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Instant curing adhesives typically fall within three categories, being activated by either light (photocuring), heat (thermocuring) or chemical means. These curing strategies limit applications to specific substrates and can only be activated under certain conditions. Here we present the development of an instant curing adhesive through low-voltage activation. The electrocuring adhesive is synthesized by grafting carbene precursors on polyamidoamine dendrimers and dissolving in aqueous solvents to form viscous gels. The electrocuring adhesives are activated at −2 V versus Ag/AgCl, allowing tunable crosslinking within the dendrimer matrix and on both electrode surfaces. As the applied voltage discontinued, crosslinking immediately terminated. Thus, crosslinking initiation and propagation are observed to be voltage and time dependent, enabling tuning of both material properties and adhesive strength. The electrocuring adhesive has immediate implications in manufacturing and development of implantable bioadhesives.

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A potential siRNA carrier for pulmonary gene delivery was assessed by encapsulating siRNA into biodegradable polyester nanoparticles consisting of tertiary-amine-modified polyvinyl alcohol (PVA) backbones grafted to poly(d,l-lactide-co-glycolide) (PLGA). The resulting siRNA nanoparticles were prepared using a solvent displacement method that offers the advantage of forming small nanoparticles without using shear forces. The nanoparticles were characterized with regard to particle size, zeta-potential, and degradation at pH 7.4 using dynamic and static light scattering. SiRNA release studies were performed and correlated to the nanoparticle degradation. In vitro knockdown of firefly luciferase reporter gene was used to assess the potential of the nanoparticles as siRNA carriers in a human lung epithelial cell line, H1299 luc. The amine-modified-PVA-PLGA/siRNA nanoparticles form 150-200 nm particles with zeta-potentials of +15-+20 mV in phosphate buffered saline (PBS). Break down of the nanoparticles was seen within 4 h in PBS with sustained release of siRNA. These nanoparticles have achieved 80-90% knockdown of a luciferase reporter gene with only 5 pmol anti-luc siRNA, even after nebulization. Hence we conclude that amine-modified-PVA-PLGA/siRNA nanoparticles could be a promising siRNA carrier for pulmonary gene delivery due to their fast degradation and potent gene knockdown profile.

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Development of bioadhesive formulations for tissue fixation remains a challenge. The major drawbacks of available bioadhesives are low adhesion strength, toxic byproducts, and complexity of application onto affected tissues. In order to address these problems, this study has developed a hydrogel bioadhesive system based on poly amido amine (PAMAM) dendrimer, grafted (conjugated) with UV-sensitive, 4-[3-(trifluoromethyl)-3H-diazirin-3-yl] benzyl bromide (PAMAM-g-diazirine). This particular diazirine molecule can be grafted to the surface amine groups of PAMAM in a one-pot synthesis. Diazirine functionalities are carbene precursors that form covalent crosslinks with hydrated tissues after low-power UV activation without necessity of free-radical initiators. The rheological properties and adhesion strength to ex vivo tissues are highly controllable depending on diazirine grafting, hydrogel concentration, and UV dose intensity fitting variety types of tissues. Covalent bonds at the tissue/bioadhesive interface provide robust adhesive and mechanical strength in a highly hydrated environment. The free flowing hydrogel conversion to elastic adhesive after UV activation allows intimate contact with the ex vivo swine tissue surfaces with low in vitro cytotoxicity observed, making it a promising bioadhesive formulation toward clinical applications.

Soft tissue fixation of implant and bioelectrodes relies on mechanical means (e.g. sutures, staples, screws), with associated complications of tissue perforation, scarring, and interfacial stress concentrations. Adhesive bioelectrodes address these shortcomings with voltage cured carbene-based bioadhesives, locally energized through graphene interdigitated electrodes.Electro-rheometry and adhesion structure activity relationships were explored with respect to voltage and electrolyte on bioelectrodes synthesized from graphene 3D-printed onto resorbable polyester substrates. Adhesive leachates effects on in vitro metabolism and human derived platelet rich plasma response serves to qualitatively assess biological response. The voltage activated bioadhesives are found to have gelation times of 60 sec or less with maximum shear storage modulus (G') of 3 kPa. Shear modulus mimics reported values for human soft tissues (0.1-10 kPa). The maximum adhesion strength achieved for the ~50 mg bioelectrode films is 170 g cm -2 (17 kPa), which exceeds the force required for tethering of electrodes on dynamic soft tissues. The method provides the groundwork for implantable bio/electrodes that may be permanently incorporated into soft tissues, vis-à-vis graphene backscattering wireless electronics since all components are bioresorbable.