Designing injectable peptide-based hydrogels for TERM applications

Jun 30, 2022, 4:30 PM
10m
Room: S2

Room: S2

Speaker

Saiani, Alberto (University of Manchester)

Description

"Introduction
The use of non-covalent self-assembly to construct materials has become a prominent strategy in biomaterial science offering practical routes for the construction of increasingly functional materials for a variety of applications ranging from cell culture and tissue engineering to in-vivo cell and drug delivery.[1] A variety of molecular building blocks can be used for this purpose, one such block that has attracted considerable attention in the last 20 years is de-novo designed peptides. The beta-sheet motif is of particular interest as short peptides can be designed to form beta-sheet rich fibres that entangle and consequently form very stable shear-thinning (injectable) hydrogels. The intrinsic biocompatibility and low immunogenicity of these materials makes them ideal for TERM applications. [2-8]

Methodology
We explored the unique shear thinning properties (injectability) of a family of short beta-sheet forming peptides (8-10 amino acids long). Through in-depth structural characterisation (AFM, TEM, SAXS, FTIR) and detailed rheological studies (shear rheometry and SIPLI) and modelling of dynamic behaviour (Standard mechanical models) we were able to develop a fundamental understanding of how design affects injectability. This understanding was then used to develop injectable system for the delivery of cell for a range of TERM applications.

Results & Discussion
Due to the self- assembled nature and dynamic properties of this family of peptides we were able to design readily injectable systems. We showed how the beta-sheet fibre edges properties (hydrophilic vs hydrophobic) could be modified by adding lysine end-residues. This allowed to design highly dynamic systems that were able to “liquify” (shear-thin) upon application of a large strain (e.g.: pressure) and then recover instantaneously their gel-like properties upon removal of the strain. [3] We showed that these hydrogels allowed the successful delivery of cells through injections using very small needle gauges.
In recent work performed in the context of nucleus pulposus repair and heart regeneration using a rat model we showed the potential of these systems as injectable functional materials for TERM applications. [4-6] In addition, we also used 3D-briorinting approaches to show that these shear-thinning materials are ideal bioinks for the 3D printing of cells. [7-8]

Conclusion
The intrinsic biocompatibility and non-immunogenic nature of these system combined with their unique shear-thinning properties allowed us to develop a family or injectable system for TERM applications. We demonstrate how design rule can be manipulated to tailor the properties of these materials to the application intended.

References:
1. Zhang S. G., Nature Biotechnology 2003, 21, 1171.
2. Gao J. et al., Biomacromolecules 2017, 18, 826.
3. Wychowaniec J. et al., Biomacromolecules 2020, 21, 2285.
4. Corimo L. et al., Acta Biomaterialia 2019, 92, 92.
5. Cosimo L. et al., Acta Biomaterialia 2021, 127, 116.
6. Burgess K. et al., Materials Science & Engineering C 2020, 119, 111539.
7. Raphael B. et al., Materials Letters 2017, 190, 103.
8. Chiesa I. et al., Frontiers in Medical Technology 2020, 2, 571626."

62825435106

Presentation materials

There are no materials yet.