Comparison of Bulk- vs Layer-by-Layer-Cured Stimuli-Responsive PNIPAM–Alginate Hydrogel Dynamic Viscoelastic Property Response via Embedded Sensors

Abstract

While stimuli-responsive hydrogels are now being widely investigated, such as for additive manufacturing applications, it remains a challenge to continuously monitor the dynamic response of their material properties to stimuli using traditional characterization methods. Here, we report that dynamic-mode piezoelectric milli-cantilever sensors enable real-time monitoring of the viscoelastic response of bulk-and layer-by-layer (LBL)-cured composite poly(N-isopropylacrylamide) (PNIPAM)−alginate hydrogel constructs to thermal changes across the 25−37 °C temperature range. Scanning electron microscopy and sensing studies revealed that the network structure and viscoelastic response of ionic−covalent entanglement composite PNIPAM−alginate hydrogel constructs are dependent on the hydrogel processing method. Composite PNIPAM−alginate constructs fabricated using LBL curing exhibited relatively increased responsiveness compared to bulk-cured constructs in terms of the magnitude of thermal stimulus-driven shear storage modulus change, suggesting opportunities for additive manufacturing applications. In summary, we show that sensors, in combination with traditional characterization methods, enable the study of dynamic process−structure−rheological property relations of stimuli-responsive soft materials and real-time monitoring of material rheological properties using a low-sample volume measurement format.

Accelerated Engineering of Optimized Functional Composite Hydrogels via High-Throughput Experimentation

“…The reported results correspond to the mean and standard deviation of all experiments. Details associated with conversion of PEMC sensor data to mechanical property information (i.e., G ′) can be found in our previous work and the Supporting Information. , …”

“…Rheological properties of the synthesized hydrogel libraries were characterized in high throughput via robotically directed sensing using PEMC sensors (see Figure S1) and a recently reported method . The PEMC sensor fabrication method and measurement principle can be found in our previous reports. − PEMC sensor phase angle at resonance, which correlates with the material shear storage modulus ( G ′), − was continuously monitored using an impedance analyzer (e5061b; Keysight) and custom Matlab program for data acquisition. The path planning parameters for HTC in 96-well formats, which included a 30 or 60 s dwell time per well, is provided in our recent report .…”

“…Details associated with conversion of PEMC sensor data to mechanical property information (i.e., G′) can be found in our previous work and the Supporting Information. 21,24 3. RESULTS AND DISCUSSION…”

“…Thus, we next examined the integration of complementary tools and methods for HTC of hydrogel optical and electrical properties with the established HTE method. Given the use of stimuli-responsive alginate/PNIPAM composite hydrogels for a range of applications, including soft robotics and 4D printing, and the ability to characterize the rheological properties of alginate/PNIPAM composite hydrogels using PEMC sensors, 24 we next leveraged the HTE method for multiproperty HTC of alginate/PNIPAM composite hydrogel libraries. Figure 5A illustrates the process of alginate/PNIPAM composite hydrogel formation.…”

“…Oevreeide et al described the potential to characterize microgel mechanics in microchannels . Marquez et al developed an indentation system for HTC of hydrogel tissue construct mechanics, while Xu et al used a commercial indenter for HTC of hydrogel swelling characteristics and mechanical properties. , Zhang et al recently established a method for HTC of hydrogel rheological properties in 96-well plate formats via robotically directed sensing using piezoelectric milli-cantilever (PEMC) sensors. ,− However, there remains a need for HTE formats capable of integrated high-throughput formulation, HTS, and HTC of complementary multiproperty information that can support the accelerated engineering of functional composite hydrogels with optimized processability and performance, particularly in practical cross-disciplinary formats, such as well plates.…”