Photoinitiated polymerization of PEG-diacrylate with lithium phenyl-2,4,6-trimethylbenzoylphosphinate: polymerization rate and cytocompatibility

Abstract

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.

Complementary, Semiautomated Methods for Creating Multidimensional PEG-Based Biomaterials

“…[35][36][37] However, this initiator could not be used in a black-walled 96-well plate due to light intensity loss. To overcome this, we used LAP, 26 which forms free radicals more efficiently at 365 nm light than Irgacure. 26 We made 1, 3, 6, and 10 wt% PEGDMA hydrogels with a constant 17 wt% PC.…”

“…To overcome this, we used LAP, 26 which forms free radicals more efficiently at 365 nm light than Irgacure. 26 We made 1, 3, 6, and 10 wt% PEGDMA hydrogels with a constant 17 wt% PC. In the multi-well plates, varying the crosslinker (PEGDMA) in the hydrogels allowed for control of the effective Young's modulus (Figure 3a).…”

“…Others have developed 2D hydrogel platforms, 7,20 which produce perfectly flat hydrogels, but they are complicated to fabricate 7 [35][36][37] and it was used for 2D PEG-PC hydrogels when they were first developed for coverslips. 34 Irgacure is not a very efficient photoinitiator 26 because it does not absorb light readily at 365 nm, 35 but this wavelength is used in other platforms that include cell encapsulation to limit damage to the cells. 35,[55][56] Since the pre-polymer solution resides deep within the wells of black-walled plates, the efficacy of Irgacure was particularly problematic, and therefore it was not possible to form PEG-PC hydrogels in 96-well plates.…”

“…Hydrogel polymerization was initiated by lithium phenyl(2,4,6-trimethylbenzoyl)phosphinate (LAP, TCI America, Portland, OR). 26 LAP at 200 mM dissolved in 70% ethanol was added to the pre-polymer solutions to a final concentration of 2 mM to polymerize the hydrogels. 26 PEG-PC hydrogels were formed either manually using a multi-channel pipette or with liquid handling robotics (Biomek) by adding 40 L of the pre-polymer solution to the wells and placing the plates under UV light (365 nm, UV Panel HP, American DJ, Los Angeles, CA) to induce hydrogel polymerization for at least 20 minutes.…”

A microfluidic-based cell encapsulation platform to achieve high long-term cell viability in photopolymerized PEGNB hydrogel microspheres

“…In recent years, PEG-based, free-radical photopolymerized hydrogels have been intensively studied and developed as a cell encapsulant due to their synthetic versatility and ability to spatially and temporally control hydrogel network properties 16-18 . Also, PEG hydrogels have displayed excellent cytocompatibility for many cell types including mesenchymal stem cells (MSCs) 19 , β cells 20 , fibroblasts 21 , and neural cells 22 .…”