Engineering large cartilage tissues using dynamic bioreactor culture at defined oxygen conditions.
Engineering large cartilage tissues using dynamic bioreactor culture at defined oxygen conditions.
复制标题
使用动态生物反应器培养在定义的氧气条件下对大软骨组织进行工程。
DOI：
10.1177/2041731417753718
复制
发表时间：
2018-01
影响因子：
8.2
通讯作者：
Kelly DJ
中科院分区：
文献类型：
--
作者：
Daly AC;Sathy BN;Kelly DJ
在适当的培养条件下，间充质干细胞能够产生健壮的软骨组织。然而，在三维培养过程中出现的营养可利用性的梯度可能导致核心区域缺乏基质的空间不均匀软骨组织的发展。以前开发动态培养系统以克服这些限制的尝试报告了与静态条件相比对间充质干细胞软骨形成的抑制。我们假设，通过调节生物反应器培养过程中的氧气供应，有可能设计出规模化的软骨组织。这项研究的目的是确定动态生物反应器培养，在特定的氧气条件下，是否可以促进大的，空间均一的软骨组织的发展，使用间充质干细胞水凝胶。将动态培养体系与静态培养体系进行直接比较，发现动态培养体系在小藻酸盐水凝胶和大藻酸盐水凝胶中均能支持间充质干细胞的软骨形成。通过在20%O2和3%O2条件下进行实验，探讨了外氧压力对动态培养条件响应的影响。在20%O2中，动态培养显著抑制了所有大小的工程化组织中的软骨生成。相比之下，与静态培养相比，在3%O2条件下，动态培养显著增加了软骨基质成分(硫酸糖胺聚糖和II型胶原)在较大结构中的分布和数量。综上所述，这些结果表明，提供充足营养供应和低氧环境的动态培养制度可以用于工程大而均匀的软骨组织。这样的培养系统可以促进软骨组织工程策略向临床相关维度的扩展。
Mesenchymal stem cells maintained in appropriate culture conditions are capable of producing robust cartilage tissue. However, gradients in nutrient availability that arise during three-dimensional culture can result in the development of spatially inhomogeneous cartilage tissues with core regions devoid of matrix. Previous attempts at developing dynamic culture systems to overcome these limitations have reported suppression of mesenchymal stem cell chondrogenesis compared to static conditions. We hypothesize that by modulating oxygen availability during bioreactor culture, it is possible to engineer cartilage tissues of scale. The objective of this study was to determine whether dynamic bioreactor culture, at defined oxygen conditions, could facilitate the development of large, spatially homogeneous cartilage tissues using mesenchymal stem cell laden hydrogels. A dynamic culture regime was directly compared to static conditions for its capacity to support chondrogenesis of mesenchymal stem cells in both small and large alginate hydrogels. The influence of external oxygen tension on the response to the dynamic culture conditions was explored by performing the experiment at 20% O2 and 3% O2. At 20% O2, dynamic culture significantly suppressed chondrogenesis in engineered tissues of all sizes. In contrast, at 3% O2 dynamic culture significantly enhanced the distribution and amount of cartilage matrix components (sulphated glycosaminoglycan and collagen II) in larger constructs compared to static conditions. Taken together, these results demonstrate that dynamic culture regimes that provide adequate nutrient availability and a low oxygen environment can be employed to engineer large homogeneous cartilage tissues. Such culture systems could facilitate the scaling up of cartilage tissue engineering strategies towards clinically relevant dimensions.
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影响因子：
3.1
作者：
Farrell, Megan J.;Comeau, Eric S.;Mauck, Robert L.
通讯作者：
Mauck, Robert L.
影响因子：
7
作者：
Bian L;Angione SL;Ng KW;Lima EG;Williams DY;Mao DQ;Ateshian GA;Hung CT
通讯作者：
Hung CT
DOI：
10.1073/pnas.1214100110
发表时间：
2013-06-18
影响因子：
11.1
作者：
Bian, Liming;Guvendiren, Murat;Burdick, Jason A.
通讯作者：
Burdick, Jason A.
影响因子：
6
作者：
Cunniffe, G. M.;Vinardell, T.;Kelly, D. J.
通讯作者：
Kelly, D. J.
影响因子：
14
作者：
Awad, HA;Wickham, MQ;Guilak, F
通讯作者：
Guilak, F