Self-assembled nanofibrous and nanocomposite hydrogels for bone and cardiac tissue engineering

Place: conference room, IMDEA Nanociencia.

Abstract:

Hydrogels are increasingly explored in tissue engineering and regenerative medicine to support cell growth and tissue regeneration. In particular, low molecular weight gelators (LMWGs) are a promising class of small molecules that can form hydrogels through self-assembly; however, hydrogels prepared from LMWGs, especially bis-urea-based gelators, are less well explored than those based on polymers. Key open questions include the biocompatibility and bioactivity of these hydrogels as well as the ability to tune their chemical and physical properties.

The first part of this talk will explore the hypothesis that the incorporation of metal ions (Mg²⁺, Ca²⁺, Zn²⁺, Na⁺/K⁺) into bis-urea LMWG hydrogels can enhance their mechanical and biological properties. Rheological analysis reveals that the ion-modified hydrogels exhibit increased mechanical strength while still demonstrating shear-thinning and self-healing behavior, which makes the hydrogels suitable for applications such as injection for minimally invasive delivery and 3D bioprinting. Furthermore, L929 fibroblasts demonstrate high viability and proliferation, both when cultured on the surface of the hydrogels and when encapsulated inside them in 3D, with these effects being further amplified by the presence of metal ions. As additional proof-of-concept for bone tissue engineering, the ion-modified hydrogels are used to promote the in vitro differentiation of MC3T3-E1 pre-osteoblasts, with the hydrogels containing Ca²⁺ ions leading to robust collagen deposition and matrix mineralization.

Further, the hydrogels support the co-culture of induced pluripotent stem cell derived cardiomyocytes and cardiac fibroblasts for applications in cardiac tissue engineering. The second part of this talk will systematically investigate the incorporation of four nanoparticle types (carbon nanotubes, cellulose nanocrystals, hydroxyapatite nanoparticles, and magnesium carbonate nanoparticles) into the hydrogels at concentrations of 0.15, 0.5, and 1.0 wt.%. Rheological characterization reveals that all nanoparticle types enhance storage and loss moduli in a concentration-dependent manner, with carbon nanotubes producing the greatest effect.

Biological assessment using L929 fibroblasts demonstrates high cell viability across all formulations, with a clear inverse relationship with nanoparticle loading. For example, metabolic activity and DNA quantification assays show that low nanoparticle concentrations (0.15 wt.%) support proliferation comparable to or exceeding controls while higher concentrations progressively reduce cell survival. An optimal concentration range of 0.15 to 0.5 wt.% nanoparticles is identified for balancing mechanical reinforcement with cellular compatibility.

Overall, these findings suggest that ion-modified or nanoparticle-reinforced bis-urea LMWG hydrogels offer significant potential for applications ranging from advanced scaffolds for tissue engineering and regenerative medicine to drug delivery systems.

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