Crosslinker length dictates step-growth hydrogel network formation dynamics and allows rapid on-chip photoencapsulation

Abstract

Hydrogels formed via free radical-mediated thiol-ene step-growth photopolymerization have been developed for a broad range of tissue engineering and regenerative medicine applications. While the crosslinking mechanism of thiol-ene hydrogels has been well-described, there has been only limited work exploring the physical differences among gels arising from variations in crosslinker properties. Here, we show that the character of linear polyethylene glycol (PEG) dithiols used to crosslink multi-arm polyethylene glycol norbornene (PEGNB) can be used as a facile strategy to tune hydrogel formation kinetics, and therefore the equilibrium hydrogel network architecture. Specifically, we report the dramatic effect of crosslinker length on PEGNB hydrogel formation kinetics and the formed hydrogel properties. It is shown that the hydrogel formation kinetics and formed hydrogel properties can be tuned by solely varying the crosslinker length. It was hypothesized that under identical reaction conditions, a more accessible 3.5 k PEG dithiol crosslinker would improve network ideality relative to a shorter 1.5 k crosslinker. Longer linkers consequently promote significantly more rapid macromer crosslinking and therefore gelation. Accelerated gel formation satisfies an urgent unmet need for rapid polymerization in droplet microfluidics. Using long linkers, we demonstrate the ability to photopolymerize PEGNB microgels under flow on a microfluidic chip, with reliable control over microgel size and shape in a high-throughput manner. To further validate the potential of this platform to produce novel, microstructured cell carrier vehicles, 3T3 fibroblasts were successfully encapsulated and cultured over 14 days with excellent cell viability. This study demonstrates that PEGNB hydrogel dynamics could be readily customized to fulfill a variety of needs in tissue engineering, controlled cell delivery, or drug release applications.

Microgels Formed by Spontaneous Click Chemistries Utilizing Microfluidic Flow Focusing for Cargo Release in Response to Endogenous or Exogenous Stimuli

“…In addition, all formulations had low coefficients of variation (CV 90% = 15%; CV 50% = 8%; CV 0% = 13%), indicating homogenous microgels especially when compared to batch emulsion or extrusion fragmentation techniques that typically result in higher levels of dispersity (e.g., CV ~30–40% for batch emulsions [ 15 ]; preliminary findings with inverse suspension polymerization resulted in CV ~70% ( Figure S16 )). The dispersity of particles formed here was within the range of that observed for other PEG-based microgels formed using microfluidic flow-focusing methods (CV = 5–20%) [ 19 , 49 ].…”

Microfluidic Production of Cell-Laden Microspheroidal Hydrogels with Different Geometric Shapes

“…Varying the flow ratio in a T-junction device tends to be more easily used to adjust the microspheroid AR than their diameter . In contrast for flow focusing and coflow junction designs, although it is also possible to control the AR, , changing the flow ratio is more likely to influence the final microspheroid diameter. , Due to the complex and resource-intensive nature of traditional microfluidic device fabrication, computational simulation has previously been done for a range of junction designs to provide researchers with a better understanding of the mechanisms controlling microspheroid geometries. − …”

Robust, anti-biofouling 2D nanogel films from poly(N-vinyl caprolactam-co-vinylimidazole) polymers

“…40,41 Also, regulation of the size and swelling ratio depends on the density of cross-linking sites and the length of the cross-linker. [42][43][44] As discussed above, the optimum cross-linking density was provided by the PNVCL4 copolymer. The results of the elemental composition of PNVCL nanogels showed that the bromine content of the different nanogels was around 2% (Table S2, ESI †), so the length of the cross-linker should be the main factor to be considered.…”