Alireza Sharafiyan Sikaroodi

Master student

Systematic Investigation of Mechanical Properties and their Optimization in  Hyaluronic Acid Based Hydrogels

Supervisors: Markus Lorke, Prof. Aldo R. Boccaccini

The limited regenerative capacity of the central nervous system (CNS) has driven the development of biomimetic hydrogel scaffolds for neural repair, where extracellular matrix (ECM) mechanics critically govern cell behavior and stem cell fate [1,2]. Hyaluronic acid (HA), oxidized with NaIO₄ to introduce aldehyde groups, can be combined with gelatin (GEL) and enzymatically crosslinked via microbial transglutaminase (mTG) to yield soft, brain ECM mimicking hydrogels [3,4]. However, the understanding of interactions between molecular weight, oxidation time, and polymer concentration, which collectively shape the resulting mechanics, is not fully characterized. This thesis investigates these parameters across HA molecular weights, oxidation times, and a range of OHA and GEL concentrations. The goal is to establish clear structure–property relationships for the rational design of neural ECM mimicking scaffolds.

[1] E. K. Pillai and K. Franze, “Mechanics in the nervous system: From development to disease,” Neuron, vol. 112, no. 3, pp. 342–361, Feb. 2024, doi: 10.1016/J.NEURON.2023.10.005.

[2] P. Yang et al., “Test and tune: evaluating, adjusting and optimising the stiffness of hydrogels to influence cell fate,” Chemical Engineering Journal, vol. 505, p. 159295, Feb. 2025, doi: 10.1016/J.CEJ.2025.159295.

[3] A. H. Pandit, N. Mazumdar, and S. Ahmad, “Periodate oxidized hyaluronic acid-based hydrogel scaffolds for tissue engineering applications,” Int. J. Biol. Macromol., vol. 137, pp. 853–869, Sep. 2019, doi: 10.1016/J.IJBIOMAC.2019.07.014.

[4] M. Lorke, S. Kuth, R. Frischknecht, and A. R. Boccaccini, “Development of oxidized hyaluronic acid based hydrogels for neuronal tissue engineering: Effects of matrix stiffness on primary neurons,” Acta Biomater., vol. 205, pp. 454–466, Oct. 2025, doi: 10.1016/J.ACTBIO.2025.09.007.