Hydrogels Formed by Oxo-ester Mediated Native Chemical Ligation
Iossif Strehin1, Dmitri Gourevitch, Yong Zhang
1Northwestern University, Evanston, IL 60208, Biomedical Engineering Department, Materials Science and Engineering Department, Chemical and Biological Engineering Department, Chemistry of Life Processes Institute, Institute for Bionanotechnology in Medicine, Robert H. Lurie Comprehensive Cancer Center.
Biomaterials Science
|July 30, 2013
Summary
Oxo-ester mediated native chemical ligation enables rapid hydrogel formation for cell encapsulation and in-vivo applications. This biocompatible cross-linking strategy shows promise for tissue engineering and drug delivery.
Area of Science:
- Biomaterials Science
- Polymer Chemistry
- Biotechnology
Background:
- Native chemical ligation (NCL) is a peptide ligation method.
- Oxo-ester mediated native chemical ligation (OMNCL) is a variation of NCL.
- Current OMNCL methods require harsh conditions unsuitable for biological applications.
Purpose of the Study:
- To develop and evaluate OMNCL for polymer hydrogel formation in a biological context.
- To assess the utility of OMNCL hydrogels for in-vitro cell encapsulation and in-vivo implantation.
- To explore OMNCL as a cross-linking strategy for tissue engineering and regenerative medicine.
Main Methods:
- Synthesis of branched poly(ethylene glycol) (PEG) precursors with NHS-activated oxo-esters and N-cysteine (N-Cys) endgroups.
- Hydrogel formation via mixing aqueous solutions of functionalized PEGs at physiological pH.
- Characterization of hydrogel properties, including gelation kinetics, swelling behavior, mechanical strength, and tissue adhesion.
- In-vitro cell encapsulation and viability assessment.
- In-vivo subcutaneous implantation in mice to evaluate biocompatibility and inflammatory response.
Main Results:
- Rapid hydrogel formation at physiological pH using OMNCL.
- Quantitative 1H NMR confirmed OMNCL pathway with amide bond formation.
- Gelation rate tunable by pH and temperature (seconds to minutes).
- Unique swelling-contraction behavior attributed to disulfide cross-linking.
- High lap shear adhesion strength (46 kPa) to hydrated tissue.
- High cell viability in encapsulated cells.
- Minimal acute inflammatory response in vivo.
Conclusions:
- OMNCL is a viable method for creating biocompatible hydrogels under physiological conditions.
- OMNCL hydrogels exhibit tunable properties, good adhesion, and support cell viability.
- OMNCL is a promising strategy for in-vivo applications like wound healing, tissue repair, drug delivery, and tissue engineering.
