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Engraftment of Prevascularized, Tissue Engineered Constructs in a Novel Rabbit Segmental Bone Defect Model.

Kaempfen A, Todorov A, Güven S, Largo RD, Jaquiéry C, Scherberich A, Martin I, Schaefer DJ - Int J Mol Sci (2015)

Bottom Line: Instead, a variable amount of necrotic tissue formed.Although necrotic area correlated significantly with amount of vessels and the 2-step strategy had significantly more vessels than the 1-step strategy, no significant reduction of necrotic area was found.In conclusion, the animal model developed here represents a highly challenging situation, for which a suitable engineered bone graft with better prevascularization, better resorbability and higher osteogenicity has yet to be developed.

View Article: PubMed Central - PubMed

Affiliation: Clinic for Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, 4031 Basel, Switzerland. alexander.kaempfen@usb.ch.

ABSTRACT
The gold standard treatment of large segmental bone defects is autologous bone transfer, which suffers from low availability and additional morbidity. Tissue engineered bone able to engraft orthotopically and a suitable animal model for pre-clinical testing are direly needed. This study aimed to evaluate engraftment of tissue-engineered bone with different prevascularization strategies in a novel segmental defect model in the rabbit humerus. Decellularized bone matrix (Tutobone) seeded with bone marrow mesenchymal stromal cells was used directly orthotopically or combined with a vessel and inserted immediately (1-step) or only after six weeks of subcutaneous "incubation" (2-step). After 12 weeks, histological and radiological assessment was performed. Variable callus formation was observed. No bone formation or remodeling of the graft through TRAP positive osteoclasts could be detected. Instead, a variable amount of necrotic tissue formed. Although necrotic area correlated significantly with amount of vessels and the 2-step strategy had significantly more vessels than the 1-step strategy, no significant reduction of necrotic area was found. In conclusion, the animal model developed here represents a highly challenging situation, for which a suitable engineered bone graft with better prevascularization, better resorbability and higher osteogenicity has yet to be developed.

No MeSH data available.


Related in: MedlinePlus

(A) Follow-up radiological image showing scaffold in orthotopical defect after 10 weeks. Callus formation is visible on the opposite side of the plate. Arrows indicate proximal and distal edges of defect, white bar represents 5 mm; (B) Radiological quantification of callus as seen in (A), represented as average mm of radioopaque mass at the proximal and distal edges of the defect. Dotted line represents normal bone diameter at the same location; (C) Macroscopical appearance after plate removal. Arrows indicate the edges of the defect; (D) Post-explantation microtomography. Red bar represents 1 mm. None of the groups displayed macroscopic or microradiographic evidence of fracture consolidation during the experimental period.
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ijms-16-12616-f003: (A) Follow-up radiological image showing scaffold in orthotopical defect after 10 weeks. Callus formation is visible on the opposite side of the plate. Arrows indicate proximal and distal edges of defect, white bar represents 5 mm; (B) Radiological quantification of callus as seen in (A), represented as average mm of radioopaque mass at the proximal and distal edges of the defect. Dotted line represents normal bone diameter at the same location; (C) Macroscopical appearance after plate removal. Arrows indicate the edges of the defect; (D) Post-explantation microtomography. Red bar represents 1 mm. None of the groups displayed macroscopic or microradiographic evidence of fracture consolidation during the experimental period.

Mentions: During the 12-week in vivo period, radiographs showed a variable amount of radiopaque mineralized callus tissue, which grew at both ends of the segmental defect (Figure 3A). There were no significant differences in callus formation between groups (Figure 3B). No bridging of the fracture or integration of the scaffold up to 12 weeks was observed in any of the experimental groups. The macroscopic assessment allowed the same observation (Figure 3C). A closer investigation using microtomography and 3D image reconstructions showed that the scaffold and surrounding bone and callus had very similar densities, yet there was no calcified connection between host and scaffold in any of the groups (Figure 3D).


