Uncultured Marrow Mononuclear Cells Delivered Within Fibrin Glue Hydrogels to Porous Scaffolds Enhance Bone Regeneration Within Critical-Sized Rat Cranial Defects

Uncultured Marrow Mononuclear Cells Delivered Within Fibrin Glue Hydrogels to Porous Scaffolds Enhance Bone Regeneration Within Critical-Sized Rat Cranial Defects
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DOI:
10.1089/ten.tea.2010.0471
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发表时间:
2010-12-01
影响因子:
4.1
通讯作者:
Mikos, Antonios G.
Mikos, Antonios G.
中科院分区:
医学3区
文献类型:
--
作者:
Kretlow, James D.;Spicer, Patrick P.;Mikos, Antonios G.

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对于骨组织工程来说,将间充质干细胞 (MSC) 纳入多孔支架的好处是众所周知的。然而,对于 MSC 离体处理的影响或必要性,几乎没有达成共识。间充质干细胞的培养和扩增会增加时间和成本,并可能增加与治疗相关的风险。我们评估了使用包裹在纤维蛋白胶水凝胶中的未培养的骨髓单核细胞 (bmMNC) 并接种到多孔支架中,在 8 毫米直径、临界尺寸的大鼠颅骨缺损中在 12 周内再生骨骼的效果。采用全析因实验设计来评估模型聚(L-乳酸)和珊瑚羟基磷灰石支架内的骨形成,有或没有富血小板血浆(PRP)和bmMNC。进行了机械推出测试、显微计算机断层扫描分析和组织学分析。 PRP 对骨形成没有任何好处。与对照(无细胞)支架相比,不含 PRP 的充满细胞的聚(L-乳酸)支架需要更大的力才能从周围组织中移位,但在珊瑚支架的推出测试中没有观察到差异。对于通过微型计算机断层扫描分析的骨体积形成,观察到 bmMNC 掺入具有显着的积极总体效果。这些数据表明,bmMNC 可以在骨组织工程应用中提供治疗优势,而无需培养、扩增和纯化。
For bone tissue engineering, the benefits of incorporating mesenchymal stem cells (MSCs) into porous scaffolds are well established. There is, however, little consensus on the effects of or need for MSC handling ex vivo. Culture and expansion of MSCs adds length and cost, and likely increases risk associated with treatment. We evaluated the effect of using uncultured bone marrow mononuclear cells (bmMNCs) encapsulated within fibrin glue hydrogels and seeded into porous scaffolds to regenerate bone over 12 weeks in an 8-mm-diameter, critical-sized rat cranial defect. A full factorial experimental design was used to evaluate bone formation within model poly(L-lactic acid) and corraline hydroxyapatite scaffolds with or without platelet-rich plasma (PRP) and bmMNCs. Mechanical push-out testing, microcomputed tomographical analyses, and histology were performed. PRP showed no benefit for bone formation. Cell-laden poly(L-lactic acid) scaffolds without PRP required significantly greater force to displace from surrounding tissues than control (cell-free) scaffolds, but no differences were observed during push-out testing of coral scaffolds. For bone volume formation as analyzed by microcomputed tomography, significant positive overall effects were observed with bmMNC incorporation. These data suggest that bmMNCs may provide therapeutic advantages in bone tissue engineering applications without the need for culture, expansion, and purification.