The response of macrophages to particles of resorbable polymers and their degradation products

Alpha polyesters such as poly(L-lactide) and poly(glycolide) are biodegradable materials used in fracture fixation and they need to be assessed for problems associated with their degradation products. This study has compared cell responses to low molecular weight poly(L-lactide) particles, lactate monomer, poly(glycolide) particles and glycolic acid at cytotoxic and sub-cytotoxic concentrations. Murine macrophages were cultured in vitro and the release of lactate dehydrogenase (LDH), prostaglandin E-2 (PGE(2)) and interleukin-1 alpha IL-1alpha was measured following the addition of particles or monomer. Experiments revealed that both the poly(L-lactide) and poly(glycolide) particles gave rise to dose dependent increases in LDH release and an increase in IL-1alpha and PGE(2) release. Comparisons of the poly(L-lactide) particles to the poly(glycolide) particles did not reveal any differences in their stimulation of LDH, IL-1alpha and PGE(2) release. The lactate and glycolate monomers did not increase PGE(2) or IL-1alpha release above control levels. There was no difference in biocompatibility between the poly(L-lactide) and poly(glycolide) degradation products both in particulate and monomeric form. (C) 2003 Kluwer Academic Publishers.

Propionibacterium acnes and Staphylococcus lugdunensis Cause Pyogenic Osteomyelitis in an Intramedullary Nail Model in Rabbits

Propionibacterium acnes and coagulase-negative staphylococci (CoNS) are opportunistic pathogens implicated in prosthetic joint and fracture fixation device-related infections. The purpose of this study was to determine whether P. acnes and the CoNS species Staphylococcus lugdunensis, isolated from an "aseptically failed" prosthetic hip joint and a united intramedullary nail-fixed tibial fracture, respectively, could cause osteomyelitis in an established implant-related osteomyelitis model in rabbits in the absence of wear debris from the implant material. The histological features of P. acnes infection in the in vivo rabbit model were consistent with localized pyogenic osteomyelitis, and a biofilm was present on all explanted intramedullary (IM) nails. The animals displayed no outward signs of infection, such as swelling, lameness, weight loss, or elevated white blood cell count. In contrast, infection with S. lugdunensis resulted in histological features consistent with both pyogenic osteomyelitis and septic arthritis, and all S. lugdunensis-infected animals displayed weight loss and an elevated white blood cell count despite biofilm detection in only two out of six rabbits. The differences in the histological and bacteriological profiles of the two species in this rabbit model of infection are reflective of their different clinical presentations: low-grade infection in the case of P. acnes and acute infection for S. lugdunensis. These results are especially important in light of the growing recognition of chronic P. acnes biofilm infections in prosthetic joint failure and nonunion of fracture fixations, which may be currently reported as "aseptic" failure. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Fracture Mechanics Analysis of the Dentine-Luting Cement Interface.

The objectives of this study were to determine the fracture toughness of adhesive interfaces between dentine and clinically relevant, thin layers of dental luting cements. Cements tested included a conventional glass-ionomer, F (Fuji I), a resin-modified glass-ionomer, FP (Fuji Plus) and a compomer cement, D (DyractCem). Ten miniature short-bar chevron notch specimens were manufactured for each cement, each comprising a 40 µm thick chevron of lute, between two 1.5 mm thick blocks of bovine dentine, encased in resin composite. The interfacial KIC results (MN/m3/2) were median (range): F; 0.152 (0.14-0.16), FP; 0.306 (0.27-0.37), D; 0.351 (0.31-0.37). Non-parametric statistical analysis showed that the fracture toughness of F was significantly lower (p

Time for treating bone fracture using rhBMP-2: a randomised placebo controlled mouse fracture trial.

Although the mechanisms of osteoinduction by bone morphogenic proteins (BMPs) are increasingly understood, the most appropriate time to administer BMPs exogenously is yet to be clarified.The purpose of this study was to investigate when BMP may be administered to a fracture arena to maximise the enhancement of healing.Forty mice with externally fixed left femoral fractures were randomised into four groups: Group I, the control group was given a placebo of 30 ll saline at day 0; Groups II, III and IV were given 30 ll saline plus 2.5 lg rhBMP-2, at post-operative days 0, 4 or 8, respectively.Sequential radiographs were taken at days 0, 8, 16.On day 22 the mice were sacrificed and both femora were harvested for biomechanical assessment in 3-point bending and histological evaluation.Radiographic analysis indicated that healing of fractures in Groups II and III was significantly greater (p <0.05) than those in Groups I and IV, at both 16 and 22 days post-fracture. The highest median bone mineral content at the fracture site was evidenced in Group III and II.Furthermore, Group III also had the highest relative ultimate load values, followed by Groups II, IV and I.Greater percentage peak loads were observed between Group I and both Groups II and III (p <0.05). Histological examination confirmed that at 22 days post-fracture, only fractures in Groups II and III had united with woven bone, and Groups I and IV still had considerable amounts of fibrous tissue and cartilage at the fracture gap.Data presented herein indicates that there is a time after fracture when rhBMP administration is most effective, and this may be at the time of surgery as well as in the early fracture healing phases.

A reliable externally fixated murine femoral fracture model that accounts for variation in movement between animals.

Fifty-two CFLP mice had an open femoral diaphyseal osteotomy held in compression by a four-pin external fixator. The movement of 34 of the mice in their cages was quantified before and after operation, until sacrifice at 4, 8, 16 or 24 days. Thirty-three specimens underwent histomorphometric analysis and 19 specimens underwent torsional stiffness measurement. The expected combination of intramembranous and endochondral bone formation was observed, and the model was shown to be reliable in that variation in the histological parameters of healing was small between animals at the same time point, compared to the variation between time-points. There was surprisingly large individual variation in the amount of animal movement about the cage, which correlated with both histomorphometric and mechanical measures of healing. Animals that moved more had larger external calluses containing more cartilage and demonstrated lower torsional stiffness at the same time point. Assuming that movement of the whole animal predicts, at least to some extent, movement at the fracture site, this correlation is what would be expected in a model that involves similar processes to those in human fracture healing. Models such as this, employed to determine the effect of experimental interventions, will yield more information if the natural variation in animal motion is measured and included in the analysis.