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

We investigated the antibiotic concentration in fresh-frozen femoral head allografts harvested from two groups of living donors. Ten samples were collected from patients with osteoarthritis of the hip and ten from those with a fracture of the neck of the femur scheduled for primary arthroplasty. Cefazolin (1 g) was administered as a pre-operative prophylactic antibiotic. After storage at −80°C for two weeks the pattern of release of cefazolin from morsellised femoral heads was evaluated by an in vitro broth elution assay using high-performance liquid chromatography. The bioactivity of the bone was further determined with an agar disc diffusion and standardised tube dilution bioassay. The results indicated that the fresh-frozen femoral heads contained cefazolin. The morsellised bone released cefazolin for up to four days. The concentration of cefazolin was significantly higher in the heads from patients with osteoarthritis of the hip than in those with a fracture. Also, in bioassays the bone showed inhibitory effects against bacteria. We concluded that allografts of morsellised bone from the femoral head harvested from patients undergoing arthroplasty of the hip contained cefazolin, which had been administered pre-operatively and they exhibited inhibitory effects against bacteria in vitro

Platelet-leucocyte gel (PLG), a new biotechnological blood product, has hitherto been used primarily to treat chronic ulcers and to promote soft-tissue and bone regeneration in a wide range of medical fields. In this study, the antimicrobial efficacy of PLG against Staphylococcus aureus (ATCC 25923) was investigated in a rabbit model of osteomyelitis. Autologous PLG was injected into the tibial canal after inoculation with Staph. aureus. The prophylactic efficacy of PLG was evaluated by microbiological, radiological and histological examination. Animal groups included a treatment group that received systemic cefazolin and a control group that received no treatment. Treatment with PLG or cefazolin significantly reduced radiological and histological severity scores compared to the control group. This result was confirmed by a significant reduction in the infection rate and the number of viable bacteria. Although not comparable to cefazolin, PLG exhibited antimicrobial efficacy in vivo and therefore represents a novel strategy to prevent bone infection in humans

Treatment of bone infection often includes a burdensome two-stage revision. After debridement, contaminated implants are removed and replaced with a non-absorbable cement spacer loaded with antibiotics. Weeks later, the spacer is exchanged with a bone graft aiding bone healing. However, even with this two-stage approach infection persists. In this study, we investigated whether a novel 3D-printed, antibiotic-loaded, osteoinductive calcium phosphate scaffold (CPS) is effective in single-stage revision of an infected non-union with segmental bone loss in rabbits. A 5 mm defect was created in the radius of female New Zealand White rabbits. The bone fragment was replaced, stabilized with cerclage wire and inoculated with Staphylococcus aureus (MSSA). After 4 weeks, the infected bone fragment was removed, the site debrided and a spacer implanted. Depending on group allocation, rabbits received: 1) PMMA spacer with gentamycin; 2) CPS loaded with rifampin and vancomycin and 3) Non-loaded CPS. These groups received systemic cefazolin for 4 weeks after revision. Group 4 received a loaded CPS without any adjunctive systemic therapy (n=12 group1-3, n=11 group 4). All animals were euthanized 8 weeks after revision and assessed by quantitative bacteriology or histology. Covariance analysis (ANCOVA) and multiple regression were performed. All animals were culture positive at revision surgery. Half of the animals in all groups had eliminated the infection by end of study. In a historical control group with empty defect and no systemic antibiotic treatment, all animals were infected at euthanasia. There was no significant difference in CFU counts between groups at euthanasia. Our results show that treating an osteomyelitis with segmental bone loss either with CPS or PMMA has a similar cure rate of infection. However, by not requiring a second surgery, the use of CPS may offer advantages over non-resorbable equivalents such as PMMA

Administration of perioperative antibiotic prophylaxis (AP) reduces the risk of prosthetic joint infection (PJI) following primary total hip (THA) and knee (TKA) arthroplasty. The optimal type of antibiotic used, and duration of prophylaxis are subject to debate. We compared the risk of revision surgery for PJI in the first year following THA and TKA by AP regimen. A national survey collecting information on hospital-level AP regimen policy was conducted across the Netherlands and linked to data from the LROI arthroplasty registry for 2011–2015. PJI status was defined using the surgical indication reported at revision by surgeons in the registry form. Restricted cubic splines Poisson model adjusted for hospital clustering were used to conduct the comparisons on 130,712 THAs and 111,467 TKAs performed across 99 institutions. These included 399 THAs and 303 TKAs revised for an indication of PJI. Multiple shot of Cefazolin (MCZ), of cefuroxime (MCX) and single shot of Cefazolin (SCZ) were respectively administrated to 87%, 4% and 9% of patients. For THA, the rates of revision for PJI were respectively 31/10,000 person-years 95%CI[28, 35], 39[25, 59] and 23[15, 34] in the groups which received MCZ, MCX and SCZ; respectively, the rates for TKA were 27[24, 31], 40[24, 62] and 24[16, 36]. No evidence of difference between AP regimens was found in the unadjusted and adjusted model (age, gender, BMI and ASA grade). Further work is advocated to confirm whether there is an association between AP regimen collected at patient-level and the risk of subsequent revision for PJI

