Tougher Bioadhesives through Dual Stimulation Strategies.

Carbene-based bioadhesives have favourable attributes for tissue adhesion, including non-specific bonding to wet and dry tissues, but suffer from relatively weak fracture strength after photocuring. Light irradiation of carbene-precursor (diazirine) also creates inert side products that are absent under thermal activation. Herein, a dual activation method combines light irradiation at elevated temperatures for the evaluation of diazirine depletion and effects on cohesive properties.

Color changing bioadhesive barrier for peripherally inserted central catheters.

Bacteria migration at catheter insertion sites presents a serious complication (bacteraemia) with high mortality rates. One strategy to mediate bacteraemia is a physical barrier at the skin-catheter interface. Herein a colorimetric biosensor adhesive (CathoGlu) is designed and evaluated for both colorimetric detection of bacterial infection and application as a bacteria barrier.

Synthesis and Evaluation of Metal Lipoate Adhesives.

The development of new bioadhesives with integrated properties remains an unmet clinical need to replace staples or sutures. Current bioadhesives do not allow electronic activation, which would allow expansion into laparoscopic and robotic surgeries. To address this deficiency, voltage-activated adhesives have been developed on both carbene- and catechol-based chemical precursors.

Bacterial cellulose adhesive patches designed for soft mucosal interfaces.

The wet environment in the oral cavity is challenging for topical disease management approaches. The compromised material properties leading to weak adhesion and short retention (<8 h) in such environment result in frequent reapplication of the therapeutics. Composites of bacterial cellulose (BC) and carbene-based bioadhesives attempt to address these shortcomings.

Hydrophobic Bioadhesive Composites for Human Motion Detection.

Conductive hydrogels are rapidly rising as sensing materials for bioelectronics applications, but lack mechanical and adhesion strength due to their excess water content. We propose a diazirine-grafted polycaprolactone adhesive (CaproGlu)/carbon nanotubes (CNTs) composite that can provide wet adhesion and strong mechanical properties at the tissue-machine interface. The introduced CNTs not only reinforced the CaproGlu, but also formed electrically conducting pathways.

Fibrillated bacterial cellulose liquid carbene bioadhesives for mimicking and bonding oral cavity surfaces.

Topical treatments for oral wounds and infections exhibit weak adhesion to wet surfaces which results in short retention duration (6-8 hours), frequent dosing requirement and patient incompatibility. To address these limitations, aqueous composites made of fibrillated bacterial cellulose and photoactive bioadhesives are designed for soft epithelial surfaces. The aqueous composites crosslink upon photocuring within a minute and exhibit a transition from viscous to elastic adhesive hydrogels.

A Fluorescence Kinetic-Based Aptasensor Employing Stilbene Isomerization for Detection of Thrombin.

It is important to detect thrombin due to its physiological and pathological roles, where rapid and simple analytical approaches are needed. In this study, an aptasensor based on fluorescence attenuation kinetics for the detection of thrombin is presented, which incorporates the features of stilbene and aptamer. We designed and synthesized an aptasensor by one-step coupling of stilbene compound and aptamer, which employed the adaptive binding of the aptamer with thrombin to cause a change in stilbene fluorescence attenuation kinetics.

Bacterial cellulose adhesive composites for oral cavity applications.

Topical approaches to oral diseases require frequent dosing due to limited retention time. A mucoadhesive drug delivery platform with extended soft tissue adhesion capability of up to 7 days is proposed for on-site management of oral wound. Bacterial cellulose (BC) and photoactivated carbene-based bioadhesives (PDz) are combined to yield flexible film platform for interfacing soft tissues in dynamic, wet environments.

Fixation of Transparent Bone Pins with Photocuring Biocomposites.

Bone fractures are in need of rapid fixation methods, but the current strategies are limited to metal pins and screws, which necessitate secondary surgeries upon removal. New techniques are sought to avoid surgical revisions, while maintaining or improving the fixation speed. Herein, a method of bone fixation is proposed with transparent biopolymers anchored in place via light-activated biocomposites based on expanding CaproGlu bioadhesives.

