Bioinspired Printable Tough Adhesive with Tunable Mechanics via Molecular Topology Design

Hydrogels, composed of both natural and synthetic polymers, are emerging as promising materials for a range of 3D printing applications, particularly in the field of regenerative medicine. These materials offer significant potential for creating scaffolds for tissue regeneration, as well as for loading and delivering therapeutics on demand. The challenge, however, lies in the in situ additive manufacturing of tough adhesive hydrogels that can withstand the harsh mechanical environment required for repairing certain mechanically active tissues. This is especially relevant in the context of reconstructive surgeries for head and neck cancer patients, where the need for durable and biocompatible materials that can mimic the architecture and properties of damaged tissues is critical.
In this study, we present a novel printable tough adhesive hydrogel inspired by the adhesion mechanisms of sandcastle worms, which form strong attachments to sand grains through a combination of supramolecular interactions. Our hydrogel system is composed of polyacrylic acid (PAA), a negatively charged synthetic polymer, and chitosan, a positively charged natural polymer found abundantly in shrimp shells and other marine organisms. The electrostatic interaction between these two polymers enables the formation of a stable scaffold.
A key feature of this material system is its ability to be mechanically enhanced with benigh triggers, such as body fluids, a process involving the orders-of-magnitude increase of their toughness, bioadhesion and stiffness. This phenomenon is crucial for their potential long-term usage to serve as a biomimetic replacement for damaged tissues and for tissue repair.
We further investigated how the molecular weight of the adhesive polymer (e.g. PAA) would influence the mechanical properties of the hydrogel. Among various molecular weights of PAA tested (from 100 to 3000 kDa), with the same chitosan biopolymer, the 1250kDa variant resulted in a hydrogel demonstrating superior toughness, stiffness, and bioadhesion. Among all molecular weights, 1250kDa and 3000kDa has exhibited optimal printability due to their shear thining and high yield strength. Upon triggered mechanical enhancement in water, 1250kDa formula obtained significantly higher stiffness and toughness than all other molecular weights.
Furthermore, we explored the role of charge interactions by substituting uncharged materials, such as cellulose (which lacks positive charge) and polyethylene oxide (which lacks negative charge), for chitosan and PAA in control experiments. This demonstrated the critical importance of electrostatic interactions in the hydrogel's mechanical performance and overall efficacy.
To assess the biocompatibility and long-term stability of the hydrogel, we implanted the hyrdogels subcutaneously in mice over a 28-day period. The results showed that the hydrogel triggered minimal inflammatory responses and maintained its structural integrity throughout the duration of the study. This suggests that the hydrogel is not only mechanically robust but also biocompatible for in vivo applications.
In conclusion, this study highlights the potential of tuning hydrogel mechanics by manipulating the hydrogel network topology. The ability to control the mechanical properties of the hydrogel by varying the molecular weight of adhesive polymers and modulating electrostatic interactions opens up new avenues for the design of hydrogel systems with tunable mechanics that can be tailored to specific clinical needs. The combination of mechanical strength, biocompatibility positions these hydrogels as a promising material for patients undergoing complex reconstructive surgeries, offering hope for improved clinical outcomes in the field of regenerative medicine.