The rational use of animal models in the evaluation of novel bone regenerative therapies

Perić, Mihaela; Dumić-Čule, Ivo; Grčević, Danka; Matijašić, Mario; Verbanac, Donatella; Paul, Ruth; Grgurević, Lovorka; Trkulja, Vladimir; Bagi, Cedo M.; Vukičević, Slobodan

doi:10.1016/j.bone.2014.07.010

Cited by 126 publications

(133 citation statements)

References 225 publications

(220 reference statements)

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“…These results were further supported by recent preclinical findings of endosteal site resorption after application of BMP7 around femoral prostheses in large animals [10]. To avoid similar unwanted misapprehensions, an appropriate guideline of drug discovery aimed for accelerating bone healing was proposed for the non-clinical development [11].…”

Section: Introductionsupporting

confidence: 65%

Systemically available bone morphogenetic protein two and seven affect bone metabolism

Dumić-Čule

Brkljačić

Rogić

et al. 2014

International Orthopaedics (SICOT)

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A., Drača N., Kufner V., Trkulja V., Grgurević L., Vukičević S. (2014 To answer this question we examined effects of systemically administered BMP2 and 7 on bone in a newly developed rat model with low level of calciotropic hormones.Methods: Removal of thyroid and parathyroid glands (TPTx) in rats resulted in decreased level of calciotropic hormones and a subsequent bone loss assessed by microCT and measurement of serum bone formation and resorption markers, including osteocalcin, Ctelopeptide, osteoprotegerin and RANKL. Results were complemented with in vitro studies on osteoblast and osteoclast activity by both BMP2 and 7. The doses used have been calculated from published pharmacodynamic (PD) and bioavailability results from preclinical BMP2 and 7 studies.Results: TPTx resulted in bone loss which was restored by systemic administration of 10-70 µg/kg of BMP2 and 10-250 µg/kg of BMP7. BMP2 showed a higher capacity for enhancing trabecular microarchitecture, while BMP7 augmented trabecular thickness. In vitro experiments revealed that BMP2 and 7, when uncoupled, increased the number and activity of both osteoblasts and osteoclasts.Conclusions: Surprisingly, both BMP2 and 7 showed an increased bone volume in an in vivo environment of low calciotropic hormones. Locally administered BMP2 and 7 from bone devices might become partially available in circulation but will not mediate a systemic bone loss.

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Section: Introductionsupporting

confidence: 65%

Systemically available bone morphogenetic protein two and seven affect bone metabolism

Dumić-Čule

Brkljačić

Rogić

et al. 2014

International Orthopaedics (SICOT)

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“…µCT is extremely efficient in detecting three-dimensional features of solid samples, but this ability is also limited by device resolution (32,33,(35)(36)(37)(38). Improving this aspect would highlight the detailed differences between the two groups tested in the present study.…”

Section: Discussionmentioning

confidence: 97%

<i>In vivo</i> evaluation of chitosan-glycerol gel scaffolds seeded with stem cells for full-thickness mandibular bone regeneration

et al. 2017

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The aim of this study was to evaluate in vivo bone regeneration, mediated by adipose-derived stem cells (ADSCs), induced to differentiate into osteoblasts and carried by a scaffold gel. In the test group, bone regeneration was mediated by ADSCs, induced to differentiate into osteoblasts, and carried by a scaffold gel. In the control group a scaffold without cells was used. The scaffold, consisting of chitosan and glycerol phosphate, was maintained in situ by a cross-linked resorbable membrane. The osteogenic potential of ADSCs was confirmed by osteocalcin assay and Von Kossa staining performed before implantation. Histological assays detected an initial increase in bone formation in the test group compared with the control group. Microcomputed tomography analysis did not show significant differences between the two groups. Both histological and microcomputed tomography analysis were performed on the ex vivo specimens after a follow-up period of 8 weeks. We observed that differentiated ADSCs could increase bone regeneration and that the scaffold used here can be a suitable carrier to entrap and maintain the cells in situ. On the contrary, the membrane used was not functional in isolating the site of the defect from surrounding soft tissues and caused a significant inflammatory reaction.

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“…Therefore, numerous studies have investigated ways to successfully engineer new bone that is efficient and safe for clinical therapy [3]. However, because alveolar bone is in a constant state of remodeling-more so than most other bony regions-it can be difficult to evaluate whether a method has been successful in regenerating bone at the intended site [4][5][6]. Moreover, bone and teeth are generally more difficult to handle than other types of tissues, requiring lengthy decalcification procedures before the specimens can be assessed [7].…”

Section: Introductionmentioning

confidence: 99%

Histomorphometric Analysis of the Alveolar Bone for Two Weeks after Bone Morphogenetic Protein Transfer

Kawai¹,

Ohura²

2017

J Cytol Histol

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The rational use of animal models in the evaluation of novel bone regenerative therapies

Cited by 126 publications

References 225 publications

Systemically available bone morphogenetic protein two and seven affect bone metabolism

Systemically available bone morphogenetic protein two and seven affect bone metabolism

<i>In vivo</i> evaluation of chitosan-glycerol gel scaffolds seeded with stem cells for full-thickness mandibular bone regeneration

Histomorphometric Analysis of the Alveolar Bone for Two Weeks after Bone Morphogenetic Protein Transfer

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