Photo Processing for Biomedical Hydrogels Design and Functionality: A Review

Abstract

A large number of opportunities for biomedical hydrogel design and functionality through photo-processing have stretched the limits of innovation. As both photochemical understanding and engineering technologies continue to develop, more complicated geometries and spatiotemporal manipulations can be realized through photo-exposure, producing multifunctional hydrogels with specific chemical, biological and physical characteristics for the achievement of biomedical goals. This report describes the role that light has recently played in the synthesis and functionalization of biomedical hydrogels and primarily the design of photoresponsive hydrogels via different chemical reactions (photo crosslinking and photo degradation) and conventional light curing processes (micropatterning, stereolithography and two/multiphoton techniques) as well as typical biomedical applications of the hydrogels (cell culture, differentiation and in vivo vascularization) and their promising future.

Keywords: biomedical; hydrogels; photo crosslinking; photo degradation; photo dimerization.

Figure 1

Upon generation of a free radical (by different types light exposure that depend on the type of photo initiator), the methacryloyl terminals on hydrogel backbone chains, such those of as GelMA, hyaluronic acid MA and PEGDA, polymerize to generate a more connected network through the formation of short oligomethacryloyl chains.

Figure 2

Several indirect photo regulation strategies combining click reactions and photochemistry, such as (a) redox reduction of Cu(II) to Cu(I) via photo initiator radicals [43], (b) light oxidation [50] and (c) photo cleavage via hydrazone adduction [30].

Figure 3

Mechanism of photo dimerization. The monomers (e.g., anthracene, coumarin) dimerize under UV exposure at wavelengths larger than 350 nm and divide under irradiation at wavelengths below 300 nm.

Figure 4

Schematic of the micropatterning technique. The type of the micropattern is divided into contact printing, proximity printing and projection printing due to the different exposure modes.

Figure 5

Overview of the processes that the constructs are fabricated using SLA. Reproduced with permission from Reference [79].

Figure 6

Schematic of two kinds of SLA approaches. (a) Bottom-up setup. In the top-down setup (b), every newly fabricated layer is underneath the previous layers and the polymerization of the light-sensitive material is performed by irradiation from underneath. Reproduced with permission from Reference [101].

Figure 7

(a) Working principle of the two-photon photo polymerization technique. In the focal spot of the near-infrared laser beam, the photo initiator is excited and the photosensitive polymer is crosslinked; (b) 3D structure fabricated using two-photon polymerization. Reproduced with permission from Reference [101,110].

Figure 8

Layout of the grid-shaped micropattern and the process of lithography on the photocrosslinkable hydrogel.

Figure 9

(a) Self-assembly of multiple micro-constructs to form a macroscale, aligned 3D tissue construct. Reproduced with permission from Reference [11]; (b) Micropatterned cell-laden GelMA constructs comprised of micro-constructs with variable heights (50 mm, 100 mm and 150 mm) and representative 3D confocal images of the inner layer of the cord formed within the hydrogels after 5 days of culture. Scare bars represents 100 μm in (b). Reproduced with permission from Reference [12].

Figure 10

(a) Schematic representation of the maleimide-VEGF-165 concentration gradient in hydrogels; (b) Schematic of the co-culture system of ECs and RSCs in the VEGF-165 concentration gradient with uniform GRGDS immobilized; (c,d) Close interactions between the ECs and RSCs and the formation of EC tubular-like structures after 14 days in the presence of RSCs. Reproduced with permission from Reference [119].

Figure 11

(a) Schematic representation of transdermal UV light exposure through a mask; (b) Photographs of explanted hydrogels stained for adherent cell nuclei for caged RGD and RDG presenting hydrogels at different distances from the center of irradiation (DAPI, color-coded cyan, scale bar, 40 µm); (c) PEG-maleimide hydrogels presenting peptides were implanted subcutaneously and exposed to UV light transdermally at selected time points (scale bar, 100 µm); (d) Representative images of a mouse receiving transdermal UV light at day 0 and the construct in the subcutaneous space after 7 days (scale bar 1 cm); (e) Representative H&E-stained section from a day 7 construct that was in vivo-UV polymerized (yellow arrowheads mark perfused blood vessels) (scale bars 50 mm). (a–c) reproduced with permission from Reference [13] and (d,e) reproduced with permission from Reference [14].