Multifunctional Biomedical Adhesives

Abstract

Currently available biomedical adhesives are mainly engineered to have one function (i.e., providing mechanical support for the repaired tissue). To improve the performance of existing bioadhesives and broaden their applications in medicine, numerous multifunctional bioadhesives are reported in the literature. These adhesives can be categorized as passive or active by design. Passive multifunctional bioadhesives contain inherent compositions and structural designs that can carry out additional functions without added external influences. These adhesives exhibit new functionalities such as antimicrobial properties, self-healing abilities, the ability to promote cellular ingrowth, and the ability to be reshaped. Conversely, active multifunctional bioadhesives respond to environmental changes (e.g., pH, temperature, electricity, light, and biomolecule concentration), which initiate a change in the adhesive to release encapsulated drugs or to activate or deactivate the bioadhesive for interfacial binding. This review article highlights recent advances in multifunctional bioadhesives.

Keywords: biomedical adhesives; multifunctionality; passive and active design; stimuli-responsiveness.

Figure 1.. Multifunctional biomedical adhesive design considerations.

The fundamental attributes of any successful biomedical adhesive include an application specific balance of appropriate cohesive and adhesive interactions coupled with the biocompatibility of the bulk adhesive material as well as any products generated during the curing process or degradation of the adhesive with time. Passive and active design elements can be used to ultimately tailor or refine these core attributes in multi-functional bioadhesives to more specifically target an overall desired outcome.

Figure 2.

Interfacial crosslinking chemistries between adhesive functionalized using NHS-activated ester (A), isocyanate (B), aldehyde (C), and catechol (D) with nucleophilic functional groups (e.g., -NH₂ of lysine) found on soft tissues. Catechol can also form coordination bonds with metal oxide surfaces, which may be present on the surface of an implant or medical device (E).

Figure 3.

Schematic illustration of the shape-to-fit sealant consisted of PEG-modified with dopamine (PEG-D) and nano silicate, Laponite (A). The adhesive transitions from a predominantly physically crosslinked network to covalently crosslinked network (B). The adhesive relies on reversible catechol-Laponite interactions (C) and slow oxidative catechol crosslinking over time (D). The adhesive was stretchable and adhesive (E), can be remolded to different shapes (F), and can apply around a convex pericardium (G) and collagen tubing (H) via a syringe. As the covalent crosslinking density increased, the hydrogel was shape-fixed and bound to the tissue via interfacial covalent bonds (I). Scale bar: 10 mm. Reproduced with permission ^[58]. Copyright 2017, John Wiley and Sons, Inc.

Figure 4.

Schematic of a pH-responsive adhesive containing catechol and phenylboronic acid (PBA). At an acidic pH, both the catechol and PBA contribute to strong interfacial binding to the wetted quartz substrate. The presence of the anionic, acrylic acid reduced local pH and prevented catechol–boronate complexation at a physiologically relevant pH for strong adhesion. When the pH was increased to a more basic value (i.e., pH 9.0), AAc lost its buffering capacity, which resulted in the formation of the catechol–boronate complex while inactivating the adhesive. Reproduced with permission ^[86]. Copyright 2018, American Chemical Society.

Figure 5.

A schematic illustration of composite adhesive consisting of a dopamine-conjugated hyaluronic acid (DOP-HA) adhesive matrix and PBA-modified porous PLGA microparticles (PBA-PLGA-MPs) loaded with insulin. In the design, the particles serve as both the insulin reservoir and the cross-linker of HA chain. At a low glucose level, DOP-HA densely packs on the surface of PBA-PLGA MPs, acting as a diffusion barrier to block insulin release. At a high glucose level, DOP-HA coating detaches from the particles, causing fast insulin release. Reproduced with permission ^[108], Copyright 2017, Elsevier.

Figure 6.

Schematic representation of PEG-PSMEU-based bioadhesive, which contains cationic sulfamethazine (blue) capable of reversible π-π interactions and binding to anionic DNA for the sustained release and localized delivery of DNA. PEG−PSMEU can be injected from a solution with a relatively high pH and room temperature (pH 8.5, 23 °C) into physiological condition (pH 7.4, 37 °C) for wound healing applications. Reproduced with permission ^[127]. Copyright 2018, American Chemical Society.

Figure 7.

Photographs and schematic representations of PDMS imbedded with Fe₃O₄ nanoparticles and modified with surface micropillars that were coated with thermoresponsive adhesive, p(DMA-co-MEA-co-NIPAAm) (a). NIR irradiation resulted in localized photothermal effect to increase adhesion in the NIR-irradiated region (b). Transmission electron microscope (TEM) image showing the distribution of Fe₃O₄ nanoparticles (c). The adhesion strength increased with increasing radiation time by NIR laser underwater (d). Schematic diagram showing the switchable adhesion mechanism of the NIR‐responsive adhesive device and its photograph (e), demonstrating reverse adhesion to a 110-g steel ball (f). Reproduced with permission ^[94]. Copyright 2018, John Wiley and Sons, Inc.