Synergistic action of growth factors and dynamic loading for articular cartilage tissue engineering
Synergistic action of growth factors and dynamic loading for articular cartilage tissue engineering
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DOI：
10.1089/107632703768247304
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发表时间：
2003-08-01
影响因子：
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通讯作者：
Hung, CT
中科院分区：
文献类型：
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作者：
Mauck, RL;Nicoll, SB;Hung, CT
先前已经证明，相对于自由溶胀对照，软骨细胞接种的琼脂糖水凝胶在1个月的过程中的动态变形加载可以增加构建体的机械和生物化学性质。本研究探讨了基质生物合成的两种介质，生长因子TGF-β（1）和IGF-I与施加的动态变形载荷相互作用的方式。在对照培养基（C）中的自由溶胀条件下，（10 × 101个细胞/mL）2%琼脂糖构建体达到峰值[0.54%湿重（ww）][0.16%ww][13.4 kPa]（c），而向对照培养基中加入TGF-β（1）或IGF-I导致显著更高的峰[1.18%ww][0.97%ww][23.6 kPa]（C-TGF）和[1.00%ww][0.63%ww][23.6 kPa]（C-TGF）。ww][19.3kPa]（C-IGF）（p < 0.01）。在对照培养基（L）中的动态负荷下，测量的参数为[1.10%ww][0.52%ww][24.5 kPa]（L），并且随着TGF-β（1）或IGF-I添加到对照培养基中，这些参数进一步增加到[1.49%ww][1.07%ww][50.5 kPa]（L-TGF）和[1.48%ww][0.81%ww][46.2 kPa]（L-IGF），P < 0.05。免疫组织化学染色显示，11型胶原蛋白主要积累在细胞周围区域的自由肿胀条件下，但跨越整个组织的动态加载结构。协同应用，动态变形负荷和TGF-β（1）或IGF-I分别使工程化构建体的聚集体模量增加277或245%，增加大于单独应用任一刺激的总和。这些结果支持了这样的假设，即基质生物合成的化学和机械促进剂的组合可以优化组织工程软骨构建体的生长。
It has previously been demonstrated that dynamic deformational loading of chondrocyte-seeded agarose hydrogels over the course of I month can increase construct mechanical and biochemical properties relative to free-swelling controls. The present study examines the manner in which two mediators of matrix biosynthesis, the growth factors TGF-beta(1) and IGF-I, interact with applied dynamic deformational loading. Under free-swelling conditions in control medium (C), the [proteoglycan content][collagen content][equilibrium aggregate modulus] of cell-laden (10 X 101 cells/mL) 2% agarose constructs reached a peak of [0.54% wet weight (ww)][0.16% ww][13.4 kPa](c), whereas the addition of TGF-beta(1) or IGF-I to the control medium led to significantly higher peaks of [1.18% ww][0.97% ww][23.6 kPa](C-TGF) and [1.00% ww][0.63% ww][19.3 kPa](C-IGF), respectively, by day 28 or 35 (p < 0.01). Under dynamic loading in control medium (L), the measured parameters were [1.10% ww][0.52% ww][24.5 kPa](L), and with the addition of TGF-beta(1) or IGF-I to the control medium these further increased to [1.49% ww][1.07% ww][50.5 kPa](L-TGF) and [1.48% ww][0.81% ww][46.2 kPa](L-IGF), respectively (p < 0.05). Immunohistochemical staining revealed that type 11 collagen accumulated primarily in the pericellular area under free-swelling conditions, but spanned the entire tissue in dynamically loaded constructs. Applied in concert, dynamic deformational loading and TGF-beta(1), or IGF-I increased the aggregate modulus of engineered constructs by 277 or 245%, respectively, an increase greater than the sum of either stimulus applied alone. These results support the hypothesis that the combination of chemical and mechanical promoters of matrix biosynthesis can optimize the growth of tissue-engineered cartilage constructs.