Hydrolytically-degradable click alginate hydrogels
Daniela Garske a, Aline Lueckgen a, Georg N. Duda a e, Amaia Cipitria a e, Rajiv M. Desai b c, David J. Mooney b c, Peter Fratzl d
a Julius Wolff Institute & Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, 13353 Berlin
b School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138
c Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115
d Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam
e Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, 13353 Berlin
Proceedings of New Advances in Probing Cell-ECM Interactions (CellMatrix)
Berlin, Germany, 2016 October 20th - 21st
Organizers: Ovijit Chaudhuri, Allen Liu and Sapun Parekh
Poster, Aline Lueckgen, 055
Publication date: 25th July 2016

Novel biomaterials are intensely investigated to offer improved therapeutic options for human trauma cases in the skull and load-bearing bones. We aim to contribute to this exciting field by creating constructs featuring spatial and temporal control over the material’s degradation properties. This project thus aims to create hydrogels with dynamic patterns in degradation to direct cell infiltration, guide extracellular matrix deposition and eventually pattern in vivo tissue formation. 

Alginate hydrogels possessing regions of different degradation properties can be attained by altering the material’s (i) physical properties, (ii) crosslinking mechanism and degree of crosslinking, and (iii) degradation mode and kinetics. The molecular weight distribution and polymer concentration (physical properties) are optimized for targeted initial mechanical properties and cell compatibility in 3D, and then held constant. Prior to crosslinking, the alginate polymer is modified by carbodiimide chemistry to introduce RGD peptides that facilitate cell adhesion, as well as norbornene and tetrazine moieties that enable a rapid, specific, and bioorthogonal click reaction (crosslinking mechanism) [1]. The degree of crosslinking can be controlled by varying the degree of substitution and/or the ratio of click functional groups. Regarding the degradation mode, alginate chains are oxidized to impart passive hydrolytic degradation, and the targeted degradation rate can be achieved by adjusting the percent of oxidation.  

The synthesized materials are characterized for their gelation kinetics, loss and storage modulus measured by rheology, elastic modulus and stress relaxation behavior determined by unconfined compression testing, and degradation behavior determined by swelling ratio and dry mass weight changes over a time frame of 4 weeks. Mouse pre-osteoblasts are seeded on top of the hydrogel surface in order to study their viability, morphology, proliferation, and invasion into the 3D gel. While this initial study focuses on fabricating single-phase hydrolytically-degradable systems, later iterations will explore multi-phase systems with regions of different degradation mode and/or kinetics within the same hydrogel system with simple geometrical patterning in the μm range.   

[1] Rajiv M. Desai, Sandeep T. Koshy, Scott A. Hilderbrand, David J. Mooney, and Neel S. Joshi. "Versatile Click Alginate Hydrogels Crosslinked via Tetrazine–Norbornene Chemistry." Biomaterials 50 (2015): 30-37.



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