UCLA

Bioadhesives, such as tissue sealants, hemostatic agents, and tissue sealants have gained increasing popularity for addressing wound management for traumatic and surgical injuries. This new generation of adhesive demonstrates significant advantages over traditional suturing and stapling techniques that can lead to infection, leakage of bodily fluid and gas, as well as secondary damage to tissues. Bioadhesives can be most broadly classified based on internal or external administration. While bioadhesives designed for external use are most widely used for topical application, such as wound closure, internal bioadhesives are surgically implanted and, therefore, require biocompatibility and strong adhesive ability to wet tissues. Further, hydrogel-based bioadhesives may be designed with nanoparticles or biopolymers that impart specific functionality, such as conductive or hemostatic properties. Scaffolds designed with conductive biomaterials have been extensively investigated in the field of tissue engineering based on their ability to support the function of excitable cell types, such as cardiomyocytes and neurons. Bioadhesives have also been designed to promote hemostasis for applications such as surgical sealants. In first two sections of this project, we aimed to develop conductive bioadhesives for cardiac tissue repair by combining highly biocompatible gelatin methacryloyl (GelMA), with an electrically conductive choline-based bio ionic liquid (Bio-IL). Here, we chemically modified gelatin to form photocrosslinkable hydrogels in the presence of visible or UV light, depending on the photoinitiator used. Conductive hydrogels were fabricated with varying concentrations of GelMA and Bio-IL, which resulted in scaffolds with high biocompatibility, as well as tunable electrical conductivity, and mechanical strength. We then demonstrated the ability of Bio-IL conjugated hydrogels to transduce physicochemical stimuli and modulate the growth of primary CMs in both 2D and 3D cultures in vitro. In addition, we demonstrated that the engineered hydrogels were highly biodegradable and biocompatible in vitro, and that they did not elicit inflammatory responses when implanted in vivo. Our following project investigated the development of cardiopatches using electrospun GelMA conjugated with Bio-IL. The resulting cardiopatches demonstrated tunable conductive and mechanical properties by optimizing the concentration of GelMA and Bio-IL used during synthesis. GelMA/Bio-IL cardiopatches exhibited excellent adhesiveness to cardiac tissues, and biocompatibility both in vitro and in vivo. CMs and CFs seeded on the surface of cardiopatches demonstrated excellent cell attachment and proliferation, and the scaffold supported the expression of gap junction proteins indicating the cells ability to function synchronously. Taken together, these conductive bioadhesives demonstrated excellent potential to be readily tailored to cardiac tissue regenerative therapies. Lastly, our group developed a hemostatic surgical sealant with robust mechanical properties based on the biopolymers GelMA and elastin-like polypeptide (ELP). These adhesive hydrogels were rendered hemostatic by the incorporation of the synthetic clay Laponite (LA) and were rapidly photocrosslinked in the presence of UV radiation using the photoinitiator Irgacure 2959. We demonstrated the highly tunable mechanical and adhesive properties of these nanocomposite hydrogels by varying the concentrations of GelMA and ELP. Likewise, we demonstrated the excellent hemostatic performance of these scaffolds both in vitro and in vivo by varying the concentration of LA. Our nanocomposite GelMA/ELP/LA hydrogels also showed remarkable biocompatibility both in vitro and in vivo and did not elicit an inflammatory response when implanted subcutaneously.