Correction to: The effect of cationically-modified phosphorylcholine polymers on human osteoblasts in vitro and their effect on bone formation in vivo.

The article "The effect of cationically modified phosphorylcholine polymers on human osteoblasts in vitro and their effect on bone formation in vivo", written by Jonathan M. Lawton, Mariam Habib, Bingkui Ma, Roger A. Brooks, Serena M. Best, Andrew L. Lewis, Neil Rushton and William Bonfield, was originally published Online First without open access. After publication in volume 28, issue 9, page 144 it was noticed that the copyright was wrong in the PDF version of the article. The copyright of the article should read as "

The effect of cationically-modified phosphorylcholine polymers on human osteoblasts in vitro and their effect on bone formation in vivo.

The effect of introducing cationic charge into phosphorylcholine (PC)-based polymers has been investigated in this study with a view to using these materials as coatings to improve bone formation and osseointegration at the bone-implant interface. PC-based polymers, which have been used in a variety of medical devices to improve biocompatibility, are associated with low protein adsorption resulting in reduced complement activation, inflammatory response and cell adhesion. However, in some applications, such as orthopaedics, good integration between the implant and bone is needed to allow the distribution of loading stresses and a bioactive response is required. It has previously been shown that the incorporation of cationic charge into PC-based polymers may increase protein adsorption that stimulates subsequent cell adhesion. In this paper, the effect of cationic charge in PC-based polymers on human osteoblasts (HObs) in vitro and the effect of these polymers on bone formation in the rat tibia was assessed. Increasing PC positive surface charge increased HOb cell adhesion and stimulated increased cell differentiation and the production of calcium phosphate deposits. However, when implanted in bone these materials were at best biotolerant, stimulating the production of fibrous tissue and areas of loosely associated matrix (LAM) around the implant. Their development, as formulated in this study, as bone interfacing implant coatings is therefore not warranted.

The effect of simvastatin on bone formation and ceramic resorption in a peri-implant defect model.

Experimental use of statins as stimulators of bone formation suggests they may have widespread applicability in the field of orthopaedics. With their combined effects on osteoblasts and osteoclasts, statins have the potential to enhance resorption of synthetic materials and improve bone ingrowth. In this study, the effect of oral and local administration of simvastatin to a beta tricalcium phosphate (betaTCP)-filled defect around an implant was compared with recombinant human bone morphogenetic protein 2 (rhBMP2). On hundred and sixty-two Sprague-Dawley rats were assigned to treatment groups: local application of 0.1, 0.9 or 1.7 mg of simvastatin, oral simvastatin at 5, 10 or 50 mg kg(-1) day(-1) for 20 days, local delivery of 1 or 10 microg of rhBMP2, or control. At 6 weeks rhBMP2 increased serum tartrate-resistant acid phosphatase 5b levels and reduced betaTCP area fraction, particle size and number compared with control, suggesting increased osteoclast activity. There was reduced stiffness and increased mechanical strength with this treatment. Local simvastatin resulted in a decreased mineral apposition rate at 6 weeks and increased fibrous area fraction, betaTCP area fraction, particle size and number at 26 weeks. Oral simvastatin had no effect compared with control. Local application of rhBMP2 increased resorption and improved mechanical strength whereas simvastatin was detrimental to healing. Oral simvastatin was ineffective at promoting either ceramic resorption or bone formation. The effect of statins on the repair of bone defects with graft substitute materials is influenced by its bioavailability. Thus, further studies on the optimal delivery system are needed.

A histomorphometric study of adaptive responses of cancellous bone in different regions in the sheep mandibular condyle following experimental forward mandibular displacement.

Forward mandibular displacement in animal models is associated with faster and/or redirected condylar growth. Here the effect of forward displacement induced with an intraoral appliance on modelling/remodelling of the mandibular condyle was investigated in eight, 4-month-old, castrated male Merino sheep, randomly allocated to experimental and control groups (n=4 in each group). The study period was 15 weeks, during that time, (1). calcein, (2). tetracycline, and (3). alizarin red S fluorochromes were given to all animals from day 1. Midsagittal sections of the temporomandibular joints were selected for analysis. Dynamic variables of bone formation, static indices of bone-forming and -resorbing activity, and structural indices of trabecular bone were estimated histomorphometrically. The sampling site was divided into two regions for analysis: (a). a 'subchondral region' (2 and 3 labels only), believed to be the bone newly formed during the experimental period; (b). a 'central region' (labelled by all three fluorochromes), believed to be the bone that existed before the experiment. Regional differences in adaptive response were found. In the experimental group, the bone-volume fraction (BV/TV) of the subchondral regions had decreased, although the specific bone-surface and bone-formation rates had increased. This low BV/TV was associated with decreased trabecular thickness and increased trabecular separation. In the central condylar region of the experimental group, BV/TV was unchanged, but an increased osteoid surface was apparent when the eroded surface was taken into consideration. These adaptive condylar responses to forward mandibular displacement appeared to be the result of increased osteoblastic activity. Further studies are recommended to examine why the subchondral and central regions responded differently.

Experimental forward mandibular displacement in sheep.

In order to investigate growth modifications of the temporomandibular joint (TMJ) during dentofacial orthopaedic treatment, specific functional appliances have been used experimentally to prompt the mandible into a protrusive position in various animal models. The purpose of this study was to test the effectiveness of a functional appliance specially designed for sheep and to evaluate the sheep as a model for dentofacial orthopaedic research. Eight, 4-month-old, castrated male Merino sheep were randomly assigned to experimental or control groups, with four in each group. Cast functional appliances were fabricated for the animals in the experimental group. The treatment period was 15 weeks. Dental casts, endosseous implant markers and cephalograms were used to analyse the displacement of the mandible. Undemineralised sagittal sections of TMJ were used to evaluate the tissue responses induced by the appliances. The weight of the animals was measured monthly to monitor their growth. The growth of the metacarpus was also measured. During the experimental period, the animals maintained their weight within the normal range and grew normally. The appliance displaced the mandible to a downward and forward position. The adaptive responses in the TMJ induced by the appliances included changed anteroposterior shape of the condylar process, anteriorly thickened condylar cartilage, and a thickened compact bone layer along the anterior surface of the posterior wall of the glenoid fossa. The sheep coped well with the experimental procedures and the appliance used was demonstrably effective in inducing adaptive responses in the TMJ. Consequently, it is believed that the sheep is an appropriate animal model to study growth modifications in the TMJ region.