Tougher Bioadhesives through Dual Stimulation Strategies

Abstract

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.

Keywords: bioadhesive; carbene; diazirine; dual‐activation; nuclear magnetic resonance spectroscopy; polycaprolactone; rheology.

Figure 1

Photorheometry correlates the effect of change in activation temperature on the material properties of CG2000 upon photoactivation, while ¹⁹F NMR quantifies the corresponding changes in the ratio of carbene and diazoalkane normalized to temperature and light dose. R₁ = polycaprolactone, M_w = 2000 Da.

Figure 2

A) Cross section schematics of the customized rheometer plate and sample placement of diazirine‐grafted polycaprolactone polyol (CG2000) to allow for both temperature and UVA light dosage control simultaneously; representative rheometry results of CG2000: B) change in storage modulus (G′) during photoactivation at 35, 50, 70, and 90 °C using 10 J UVA dosage; C) stress‐strain curves during amplitude sweep after cooling down to 35 °C; statistical comparison of D) maximum G′ achieved, E) modulus of toughness calculated from amplitude sweep and F) yield stress of CG2000 at 35, 50, 70, and 90 °C after 10 J UVA dosage (n = 3, One‐Way ANOVA, Tukey means comparison: p < 0.05; Statistical difference = SD; taken with respect to 35 °C).

Figure 3

Representative plots of CG2000 at activation temperature T_A = 35 °C: A) changes in G′ during photoactivation using 3, 5, and 10 J, B) amplitude sweep stress‐strain curve after 3, 5, and 10 J UVA dosage, C) statistical comparison of the yield stress of CG2000 after 3, 5, and 10 J UVA dosage; Representative plots of CG2000 at T_A = 70 °C: D) changes in G′ during photoactivation using 3, 5, and 10 J, E) amplitude sweep stress‐strain curve upon cooling down to 35 °C after 3, 5, and 10 J UVA dosage and F) statistical comparison of the yield stress of CG2000 after 3, 5, and 10 J UVA dosage (n = 3, One‐Way ANOVA, Tukey means comparison: p < 0.05; Statistical difference = SD; taken with respect to 10 J).

Figure 4

Trendline for A) maximum G′ achieved, B) modulus of toughness and C) yield stresses of the cured CG2000 in kPa, with respect to the activation temperature from 35 to 90 °C, using 3, 5, and 10 J UVA dosage; Box charts with statistical analysis of D) maximum G′ achieved, E) modulus of toughness, and F) yield stresses grouped by activation temperatures (y‐axis) in the respective UV dose of 3, 5, and 10 J (n = 3, One‐Way ANOVA, Tukey means comparison: p < 0.05; Statistical difference = SD; taken with respect to photoactivation using 10 J at 35 °C).

Figure 5

¹⁹F NMR spectra of CaproGlu (CG2000) dissolved in triacetin taken at activation temperature T_A = 70 °C, from 0 to 50 J UVA dosage. The integrals of the species measured in this experiment are diazirine (δ = −64.4 ppm) and diazoalkane (δ = −56.4 ppm). The dimer peak (δ = – 65.5 ppm) is not included when calculating carbene generated.

Figure 6

Percentage change in species measured by F NMR spectroscopy: A) diazirine depletion, B) diazoalkane generation, C) calculated carbene concentration of CG2000 dissolved in triacetin; and D) carbene to diazoalkane ratio at the temperatures of 25, 35, 50, 70, and 90 °C as UVA dosage increases up to 50 J. * indicates a statistical difference compared to the rate of diazirine depletion at the other temperatures.

Figure 7

Validating adhesion on human skin: A) the silicone rubber pieces are heated to 70 °C before application of adhesive followed by UVA activation. Bonding is challenged through addition of mass standards from B) 100 g; C) 200 g; D) 300 g; E) 400 g; F) 500 g and G) 1 kg. Failure was observed within 3 s with the 1 kg mass (n = 1).