In vitro and in vivo evaluation of self-mineralization and biocompatibility of injectable, dual-gelling hydrogels for bone tissue engineering.
In vitro and in vivo evaluation of self-mineralization and biocompatibility of injectable, dual-gelling hydrogels for bone tissue engineering.
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DOI：
10.1016/j.jconrel.2014.11.028
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发表时间：
2015-05-10
期刊：
影响因子：
--
通讯作者：
Mikos AG
中科院分区：
文献类型：
--
作者：
Vo TN;Ekenseair AK;Spicer PP;Watson BM;Tzouanas SN;Roh TT;Mikos AG
在这项研究中，我们研究了可注射的双凝胶水凝胶在大鼠颅骨缺损中的矿化能力和生物相容性，因为水凝胶的疏水性来自可水解内酯环的共聚或水凝胶聚合物的含量。该水凝胶体系由基于聚n -异丙基丙烯酰胺的热凝胶大分子（TGM）和聚酰胺胺交联剂组成。热凝胶大分子与（TGM/DBA）或不与（TGM）含二甲基-γ-丁内酯丙烯酸酯（DBA）的内酯环共聚，该内酯环可以调节较低的临界溶液温度，从而随着时间的推移调节水凝胶的疏水性。研究了三个水凝胶组：(1)15 wt% TGM, (2) 15 wt% TGM/DBA, (3) 20 wt% TGM/DBA。水凝胶分别植入临界尺寸8 mm的大鼠颅骨缺损4周和12周。在每个时间点采集种植体，并使用微计算机断层扫描（microcomputer tomography, microCT）分析骨形成、水凝胶矿化和组织反应。组织学和纤维囊评分显示4周时轻度炎症反应，12周后所有组均有所缓解。MicroCT评分和骨体积量化显示，4周时骨形成相似，从4周到12周，更疏水的水凝胶配方（15 wt% TGM和20 wt% TGM/DBA）显著增加。一项补充的体外脱细胞矿化研究表明，水凝胶在含血清介质存在时表现出钙结合特性，这是由水凝胶的疏水性调节的。这些可注射的、具有水解依赖疏水性的双凝胶水凝胶具有定制的矿化能力，在骨组织工程应用中具有令人兴奋的特性。
In this study, we investigated the mineralization capacity and biocompatibility of injectable, dual-gelling hydrogels in a rat cranial defect as a function of hydrogel hydrophobicity from either the copolymerization of a hydrolyzable lactone ring or the hydrogel polymer content. The hydrogel system comprised a poly(N-isopropylacrylamide)-based thermogelling macromer (TGM) and a polyamidoamine crosslinker. The thermogelling macromer was copolymerized with (TGM/DBA) or without (TGM) a dimethyl-γ-butyrolactone acrylate (DBA)-containing lactone ring that modulated the lower critical solution temperature and thus, the hydrogel hydrophobicity, over time. Three hydrogel groups were examined: (1) 15 wt% TGM, (2) 15 wt% TGM/DBA, and (3) 20 wt% TGM/DBA. The hydrogels were implanted within an 8 mm critical size rat cranial defect for 4 and 12 weeks. Implants were harvested at each timepoint and analyzed for bone formation, hydrogel mineralization and tissue response using microcomputed tomography (microCT). Histology and fibrous capsule scoring showed a light inflammatory response at 4 weeks that was mitigated by 12 weeks for all groups. MicroCT scoring and bone volume quantification demonstrated similar bone formation at 4 weeks that was significantly increased for the more hydrophobic hydrogel formulations - 15 wt% TGM and 20 wt% TGM/DBA - from 4 weeks to 12 weeks. A complementary in vitro acellular mineralization study revealed that the hydrogels exhibited calcium binding properties in the presence of serum-containing media, which was modulated by the hydrogel hydrophobicity. The tailored mineralization capacity of these injectable, dual-gelling hydrogels with hydrolysis-dependent hydrophobicity presents an exciting property for their use in bone tissue engineering applications.
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影响因子：
6.2
作者：
Kretlow, James D.;Hacker, Michael C.;Klouda, Leda;Ma, Brandy B.;Mikos, Antonios G.
通讯作者：
Mikos, Antonios G.
影响因子：
4.1
作者：
Patel, Zarana S.;Young, Simon;Tabata, Yasuhiko;Jansen, John A.;Wong, Mark E. K.;Mikos, Antonios G.
通讯作者：
Mikos, Antonios G.
影响因子：
16.1
作者：
Ekenseair, Adam K.;Kasper, F. Kurtis;Mikos, Antonios G.
通讯作者：
Mikos, Antonios G.
影响因子：
3.6
作者：
Cui, Zhanwu;Lee, Bae Hoon;Vernon, Brent L.
通讯作者：
Vernon, Brent L.
影响因子：
6.2
作者：
Ekenseair, Adam K.;Boere, Kristel W. M.;Tzouanas, Stephanie N.;Vo, Tiffany N.;Kasper, F. Kurtis;Mikos, Antonios G.
通讯作者：
Mikos, Antonios G.