Hydrogel for light delivery in biomedical applications

Abstract

Traditional optical waveguides or mediums are often silica-based materials, but their applications in biomedicine and healthcare are limited due to the poor biocompatibility and unsuitable mechanical properties. In term of the applications in human body, a biocompatible hydrogel system with excellent optical transparency and mechanical flexibility could be beneficial. In this review, we explore the different designs of hydrogel-based optical waveguides derived from natural and synthetic sources. We highlighted key developments such as light emitting contact lenses, implantable optical fibres, biosensing systems, luminating and fluorescent materials. Finally, we expand further on the challenges and perspectives for hydrogel waveguides to achieve clinical applications.

Keywords: Biocompatibility; Flexibility; Optical fibres; Photodynamic therapy; Transparent hydrogels.

Graphical abstract

Fig. 1

a) An overview of the optical materials across the mechanical properties and refractive index, b) An Ashby Plot of the different hydrogels [9,[12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24]].

Fig. 2

An overview of the light propagation in human tissues without waveguides, that leads to scattering and absorption of light. The longer wavelength of red light (625–750 nm) is able to penetrate deeper into the skin as compared to shorter wavelengths of blue light (450–485 nm). The use of a waveguide enables direct and greater depth access in the delivery of light through the concept of total internal reflection with two conventional designs, step index fibre and graded index fibre.

Fig. 3

Illustrates one of the classification methods of hydrogel-based light guides in terms of its polymers and the biomedical applications.

Fig. 4

Silk hydrogel for optic applications. a) i) Schematic illustration of the SF hydrogel fabrication from treating silk cocoons in 0.02 M sodium carbonate, dissolving the SF in lithium bromide to purifying through dialysis and forming hydrogel by mixing the purified SF solution with acetone. ii) Transparent hydrogel formed from SF solution mixed with acetone. Scale bar = 7.5 mm. iii) SF hydrogel prepared in the shape of meniscus lens. Scale bar = 5 mm, adapted with permission from © 2015 American Chemical Society [79], b)i) Illustration of using SF ink to attain both straight and curvy silk waveguides via direct-write assembly. ii) Schematic representation of the set up for capturing and analyzing the transverse face of silk waveguides and the optimization could be attained by controlling the position of the optical condenser. These images were adapted with permission from © 2009 Advanced Materials [81]. c) i) Schematic representation of printed SF with straight and curved designs. ii) Absolute irradiance measured for the different wavelengths using cool white LED and warm white LED. iii) Influence of the concentration of silk hydrogels on the transmittance, adapted © 2017 Springer Nature [64].

Fig. 5

Chitosan hydrogels. a) i) Schematic illustration of the fabrication of dendronized chitosan hydrogel via self-assembly and heating ii) Chemical structure representation of the dendronized chitosan hydrogel synthesis iii) Optical image of the thermoresponsive dendronized chitosan hydrogel. Adapted with permission from © 2021 American Chemical Society [85]. b) Optical image of transparent chitosan hydrogels after different rounds of deacetylation. Adapted with permission from © 2016 American Chemical Society [86]. c) i) Optical image of N-acetylated chitosan hydrogel ii) Benchmark of the light transmittance capability of the N-acetylated chitosan hydrogel based on high degree of polymerization against commercial contact lens iii) Photo of the N-acetylated chitosan hydrogel fabricated into the shape of contact lens. Adapted with permission from © 2020 American Chemical Society [87].

Fig. 6

Structures, gelation approaches, optical properties, mechanical properties, and applications of synthetic hydrogels in waveguide-related applications [4,[107], [108], [109], [110], [111], [112]]. The images were adapted with permission © 2018, Springer Nature [109]. © 2019 Sensors [112], © 2019 Optical Publishing Group [113], © 2021 Wiley‐VCH GmbH [4].

Fig. 7

Fabrication of transparent hydrogels from synthetic polymers for biomedical purposes. a) (i) Printing setup for the printing of (ii) degradable and optically transparent 70% wt% PEGDA-DTT fibres. Adapted with permission from © 2020 Wiley‐VCH GmbH [115], b) PEGDA hydrogel (i) used in an optical setup in a microfluidic chip as an integrated waveguide (ii) exhibiting excellent transparency at 60% w/v concentration (iii) fabricated into a 1 × 4 waveguide splitter. Adapted from © 2019 Sensors [112]. c) PEGDMA hydrogel with fibre inserted, adapted with permission from © 2019 Optical Publishing Group [113].

Fig. 8

a) Schematic of the preparation process of the ADN hydrogel, adapted from © 2022 Frontiers in Bioengineering and Biotechnology [124], b) The fabrication process of the magneto-birefringence-based transparent hydrogel (MB-hydrogel), adapted from © 2022 Nature Communications [125] The MB-resin is a mixed suspension, comprising 2D Co-doped TiO2 (CTO) materials, water, monomer (PEGDA, molecular weight MW of 700 g/mol), and photo-initiator (Irgacure 2959, MW of 224.25 g/mol). c) The schematic illustration of the alginate/P(SBMA-co-HEMA) hydrogel (AHS) with a semi-interpenetrating network cross-linked by reversible noncovalent interactions, adapted with permission from © 2021 American Chemical Society [126].

Fig. 9

a) Two photographic images of smart CLs that emits red, blue, and green light for phototherapy in diabetes retinopathy. Images were adapted with permission from ©Advanced Science, 2022 [163], b) a photograph image of the pHEMA hydrogel substrate and functional device sensing IOP and the SEM image of the pyramid microstructures. Images were retrieved with permission from ©ACS Sensors, 2022 [161] c) the schematic diagram of glucose monitoring smart CLs. Images were adapted with permission from ©Advanced Materials, 2022 [160].

Fig. 10

I) Comb-shaped waveguide connected to a light source via optical fibre with light being distributed via each protrusion, ii) difference int the delivery of light between waveguide and without, iii) the employment of waveguide significantly increased the depth of light penetration Adapted from, © 2016 Springer Nature [166], b) the blue laser light (492 nm) delivery of step-index hydrogel optic fibre in air, (ii) in tissues (ex vivo), (iii) the light propagation loss in different mediums. Adapted from © 2015 John Wiley and Sons [17] c) a diagram excerpt of i) the PDT activation in mouse model, ii) the H&E staining of muscle slices, iii) the temperature change during activation and an illustration of heat conductivity at the localised area. Adapted from © Nature Communications [168].