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

Engraftment of Prevascularized, Tissue Engineered Constructs in a Novel Rabbit Segmental Bone Defect Model.
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DOI:
10.3390/ijms160612616
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发表时间:
2015-06-04
影响因子:
5.6
通讯作者:
Schaefer DJ
Schaefer DJ
中科院分区:
生物学2区
文献类型:
--
作者:
Kaempfen A;Todorov A;Güven S;Largo RD;Jaquiéry C;Scherberich A;Martin I;Schaefer DJ

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大段骨缺损的金标准治疗是自体骨移植,其存在可用性低和额外发病率的问题。因此,迫切需要能够原位植入的组织工程骨和合适的动物模型进行临床前试验。本研究旨在评价不同预血管化策略的组织工程骨在兔肱骨节段性缺损模型中的植入效果。直接原位使用接种有骨髓间充质基质细胞的脱细胞骨基质(Tutobone)或与血管结合使用,并立即(1步)或仅在皮下“孵育”6周后(2步)插入。12周后,进行组织学和放射学评估。观察到不同的愈伤组织形成。没有骨形成或重建的移植物通过TRAP阳性破骨细胞可以检测到。相反,形成了数量不等的坏死组织。尽管坏死面积与血管数量显著相关,2步策略比1步策略有更多的血管,但坏死面积没有显著减少,因此,在此建立的动物模型代表了一种极具挑战性的情况,一种具有更好的预血管化、更好的可吸收性和更高的成骨性的合适的工程化骨移植物尚待开发。
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.
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