Characterisation of a phenol-derived polymeric bone glue

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Background: There are several different fixation techniques for bone fractures that are continually refined. Bio-compatibility, in terms of fracture healing and soft tissue damage, becomes more and more important. Especially complex multi-fragment fractures and intraarticular fractures remain a challange for surgical reconstruction and fixation. Therefore, the development of an in-vivo applicable bone glue would be a substantial advancement in osteosynthesis techniques. The vast majority of the reported conjugation reactions of bio-adhesive molecules to biopolymers are performed by direct amidation reaction. A major problem in the develoment of an effective bone glue in vivo is the need of accurate pH control, addition of excess of reactant to graft on the biopolymer and the presence of by-products. Our aim is to examine a novel bone adhesive using polymeric composition containing phenol derived bio-adhesive molecules. There is evidence that this conjugation reaction is more efficient than current methods for ligation of amines to biopolymers and does not require accurate pH control or pH shift during the reaction to be effective. Material and Methods: First, synthesis of bio-adhesive molecules onto biopolymes such as gelatin by a robust amidation technique has to be established. The characterisation of the synthesised bioconjugates will be done via 1H NMR, spectrophotometry, rheology and chromatography. Typically, grafting efficiency, yield, conservation of biopolymers molecular weight, changes in viscoelastic properties of the solutions will be collected. Cytotoxicity will be evaluated assessing the viability of hTERT-BJ1 fibroblasts after contact with conjugates and extracts from the crosslinked conjugates. After this first step is done, the bioadhesion property of prepared formulations will be analysed as well as hemostatic property of prepared formulations.Objective: Primary aim of this project is the preclinical characterisation of a novel bio-adhesive in terms of adhesion to moist surfaces, non toxicicty, preparation and sterilisation feasibility, sufficient strength to stabilise the bone-bone interface for the required time and no interference with the bone repair. We hypothesised that gelatin, already used as an hemostatic, modified with bio-adhesive phenol derived functionalities could be applied in solution with Rose Bengal to glue bone pieces using visible light. The formulation could set in vivo due to the hemostatic effect and simultaneously adhere to the surrounding tissue upon visible light activation.Clinical relevance: The development of an effective and bio-compatative bone glue would mean a crucial advancement in up to date osteosynthesis techniques. Promising areas of application would be complex multi-fragment fractures as well as treatment of infantile fractures.