Nanomechanics of Engineered Articular Cartilage: Synergistic Influences of Transforming Growth Factor-β3 and Oscillating Pressure.
Nanomechanics of Engineered Articular Cartilage: Synergistic Influences of Transforming Growth Factor-β3 and Oscillating Pressure.
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工程关节软骨的纳米力学：转化生长因子-β3 和振荡压力的协同影响。
DOI：
10.1166/jnn.2016.12564
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发表时间：
2016
影响因子：
--
通讯作者：
Abu-Lail,NehalI
中科院分区：
文献类型：
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作者：
Nazempour,Arshan;Quisenberry,ChrystalR;VanWie,BernardJ;Abu-Lail,NehalI
关节软骨（AC），具有最低体积细胞密度的组织，没有血液和神经组织供应，导致损伤后自我修复的能力有限。由于没有能够完全恢复受损AC的治疗方法，因此正在研究组织工程。该领域的重点是在生物反应器中体外工程化功能组织，该生物反应器能够模拟适当细胞生长和分化所需的体内环境。在工程化AC的一个步骤中，人脂肪来源的干细胞在独特的离心生物反应器中在振荡静水压力（OHP）和模拟体内环境的转化生长因子β 3（TGF-β3）的供应下分化。静态微团和沉淀培养物用作对照。由于承受和吸收负载是AC的主要功能之一，因此使用原子力显微镜（AFM）在100 nm的受控压痕深度下测定工程化AC组织的机械性能。杨氏弹性模量进行了量化建模AFM力压痕数据使用赫兹接触力学模型。我们发现暴露于OHP导致软骨结构具有比静态培养物高45倍的杨氏模量。加入TGF-β3进一步增加了生物反应器样品中的杨氏模量1.9倍，使其在天然软骨估计值的70.6%内。我们的研究结果表明，OHP和TGF-β3协同作用，以改善工程组织的力学。
Articular cartilage (AC), tissue with the lowest volumetric cellular density, is not supplied with blood and nerve tissue resulting in limited ability for self-repair upon injury. Because there is no treatment capable of fully restoring damaged AC, tissue engineering is being investigated. The emphasis of this field is to engineer functional tissues in vitro in bioreactors capable of mimicking in vivo environments required for appropriate cellular growth and differentiation. In a step towards engineering AC, human adipose-derived stem cells were differentiated in a unique centrifugal bioreactor under oscillating hydrostatic pressure (OHP) and supply of transforming growth factor beta 3 (TGF-β3) that mimic in vivo environments. Static micromass and pellet cultures were used as controls. Since withstanding and absorbing loads are among the main functions of an AC, mechanical properties of the engineered AC tissues were assayed using atomic force microscopy (AFM) under a controlled indentation depth of 100 nm. Young's moduli of elasticity were quantified by modeling AFM force-indentation data using the Hertz model of contact mechanics. We found exposure to OHP causes cartilage constructs to have 45-fold higher Young's moduli compared to static cultures. Addition of TGF-β3 further increases Young's moduli in bioreactor samples by 1.9-fold bringing it within 70.6% of the values estimated for native cartilage. Our results imply that OHP and TGF-β3 act synergistically to improve the mechanics of engineered tissues.