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. A customized photo/thermal-rheometer evaluates viscoelastic properties, correlated to the kinetics of carbene:diazoalkane ratios via 19F NMR). The latter exploits the sensitive -CF3 functional group to determine joule-based light/temperature kinetics on trifluoroaryl diazirine consumption. The combination of heat and photoactivation produced bioadhesives that are 3× tougher compared to control. Dual thermal/light irradiation may be a strategy to improve viscoelastic dissipation and toughness of photo-activated adhesive resins.

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. The transparent biopolymers serve as a UV light guide for the activation of CaproGlu biocomposites, which results in evolution of molecular nitrogen (from diazirine photolysis), simultaneously expanding the covalently cross-linked matrix. Osseointegration additives of hydroxyapatite or Bioglass 45S5 yield a biocomposite matrix with increased stiffness and pullout strength. The structure-property relationships of UV joules dose, pin diameter, and biocomposite additives are assessed with respect to the apparent viscosity, shear modulus, spatiotemporal pin curing, and lap-shear adhesion. Finally, a model system is proposed based on ex vivo investigation with bone tissue for the exploration and optimization of UV-active transparent biopolymer fixation.

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. Iridium photocatalysts serve to initiate diazirine, despite having little to no absorption at 445 nm. CaproGlu's liquid organic matrix dissolves the photocatalyst with no solvents required, creating a light transparent matrix. Considerable differences in cross-linking chemistry are observed in UVA vs visible/photocatalyst formulations. Empirical analysis and theoretical calculations reveal a more efficient conversion of diazirine directly to carbene with no diazoalkane intermediate detected. Photorheometry results demonstrate a correlation between shear moduli, joules light dose, and the lower limits of photocatalyst concentration required for the liquid-to-biorubber transition. Adhesion strength on ex vivo hydrated tissues exceeds that of cyanoacrylates, with a fixation strength of up to 20 kg·f·cm2. Preliminary toxicity assessment on leachates and materials directly in contact with mammalian fibroblast cells displays no signs of fibroblast cytotoxicity.

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-NH2; generation-5) or hydrophobic liquid polycaprolactone tetrol to yield G5-Dzx and CaproGlu, respectively. For the first time the activation of G5-Dzx and CaproGlu is investigated by natural sunlight with intensities up to 10 mW·cm-2. Structure-property relationships of bioadhesion are investigated by: (1) joules dose of sunlight; (2) bioadhesive polymer structure; and (3) optical concentrators of magnifying glass and Fresnel lens. Using only natural sunlight, adhesion strength could be tuned from 20 to 150 kPa with crosslinking achieved in under 1 min. The results show that carbene-based polymers are a class of stimuli-sensitive biomaterials that are stable to indoor lighting, yet can be rapidly activated under direct sunlight, which may be useful for topical film forming polymers or as active ingredients in sunscreen formulations.

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. The CaproGlu composites exhibited conductivity of 0.1 S m-1 and a charge storage capacity of 5 µC cm-2. The resulting composites are biocompatible and can be used as strain sensors to detect mechanical deformations.

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. Herein, a stimuli-sensitive biomaterial is formulated from diazirine-grafted polycaprolactone tetrol. Also known as CaproGlu, this biomaterial undergoes UVA-activated crosslinking, with many positive attributes toward bioadhesive applications; hydrophobic, solvent-free, liquid at room temperature, and transitions into a foam biorubber after mild UVA illumination. As a model diazirine-grafted biomaterial, hydrolyzed CaproGlu leachates are evaluated for genotoxicity and skin sensitization, namely, Ames test, direct peptide reactivity, and ARE-Nrf2 luciferase assays. The degradation products of diazirine-mediated crosslinking observe little to no risk of in vitro genotoxicity or skin sensitization.

Scandium as a pre-catalyst for the deoxygenative allylation of benzylic alcohols.

Scandium triflate is an effective pre-catalyst for the deoxygenative allylation of benzylic alcohols with a narrow substrate window. The reaction is shown to proceed through a "hidden Brønsted acid" mechanism. The reaction is efficient provided that the aryl group is neither too electron rich nor too electron poor. It is shown that this allows useful selectivity. The reaction also works for benzyhydryl alcohols with broader scope. The reaction may also be catalysed by Nafion.