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Publication Detail
Healing of fibular osteotomy after treatment with a novel calcium phosphate -containing, fast photo-curing, degradable, polymeric bone adhesive
  • Publication Type:
  • Authors:
    Revell PA, Abou Neel EA, Young AM, Salih V
  • Publication date:
  • Name of conference:
    European Society of Biomaterials 2011
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INTRODUCTION The incidence of both osteoarthritis and osteoporosis with bone fractures is rising because of increased longevity. More effective fracture fixation and better cementation of total joint prostheses are in prospect from the use of composites developed by the group. These are based on fluid, degradable poly(ABA)dimethacrylates with short polylactide A and polypropylene glycol B blocks (mol.wt. 288 and 425 g/mol respectively) (PPGLDMA). With 70 wt% filler [equimolar (MCPM)/ ( -TCP)] these remain fast photo-curing and injectable. These composites degrade slowly in water over several months but increased adhesive degradation kinetics is expected in vivo. Additionally, calcium and phosphate ion release might improve bone formation. The aim of this study was to evaluate one of these adhesives in bone healing using a lapine fibular osteotomy model. Comparisons were made with a brushite-forming bone cement (equimolar MCPM / -TCP, 800 mM aqueous citric acid solution, powder to liquid ratio of 3:1). EXPERIMENTAL METHODS Operative procedures were performed on female NZW rabbits (~2.5 Kg) under national licensing control and full ethical committee approval using general anaesthesia and with full aseptic surgical conditions. After skin incision and exposure of the tibia and fibula, the latter was divided mid-shaft with a fine electrical saw to produce an osteotomy defect (1mm). Osteotomies were filled with injectable PPGLDMA/MCPM- TCP (composite) (n=7), blue light cured (60s), or brushite cement (n=7). Controls (n=4) were left unfilled to heal spontaneously. Postoperative analgesia and broad spectrum antibiotics were provided routinely. Samples of the osteotomy site were retrieved after 5 wks and fixed in 10% formal saline. The three dimensional bone architecture of the sites was analysed using micro-computerised tomography (Skyscan 1174) (micro-CT) after which specimens were embedded in Technovit 4000 resin before cutting and grinding of sections using the Exakt system (Hamburg). Sections (60- 70 μm) were stained with toluidine blue and Goldner’s trichrome methods and examined on a Leitz DM light microscope. RESULTS AND DISCUSSION All animals were fully mobile within 6 hours of operation and remained in normal health throughout the study. At retrieval, all composite treated osteotomies showed firm union while in one each of the control and brushite treated sites there was mobility, though complete union occurred in the others. External callus was present macroscopically in relation to 5/7 composite, 4/7 brushite and 1/4 control osteotomies. Micro-CT confirmed these findings. Figure 1. Osteotomy site treated with composite for 5 weeks, showing newly formed woven bone (centre) between ends of original bone (left and right). Goldner’s trichrome method. Histological examination of composite treated sites showed complete healing of the defect with no evidence of residual material. There was no evidence of damage to bone or other tissues in any sample. No evidence of inflammation was present. The gap between the bone ends was filled with new woven bone forming an internal callus in all cases (Fig.1). There was additionally a fusiform external callus present in 5/7 cases, confirming the naked eye appearances seen at retrieval. Brushitetreated osteotomy sites showed no evidence of bone damage or inflammation, but in 2 animals there was focal soft tissue necrosis with accompanying inflammation related to foreign material. The osteotomy space was filled with new bone in 6/7 samples, in one of which there was also cartilage formation. External callus was present in 4 of these cases. New bone bridged the gap between the edges of the osteotomy in 3 untreated controls, one of which also showed the presence of cartilage. External callus formation was not seen in one control. The results show that the novel composite (PPGLDMA/MCPM- TCP) is biocompatible when used as an adhesive cement in bone. The material had disappeared completely after 5 weeks, as had brushite used as a comparator. The degradation products of the composite are fully metabolized in vivo. The composite sets reliably under blue light and has excellent handling properties compared with brushite which is moisture and blood sensitive making control of the setting process difficult. Cartilage formation in the brushite filled and unfilled osteotomies also indicates that immobilization was not optimal in these cases. CONCLUSIONS An adhesive rapidly curing PPGLDMA/MCPM- TCP composite is effective in promoting firm fixation and healing of fibular osteotomies in the rabbit. . ACKNOWLEDGMENTS. EPSRC for funding (grant no. EP/F01970X/1) and providing access to micro-CT
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