Rapid Activation of Diazirine Biomaterials with the Blue Light Photocatalyst.

Carbene-based macromolecules are an emerging new stimuli-sensitive class of biomaterials that avoid the impediments of free radical polymerization but maintain a rapid liquid-to-biorubber transition. Activation of diazirine-grafted polycaprolactone polyol (CaproGlu) is limited to UVA wavelengths that have tissue exposure constraints and limited light intensities. For the first time, UVA is circumvented with visible light-emitting diodes at 445 nm (blue) to rapidly activate diazirine-to-carbene covalent cross-linking.

Sunlight activated film forming adhesive polymers.

Stimuli-sensitive biomaterials that are activated by light are in need of formulations that are stable under indoor lighting yet can be activated under direct sunlight. Carbene-based bioadhesives are a new generation of film-forming polymers that are stable under indoor lighting yet are rapidly activated with low-energy UVA light, but have never been evaluated under sunlight exposure. Previous investigations have evolved two flexible carbene-based platforms, where aryl-diazirine is grafted on to polyamidoamine dendrimers (PAMAM-NH; generation-5) or hydrophobic liquid polycaprolactone tetrol to yield G5-Dz and CaproGlu, respectively.

Minimally invasive electroceutical catheter for endoluminal defect sealing.

Surgical repair of lumen defects is associated with periprocedural morbidity and mortality. Endovascular repair with tissue adhesives may reduce host tissue damage, but current bioadhesive designs do not support minimally invasive deployment. Voltage-activated tissue adhesives offer a new strategy for endoluminal repair.

An organosynthetic dynamic heart model with enhanced biomimicry guided by cardiac diffusion tensor imaging.

The complex motion of the beating heart is accomplished by the spatial arrangement of contracting cardiomyocytes with varying orientation across the transmural layers, which is difficult to imitate in organic or synthetic models. High-fidelity testing of intracardiac devices requires anthropomorphic, dynamic cardiac models that represent this complex motion while maintaining the intricate anatomical structures inside the heart. In this work, we introduce a biorobotic hybrid heart that preserves organic intracardiac structures and mimics cardiac motion by replicating the cardiac myofiber architecture of the left ventricle.

Photocurable platelet rich plasma bioadhesives.

Closure of wounds with tissue adhesives has many advantages over sutures, but existing synthetic adhesives are toxic and have poor workability. Blood-derived adhesives display complete resorption but have adhesion too weak for reliable wound dressings. We propose a semi-synthetic design that combines the positive attributes of synthetic and blood-derived tissue adhesives.

In Vitro Biocompatibility of Diazirine-Grafted Biomaterials.

Photoactivation of aryl-diazirines is an emerging method of rapid, covalent crosslinking under ambient conditions. These attributes make those compounds candidates for grafting onto inert polymer backbones in order to produce stimuli-sensitive biomaterials. However, no risk assessments are available to gauge the toxicity of the leachable components after crosslinking activation.

CaproGlu: Multifunctional tissue adhesive platform.

Driven by the clinical need for a strong tissue adhesive with elastomeric material properties, a departure from legacy crosslinking chemistries was sought as a multipurpose platform for tissue mending. A fresh approach to bonding wet substrates has yielded a synthetic biomaterial that overcomes the drawbacks of free-radical and nature-inspired bioadhesives. A food-grade liquid polycaprolactone grafted with carbene precursors yields CaproGlu.

Structure-Activity Relationships of Voltaglue Organic Blends.

Voltage-activated, one-pot adhesives are an emerging platform with many potential advantages, but require multicomponent grafting of electrochemical donors and acceptors for operation in organic environments. This formulation strategy reduces throughput efficiency, organic solubility, and requires additional purification of the grafted dendrimers. A more advanced strategy is proposed for setting up the donor-acceptor conductive network by exploiting a flexible blending design, providing faster throughput of structure-activity analyses with less synthetic investment.

