely used as the prophylactic antibiotic of choice. Systemic antibiotic therapy may however be less effective in longstanding surgery where bone allografts are used. Bone chips have been shown to be an effective carrier for certain types of antibiotics. Bone allografts impregnated with antibiotics may therefore provide the necessary local antibiotic levels for prophylaxis. To be efficient, a prolonged release from these bonechips is required. In contrast to vancomycin, for which prolonged release has clearly been proven effective from Osteomycin®, a commercially available impregnated bone allograft, no prolonged release bone chip preparations have been described so far for cefazolin. We developed a protocol to bind cefazolin in the porous structure of bone chips by means of a hydrogel composed of proteins naturally present in the human body. Three types of bone chips were evaluated: fresh frozen, decellularized frozen and decellularized lyophilized. Bone chips were incubated with 20 mg/ml cefazolin or treated with liquid hydrogel containing either 1 mg/ml fibrin or 1 mg/ml collagen and 20 mg/ml cefazolin. The cefazolin hydrogel was distributed in the porous structure by short vacuum treatment. Bone chips with cefazolin but without hydrogel were either incubated for 20 min- 4h or also treated with vacuum. Cefazolin elution of bone chips was carried out in fetal bovine serum and analyzed by Ultra Performance Liquid Chromatography – Diode Array Detection. Soaking of bone chips without hydrogel resulted in a quick release of cefazolin, which was limited to 4 hours. When vacuum was applied elution of >1 µg/ml cefazolin was measured for up to 36 hours. Combination with collagen hydrogel resulted in a higher cefazolin concentration released at 24 hours (3.9 vs 0.3 µg/ml), but not in a prolonged release. However, combination of decellularized frozen bone chips with fibrin hydrogel resulted in an initial release of 533 µg/ml followed by a gradual decline reaching the minimal inhibitory concentration for S. aureus at 72 hours (1.7 µg/ml), while not measurable anymore after 92 hours. Processed bone chips with hydrogel-cefazolin showed a markedly prolonged cefazolin release. When combined with a fibrin hydrogel, high initial peak levels of cefazolin were obtained, followed by a decreasing release over the following three days. This elution profile is desirable, since high initial levels are important to maximize anti-bacterial action whereas low levels of antibiotic for a limited time may stimulate osteogenesis. It is important that antibiotic release is ending after a few days as prolonged low levels of antibiotics are not clinically helpful and may lead to antibiotic resistance. Further preclinical studies are warranted to show effectiveness of hydrogel-cefazolin impregnated bone chips

Purpose. Gustilo type III open fractures are associated with high infection rates in spite of instituting a standard of care (SOC) consisting of intravenous antibiotics, irrigation and debridement (I&D), and delayed wound closure. Locally-delivered antibiotic has been proven to assist in reducing infection in open fractures. The aims of this study are to determine the effectiveness and safety of a new implantable and biodegradable antibacterial product. 1. in preventing bacterial infections and initiating bone growth in open fractures. Methods. The osteoconductive antibacterial BonyPid. TM. used is a synthetic bone void filler (comprised of ≤1 mm β-tricalcium phosphate granules) coated by a thin layer (≤20 µm) of PolyPid nanotechnology formulation. −. Upon implantation, the coating releases doxycycline at a constant rate for a predetermined period of 30 days. One BonyPid. TM. vial of 10 grams contains 65 mg of formulated doxycycline. After approval, sixteen subjects with Gustilo type III open tibia fractures, were implanted with the BonyPid. TM. immediately on the first surgical intervention (I&D), followed by external fixation. Patients had periodic laboratory, bacteriology and radiology follow-up. Results. Six months results showed that no infection developed and only one BonyPid. TM. implantation was needed with no subsequent I&D, in the target tibia fracture. Immediate soft wound closure was done in 6/16 subjects following implantation. Out of 10 remaining subjects, 3 needed soleus muscle transfer-skin grafting and 7 required delayed primary closure; by skin grafting (5) or suturing (2). Early callus formation was seen at 8–12 weeks post-surgery, followed by bone healing seen from 16 weeks onwards. Safety of implantation was remarkable, with only one deep infection at a fibular open fracture without BonyPid. TM. implantation. One BonyPid. TM. -related adverse event caused delay in skin healing due to excessive granules in the superficial soft tissues. Conclusion. BonyPid. TM. is effective in reducing bone infection and promoting early callus formation, resulting in early bone healing. BonyPid. TM. is safe for immediate implantation into contaminated/infected severe open-bone fractures. Results support that one month release of doxycycline in a controlled manner provides an effective way for treating open fractures. This new local antibiotic delivery system is applicable in unmet medical situations associated with localised infections

