高等学校化学学报

高等学校化学学报

• 研究论文 • 上一篇    下一篇

动力学控制多乙烯基单体可控均聚制备超支化聚乙二醇及其干细胞培养应用

李智立,周德重   

  1. 西安交通大学化学工程与技术学院

  • 收稿日期:2024-12-18 修回日期:2025-03-05 网络首发:2025-04-14 发布日期:2025-04-14
  • 通讯作者: 周德重 E-mail:dezhong.zhou@xjtu.edu.cn
  • 基金资助:
    国家自然科学基金(批准号：52473147)资助

Preparation of hyperbranched poly(ethylene glycol) via kinetically controlled homopolymerization of multivinyl monomers and its application in stem cell culture

LI Zhili, ZHOU Dezhong   

  1. School of Chemical Engineering and Technology, Xi’an Jiaotong University
  • Received:2024-12-18 Revised:2025-03-05 Online First:2025-04-14 Published:2025-04-14
  • Contact: ZHOU Dezhong E-mail:dezhong.zhou@xjtu.edu.cn
  • Supported by:
    Supported by the National Natural Science Foundation of China(No.52473147)

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摘要： 本研究采用动力学控制的多乙烯基单体（MVMs）可控均聚合成超支化聚乙二醇（HBP）并探究其干细胞培养应用。以聚（乙二醇）二丙烯酸酯（PEGDA）为MVM，4-氰基-4-（硫代苯甲酰硫基）戊酸（CPADB）为链转移剂（CTA），2,2'-偶氮二异丁腈（AIBN）为引发剂，采用一锅法可逆加成断裂链转移（RAFT）自由基聚合，通过调控反应参数特异性促进聚合过程中大分子间结合，成功合成了两种支化度（BD）且带有大量悬挂双键的HBP。HBP可与巯基化明胶（gel-SH）通过硫醇-烯点击化学反应交联形成HBP/gel-SH水凝胶，用于人诱导间充质干细胞（iMSCs）培养。采用凝胶渗透色谱（GPC）和核磁共振波谱仪（NMR）对HBP的化学组成和结构进行表征。结果表明，通过调控PEGDA浓度及PEGDA:CPADB:AIBN投料比能够有效调控HBP的BD。流变仪学表征结果表明，HBP和gel-SH能够快速交联在2 min内形成水凝胶。iMSCs培养实验证明HBP/gel-SH水凝胶无明显细胞毒性，且高BD聚合物形成的水凝胶具有更好的生物相容性。该水凝胶在干细胞培养和扩增领域具有广阔的应用前景。

关键词: 超支化聚合物, 水凝胶, 硫醇-烯点击化学, 细胞培养

Abstract: In this study, we explore the synthesis of hyperbranched poly(ethylene glycol) (HBP) through kinetically controlled homopolymerization of multivinyl monomers (MVMs) and its application in stem cell culture. Using poly(ethylene glycol) diacrylate (PEGDA) as the MVM, 4-Cyano-4-(phenylcarbonothioylthio)pentanoic acid (CPADB) as the chain transfer agent (CTA), and 2,2'-azobisisobutyronitrile (AIBN) as the initiator, two HBPs with different branching degrees (BD) and multiple pendent vinyl groups were successfully synthesized in a one-pot reversible addition-fragmentation chain transfer (RAFT) polymerization, which by regulating reaction parameters to specifically promote intermolecular combination. HBP can react with thiolated gelatin (gel-SH) via thiol-ene click chemistry to form HBP/gel-SH hydrogels and used for the culture of human induced mesenchymal stem cells (iMSCs). The chemical composition and structure of the HBP were characterized using gel permeation chromatography (GPC) and nuclear magnetic resonance (NMR). Results indicated that the BD of HBP can be effectively regulated by adjusting PEGDA concentration and the ratio of PEGDA:CPADB:AIBN. Rheological analysis showed that HBP and gel-SH could cross-link to form a hydrogel within 2 min. Cell culture experiments demonstrated that the HBP/gel-SH hydrogels exhibit no significant cytotoxicity, with the hydrogel formed by HBP with a higher BD displaying better biocompatibility. These hydrogels hold great potential for applications in stem cell culture and expansion.

Key words: Hyperbranched polymer; Hydrogel, Thiol-ene click chemistry, Cell culture

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