Reversible Modulation of Elasticity in Fluoroazobenzene‐Containing Hydrogels Using Green and Blue Light

Abstract

Gels are especially sensitive to their environment and can be designed to readily respond to variations in, typically, pH or temperature. [5] Light is another trigger of choice offering the advantage of precise photopatterning [4] and allows to alter hydrogels' mechanical properties either permanently by implementing photo cleavable groups [6] or reversibly using photochromic molecules, such as spiro pyrans [7,8] or azobenzenes. [9] Following the latter strategy, noncovalent physical gels typically lead to materials with light induced sol-gel transitions, [10][11][12][13] whereas covalent chemical gels can exhibit more finely tuneable phenomena such as pho toinduced motion, [14][15][16][17][18] or softening/ hardening. Photoswitchable hydrogels exhibiting modulation of their mechanical properties have been described; [16,19] how ever, their activation requires UV light, which displays several drawbacks related to its damaging character for the materials and its surrounding, as well as its limited light penetration. [20] Here, we present a polyethylene glycol (PEG) hydrogel incorporating ortho fluoroazobenzenes [21] as cross linkers (see F4-azo-PEG; Figure 1) and exhibiting reversible photomodula tion of elasticity using blue and green light. Ortho fluoroazoben zenes (abbreviated to F azos in the following) were selected as photochromic moieties due to their full addressability with visible light and very high thermal stabilities of the thermo dynamically less stable Z isomers. F azos were functionalized in para positions with amide linkers, since such electron with drawing groups maximize the separation of E and Z isomers' n→π* bands in the visible region [22] (see Figure 2a) and hence promote higher photoisomerization yields using blue (Z→E) or green (E→Z) light. Results and DiscussionF4-azo-PEG gel samples were prepared via strain promoted click cycloaddition between a tetra armed PEG macromon omer (M n = 10 kg mol −1 ) terminated with azide groups (tetra-N3-PEG) and the F azo derivative functionalized with aza dibenzocyclooctynes [23,24] (F4-azo-bis-DBCO). This reac tion typically exhibits fast kinetics at room temperature and does not necessitate the presence of a Cu catalyst, which might be beneficial for the formation of the gel, since once the gelation starts, diffusion of the reactants is reduced. The two starting materials were dissolved in stoichiometric amount in Synthetic Macromolecular Machines Hydrogels are soft materials that have found multiple applications in biomedicine and represent a good platform for the introduction of molecular switches and synthetic machines into macromolecular networks. Tuning their mechanical properties reversibly with light is appealing for a variety of advanced applications and has been demonstrated in the past; however, their activation typically requires the use of UV light, which displays several drawbacks related to its damaging character and limited penetration in tissues and materials. This study circumvents this limitation by introducing all-visible ortho-fluor...

Engineering the cellular mechanical microenvironment – from bulk mechanics to the nanoscale

“…Switchable hydrogels are an ideal platform to study mechanical memory, since the cellular response to both softening and stiffening can be analysed using the same substrate without changing the chemical composition of the hydrogel. Azobenzene-based hydrogels are some of the most common photo-switchable hydrogels, but they still require cytotoxic levels of UV irradiation (Lee et al, 2018b) To overcome this limitation, systems that are responsive to two different bands of visible light (Zhao et al, 2018), or that incorporate near-infrared (NIR)responsive nanoparticles (Mandl et al, 2018), have been developed. As an alternative to photoresponsive hydrogels, switchable substrates have also been generated using other 'smart hydrogels', including pH-responsive (Yoshikawa et al, 2011), enzyme-activated (Liu et al, 2017), temperature-responsive (Uto et al, 2014) or redox-switchable (Fadeev et al, 2018) hydrogels.…”

Reversibly tuning hydrogel stiffness through photocontrolled dynamic covalent crosslinks

“…Unlike literature examples of reversibly controlled hydrogels based on azobenzene photoswitching, this system stiffens in the Z conformation and softens in the E conformation. 8 , 9c We cannot directly correlate our measured rate and equilibrium constants in the small-molecule model system ( Table 1 ) to the viscoelastic behavior of the P1 / P2 hydrogel because P1 bears less sterically hindered diols. Nevertheless, in analogy to the small-molecule model system, we hypothesize that the Z azobenzene boronic acid experiences more favorable equilibrium towards the boronic ester compared to the E isomer.…”

“…This observation suggests that proximity to the azo group, rather than an inductive/resonance or rigidity effect, is responsible for the photoresponse. 8 The combination of P1 and P4 , lacking a boronic acid, forms a sol regardless of irradiation, providing evidence that the boronic ester is the crosslink (see ESI † for photographs and rheological characterization of the control gels).…”

“… 7 Rosales and coworkers enchained azobenzene in an elastic network and observed small but reproducible changes in stiffness. 8 It is important to note that the above systems are not dynamic or adaptable in the absence of light; these elastic networks store, rather than dissipate, energy from applied strain. To achieve a sol–gel transition in a stress-relaxing network, Harada and coworkers designed a supramolecular hydrogel based on cyclodextrin/azobenzene complexes, which has been leveraged in multiple contexts ( Fig.…”

Hydrogels: soft matters in photomedicine

“…Recently, o-fluoroazobenzene has been used as a green/blue light activated switch in hydrogels allowing a reversible tuning of the elastic modulus. 284 Furthermore, free radical cross-linking techniques have been used for highly versatile and robust materials in soft imprinting lithography and nanoimprinting. 285 In molecule-specific photochemistry a chromophore absorbs light at a specific wavelength and the polymeric material does not.…”