Due to mild reaction conditions and temporal and spatial control over material formation, photopolymerization has become a valuable technique for the encapsulation of living cells in three dimensional, hydrated, biomimetic materials. For such applications,2-hydroxy-1-[4-(2-hydroxyethoxy) phenyl]-2-methyl-1-propanone (I2959) is the most commonly used photoinitiator (by virtue of its moderate water solubility), yet this initiator has an absorption spectrum that is poorly matched with wavelengths of light generally regarded as benign to living cells, limiting the rate at which it may initiate polymerization in their presence. In contrast, acylphosphine oxide photoinitiators, generally exhibit absorption spectra at wavelengths suitable for cell encapsulation, yet commercially available initiators of this class have low water solubility. Here, a water soluble lithium acylphosphinate salt is evaluated for its ability to polymerize diacrylated poly(ethylene glycol) (PEGDA) monomers rapidly into hydrogels, while maintaining high viability during direct encapsulation of cells. Through rheometric measurements, the time to reach gelation of a PEGDA solution with the phosphinate initiator is one tenth the time for that using I2959 at similar concentrations, when exposed to 365 nm light. Further, polymerization with the phosphinate initiator at 405 nm visible light exposure is achieved with low initiator concentrations and light intensities, precluded in polymerizations initiated with I2959 by its absorbance profile. When examined 24 hours after encapsulation, survival rates of human neonatal fibroblasts encapsulated in hydrogels polymerized with the phosphinate initiator exceed 95%, demonstrating the cytocompatibility of this initiating system.

Synthetic hydrogels with engineered, cell-mediated degradation sites are an important category of biomimetic materials. Here, hydrogels are synthesized by a step-growth reaction mechanism via a radically mediated thiol-norbornene (thiol-ene) photopolymerization. This reaction combines the advantages of ideal, homogeneous polymer network formation, facile incorporation of peptides without post-synthetic modification, and spatial and temporal control over the network evolution into a single system to produce proteolytically degradable poly(ethylene glycol) (PEG) peptide hydrogels. Using a thiol-ene photopolymerization, rapid gelation times are achieved, while maintaining high cell viability for cell encapsulation. The enzyme- and cellresponsive characteristics are demonstrated by tailoring the rate of spreading of human mesenchymal stem cells (hMSCs) through both the selection of proteolytically degradable crosslinkers and the density of the adhesion peptide RGDS. Furthermore, cellular function is manipulated spatially within the thiol-ene hydrogels through biochemical photopatterning. The high degree of spatial and temporal control over gelation, combined with robust material properties, makes thiol-ene hydrogels an excellent tool for a variety of medical and biological applications.

Radical-mediated thiol−yne step-growth photopolymerizations are utilized to form highly cross-linked polymer networks. This reaction mechanism is shown to be analogous to the thiol−ene photopolymerization; however, each alkyne functional group is capable of consecutive reaction with two thiol functional groups. The thiol−yne reaction involves the sequential propagation of a thiyl radical with either an alkyne or a vinyl functional group followed by chain transfer of the radical to another thiol. The rate of thiyl radical addition to the alkyne was determined to be approximately one-third of that to the vinyl. Chain-growth polymerization of alkyne and vinyl functionalities was only observed for reactions in which the alkyne was originally in excess. Analysis of initial polymerization rates demonstrated a near first-order dependence on thiol concentration, indicating that chain transfer is the rate-determining step. Further analysis revealed that the polymerization rate scaled with the initiation rate to an exponent of 0.65, deviating from classical square root dependence predicted for termination occurring exclusively by bimolecular reactions. A tetrafunctional thiol was photopolymerized with a difunctional alkyne, forming an inherently higher cross-link density than an analogous thiol−ene resin, displaying a higher glass transition temperature (48.9 vs −22.3 °C) and rubbery modulus (80 vs 13 MPa). Additionally, the versatile nature of this chemistry facilitates postpolymerization modification of residual reactive groups to produce materials with unique physical and chemical properties.

Various techniques have been adopted to impart a biological responsiveness to synthetic hydrogels for the delivery of therapeutic agents as well as the study and manipulation of biological processes and tissue development. Such techniques and materials include polyelectrolyte gels that swell and deswell with changes in pH, thermosensitive gels that contract at physiological temperatures, and peptide cross-linked hydrogels that degrade upon peptidolysis by cell-secreted enzymes. Herein we report a unique approach to photochemically deform and degrade disulfide cross-linked hydrogels, mitigating the challenges of light attenuation and low quantum yield, permitting the degradation of hydrogels up to 2 mm thick within 120 s at low light intensities (10 mW/cm2 at 365 nm). Hydrogels were formed by the oxidation of thiol-functionalized 4-armed poly(ethylene glycol) macromolecules. These disulfide cross-linked hydrogels were then swollen in a lithium acylphosphinate photoinitiator solution. Upon exposure to light, photogenerated radicals initiate multiple fragmentation and disulfide exchange reactions, permitting and promoting photodeformation, photowelding, and photodegradation. This novel, but simple, approach to generate photoadaptable hydrogels portends the study of cellular response to mechanically and topographically dynamic substrates as well as novel encapsulations by the welding of solid substrates. The principles and techniques described herein hold implications for more than hydrogel materials but also for photoadaptable polymers more generally.