Correction of large jawbone defect in the mouse using immature osteoblast-like cells and a 3D polylactic acid scaffold.

Correction of large jawbone defect in the mouse using immature osteoblast-like cells and a 3D polylactic acid scaffold.
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DOI:
10.1093/pnasnexus/pgac151
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发表时间:
2022-09
期刊:
PNAS NEXUS
影响因子:
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通讯作者:
Saito, Masahiro
Saito, Masahiro
中科院分区:
其他
文献类型:
--
作者:
Suzuki, Shigeto;Venkataiah, Venkata Suresh;Yahata, Yoshio;Kitagawa, Akira;Inagaki, Masahiko;Njuguna, Mary M.;Nozawa, Risako;Kakiuchi, Yusuke;Nakano, Masato;Handa, Keisuke;Yamada, Masahiro;Egusa, Hiroshi;Saito, Masahiro

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骨组织工程已开发使用间充质干细胞(MSC)和磷酸钙基支架的组合。然而,这些复合体不能再生大的颌骨缺损。为了克服MSC和陶瓷支架的这种限制,必须开发一种新的骨再生技术,使用具有高骨形成能力的细胞和为垂直骨增量提供空间的支架。为了在我们的研究中解决这个问题,我们开发了牙槽骨来源的未成熟成骨细胞样细胞(HAOBs),当用作与聚乳酸纤维结合的移植材料时,其具有骨再生能力以纠正大的骨缺损,聚乳酸纤维组织3D结构并增加支架材料(3DPL)的强度。HAOB-3DPL构建体不能通过异种移植在微小型猪牙槽骨缺损模型中再生骨。然而,与单独的3DPL支架相比,使用与HAOB相同的方案分离并与3DPL支架混合的小鼠颅骨衍生的未成熟成骨细胞样细胞(MCOB)的自体移植在大颌骨缺损小鼠模型中成功地再生了骨。纳米压痕分析表明,再生骨具有与天然骨相似的微机械强度。此外,该MCOB-3DPL再生骨具有骨整合能力,其中与钛植入物表面建立了直接的结构连接。因此,3DPL支架和未成熟成骨细胞样细胞如MCOB之间形成的复合物代表了一种新的骨组织工程方法,该方法能够形成具有治疗大骨缺损所需的微机械性能的垂直骨。
Bone tissue engineering has been developed using a combination of mesenchymal stem cells (MSCs) and calcium phosphate–based scaffolds. However, these complexes cannot regenerate large jawbone defects. To overcome this limitation of MSCs and ceramic scaffolds, a novel bone regeneration technology must be developed using cells possessing high bone forming ability and a scaffold that provides space for vertical bone augmentation. To approach this problem in our study, we developed alveolar bone–derived immature osteoblast–like cells (HAOBs), which have the bone regenerative capacity to correct a large bone defect when used as a grafting material in combination with polylactic acid fibers that organize the 3D structure and increase the strength of the scaffold material (3DPL). HAOB-3DPL constructs could not regenerate bone via xenogeneic transplantation in a micromini pig alveolar bone defect model. However, the autogenic transplantation of mouse calvaria–derived immature osteoblast–like cells (MCOBs) isolated using the identical protocol for HAOBs and mixed with 3DPL scaffolds successfully regenerated the bone in a large jawbone defect mouse model, compared to the 3DPL scaffold alone. Nanoindentation analysis indicated that the regenerated bone had a similar micromechanical strength to native bone. In addition, this MCOB-3DPL regenerated bone possesses osseointegration ability wherein a direct structural connection is established with the titanium implant surface. Hence, a complex formed between a 3DPL scaffold and immature osteoblast–like cells such as MCOBs represents a novel bone tissue engineering approach that enables the formation of vertical bone with the micromechanical properties required to treat large bone defects.
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