Controlled Tough Bioadhesion with Ultrasound

Tough adhesion of hydrogels and biological tissues has significant implications in engineering and medicine, but remains challenging to form and control. Here, we report an ultrasound (US)-mediated bioadhesion technology to achieve tough bioadhesion with controllability and fatigue resistance. Without chemical reactions, our strategy amplifies the adhesion energy and interfacial fatigue threshold between hydrogels and porcine or rat skin by up to 100 and 10 times. Combined experiments and theoretical modeling identify the key mechanism to be US-induced cavitation, which propels and anchors primers into tissues with mitigated barrier effects. The US effects are potent yet localized to enable spatial patterning of tough bioadhesion, on-demand detachment, and transdermal drug delivery. This work expands the material repertoire for tough bioadhesion and enables bioadhesive technologies with high-level controllability.<br/><br/>The US-mediated bioadhesion is achieved in two steps. We first apply the US to a primer solution/suspension of anchoring agents spread on tissue substrates with an ultrasonic transducer for a short period of time. Sequentially, we cover the treated area with a hydrogel patch with gentle compression. As a model system, we deploy a chitosan (Chi) solution and a polyacrylamide-alginate (PAAm-alg) hydrogel as the primer and the hydrogel patch, respectively. Our results show an adhesion energy of 1500 J m^-2 obtained on porcine skin with the US treatment, more than 15 times higher than that of the no-US control. Our strategy is demonstrated with a large repertoire of materials. We confirm the adhesion enhancement by US with other hydrogels, including another double-network poly(N-isopropylacrylamide)-alginate (PNIPAm-alg) hydrogel and a single-network PAAm hydrogel. The same efficacy is observed with other anchoring primers such as proteins (gelatin) and nanoparticles (chitosan nanocrystals, aldehyde-functionalized cellulose nanocrystals). Besides skin, our strategy is applicable to various biological tissues, including buccal mucosa and aorta.<br/><br/>We then delve into the mechanism underlying US-mediated bioadhesion, where we combine experiments and theoretical modeling to substantiate the link between the US-mediated cavitation and bioadhesion. The US substantially enhances both the peak intensity of cavitation microbubble and bioadhesion. Fatigue fracture tests reveal a significantly enhanced interfacial fatigue threshold Γ₀from ~5 J m^-2 (no-US) to ~65 J m^-2. The results substantiate the existence of strong interfacial bonding, which typically only observed with covalent bonds, in contrast to often weak physical interactions such as entanglement resulted from interdiffusion. US also serves as a regulator for tough bioadhesion. As the US effects scale with the distance between the transducer and the tissue (d), simply maneuvering the US transducer could control the bioadhesion in magnitude and space. To understand and predict the spatially controlled bioadhesion, we conduct theoretical modeling on the acoustic field produced by the US transducer between the horn and the substrate. We extract the area on the substrate where the absolute pressure drops below the vapor pressure in every acoustic cycle, thereby enabling the formation of cavitation bubbles. At various d, we obtain drastically different pressure profiles on the tissue substrate, from which the regions impacted by cavitation are estimated. The simulation results agree with the experimental measurements. Besides the spatial control, we demonstrate that US can enable temporal control over bioadhesion by using a thermo-gelling gelation as anchoring primer and the heating effect of US.<br/><br/>Together, we report US-mediated bioadhesion to precisely control hydrogel bioadhesion in space and time. The universal applicability of our strategy promises impacts in broad areas ranging from human-machine interface and precision medicine.