Kim Soyeon, Healy Kevin E
Departments of Bioengineering and Materials Science and Engineering, University of California at Berkeley, Berkeley, California 94720, USA.
Biomacromolecules. 2003 Sep-Oct;4(5):1214-23. doi: 10.1021/bm0340467.
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 approximately 34.5 degrees C. 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 degrees C. 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.
由N-异丙基丙烯酰胺（NIPAAm）和丙烯酸（AAc）组成的水凝胶通过氧化还原聚合反应与肽交联剂制备而成，以创建一种适合测试有关细胞在三维空间中增殖和迁移假设的人工细胞外基质（ECM）。肽可降解交联剂是通过对谷氨酰胺和赖氨酸残基的胺基进行丙烯酰化合成的，这些残基位于可能被哺乳动物细胞（如成骨细胞）合成的基质金属蛋白酶裂解的肽序列中。使用肽交联剂，制备了松散交联的聚（N-异丙基丙烯酰胺-共-丙烯酸）[P（NIPAAm-共-AAc）]水凝胶，并研究了它们的相变行为、低临界溶液温度（LCST）、含水量和酶降解特性。肽交联的P（NIPAAm-共-AAc）水凝胶在室温下柔韧且呈流体状，可通过小直径孔进行注射。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的肽交联水凝胶的LCST约为34.5摄氏度。溶胀受NIPAAm/AAc单体比例、交联密度和溶胀介质的影响；然而，即使在37摄氏度时，所有水凝胶的含水量仍保持在90%以上。在酶降解研究中，肽交联的P（NIPAAm-共-AAc）水凝胶的分解取决于胶原酶的浓度和交联密度。这些结果表明，肽交联的P（NIPAAm-共-AAc）水凝胶可以进行定制，以创建可被蛋白酶降解的环境响应性人工细胞外基质。
