Influence of decreasing nutrient path length on the development of engineered cartilage.

Influence of decreasing nutrient path length on the development of engineered cartilage.
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DOI:
10.1016/j.joca.2008.10.003
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发表时间:
2009-05
影响因子:
7
通讯作者:
Hung CT
Hung CT
中科院分区:
医学2区
文献类型:
--
作者:
Bian L;Angione SL;Ng KW;Lima EG;Williams DY;Mao DQ;Ateshian GA;Hung CT

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直径4毫米(厚度2.34毫米)的软骨细胞种子琼脂糖构建物具有空间不均匀的材料特性,外缘较硬,核心较软,表明营养物质在中心构建区域的扩散受到限制。研究了减少结构厚度和创建贯穿厚结构深度的通道的效果。在研究1中,比较了0.78mm(薄)和2.34mm(厚)的工程软骨的性能。在研究2中,在每个厚结构的中间建立一个单一的营养通道(直径1毫米)。在研究3中,研究了通道对直径较大的10毫米厚结构体的影响。薄结构体比厚结构体具有更好的机械和生化性能。与无通道结构相比,有通道结构具有更高的机械性能,同时具有相似的GAG和胶原含量。胶原染色表明通道导致更均匀的纤维网络。直径为10mm的构造体也有类似的改善。本研究表明,通过减少组织工程软骨的厚度或加入宏观营养通道,可以获得更均匀的组织工程软骨结构,并改善其力学性能。我们的数据进一步表明,这些宏观通道保持开放的时间足够长,以促进这种增强的组织发育,同时显示出通过额外的培养时间重新填充细胞精心制作的基质的潜力。有报道称,软骨中小于3毫米的缺损在体内愈合,不规则的孔洞与临床使用的骨软骨移植手术有关,我们预计,结合宏观通道的策略可能有助于开发具有功能特性的临床相关工程软骨。
Chondrocyte-seeded agarose constructs of 4 mm diameter (2.34 mm thickness) develop spatially inhomogeneous material properties with stiffer outer edges and a softer central core suggesting nutrient diffusion limitations to the central construct region. The effects of reducing construct thickness and creating channels running through the depth of the thick constructs were examined. In Study 1, the properties of engineered cartilage of 0.78mm (thin) or 2.34mm (thick) thickness were compared. In Study 2, a single nutrient channel (1 mm diameter) was created in the middle of each thick construct. In Study 3, the effects of channels on larger 10 mm diameter, thick constructs was examined. Thin constructs developed superior mechanical and biochemical properties than thick constructs. The channeled constructs developed significantly higher mechanical properties versus control channel-free constructs while exhibiting similar GAG and collagen content. Collagen staining suggested that channels resulted in a more uniform fibrillar network. Improvements in constructs of 10mm diameter were similarly observed. This study demonstrated that more homogeneous tissue engineered cartilage constructs with improved mechanical properties can be achieved by reducing their thickness or incorporating macroscopic nutrient channels. Our data further suggests that these macroscopic channels remain open long enough to promote this enhanced tissue development while exhibiting the potential to refill with cell elaborated matrix with additional culture time. Together with reports that <3 mm defects in cartilage heal in vivo and that irregular holes are associated with clinically used osteochondral graft procedures, we anticipate that a strategy of incorporating macroscopic channels may aid the development of clinically-relevant engineered cartilage with functional properties.
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