Department of Chemical Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 106, Taiwan.
Biomater Sci. 2017 Jan 31;5(2):322-330. doi: 10.1039/c6bm00687f.
Hydrogels provide three-dimensional (3D) frames with tissue-like elasticity and high water content for tissue scaffolds. Previously, we reported the design and synthesis protocol of a biodegradable poly(carboxybetaine) poly(CB) hydrogel with a zwitterionic carboxybetaine methacrylate (CBMA) monomer and a disulfide-containing crosslinker via free radical polymerization. We also demonstrated that cells could be successfully encapsulated in the hydrogels without compromising cytoviability. In this study, we evaluated the cytoviability of three commonly used zwitterionic monomers (CBMA, 2-methacryloyloxyethyl phosphorylcholine (MPC) and sulfobetaine methacrylate (SBMA)) and the suitability of being utilized as precursor materials for in situ gel forming implants. These three zwitterionic monomers exhibited lower cell toxicity than other methacrylated monomers. Mixing these monomers with dimethacrylate crosslinkers initiated the gelation process in situ, which was further tested in vivo by injecting the precursor solutions subcutaneously into murine models. Poly(CB) implants retained their original shape up to 3 weeks, while poly(MPC) and poly(SB) hydrogels for shorter periods of time due to lower mechanical strengths. These hydrogels showed minimal inflammation at the injection site. We subsequently showed that the CBMA precursor solution mixed with Arg-Gly-Asp (RGD) and hydroxyapatite (HAp) nanoparticles could be applied in bone tissue engineering. Both in vitro and in vivo studies demonstrated that HAp containing poly(CB) hydrogels greatly enhanced the mineralization process of bone tissue formation. The non-cytotoxic and biodegradable poly(CB) hydrogel conjugated with cell affinity moieties is an excellent material for 3D tissue scaffolds.
水凝胶为组织支架提供了具有类似组织弹性和高含水量的三维（3D）框架。此前，我们报道了通过自由基聚合设计和合成可生物降解的聚（羧酸甜菜碱）聚（CB）水凝胶的方法，该水凝胶使用两性离子羧酸甜菜碱甲基丙烯酰胺（CBMA）单体和含有二硫键的交联剂。我们还证明了可以成功地将细胞包封在水凝胶中，而不会影响细胞活力。在这项研究中，我们评估了三种常用的两性离子单体（CBMA、2-甲基丙烯酰氧基乙基磷酸胆碱（MPC）和磺酸甜菜碱甲基丙烯酰胺（SBMA））的细胞活力，以及作为原位凝胶形成植入物的前体材料的适用性。这三种两性离子单体的细胞毒性低于其他甲基丙烯酰化单体。将这些单体与二甲基丙烯酸酯交联剂混合可在原位引发凝胶化过程，进一步通过将前体溶液皮下注射到小鼠模型中在体内进行测试。聚（CB）植入物在 3 周内保持其原始形状，而聚（MPC）和聚（SB）水凝胶的保持时间较短，这是由于机械强度较低所致。这些水凝胶在注射部位引起的炎症最小。随后我们表明，与 Arg-Gly-Asp（RGD）和羟基磷灰石（HAp）纳米颗粒混合的 CBMA 前体溶液可应用于骨组织工程。体外和体内研究均表明，含有 HAp 的聚（CB）水凝胶极大地促进了骨组织形成的矿化过程。与细胞亲和基团偶联的非细胞毒性和可生物降解的聚（CB）水凝胶是 3D 组织支架的优异材料。
