CAREER: Modular Design of Bioadhesives for Implantation

About This Grant

Non-Technical Summary Suturing is often used in surgeries to close wounds and this technology has been practiced for thousands of years. Yet, it is an uncomfortable and damaging process—causing pain, tissue damage, infection, scarring, and leakage. Hydrogel bioadhesives have thus emerged, aiming to replace sutures. Since their first development over a half-century ago, they have substantially benefitted surgeries in many ways, such as simplified procedures, short operation time, less discomfort, and reduced post-surgery complications. Hydrogel bioadhesives are soft, wet, and biocompatible and used just like common glues or duct tape. Existing hydrogel bioadhesives are mostly designed for emergency applications such as wound closure and sealing. However, when prolonged adhesion is required, typically in long-term implantation, they are unfit, owing to mechanical mismatch with target tissues and unstable adhesion in the physiological environment. The mechanical mismatch constrains natural tissue movement to cause damage, insufficiently supports tissue physiological functions, and alters the local cell microenvironment to induce abnormal cellular behaviors. Unstable adhesion leads to premature adhesion failure. To address these challenges, this project develops a class of bioadhesive implants by modular design. The bioadhesive implants integrate a liquid adhesive layer and a solid hydrogel layer, where the former provides fast, stable, and strong adhesion between the target tissue and the hydrogel layer, and the latter provides tissue-specific mechanical compliance. This project supports the fundamental research to determine the optimal formulation of bioadhesive implants, investigate adhesion kinetics and properties under various operation conditions as well as long-term adhesion behaviors under fatigue mechanical loads, and elucidate relations between adhesion supramolecular processes and adhesion behaviors. These findings expand the knowledge of bioadhesive design, principles, and mechanisms, and advance various implantable therapies such as bioelectronic medicine, regenerative medicine, and on-target drug delivery. This project also highlights the broader impacts on education and outreach by engaging grades 4-12 and undergraduate students to learn the basics of hydrogels, perform the hands-on making of hydrogels, and participate in hydrogel and bioadhesive research, and by broadly disseminating this research to the general public to increase their awareness of hydrogel bioadhesive technologies and amplify the scientific and societal impacts. Technical Summary This project develops a class of bioadhesive implants by modular design, which integrates a liquid adhesive polymer layer and a solid tissue-elasticity-matching hydrogel layer. The bioadhesion is realized by penetrating adhesive polymers into the target tissue and the hydrogel layer and then gelating inside them to form a new polymer network, connecting them through topological entanglements. The polymer gelation kinetics can be tuned to enable fast adhesion and the topological entanglements create deep adhesion to allow strong and stable adhesion. The bioadhesion does not require functional groups from hydrogels, thus broadening the choices of hydrogels (including chemically inert hydrogels) to be used to match the elasticity of diverse biological tissues. The research objectives are (i) design, formulate, and characterize bioadhesive implants, (ii) investigation of complex adhesion behaviors ex vivo, and (iii) mechanistic understanding of linking supramolecular processes to adhesion. To obtain the optimal formulation and guide the practical use of bioadhesive implants, experimental studies will be performed to evaluate adhesion energy, adhesion kinetics, adhesion behaviors associated with adhesive thicknesses, penetration depths, material properties of tissues and hydrogels, and fatigue loading, as well as biocompatibility. To fundamentally understand the adhesion mechanism, theoretical modeling will be established to elucidate the critical supramolecular process of diffusion and gelation of adhesive polymers on the effective development of bioadhesion and how they are influenced by the material properties of hydrogels and tissues. This research also offers an important and emerging topic for educational and outreach activities on hydrogels and bioadhesives and facilitates clinical collaboration and translation. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.