Synthesis of highly biocompatible and temperature-responsive physical gels for cryopreservation and 3D cell culture

Masanori Nagao, Jayeeta Sengupta, Diana Diaz-Dussan, Madeleine Adam, Meng Wu, Jason Acker, Robert Ben, Kazuhiko Ishihara, Hongbo Zeng, Yoshiko Miura, Ravin Narain

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


There is considerable interest in the cryopreservation in 3D cell culture, as structurally preserving intact cells and tissues is critical in utilizing these systems to promote cell differentiation and tissue organization. Temperatureresponsive physical gels and zwitterionic polymers are useful materials as 3D scaffolds for cell culture which may also provide cryoprotection to the composite cells. Nevertheless, there has been a lack of relevant data for polymer systems that have both of these properties. In this study, highly biocompatible triblock copolymers were examined for their effectiveness both as gelators and as cryo-protectants. The triblock copolymers were synthesized with 2-methacryloyloxyethyl phosphorylcholine (MPC) and di(ethylene glycol) methyl ether methacrylate (DEGMA) via atom transfer radical polymerization (PDEGMA113-b-PMPC243-b-PDEGMA113). ABA triblock copolymers composed of hydrophilic "B" block and temperature responsive "A" block could form physical gels above their lower critical solution temperatures (LCST). PDEGMA113-b-PMPC243-b-PDEGMA113 triblock copolymer exhibited the LCST derived from DEGMA and assembled in micellar structures forming physical gels above the LCST. The mechanical properties of the physical gels were evaluated by rheological tests, and the low toxicity of PDEGMA113-b-PMPC243-b- PDEGMA113 was confirmed by MTT assay. Interestingly, the triblock copolymer showed ice recrystallization inhibition (IRI) activity which was determined to be suitable for the cryopreservation of several cell lines. In vitro studies were conducted to demonstrate the cryo-protectant properties and the formation of two and three-dimensional (2D/3D) cell culture scaffolds with high biocompatibility. This stimuli-responsive gelator polymers can therefore be useful for cryopreservation of different cells models, and a promising material for 3D cell culture.

Original languageEnglish
Pages (from-to)356-366
Number of pages11
JournalACS Applied Bio Materials
Issue number2
Publication statusPublished - Aug 20 2018

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Chemistry(all)
  • Biomedical Engineering
  • Biochemistry, medical


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