<i>In vivo</i> analysis of biocompatibility and vascularization of the synthetic bone grafting substitute NanoBone®

Abshagen, Kerstin; Schrodi, I.; Gerber, Thomas; Vollmar, Brigitte

doi:10.1002/jbm.a.32237

Cited by 81 publications

(54 citation statements)

References 24 publications

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“…Nanobone ® is known to induce angiogenesis. 31 This was confirmed in the present study by the presence of newly formed vessels within the grafted defect. Adequate blood supply is a prerequisite for cellular activity.…”

supporting

confidence: 87%

Osteogenic capacity of nanocrystalline bone cement in a weight-bearing defect at the ovine tibial metaphysis

Harms¹,

Helms²,

Taschner³

et al. 2012

IJN

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Abstract:The synthetic material Nanobone ® (hydroxyapatite nanocrystallines embedded in a porous silica gel matrix) was examined in vivo using a standardized bone defect model in the ovine tibial metaphysis. A standardized 6 × 12 × 24-mm bone defect was created below the articular surface of the medial tibia condyles on both hind legs of 18 adult sheep. The defect on the right side was filled with Nanobone ® , while the defect on the contralateral side was left empty. The tibial heads of six sheep were analyzed after 6, 12, and 26 weeks each. The histological and radiological analysis of the defect on the control side did not reveal any bone formation after the total of 26 weeks. In contrast, the microcomputed tomography analysis of the defect filled with Nanobone ® showed a 55%, 72%, and 74% volume fraction of structures with bone density after 6, 12, and 26 weeks, respectively. Quantitative histomorphological analysis after 6, and 12 weeks revealed an osteoneogenesis of 22%, and 36%, respectively. Hematoxylin and eosin sections demonstrated multinucleated giant cells on the surface of the biomaterial and resorption lacunae, indicating osteoclastic resorptive activity. Nanobone ® appears to be a highly potent bone substitute material with osteoconductive properties in a loaded large animal defect model, supporting the potential use of Nanobone ® also in humans.

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supporting

confidence: 87%

Osteogenic capacity of nanocrystalline bone cement in a weight-bearing defect at the ovine tibial metaphysis

Harms¹,

Helms²,

Taschner³

et al. 2012

IJN

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“…For the study of the angiogenic process, the dorsal skinfold chamber offers a unique tool, because it allows for repetitive observation and determination of microcirculatory parameters over a prolonged time period of at least 2 weeks (35) the dorsal skinfold chamber model has been already used extensively, proving its enormous suitability for these purposes (36)(37)(38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

External Inosculation as a Feature of Revascularization Occurs After Free Transplantation of Murine Liver Grafts

Kuehl

Abshagen

Eipel

et al. 2013

American Journal of Transplantation

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The induction of angiogenesis is essential for successful engraftment of freely transplanted cells or cellular composites. How to augment angiogenesis to ensure an appropriate viability of the grafts is still under investigation. This study evaluated the proangiogenic capability of different syngeneic free liver transplants and elucidated the origin of the newly formed vascular network via use of an eGFP + /eGFP − (enhanced green fluorescent protein) cross-over design. Using intravital fluorescence microscopy, we found that neonatal and resected murine liver transplants implanted into dorsal skinfold chambers display a significantly enhanced vascularization compared to regular adult transplants. Immunohistochemically, less tissue hypoxia, apoptosis and macrophage infiltration was observed in the neonatal and resected transplants, which is in line with improved vascularization of those grafts. Additionally, electron microscopy revealed morphological hallmarks of liver cells. eGFP + liver transplants implanted on eGFP − recipients displayed vascular sprouting from the grafts themselves and connection to the recipients`microvasculature, which also undergoes transient proangiogenic response. This process is described as external inosculation, with microvessels exhibiting a chimeric nature of the endothelial lining. These data collectively show that proliferative stimulation is taking effect on angiogenic properties of free transplants and might provide a novel tool for modulating the revascularization of free grafts. Key words: Angiogenesis, GFP+ transgenic mice, intravital microscopy, liver cell transplantation Abbreviations: AP, alkaline-phosphatase; eGFP, enhanced green fluorescent protein; HBSS, Hanks`balanced salt solution; H&E, hematoxylin and eosin; HIF1alpha, hypoxia-inducible factor-1 alpha; HRP, horseradish peroxidase; FITC, fluorescein isothiocyanate; MARS, molecular adsorbents recirculating system; ROI, region of interest; vRBC, red blood cell velocity; VQ, volumetric blood flow.

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“…The crystallites are loosely packed and held together by SiO 2 , leading to nanopores in the range of 10-20 nm. 24 In addition, micrometer and millimeter pores led to a high porosity of about 60% and to a very large internal surface (84 m 2 /g) favoring the invasion of osteogenic cells and newly formed vessels.…”

Section: Nanostructured Bone Substitute and Its Biocompatibilitymentioning

confidence: 99%

“…The good biocompatibility has been shown previously in in vivo studies and in clinical application. 24,27 Optimal cell carrier material…”

mentioning

confidence: 99%

Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model

Boos

Weigand

Deschler

et al. 2014

IJN

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New therapeutic strategies are required for critical size bone defects, because the gold standard of transplanting autologous bone from an unharmed area of the body often leads to several severe side effects and disadvantages for the patient. For years, tissue engineering approaches have been seeking a stable, axially vascularized transplantable bone replacement suitable for transplantation into the recipient bed with pre-existing insufficient conditions. For this reason, the arteriovenous loop model was developed and various bone substitutes have been vascularized. However, it has not been possible thus far to engineer a primary stable and axially vascularized transplantable bone substitute. For that purpose, a primary stable silica-embedded nanohydroxyapatite (HA) bone substitute in combination with blood, bone marrow, expanded, or directly retransplanted mesenchymal stem cells, recombinant human bone morphogenetic protein 2 (rhBMP-2), and different carrier materials (fibrin, cell culture medium, autologous serum) was tested subcutaneously for 4 or 12 weeks in the sheep model. Autologous serum lead to an early matrix change during degradation of the bone substitute and formation of new bone tissue. The best results were achieved in the group combining mesenchymal stem cells expanded with 60 μg/mL rhBMP-2 in autologous serum. Better ingrowth of fibrovascular tissue could be detected in the autologous serum group compared with the control (fibrin). Osteoclastic activity indicating an active bone remodeling process was observed after 4 weeks, particularly in the group with autologous serum and after 12 weeks in every experimental group. This study clearly demonstrates the positive effects of autologous serum in combination with mesenchymal stem cells and rhBMP-2 on bone formation in a primary stable silica-embedded nano-HA bone grafting material in the sheep model. In further experiments, the results will be transferred to the sheep arteriovenous loop model in order to engineer an axially vascularized primary stable bone replacement in clinically relevant size for free transplantation.

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In vivo analysis of biocompatibility and vascularization of the synthetic bone grafting substitute NanoBone®

Cited by 81 publications

References 24 publications

Osteogenic capacity of nanocrystalline bone cement in a weight-bearing defect at the ovine tibial metaphysis

Osteogenic capacity of nanocrystalline bone cement in a weight-bearing defect at the ovine tibial metaphysis

External Inosculation as a Feature of Revascularization Occurs After Free Transplantation of Murine Liver Grafts

Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model

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