This longitudinal microCT study revealed the osteolytic response to a Staphylococcus epidermidis-infected implant in vivoand also demonstrates how antibiotics and/or a low bone mass state influence the morphological changes in bone and the course of the infection. Colonisation of orthopaedic implants with Staphylococcus aureusor S. epidermidisis a major clinical concern, since infection-induced osteolysis can drastically impair implant fixation or integration within bone. High fracture incidence in post-menopausal osteoporosis patients means that this patient group are at risk of implant infection. The low bone mass in these patients may exacerbate infection-induced osteolysis, or alter antibiotic efficacy. Therefore, the aims of this study were to examine the bone changes resulting from a S. epidermidisimplant infection in vivousing microCT imaging, and to determine if a low bone mass stateinfluences the course of the infection and the efficacy of antibiotic therapy. An in vivomodel system using microCT scanning [1], involving the implantation of either a sterile or a S. epidermidis-colonised PEEK screw into the proximal tibia of 24 week-old female Wistar rats, was used to investigate the morphological changes in bone following infection over a 28 day period. In addition, the efficacy of a combination antibiotic therapy (rifampin and cefazolin: administered twice daily from days 7–21 post-screw implantation) for affecting osteolysis was also assessed. A subgroup of animals was subjected to ovariectomy (OVX) at 12 weeks of age, allowing for a 12 week period for bone loss prior to screw implantation at 24 weeks. Bone resorption and formation rates, bone-implant contact and peri-implant bone volume in the proximity of the screw were assessed by microCT scanning at days 0, 3, 6, 9, 14, 20 and 28 days post-surgery. Following euthanasia at day 28, the implanted screw, bone and soft tissues were subjected to quantitative bacteriology as a measure of the efficacy of the antibiotic regimen. In non-OVX animals S. epidermidisinfection induced marked osteolysis, which peaked between 9 and 14 days post-screw implantation. Peak bone resorption was detected at day 6, before recovering to baseline levels at day 14. Infection also resulted in extensive deposition of mineralised tissue, initially within the periosteal region (day 9–14), then subsequently in the osteolytic region at day 20–28. Quantitative bacteriology indicated all non-OVX animals remained infected. Rifampin and cefazolin successfully cleared the infection in 5/6 non-OVX animals group although there was no difference observed in CT-derived bone parameters. OVX resulted in extensive loss of trabecular bone but this did not alter the temporal pattern of infection-induced osteolysis, or mineralised tissue deposition, which was similar to that observed in the non-OVX animals. Similarly, there was no difference in bacterial counts between non-OVX and OVX animals (39,005 colony-forming units (CFU) [range: 3,675–156,800] vs 37,665 CFU [range 3,250–84,000], respectively). Interestingly, antibiotic treatment was less effective in the OVX animals (3/5 remained infected), suggesting that antibiotics have reduced efficacy in OVX animals. This study demonstrates S. epidermidis-induced osteolysis displays a similar temporal pattern in both normal and low bone mass states, with comparable bacterial loads present within the localised infection site

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.

Objectives

In this study, we compared the pain behaviour and osteoarthritis (OA) progression between anterior cruciate ligament transection (ACLT) and osteochondral injury in surgically-induced OA rat models.

Aims

We aimed to evaluate the temperature around the nerve root during drilling of the lamina and to determine whether irrigation during drilling can reduce the chance of nerve root injury.

Objectives

The purpose of this study was to compare the results and complications of tibial lengthening over an intramedullary nail with treatment using the traditional Ilizarov method.

Objectives

Mesenchymal stem cells have the ability to differentiate into various cell types, and thus have emerged as promising alternatives to chondrocytes in cell-based cartilage repair methods. The aim of this experimental study was to investigate the effect of bone marrow derived mesenchymal stem cells combined with platelet rich fibrin on osteochondral defect repair and articular cartilage regeneration in a canine model.

We investigated the effect of mitomycin-C on the reduction of the formation of peritendinous fibrous adhesions after tendon repair. In 20 Wistar albino rats the tendo Achillis was cut and repaired using a modified Kessler technique. The rats were divided into two equal groups. In group 1, an injection of mitomycin-C was placed between the tendon and skin of the right leg. In group 2, an identical volume of sterile normal saline was injected on the left side in a similar fashion. All the rats received mitomycin-C or saline for four weeks starting from the day of operation. The animals were killed after 30 days. The formation of peritendinous fibrous tissue, the inflammatory reaction and tendon healing were evaluated. The tensile strength of the repaired tendons was measured biomechanically. Microscopic evidence of the formation of adhesions and inflammation was less in group 1. There was no significant difference in the tensile load required to rupture the repaired tendons in the two groups.

Mitomycin-C may therefore provide a simple and inexpensive means of preventing of post-operative adhesions.