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I research Fig. 8_Histomorphometrical analysis of the vascularization of the implantation beds of the triphasic paste-like bone-substitute material group and the three control groups, i.e., animals with -TCP granules, sham-operated animals, and animals injected with saline: a) vessel density and (b) percentage vascularisation (*/** = interindividual statistical significances, •/•• = intraindividual statistical significances). ous matrix for the -TCP granules, is a well-known and -researched polymer from wood fibres and part ofvegetablecellwalls.18,19 Inorthopaedicsurgery,the hydroexpansivity of cellulose is used for cellulose- based implants to delay the resorption of bone sub- stitute defects.18-22,42,43 Hyaluronicacid,thethirdcomponentoftheinves- tigated injectable bone substitute material, is a linear polymerofrepeatingdisaccharideunitscomposedof D-glucuronic acid and N-acetyl-D-glucosamine and canbefoundinmanytissuesofthehumanbody,such asskin,cartilageandthevitreoushumour,andiswell- suited to applications in tissue regeneration.23-25,31-35 In different studies investigating HY, the binding capacity,theabilitytocommunicatewithcellsurface receptors and to modulate the inflammatory re- sponse, contributing to the stabilisation of the gran- ulation tissue matrix within the implantation bed wereshown.44-46 Intissueengineeringthemechanical stability,osteoconductivityandtheabilitytopromote themigrationanddifferentiationofosteoblastsmake HY suitable for bone tissue augmentation.23, 25, 47, 48 From the histological and histomorphometrical re- sults it can be concluded, that both cellulose and HY contributeinasynergisticwaytothehydroexpansiv- ity, to the mechanical stability of the implant and to control the connective tissue ingrowth towards the centralpartofthebiomaterial.Anotheradvantageof the triphasic bone substitute material presented in this study is its injectability. In combination with its hydroexpansivity, all parts of the defect can be reached by the biomaterial minimal-invasively. Fur- ther,thelifetimeandthestabilityofthebiomaterialis enhanced and the connective tissue ingrowth is de- celerated. Inprevioustrialspaste-likebone-substitutemate- rials with other compositions and qualities have shown promising results and positive influence on bone regeneration.49-51 The results of the present study support the assumption that injectable bone- substitutematerialswiththeabove-mentionedcom- ponentscanbeusedasosteoconductivefillingmate- rials for reliable and successful bone tissue augmen- tation. _Conclusion Inthepresentstudy,thetissuereactiontoatripha- sic paste-like bone substitute material of -TCP, cel- lulose and hyaluronic acid was investigated in the subcutaneousimplantationmodelinWistarratsover a time period of 60 days. Implantation of pure solid -TCP, injection of sodium chloride and sham opera- tionservedascontrols.Byhistologicalandhistomor- phometrical methods, the cellular reaction, the inflammatory response and the vascularisation within the implantation bed were analysed. The combination of -TCP, Cellulose and Hyaluronic acid was shown to generate a two phasic bulkwithaninnercoreof-TCPgranulesandanouter coreofanaqueoussolution,whichinhibitedthepre- mature ingrowth of connective tissue in the inter- granularspacewithinthefirst30days.Further,andin contrasttothecontrolgroups,theouterstructurein- duced the formation of multinucleated giant cells, which resulted in a higher vascularisation of its im- plantation bed. Concluded,thecombinationofsmall-TCPgran- ules,celluloseandhyaluronicacidisanew,promising concept for a bone substitute material that can be easily applied via minimally invasive surgical tech- niques. _Acknowledgements The original article and figures are published in Acta Biomaterialia and kindly provided for reuse by Elsevier—providerofscientific,technicalandmedical information products and services. Original source: Ghanaati, S.; Barbeck, M.; Hilbig, U.; Hoffmann, C.; Unger,R.E.;Sader,R.A.etal.(2011):Aninjectablebone substitute composed of beta-tricalcium phosphate granules,methylcelluloseandhyaluronicacidinhibits connective tissue influx into its implantation bed in vivo. In: Acta Biomater 7 (11), S. 4018–4028._ 12 I implants2_2014 Dr Dr Shahram Ghanaati Department for Oral,Cranio-Maxillofacial and Facial Plastic Surgery, Medical Center of the Goethe University Frankfurt, Frankfurt/Main,Germany shahram.ghanaati@kgu.de _contact implants Fig. 8a Fig. 8b