Injectable, self-healing mesoporous silica nanocomposite hydrogels with improved mechanical properties

Self-healing hydrogels have emerged as promising biomaterials in regenerative medicine applications. However, an ongoing challenge is to create hydrogels that combine rapid self-healing with high mechanical strength to make them applicable to a wider range of organs/tissues. Incorporating nanoparticles within hydrogels is a popular strategy to improve the mechanical properties as well as to provide additional functionalities such as stimuli responsiveness or controlled drug delivery, further optimizing their use. In this context, mesoporous silica nanoparticles (MSNs) are promising candidates as they are bioactive, improve mechanical properties, and can controllably release various types of cargo. While commonly nanoparticles are added to hydrogels as filler component, in the current study we developed thiol surface-functionalized MSNs capable of acting as chemical crosslinkers with a known hydrophilic polymer, polyethylene glycol (PEG), through dynamic thiol-disulfide covalent interactions. Due to these dynamic exchange reactions, mechanically strong nanocomposites with a storage modulus of up to 32 +/- 5 kPa compared to 1.3 +/- 0.3 kPa for PEG hydrogels alone, with rapid self-healing capabilities, could be formed. When non-surface modified MSNs were used, the increase in storage modulus of the hydrogels was significantly lower (3.4 +/- 0.7 kPa). In addition, the nanocomposites were shown to degrade slowly over 6 weeks upon exposure to glutathione while remaining intact at physiological conditions. Together, the data argue that creating nanocomposites using MSNs as dynamic crosslinkers is a promising strategy to confer mechanical strength and rapid self-healing capabilities to hydrogels. This approach offers new possibilities for creating multifunctional self-healing biomaterials for a wider range of applications in regenerative medicine.