Biofouling on implantable medical devices, such as stainless steels, is a significant problem causing healthcare-associated infections (HAIs) and patient mortality. Hydrogels, known for their hydrophilicity and drug-loading capacity, offer potential as antifouling coatings. Zwitterionic polymers, inspired by cell membranes, exhibit strong antifouling properties due to their anionic and cationic groups, but suffer from poor mechanical stability. HEMA polymers offer good elastic properties, suggesting that combining zwitterions with HEMA could create more stable and effective coatings. However, traditional one-by-one synthesis and characterization methods are time-consuming and resource-intensive when exploring the vast parameter space involved (monomer content, crosslinking degree, and ratios of functional groups). High-throughput technologies offer a solution by enabling rapid screening of numerous material combinations. This work aims to develop a high-throughput strategy to design zwitterion/HEMA hydrogels with optimized mechanical stability and drug-loading capacity.

Existing literature highlights the use of HEMA, PEG, and zwitterionic polymers as antifouling hydrogel coatings. Zwitterionic polymers, while effective at preventing biofouling, often lack sufficient adhesive and mechanical stability. Various methods have been explored to improve this stability, such as incorporating dopamine side chains or phosphonate/phosphonic pendants for stronger substrate binding. However, these modifications can compromise the inherent antifouling properties. HEMA, with its good elastic properties, shows promise in improving the mechanical stability of zwitterionic hydrogels. The impact of parameters like monomer content, crosslinking degree, and functional group ratios on hydrogel properties has been previously demonstrated, but exploring the entire parameter space remains challenging with conventional methods.

The researchers employed a high-throughput strategy using an automated droplet microarray printer to create a library of 1575 unique hydrogel coating combinations with continuous gradients in reactant content. The printer generated picoliter-sized droplets, allowing for highly miniaturized synthesis using only 600 µL of reactants. The process involved sequentially depositing reactants onto a substrate to create individual spots. The homogeneity of the mixture within each spot was confirmed using Raman spectroscopy and fluorescent dye treatments. The mechanical stability of the coatings was assessed through immersion swelling tests in PBS (72 hours), flow tests simulating blood flow (500 mL/min, 72 hours), and tape-peeling tests (10 cycles). Finally, the drug-loading capacity was evaluated by staining the hydrogels with Congo red and quantifying the dye uptake via image analysis.

The high-throughput screening revealed key relationships between hydrogel composition and properties. Incorporation of HEMA significantly improved the mechanical stability of zwitterionic hydrogels, making them resistant to immersion swelling, flow, and abrasion. Hydrogels with lower molecular weight crosslinkers generally exhibited better stability than those with higher molecular weight crosslinkers. Optimal crosslinker concentrations were found to balance mechanical stability and swelling capacity. Drug-loading capacity correlated positively with the SBMA (zwitterion) ratio in the monomers and negatively with the crosslinker concentration; high SBMA ratio and low crosslinker content resulted in the best drug loading capacity. Ultimately, 10 out of 1575 hydrogel formulations were identified as having optimal stability and drug-loading capacity.

The high-throughput approach enabled efficient identification of optimal synthesis parameters from a vast combinatorial space. The results demonstrate that combining zwitterionic monomers with HEMA and careful control of crosslinker properties can yield mechanically stable and high drug-loading capacity hydrogel coatings. The optimized coatings show promise for mitigating biofouling on implantable devices, improving device longevity and patient outcomes. The strategy presented here can be generalized for rapid screening and design of other materials beyond hydrogel coatings.

This study successfully developed and validated a high-throughput methodology for optimizing zwitterion-based hydrogel coatings. The approach efficiently identified key composition-property relationships, leading to the discovery of ten optimal formulations with enhanced mechanical stability and drug-loading capacity. The method is scalable and adaptable, offering a powerful tool for accelerating the development of advanced biomaterials.

The study focused on in vitro testing. Further in vivo studies are needed to confirm the long-term stability and antifouling performance of the optimized coatings. The range of parameters explored might not fully encompass all possible combinations, and future studies could explore a broader chemical space.