UCLA

Bioadhesive hydrogels provide promising solutions for bleeding wound management to replace invasive wound closure methods such as suturing and stapling. Adhesive substances based on naturally occurring biological materials from living organisms, such as mussels and Boston ivy plants, harness phenolic compounds for their attachment to wet surfaces. Recent efforts have centered on catechol groups as effective functionality to leverage tissue adhesion in biomaterials. Bioadhesion performance in catechol-integrated biomaterials is a strong function of polyphenolic structure and the processing approach for their integration into hydrogel networks.One of the major hurdles in catechol-functionalization chemistries is insufficient phenolic uptake due to their low yield and inherently limited functionalization capacity of proteins. Polyphenols not only enable stronger attractions with various substrates but also act as crosslinking points, strengthening polymer network cohesion. Polyphenolic compounds derived synthetically from phenolic small molecules as well as those occurring naturally, such as tannins, have formed a large library of additional functionality such as antimicrobial and photothermal responsiveness, calling for further development for applications in wound management. Here, different strategies undertaken for developing bioadhesives are first introduced in terms of constitutive polymers and their crosslinking mechanisms. Then, procedures for introducing hemostatic efficacy to hydrogels are discussed in detail to enable their function for sealing bleeding wounds. Next, a mechanistic study is described that highlights current pitfalls in the design of catechol-functionalized biomaterials in free-radical-based photocrosslinking processes. Then, in situ polymerization of catecholic compounds is introduced to enable robust bioadhesion of gelatin methacryloyl (GelMA) hydrogel patches. Given the significant demand for injectable bioadhesives, a chemical procedure is proposed for high-efficacy loading of catecholic compounds covalently to gelatin backbones. Here, simple oxidative polymerization is implemented on catechol-carrying molecules (caffeic acid) prior to standard coupling amidation reactions to boost catechol attachment and their function for wound closure. Further, photothermal responsive function and rapid thermal and covalent gelation enabled by larger molecular weight polymers of polyphenolic structures (i.e., L-3,4-dihydroxyphenylalanine, L-DOPA) are obtained following the same procedure. Finally, I discuss the implication of these studies in clinical settings and potentials for further development and additional tissue regenerative functions.