Synthesis and cell adhesive properties of linear and cyclic RGD functionalized polynorbornene thin films.
Synthesis and cell adhesive properties of linear and cyclic RGD functionalized polynorbornene thin films.
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DOI：
10.1021/bm300795y
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发表时间：
2012-08-13
影响因子：
6.2
通讯作者：
Grubbs, Robert H.
中科院分区：
文献类型：
--
作者：
Patel, Paresma R.;Kiser, Rosemary Conrad;Lu, Ying Y.;Fong, Eileen;Ho, Wilson C.;Tirrell, David A.;Grubbs, Robert H.
本文描述了用于细胞粘附和铺展的生物活性甘氨酸-甘氨酸-天冬氨酸（RGD）官能化的基于聚异戊二烯的材料的有效合成和评价。以钌为引发剂[（H2 IMes）（pyr）2（Cl）2 Ru =CHPh]，通过开环易位聚合（ROMP）合成了含有线性或环状RGD肽的聚异戊二烯。三个单独的异丙基苯单体的无规共聚允许掺入水溶性聚乙二醇（PEG）部分，RGD细胞识别基序，和伯胺聚合后交联。聚合物合成后，通过与双（磺基琥珀酰亚胺基）辛二酸酯（BS 3）交联形成薄膜水凝胶，并评价和量化这些材料支持人脐静脉内皮细胞（HUVEC）粘附和铺展的能力。当与不含肽或乱序RDG肽的对照聚合物相比时，具有不同浓度的线性或环状RGD的聚合物在补充血清和无血清培养基中均显示出优异的细胞粘附特性。具有环状RGD侧链的聚合物保持细胞粘附，并且在比携带线性RGD肽的聚合物低100倍的浓度下表现出相当的整合素结合。通过ROMP实现的单体掺入的精确控制允许定量RGD结构和浓度对细胞粘附和扩散的影响。本文的研究结果将指导今后在外科手术、组织工程和再生医学中应用的RGD功能化材料的设计。
Described herein is the efficient synthesis and evaluation of bioactive arginine-glycine-aspartic acid (RGD) functionalized polynorbornene based materials for cell adhesion and spreading. Polynorbornenes containing either linear or cyclic RGD peptides were synthesized by ring-opening metathesis polymerization (ROMP) using the well-defined ruthenium initiator [(H2IMes)(pyr)2(Cl)2Ru=CHPh]. The random copolymerization of three separate norbornene monomers allowed for the incorporation of water-soluble polyethylene glycol (PEG) moieties, RGD cell recognition motifs, and primary amines for post-polymerization cross-linking. Following polymer synthesis, thin-film hydrogels were formed by cross-linking with bis(sulfosuccinimidyl) suberate (BS3), and the ability of these materials to support human umbilical vein endothelial cell (HUVEC) adhesion and spreading was evaluated and quantified. When compared to control polymers containing either no peptide or a scrambled RDG peptide, polymers with linear or cyclic RGD at varying concentrations displayed excellent cell adhesive properties in both serum-supplemented and serum-free media. Polymers with cyclic RGD side chains maintained cell adhesion and exhibited comparable integrin binding at a 100-fold lower concentration than those carrying linear RGD peptides. The precise control of monomer incorporation enabled by ROMP allows for quantification of the impact of RGD structure and concentration on cell adhesion and spreading. The results presented here will serve to guide future efforts for the design of RGD functionalized materials with applications in surgery, tissue engineering, and regenerative medicine.
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影响因子：
6.2
作者：
Biswas, Sanchita;Wang, Xuhua;Morales, Alma R.;Ahn, Hyo-Yang;Belfield, Kevin D.
通讯作者：
Belfield, Kevin D.
影响因子：
4.1
作者：
Kolhar, Poornima;Kotamraju, Venkata Ramana;Ruoslahti, Erkki
通讯作者：
Ruoslahti, Erkki
影响因子：
1.7
作者：
KOMAZAWA, H;SAIKI, I;ITOH, I
通讯作者：
ITOH, I
影响因子：
14
作者：
Heilshorn, SC;DiZio, KA;Tirrell, DA
通讯作者：
Tirrell, DA
DOI：
10.1163/156856202320253956
发表时间：
2002-01-01
影响因子：
3.6
作者：
Aucoin, L;Griffith, CM;Sheardown, H
通讯作者：
Sheardown, H