One-pot synthesis of injectable self-healing thermoresponsive halloysite nanotube-reinforced nanocomposite hydrogels for tissue engineering

Injectable hydrogels that can fill irregular defects through a minimally invasive approach are of particular interest to replace invasive surgeries in tissue scaffold implantation. However, the use of injectable hydrogels is often restricted by the drawback of having poor mechanical properties. In this work, a novel halloysite nanotube (Hal)-based hydrogel was developed using bacterial cellulose and gelatin, as well as acid-treated Hal to serve a dual purpose of providing structural support for tissue regeneration while offering possibilities for drug delivery at a local site. The fabricated hydrogels were then analyzed physically and morphologically for injectability, gelling ability, self-healing capability, as well as composition characterization, surface morphology, mechanical performance, and biodegradability. Analyses revealed that all the hydrogels could be injected as a liquid, with an in-situ sol-gel transition occurring after 10 min at 37 °C. Furthermore, the honeycomb-like structure of the hydrogel and the rougher surface where Hal dispersed over the surfaces could also provide sufficient space and anchorage sites to facilitate cell attachment. With the moisture content reaching up to 85–92%, the hydrogels could provide a moist recovery environment for the healing process. More importantly, the incorporation of Hal greatly improved the compressive strength and Young's modulus up to 60% and 40%, respectively. Furthermore, antibiotic-loaded hydrogels demonstrated effective antimicrobial activity against Staphylococcus epidermidis, methicillin-susceptible Staphylococcus aureus (MSSA), and methicillin-resistant S. aureus (MRSA). Collectively, such hydrogels with a minimally invasive delivery approach and the potential to aid in tissue regeneration can be applied in biomedical and tissue engineering applications, along with a combined local delivery of antimicrobial agents in the near future.