Size dependent induction of proinflammatory cytokines and cytotoxicity of particulate beta-tricalciumphosphate in vitro

Lange, Tobias; Schilling, Arndt F.; Peters, Fabian; Mujas, Jan; Wicklein, Daniel; Amling, Michael

doi:10.1016/j.biomaterials.2011.02.039

Cited by 47 publications

(32 citation statements)

References 48 publications

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“…In this context, it is important to state that proinflammatory cytokines, such as TNF-alpha and Interleukin 6, have been reported to act as potent inductors of osteoclast activity [21], [22]. Similarly, we have previously demonstrated a considerable release of cytokines by the mononuclear cell fraction of peripheral blood in the presence of calcium phosphate based biomaterials [23], [24]. As the whole fraction of mononuclear cells was also used in the present study, it is tempting to speculate that a differential release of cytokines may have occured in the presence of the respective calcium phosphate based materials, contributing to the differential dentin and biomaterial resorption.…”

Section: Discussionmentioning

confidence: 88%

Divergent Resorbability and Effects on Osteoclast Formation of Commonly Used Bone Substitutes in a Human In Vitro-Assay

et al. 2012

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Bioactive bone substitute materials are a valuable alternative to autologous bone transplantations in the repair of skeletal defects. However, clinical studies have reported varying success rates for many commonly used biomaterials. While osteoblasts have traditionally been regarded as key players mediating osseointegration, increasing evidence suggests that bone-resorbing osteoclasts are of crucial importance for the longevity of applied biomaterials. As no standardized data on the resorbability of biomaterials exists, we applied an in vitro-assay to compare ten commonly used bone substitutes. Human peripheral blood mononuclear cells (PBMCs) were differentiated into osteoclasts in the co-presence of dentin chips and biomaterials or dentin alone (control) for a period of 28 days. Osteoclast maturation was monitored on day 0 and 14 by light microscopy, and material-dependent changes in extracellular pH were assessed twice weekly. Mature osteoclasts were quantified using TRAP stainings on day 28 and their resorptive activity was determined on dentin (toluidin blue staining) and biomaterials (scanning electron microscopy, SEM). The analyzed biomaterials caused specific changes in the pH, which were correlated with osteoclast multinuclearity (r = 0.942; p = 0.034) and activity on biomaterials (r = 0.594; p = 0.041). Perossal led to a significant reduction of pH, nuclei per osteoclast and dentin resorption, whereas Tutogen bovine and Tutobone human strikingly increased all three parameters. Furthermore, natural biomaterials were resorbed more rapidly than synthetic biomaterials leading to differential relative resorption coefficients, which indicate whether bone substitutes lead to a balanced resorption or preferential resorption of either the biomaterial or the surrounding bone. Taken together, this study for the first time compares the effects of widely used biomaterials on osteoclast formation and resorbability in an unbiased approach that may now aid in improving the preclinical evaluation of bone substitute materials.

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Section: Discussionmentioning

confidence: 88%

Divergent Resorbability and Effects on Osteoclast Formation of Commonly Used Bone Substitutes in a Human In Vitro-Assay

et al. 2012

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“…This data became substantiated by other study results indicating that even material granules with smaller diameters can evoke higher levels of pro-inflammatory enzymes and also VEGF from macrophages, especially in the early phase after implantation. 26 Based on these data it could be concluded that the small-sized bone substitute granules might also induce a higher or faster level of bone tissue growth, as VEGF also stimulates the proliferation and differentiation of osteoblasts in a dose-dependent manner. 51,52 However, further studies have to be conducted using also bone implantation models to clarify this issue.…”

Section: 41mentioning

confidence: 91%

“…8 A variety of in vitro and in vivo studies have been conducted to quantify the impact of this factor on the progress and outcome of bone regeneration, but no definitive conclusions have thus far been reached. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Following previous studies conducted by our group analyzing tissue reactions to bone substitute materials with a special focus on their chemical composition and physical characteristics, the present study investigates the influence of granule size of a biphasic bone substitute material. In this investigation 2 granule sizes of BoneCeramic Ò (500-1000 mm and 400-700 mm) were tested with respect to the tissue reaction in a subcutaneous implantation model in Wistar rats over a 60 day period.…”

Section: Introductionmentioning

confidence: 99%

Small-sized granules of biphasic bone substitutes support fast implant bed vascularization

et al. 2015

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“…9 The reported osteoinductivity of CaP is influenced by a number of physicochemical properties of the biomaterial, such as particle size, 10 surface area, crystallinity, porosity, and composition. 11,12 Particles of sizes ranging from 80 to 300 mm in diameter can induce ectopic bone formation, whereas particles greater than 500 mm are not osteoinductive. 13 In vivo studies also indicate that a specific surface area above a threshold level of 1.0 m 2 /g is critical for CaP to exhibit osteoinduction.…”

Section: Introductionmentioning

confidence: 99%

Effects of Calcium Phosphate/Chitosan Composite on Bone Healing in Rats: Calcium Phosphate Induces Osteon Formation

Fernández

Olave

Llano

et al. 2014

Tissue Engineering Part A

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Vascularization of an artificial graft represents one of the most significant challenges facing the field of bone tissue engineering. Over the past decade, strategies to vascularize artificial scaffolds have been intensively evaluated using osteoinductive calcium phosphate (CaP) biomaterials in animal models. In this work, we observed that CaP-based biomaterials implanted into rat calvarial defects showed remarkably accelerated formation and mineralization of new woven bone in defects in the initial stages, at a rate of ∼60 μm/day (0.8 mg/day), which was considerably higher than normal bone growth rates (several μm/day, 0.1 mg/day) in implant-free controls of the same age. Surprisingly, we also observed histological evidence of primary osteon formation, indicated by blood vessels in early-region fibrous tissue, which was encapsulated by lamellar osteocyte structures. These were later fully replaced by compact bone, indicating complete regeneration of calvarial bone. Thus, the CaP biomaterial used here is not only osteoinductive, but vasculogenic, and it may have contributed to the bone regeneration, despite an absence of osteons in normal rat calvaria. Further investigation will involve how this strategy can regulate formation of vascularized cortical bone such as by control of degradation rate, and use of models of long, dense bones, to more closely approximate repair of human cortical bone.

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Size dependent induction of proinflammatory cytokines and cytotoxicity of particulate beta-tricalciumphosphate in vitro

Cited by 47 publications

References 48 publications

Divergent Resorbability and Effects on Osteoclast Formation of Commonly Used Bone Substitutes in a Human In Vitro-Assay

Divergent Resorbability and Effects on Osteoclast Formation of Commonly Used Bone Substitutes in a Human In Vitro-Assay

Small-sized granules of biphasic bone substitutes support fast implant bed vascularization

Effects of Calcium Phosphate/Chitosan Composite on Bone Healing in Rats: Calcium Phosphate Induces Osteon Formation

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