Photo-crosslinked alginate hydrogels support enhanced matrix accumulation by nucleus pulposus cells in vivo.

Photo-crosslinked alginate hydrogels support enhanced matrix accumulation by nucleus pulposus cells in vivo.
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DOI:
10.1016/j.joca.2009.04.012
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发表时间:
2009-10
影响因子:
7
通讯作者:
Nicoll SB
Nicoll SB
中科院分区:
医学2区
文献类型:
--
作者:
Chou AI;Akintoye SO;Nicoll SB

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椎间盘(IVD)退变是美国的一个主要健康问题。用可注射生物材料置换髓核(NP)代表了IVD退变的潜在治疗策略。本研究的目的是表征细胞外基质组装和功能特性的NP细胞封装,光交联藻酸盐水凝胶相比,离子交联藻酸盐结构。采用甲基丙烯酸酐与海藻酸钠的酯化反应合成了海藻酸钠甲基丙烯酸酯。通过使用CaCl2的离子交联或通过在光引发剂存在下暴露于长波UV光后的光交联,将牛髓核细胞包封在藻酸盐水凝胶中。通过大体和组织学分析在体外评价水凝胶,并使用鼠皮下囊模型在体内评价水凝胶。在体内样品进行了分析的基因表达,细胞外基质的定位和积累,和平衡力学性能。离子交联的水凝胶在体外表现出较差的蛋白聚糖积累,并且不能在体内保持结构完整性。在进一步的研究中,将光交联的藻酸盐水凝胶植入长达8周以检查NP组织形成。光交联的水凝胶显示临时增加的基因表达和II型胶原蛋白和蛋白多糖的组装。此外,水凝胶在研究期间保持完整,平衡杨氏模量从1.24 ± 0.09 kPa增加到4.31 ± 1.39 kPa,表明形成了具有与天然NP相当的性质的功能基质。这些发现支持使用光交联藻酸盐水凝胶作为NP置换的生物材料支架。
Intervertebral disc (IVD) degeneration is a major health concern in the United States. Replacement of the nucleus pulposus (NP) with injectable biomaterials represents a potential treatment strategy for IVD degeneration. The objective of this study was to characterize the extracellular matrix assembly and functional properties of NP cell-encapsulated, photo-crosslinked alginate hydrogels in comparison to ionically crosslinked alginate constructs. Methacrylated alginate was synthesized by esterification of hydroxyl groups with methacrylic anhydride. Bovine nucleus pulposus cells were encapsulated in alginate hydrogels by ionic crosslinking using CaCl2 or through photo-crosslinking upon exposure to long-wave UV light in the presence of a photoinitiator. The hydrogels were evaluated in vitro by gross and histological analysis and in vivo using a murine subcutaneous pouch model. In vivo samples were analyzed for gene expression, extracellular matrix localization and accumulation, and equilibrium mechanical properties. Ionically crosslinked hydrogels exhibited inferior proteoglycan accumulation in vitro and were unable to maintain structural integrity in vivo. In further studies, photo-crosslinked alginate hydrogels were implanted for up to 8 weeks to examine NP tissue formation. Photo-crosslinked hydrogels displayed temporal increases in gene expression and assembly of type II collagen and proteoglycans. Additionally, hydrogels remained intact over the duration of the study and the equilibrium Young’s modulus increased from 1.24 ± 0.09 kPa to 4.31 ± 1.39 kPa, indicating the formation of functional matrix with properties comparable to those of the native NP. These findings support the use of photo-crosslinked alginate hydrogels as biomaterial scaffolds for NP replacement.
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发表时间: 2002-01-17
影响因子: 10.8
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Anseth, KS;Metters, AT;Bowman, CN
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影响因子: 11.1
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