Enhancing osteoconduction of PLLA-based nanocomposite scaffolds for bone regeneration using different biomimetic signals to MSCs.

Enhancing osteoconduction of PLLA-based nanocomposite scaffolds for bone regeneration using different biomimetic signals to MSCs.
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DOI:
10.3390/ijms13022439
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发表时间:
2012
影响因子:
5.6
通讯作者:
Baldini N
Baldini N
中科院分区:
生物学2区
文献类型:
--
作者:
Ciapetti G;Granchi D;Devescovi V;Baglio SR;Leonardi E;Martini D;Jurado MJ;Olalde B;Armentano I;Kenny JM;Walboomers FX;Alava JI;Baldini N

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在骨工程中,间充质基质细胞的粘附、增殖和分化依赖于来自基质的化学-物理结构的信号,因此促进了模拟“细胞外基质”样支架的设计。在这项研究中,三维多孔聚-L-乳酸(PLLA)为基础的支架已混合不同的成分,包括单壁碳纳米管(CNT),羟基磷灰石微粒(HA),和BMP 2,并与等离子体(PT)处理,以获得四种不同的纳米复合材料:PLLA + CNT,PLLA + CNTHA,PLLA + CNT + HA + BMP 2和PLLA + CNT + HA + PT。从骨科患者股骨中分离成人骨髓间充质干细胞(MSCs),接种于支架材料上,在成骨诱导条件下培养,直至分化和矿化。在特定的时间点,骨髓来源的骨祖细胞的特定代谢产物和时间基因表达谱的释放进行了分析,相关的体外培养以及在体内分化。结果,加入PLLA基质中的不同仿生成分的作用被破译,加入BMP 2的支架对分化为成熟成骨细胞的细胞表现出最高的仿生活性。用增强组分修饰聚合物支架(其也作为细胞的仿生线索)可以有效地指导骨祖细胞分化,从而缩短矿化所需的时间。
In bone engineering, the adhesion, proliferation and differentiation of mesenchymal stromal cells rely on signaling from chemico-physical structure of the substrate, therefore prompting the design of mimetic “extracellular matrix”-like scaffolds. In this study, three-dimensional porous poly-L-lactic acid (PLLA)-based scaffolds have been mixed with different components, including single walled carbon nanotubes (CNT), micro-hydroxyapatite particles (HA), and BMP2, and treated with plasma (PT), to obtain four different nanocomposites: PLLA + CNT, PLLA + CNTHA, PLLA + CNT + HA + BMP2 and PLLA + CNT + HA + PT. Adult bone marrow mesenchymal stromal cells (MSCs) were derived from the femur of orthopaedic patients, seeded on the scaffolds and cultured under osteogenic induction up to differentiation and mineralization. The release of specific metabolites and temporal gene expression profiles of marrow-derived osteoprogenitors were analyzed at definite time points, relevant to in vitro culture as well as in vivo differentiation. As a result, the role of the different biomimetic components added to the PLLA matrix was deciphered, with BMP2-added scaffolds showing the highest biomimetic activity on cells differentiating to mature osteoblasts. The modification of a polymeric scaffold with reinforcing components which also work as biomimetic cues for cells can effectively direct osteoprogenitor cells differentiation, so as to shorten the time required for mineralization.
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