Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.
J Mater Sci Mater Med. 2012 Jan;23(1):25-35. doi: 10.1007/s10856-011-4496-z. Epub 2011 Dec 6.
Thermoresponsive polymers have been widely used for in situ formed hydrogels in drug delivery and tissue engineering as they are easy to handle and their shape can easily conform to tissue defects. However, non-covalent bonding and mechanical weakness of these hydrogels limit their applications. In this study, a physically and chemically in situ cross-linkable hydrogel system was developed from a novel thermoresponsive hyperbranched PEG based copolymer with multi acrylate functionality, which was synthesized via an 'one pot and one step' in situ deactivation enhanced atom transfer radical co-polymerization of poly(ethylene glycol) diacrylate (PEGDA, M(n) = 258 g mol(-1)), poly(ethylene glycol) methyl ether methacrylate (PEGMEMA, M(n )= 475 g mol(-1)) and (2-methoxyethoxy) ethyl methacrylate (MEO(2)MA). This hyperbranched copolymer was tailored to have the lower critical solution temperature to form physical gelation around 37°C. Meanwhile, with high level of acrylate functionalities, a chemically cross-linked gel was formed from this copolymer using thiol functional cross-linker of pentaerythritol tetrakis (3-mercaptopropionate) (QT) via thiol-ene Michael addition reaction. Furthermore, a semi-interpenetrated polymer networks (semi-IPN) structure was developed by combining this polymer with hyaluronic acid (HA), leading to an in situ cross-linkable hydrogel with significantly increased porosity, enhanced swelling behavior and improved cell adhesion and viability both in 2D and 3D cell culture models.
温敏聚合物因其易于处理且形状可轻易适应组织缺陷而被广泛应用于药物输送和组织工程中的原位形成水凝胶。然而，这些水凝胶的非共价键和机械强度的限制了它们的应用。在本研究中，通过一种新型的基于热响应超支化 PEG 的多丙烯酸酯官能化共聚物，开发了一种物理和化学原位交联水凝胶体系，该共聚物通过“一锅一步”原位失活增强原子转移自由基共聚合成，其中包括聚（乙二醇）二丙烯酸酯（PEGDA，M(n)=258gmol(-1))、聚（乙二醇）甲基醚甲基丙烯酸酯（PEGMEMA，M(n)=475gmol(-1)）和（2-甲氧基乙氧基）乙基甲基丙烯酸酯（MEO(2)MA）。该超支化共聚物具有较低的临界溶液温度，可在 37°C 左右形成物理凝胶。同时，由于具有较高的丙烯酸酯官能度，该共聚物可以使用五倍子四（3-巯基丙酸酯）（QT）作为硫醇交联剂，通过硫醇-烯迈克尔加成反应形成化学交联凝胶。此外，通过将该聚合物与透明质酸（HA）结合，开发了一种半互穿聚合物网络（semi-IPN）结构，导致原位交联水凝胶具有显著增加的孔隙率、增强的溶胀行为以及在 2D 和 3D 细胞培养模型中提高的细胞黏附和活力。