Analysis of the role played by ligand-induced folding of the cocaine-binding aptamer in the photochrome aptamer switch assay.

The Photochrome Aptamer Switch Assay (PHASA) relies on ligand binding by an aptamer to alter the local environment of a stilbene compound covalently attached to the 5' end of the aptamer. We used the PHASA with both structure switching and non-structure switching versions of the cocaine-binding aptamer. We show that the largest change in fluorescence intensity and the lowest concentration limit of detection (Co) is obtained using the structure-switching cocaine-binding aptamer.

A self-adhesive microneedle patch with drug loading capability through swelling effect.

Microneedles (MNs) offer a rapid method of transdermal drug delivery through penetration of the stratum corneum. However, commercial translation has been limited by fabrication techniques unique to each drug. Herein, a broadly applicable platform is explored by drug-loading via swelling effect of a hydrogel MN patch.

Bioadhesives in neurosurgery: a review.

Objective: Neurosurgery presents unique surgical challenges arising from delicate neural structures, limited accessibility, and the risk of CSF leakage that can lead to CNS infections. Sutures and staples may have limited applicability in the complex anatomical constraints of cranial and spinal surgeries, especially in trauma settings when time is of the essence. Surgical bioadhesives are emerging as attractive alternatives because they avoid traumatic application methods, provide a stress-distributed fixation, and provide good cosmesis and outcomes.

Light-Activated, Bioadhesive, Poly(2-hydroxyethyl methacrylate) Brush Coatings.

Rapid adhesion between tissue and synthetic materials is relevant to accelerate wound healing and to facilitate the integration of implantable medical devices. Most frequently, tissue adhesives are applied as a gel or a liquid formulation. This manuscript presents an alternative approach to mediate adhesion between synthetic surfaces and tissue.

Tertiary blends of PAMAM/PEG/PEG tissue bioadhesives.

Lack of wet adhesion and biomechanical mismatch at tissue interfaces are the major challenges related to surgical adhesive formulations. Carbene-based bioadhesives seek to address those limitations, due to their ability to covalently bond to wet tissue surfaces. Herein, diazirine-grafted polyamidoamine (PAMAM) dendrimers (PDz) dissolved in various liquid polyethylene glycols (PEG) are reported.

Self curing and voltage activated catechol adhesives.

Catechol adhesives are limited to two-part curing designs. For the first time, a one-pot catechol adhesive is demonstrated with multiple modes of external activation: self-curing, electrocuring, substrate, and two-part curing. Lap shear adhesion (50 kPa) and viscoelastic properties demonstrate that electrocuring is non-inferior to two-part curing methods.

Non-aqueous, tissue compliant carbene-crosslinking bioadhesives.

Surgical adhesives are an attractive alternative to traditional mechanical tissue fixation methods of sutures and staples. Ease of application, biocompatibility, enhanced functionality (drug delivery) are known advantages but weak adhesion strength in the wet environment and lack of tissue compliant behavior still pose a challenge. In order to address these issues, non-aqueous bioadhesive based on blends of polyamidoamine (PAMAM) dendrimer, conjugated with 4-[3-(trifluoromethyl)-3H-diazirin-3-yl] benzyl bromide (PAMAM-g-diazirine) and liquid polyethylene glycol (PEG 400) has been developed.

Design and optimisation of Photochrome Aptamer Switch Assay (PHASA).

Photochrome Aptamer Switch Assay (PHASA) is our unique and recently developed fluorescent biosensing platform that exploits the combination of aptamer adaptive binding and photoisomerisation kinetics of stilbenes. The PHASA is based on converting any suitable stilbene-ligand-aptamer complex into a reversible biosensor. Binding affinity, aptamer concentration, and stilbene molecular structure determine the PHASA performance criteria.