接种BMP-2预处理间充质干细胞的三维大/微孔-纳米纤维细菌纤维素支架显示出显著的骨组织工程潜力
3-D macro/microporous-nanofibrous bacterial cellulose scaffolds seeded with BMP-2 preconditioned mesenchymal stem cells exhibit remarkable potential for bone tissue engineering
摘要：
使用BMP-2进行骨修复在临床实践中是一种很有前途的治疗方法，然而，有效所需的高剂量带来了成本和安全性问题。本研究通过组织工程方法探索低剂量BMP-2治疗的潜力，该方法将3-D大/微孔纳米纤维细菌纤维素（mNBC）支架与低剂量BMP-2致敏的小鼠间充质干细胞（C3 H10 T1/2细胞）结合。使用未致敏的C3 H10 T1/2细胞对细胞-支架相互作用的初步研究证实，支架由于其ECM模拟的纳米-微观-宏观结构，为细胞黏附、生长和浸润提供了有利的环境。通过用50 ng/mL BMP-2预处理细胞15分钟，然后在mNBC支架上培养长达三周来进行成骨研究。结果显示，与未致敏的支架相比，接种BMP-2致敏细胞的支架中的骨基质分泌和成熟较早发生并显著增强。此外，单独的mNBC支架能够在一定程度上促进细胞的矿化。这些发现表明，在低剂量BMP-2引发的干细胞的“骨诱导”和mNBC支架的纳米-宏观/微观形貌的“骨传导”的帮助下，可以设计一种具有成本效益的骨组织工程策略，用于快速和优异的体内骨整合。
英文摘要：
Bone repair using BMP-2 is a promising therapeutic approach in clinical practices, however, high dosages required to be effective pose issues of cost and safety. The present study explores the potential of low dose BMP-2 treatment via tissue engineering approach, which amalgamates 3-D macro/microporous-nanofibrous bacterial cellulose (mNBC) scaffolds and low dose BMP-2 primed murine mesenchymal stem cells (C3H10T1/2 cells). Initial studies on cell-scaffold interaction using unprimed C3H10T1/2 cells confirmed that scaffolds provided a propitious environment for cell adhesion, growth, and infiltration, owing to its ECM-mimicking nano-micro-macro architecture. Osteogenic studies were conducted by preconditioning the cells with 50 ng/mL BMP-2 for 15 minutes, followed by culturing on mNBC scaffolds for up to three weeks. The results showed an early onset and significantly enhanced bone matrix secretion and maturation in the scaffolds seeded with BMP-2 primed cells compared to the unprimed ones. Moreover, mNBC scaffolds alone were able to facilitate the mineralization of cells to some extent. These findings suggest that, with the aid of 'osteoinduction' from low dose BMP-2 priming of stem cells and 'osteoconduction' from nano-macro/micro topography of mNBC scaffolds, a cost-effective bone tissue engineering strategy can be designed for quick and excellent in vivo osseointegration.
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