(64h) Engineered Biomaterials for Thermal Stabilization of Biomolecules

Tibbitt, M. W., University of Colorado
Sridhar, B. V., Nanoly Bioscience, Inc.
Janczy, J. R., Nanoly Bioscience, Inc.
Marco Dufort, B., ETH Zürich
A reliable supply and storage of complex biomolecules is essential for clinical medicine, biotechnology research, and diagnostics. However, many biomolecules are damaged upon exposure to thermal stress and the distribution around the world of vaccines, biotherapeutics, and proteins relies on an integrated cold chain (2–8 °C) from the point of manufacture to the point of use. Direct encapsulation of biomolecules within silk fibroin biomaterials or formulation with engineered glycopolymers have demonstrated significantly improved thermal stability for a range of relevant biomolecules.[1,2] Building on this work, we have engineered photoresponsive hydrogel networks that enable direct encapsulation of biomolecules without conjugation, thermal stability during storage and transport, and on-demand release with UV light exposure.[3] The poly(ethylene glycol) (PEG)-based network was formed via a strain-promoted azide-alkyne cycloaddtion in the presence of biomolecules without affecting their activity. A photolabile moiety, o-nitrobenzyl ether, was installed in the network backbone, which enabled on-demand dissolution of the network upon light exposure and release of the encapsulated biomolecules. Direct encapsulation improved the stability of β-galactosidase, alkaline phosphatase, and T4 DNA ligase during thermal stress as compared to non-encapsulated controls. β-galactosidase and alkaline phosphatase activity was stabilized up to 60 °C for 4 weeks and up to 85 °C for 60 min for alkaline phosphatase. The highly labile T4 DNA ligase was maintained in a stable form for 24 h at 40 °C and 30 min at 60 °C. These results suggest that direct encapsulation of biomolecules within reversible polymer networks can be used as excipients for thermal stability while providing on-demand release of active compounds at the point of use.


  1. Kluge JA et al. Natl. Acad. Sci. U. S. A. 2016, 113, 5892–5897.
  2. Lee J et al. Biomacromolecules2013, 14, 2561–2569.
  3. Sridhar BV et al. Biomacromolecules2018, 19, 740–747.