Synthesis and characterization of injectable poly(N-isopropylacrylamide-co-acrylic acid) hydrogels with proteolytically degradable cross-links
Synthesis and characterization of injectable poly(N-isopropylacrylamide-co-acrylic acid) hydrogels with proteolytically degradable cross-links
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DOI：
10.1021/bm0340467
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发表时间：
2003-09-01
影响因子：
6.2
通讯作者：
Healy, KE
中科院分区：
文献类型：
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作者：
Kim, S;Healy, KE
由N-异丙基丙烯酰胺（NIPAAm）和丙烯酸（AAc）组成的水凝胶通过与肽交联剂的氧化还原聚合来制备，以产生适于在三维中测试关于细胞增殖和迁移的假设的人工细胞外基质（ECM）。肽可降解的交联剂通过在肽序列内的谷氨酰胺和赖氨酸残基的胺基的丙烯酸酯化来合成，所述肽序列可被哺乳动物细胞合成的基质金属蛋白酶（例如，成骨细胞）。以肽为交联剂，制备了松散交联的聚（N-异丙基丙烯酰胺-co-丙烯酸）[P（NIPAAm-co-AAc）]水凝胶，并对其相变行为、低临界溶解温度（LCST）、含水量和酶降解性能进行了研究。肽交联的P（NIPAAm-co-AAc）水凝胶在室温下是柔韧的和流体状的，并且可以通过小直径的孔注射。肽交联水凝胶的LCST受NIPAAm/AAc单体比例的影响，但不受聚合物网络内交联密度的影响。NIPAAm/AAc摩尔比为97/3的肽交联水凝胶显示出类似于34.5 ℃的LCST。溶胀NIPAAm/AAc单体比例，交联密度和溶胀介质的影响，然而，所有的水凝胶保持超过90%的水，即使在37 degreesC。在酶促降解研究中，肽交联的P（NIPAAm-共-AAc）水凝胶的分解依赖于胶原酶的浓度和交联密度两者。这些结果表明，肽交联的P（NIPAAm-co-AAc）水凝胶可以被定制以产生被蛋白酶降解的环境响应性人工细胞外基质。
Hydrogels composed of N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc) were prepared by redox polymerization with peptide cross-linkers to create an artificial extracellular matrix (ECM) amenable for testing hypotheses regarding cell proliferation and migration in three dimensions. Peptide degradable cross-linkers were synthesized by the acrylation of the amine groups of glutamine and lysine residues within peptide sequences potentially cleavable by matrix metalloproteinases synthesized by mammalian cells (e.g., osteoblasts). With the peptide cross-linker, loosely cross-linked poly(N-isopropylacrylamide-co-acrylic acid) [P(NIPAAm-co-AAc)] hydrogels were prepared, and their phase transition behavior, lower critical solution temperature (LCST), water content, and enzymatic degradation properties were investigated. The peptide-cross-linked P(NIPAAm-co-AAc) hydrogels were pliable and fluidlike at room temperature and could be injected through a small-diameter aperture. The LCST of peptide-cross-linked hydrogel was influenced by the monomer ratio of NIPAAm/AAc but not by cross-linking density within the polymer network. A peptide-cross-linked hydrogel with a 97/3 molar ratio of NIPAAm/AAc exhibited a LCST of similar to34.5 degreesC. Swelling was influenced by NIPAAm/AAc monomer ratio, cross-linking density, and swelling media; however, all hydrogels maintained more than 90% water even at 37 degreesC. In enzymatic degradation studies, breakdown of the peptide-cross-linked P(NIPAAm-co-AAc) hydrogels was dependent on both the concentration of collagenase and the cross-linking density. These results suggest that peptide-cross-linked P(NIPAAm-co-AAc) hydrogels can be tailored to create environmentally-responsive artificial extracellular matrixes that are degraded by proteases.