Wavelength-Selective Coupling and Decoupling of Polymer Chains via Reversible [2 + 2] Photocycloaddition of Styrylpyrene for Construction of Cytocompatible Photodynamic Hydrogels

Abstract

Reversible photocycloaddition reactions have previously been employed in chemical cross-linking for the preparation of biomaterial scaffolds. However, the processes require activation by high-energy UV light, rendering them unsuitable for modification in biological environments. Here we demonstrate that the [2 + 2] photocycloaddition of styrylpyrene can be activated by visible light at λ = 400–500 nm, enabling rapid and effective conjugation and cross-linking of poly­(ethylene glycol) (PEG) in water and under mild irradiation conditions (I = 20 mW cm–2). Notably, the reversion of the cycloaddition can be triggered by low-energy UV light at λ = 340 nm, which allows for efficient cleavage of the dimer adduct. Using this wavelength-gated reversible photochemical reaction we are able to prepare PEG hydrogels and modulate their mechanical properties in a bidirectional manner. We also demonstrate healing of the fractured hydrogel by external light triggers. Furthermore, we show that human mesenchymal stem cells can be encapsulated within the gels with high viability post encapsulation. This photochemical approach is therefore anticipated to be highly useful in studies of cell mechanotransduction, with relevance to disease progression and tissue regeneration.

PEG–Anthracene Hydrogels as an On‐Demand Stiffening Matrix To Study Mechanobiology

“…This work uses 365 nm light for the photocyclodimerization of anthracenes, [9] awavelength commonly used for many photoinitiated cell encapsulations,b ut this can be shifted to > 400 nm by incorporating nucleophilic moieties to the 9position of anthracene,s uch as triazoyl groups, [10] or alternatively by exploiting the [2+ +2] photocycloaddition of styrylpyrene groups. [11] Specifically,a nthracene-functionalized poly(ethylene glycol) (PEG) precursors (PEG-Ant) were prepared by addition of 9-anthracenecarboxylic acid to 8-arm 20 000 gmol À1 PEG-NH 2 (Figure 1a and Scheme S1 in the Supporting Information). TheP EG-Ant was soluble in PBS up to 25 wt %, and hydrogels were readily obtained upon exposure of dilute PEG-Ant formulations to low-intensity and cytocompatible 365 nm light.…”

“…[12] One explanation for this trend is the increased probability of intermolecular photodimerization of anthracene groups over intramolecular ones with increased polymer concentration owing to decreased interpolymer distance,which has been previously observed in other one-component step-growth networks. [11] Thepresence of intramolecular bonds that do not participate in network formation was more pronounced when a4-arm, 20 000 gmol À1 PEG-Ant was used instead of an 8-arm PEG-Ant ( Figure S5). In the former case,a tl east 8wt% of 4-arm PEG-Ant was required to form an etwork, and E' max did not exceed 2kPa even when 20 wt %o fPEG-Ant was used.…”

Design and Applications of Photoresponsive Hydrogels

“…[6][7][8][9][10][11] This unprecedented level of control over material properties has driven both med ical and industrial fields into the realm of possibility: controlled drug delivery, [12] chemical sensors, [13] soft actuators or robotics, [14][15][16] or scaffolds for dynamic 3D cell culture. [18] Photoresponsive hydrogels, as externally tunable materials, strongly contribute to the field of soft smart materials in regard to the abovementioned applications. Light is non invasive and allows remote manipulation of materials without requiring additional reagents, thus, with limited byproducts.…”

“…Wavelengthselective photo chemical reactions can be used for orthogonal photomediation of hydrogel properties. [18] Photoresponsive hydrogels, as externally tunable materials, strongly contribute to the field of soft smart materials in regard to the abovementioned applications. [19] In this review, we elaborate on the design and the emerging appli cations of photoresponsive hydrogels.…”

Kontrolle über Kettenvernetzung und Einzelkettenverknüpfung durch zwei Farben des sichtbaren Lichts

“…Um die simultane Initiierung beider photoreaktiver Gruppen bei kürzerer Wellenlänge zu umgehen, separierten wir in unserer Studie nicht die Absorptionswellenlängen, sondern nutzten die aktive Unterdrückung einer Reaktion im niedrigen Wellenlängenbereich aus,i nd em die Chromophore überlappende Absorptionsbanden aufweisen. VorK urzem wurde die photoreversible [2+ +2]-Cycloaddition des Styrylpyrens [27,28] in Hinblick auf die wellenlängenabhängige Reaktivitätv on sowohl Cycloaddition als auch Cycloreversion untersucht (Schema 1B). [29] Mit dem erhaltenen Actionplot konnte gezeigt werden, dass die Cycloaddition bei einer Wellenlänge von l = 330 nm durch eine effiziente Cycloreversion vollkommen unterdrückt wurde.I mG egensatz dazu dominiert die Cycloaddition im sichtbaren Bereich des Lichts l > 400 nm.…”