CaproGlu: Multifunctional tissue adhesive platform

Djordjević, Ivan; Pokholenko, Oleksandr; Shah, Ankur Harish; Wicaksono, Gautama; Blancafort, Lluı́s; Hanna, John V.; Page, Samuel J.; Nanda, Himansu Sekhar; Ong, Chee Bing; Chung, Sze Ryn; Chin, Andrew Yuan Hui; McGrouther, Duncan Angus; Choudhury, Muntasir Mannan; Li, Fang; Teo, Jonathan Shunming; Lee, Lui Shiong; Steele, Terry W. J.

doi:10.1016/j.biomaterials.2020.120215

Cited by 23 publications

(80 citation statements)

References 74 publications

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“…Aryl‐diazirines are emerging candidates for rapid polymerization in biomaterials, as they are relatively stable under ambient conditions, but are known to be inducible by light, voltage, heat, and ultrasound. [ 3–8 ] Our efforts have explored aryl‐diazirines on several macromolecular backbones toward multifunctional bioadhesives. Others have incorporated diazirines for skin therapies and mapping cell membranes.…”

Section: Figurementioning

confidence: 99%

“…[ 11 ] If possible, in vitro tests should take priority to prevent needless animal sacrifices. Based on known biomaterial performance of polycaprolactone (PCL) medical devices [ 12 ] and proprietary technology for synthetic bioadhesives, [ 4,13 ] this paper reports the first in vitro biocompatibility evaluations of diazirine‐grafted biomaterials. The model biomaterial is CaproGlu, a hydrophobic liquid polymer formulation based on aryl‐diazirine grafted onto viscous and water‐insoluble polycaprolactone tetrol (PCLT).…”

Section: Figurementioning

confidence: 99%

“…Carbenes are known to react readily with alcohols by OH insertion; [ 25 ] both diazoalkane and ether peaks detected in 19F NMR possibly originate from premature activation of diazirine by ambient light. [ 4,13 ] Solvent‐free CaproGlu is analyzed with attenuated total reflection‐Fourier transform infrared (ATR‐FTIR) spectroscopy and the observed spectral regions are presented in Figure 1F (full IR spectra are shown in Figure S2, Supporting Information). Peak at 1631 cm −1 is assigned to diazirine (NN) [ 26 ] which disappears upon UVA activation.…”

Section: Figurementioning

confidence: 99%

“…The ultimate adhesion strength (UAS) of 120 kPa exceeds commercially available tissue sealants measured on hydrated collagen surface: fibrin‐based Tisseel (20 kPa) and cyanoacrylate‐based Dermabond (63 kPa). [ 4 ] Both rheological profile and UAS of CaproGlu are in line with PCL‐triol ( M w = 300 Da) grafted with aryl‐diazirine. [ 4 ] The surface morphology of crosslinked CaproGlu results in interconnected porous structure (Figure 2D) with pore size in the range of 20–50 µm.…”

Section: Figurementioning

confidence: 99%

“…[ 4 ] Both rheological profile and UAS of CaproGlu are in line with PCL‐triol ( M w = 300 Da) grafted with aryl‐diazirine. [ 4 ] The surface morphology of crosslinked CaproGlu results in interconnected porous structure (Figure 2D) with pore size in the range of 20–50 µm. This feature enables dual function of CaproGlu both as tissue sealant and porous tissue engineering scaffold that enables 3D organ regeneration.…”

Section: Figurementioning

confidence: 99%

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In Vitro Biocompatibility of Diazirine‐Grafted Biomaterials

Djordjević

Wicaksono

Šolić

et al. 2020

Macromol. Rapid Commun.

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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.

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

See 3 more Smart Citations

In Vitro Biocompatibility of Diazirine‐Grafted Biomaterials

Djordjević

Wicaksono

Šolić

et al. 2020

Macromol. Rapid Commun.

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Liquid Copolymers as Biodegradable Surgical Sealant

Shimony

Shagan

Eylon

et al. 2021

Adv Healthcare Materials

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Surgical sealants are widely used to prevent seepage of fluids and liquids, promote hemostasis, and close incisions. Despite the remarkable progress the field of biomaterials has undergone, the clinical uses of surgical sealants are limited because of their short persistence time in vivo, toxicity, and high production costs. Here, the development of two complementary neat (solvent-free) prepolymers, PEG 4 -PLGA-NHS and PEG 4 -NH 2 , that harden upon mixing to yield an elastic biodegradable sealant is presented. The mechanical and rheological properties and cross-linking rate can be controlled by varying the ratio between the two prepolymers. The tested sealants show a longer persistence time compared with fibrin glue, minimal cytotoxicity in vitro, and excellent biocompatibility in vivo. The neat, multiarmed approach demonstrated here improves the mechanical and biocompatibility properties and provides a promising tissue sealant solution for wound closure in future surgical procedures.

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Tougher Bioadhesives through Dual Stimulation Strategies

Ang,

Djordjevic,

Solic

et al. 2024

Adv Healthcare Materials

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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 3x tougher compared to control. Dual thermal/light irradiation may be a strategy to improve viscoelastic dissipation and toughness of photo‐activated adhesive resins.This article is protected by copyright. All rights reserved

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CaproGlu: Multifunctional tissue adhesive platform

Cited by 23 publications

References 74 publications

In Vitro Biocompatibility of Diazirine‐Grafted Biomaterials

In Vitro Biocompatibility of Diazirine‐Grafted Biomaterials

Liquid Copolymers as Biodegradable Surgical Sealant

Tougher Bioadhesives through Dual Stimulation Strategies

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