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 5×10. 5. S. 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. Conclusion. Results demonstrate that BonyPid™ nan-technology that allow one month release of doxycycline in a controlled manner provides a new way for treating open fractures. This new local antibiotic delivery system is applicable in other medical situations associated with localised infections

Objectives

Vancomycin and fosfomycin are antibiotics commonly used to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. This study compares the in vitro inhibitory effects against MRSA of articulating cement spacers impregnated with either vancomycin or fosfomycin.

Objectives

Sustained intra-articular delivery of pharmacological agents is an attractive modality but requires use of a safe carrier that would not induce cartilage damage or fibrosis. Collagen scaffolds are widely available and could be used intra-articularly, but no investigation has looked at the safety of collagen scaffolds within synovial joints. The aim of this study was to determine the safety of collagen scaffold implantation in a validated in vivo animal model of knee arthrofibrosis.

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.

We used a goat model of a contaminated musculoskeletal defect to determine the effectiveness of rapidly-resorbing calcium-sulphate pellets containing amikacin to reduce the local bacterial count. Our findings showed that this treatment eradicated the bacteria quickly, performed as well as standard polymethylmethacrylate mixed with an antibiotic and had many advantages over the latter. The pellets were prepared before surgery and absorbed completely. They released all of the antibiotic and did not require a subsequent operation for their removal. Our study indicated that locally administered antibiotics reduced bacteria within the wound rapidly. This method of treatment may have an important role in decreasing the rate of infection in contaminated wounds.

Allograft bone is widely used in orthopaedic surgery, but peri-operative infection of the graft remains a common and disastrous complication. The efficacy of systemic prophylactic antibiotics is unproven, and since the graft is avascular it is likely that levels of antibiotic in the graft are low.

Using an electrical potential to accelerate diffusion of antibiotics into allograft bone, high levels were achieved in specimens of both sheep and human allograft. In human bone these ranged from 187.1 mg/kg in endosteal (sd 15.7) to 124.6 (sd 46.2) in periosteal bone for gentamicin and 31.9 (sd 8.9) in endosteal and 2.9 (sd 1.1) in periosteal bone for flucloxacillin. The antibiotics remained active against bacteria in vitro after iontophoresis and continued to elute from the allograft for up to two weeks.

Structural allograft can be supplemented directly with antibiotics using iontophoresis. The technique is simple and inexpensive and offers a potential means of reducing the rate of peri-operative infection in allograft surgery. Iontophoresis into allograft bone may also be applicable to other therapeutic compounds.

We studied the effects of coating titanium implants with teicoplanin and clindamycin in 30 New Zealand White rabbits which were randomly assigned to three groups. The intramedullary canal of the left tibia of each rabbit was inoculated with 500 colony forming units of Staphylococcus aureus. Teicoplanin-coated implants were implanted into rabbits in group 1, clindamycin-coated implants into rabbits in group 2, and uncoated implants into those in group 3. All the rabbits were killed one week later. The implants were removed and cultured together with pieces of tibial bone and wound swabs. The rate of colonisation of the organisms in the three groups was compared.

Organisms were cultured from no rabbits in group 1, one in group 2 but from all in group 3. There was no significant difference between groups 1 and 2 (p = 1.000). There were significant differences between groups 1 and 3 and groups 2 and 3 (p < 0.001). Significant protection against bacterial colonisation and infection was found with teicoplanin- and clindamycin-coated implants in this experimental model.