Engraftment of Prevascularized, Tissue Engineered Constructs in a Novel Rabbit Segmental Bone Defect Model.

Kaempfen A, Todorov A, Güven S, Largo RD, Jaquiéry C, Scherberich A, Martin I, Schaefer DJ - Int J Mol Sci (2015)

(A) Follow-up radiological image showing scaffold in orthotopical defect after 10 weeks. Callus formation is visible on the opposite side of the plate. Arrows indicate proximal and distal edges of defect, white bar represents 5 mm; (B) Radiological quantification of callus as seen in (A), represented as average mm of radioopaque mass at the proximal and distal edges of the defect. Dotted line represents normal bone diameter at the same location; (C) Macroscopical appearance after plate removal. Arrows indicate the edges of the defect; (D) Post-explantation microtomography. Red bar represents 1 mm. None of the groups displayed macroscopic or microradiographic evidence of fracture consolidation during the experimental period.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490464&req=5

ijms-16-12616-f003: (A) Follow-up radiological image showing scaffold in orthotopical defect after 10 weeks. Callus formation is visible on the opposite side of the plate. Arrows indicate proximal and distal edges of defect, white bar represents 5 mm; (B) Radiological quantification of callus as seen in (A), represented as average mm of radioopaque mass at the proximal and distal edges of the defect. Dotted line represents normal bone diameter at the same location; (C) Macroscopical appearance after plate removal. Arrows indicate the edges of the defect; (D) Post-explantation microtomography. Red bar represents 1 mm. None of the groups displayed macroscopic or microradiographic evidence of fracture consolidation during the experimental period.
Mentions: During the 12-week in vivo period, radiographs showed a variable amount of radiopaque mineralized callus tissue, which grew at both ends of the segmental defect (Figure 3A). There were no significant differences in callus formation between groups (Figure 3B). No bridging of the fracture or integration of the scaffold up to 12 weeks was observed in any of the experimental groups. The macroscopic assessment allowed the same observation (Figure 3C). A closer investigation using microtomography and 3D image reconstructions showed that the scaffold and surrounding bone and callus had very similar densities, yet there was no calcified connection between host and scaffold in any of the groups (Figure 3D).

Bottom Line: Instead, a variable amount of necrotic tissue formed.Although necrotic area correlated significantly with amount of vessels and the 2-step strategy had significantly more vessels than the 1-step strategy, no significant reduction of necrotic area was found.In conclusion, the animal model developed here represents a highly challenging situation, for which a suitable engineered bone graft with better prevascularization, better resorbability and higher osteogenicity has yet to be developed.

View Article: PubMed Central - PubMed

Affiliation: Clinic for Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, 4031 Basel, Switzerland. alexander.kaempfen@usb.ch.

ABSTRACT
The gold standard treatment of large segmental bone defects is autologous bone transfer, which suffers from low availability and additional morbidity. Tissue engineered bone able to engraft orthotopically and a suitable animal model for pre-clinical testing are direly needed. This study aimed to evaluate engraftment of tissue-engineered bone with different prevascularization strategies in a novel segmental defect model in the rabbit humerus. Decellularized bone matrix (Tutobone) seeded with bone marrow mesenchymal stromal cells was used directly orthotopically or combined with a vessel and inserted immediately (1-step) or only after six weeks of subcutaneous "incubation" (2-step). After 12 weeks, histological and radiological assessment was performed. Variable callus formation was observed. No bone formation or remodeling of the graft through TRAP positive osteoclasts could be detected. Instead, a variable amount of necrotic tissue formed. Although necrotic area correlated significantly with amount of vessels and the 2-step strategy had significantly more vessels than the 1-step strategy, no significant reduction of necrotic area was found. In conclusion, the animal model developed here represents a highly challenging situation, for which a suitable engineered bone graft with better prevascularization, better resorbability and higher osteogenicity has yet to be developed.

No MeSH data available.


Related in: MedlinePlus