This study introduces a new buffer system with superior pH stability for gelatin methacrylate (GelMA) synthesis, addressing significant limitations of conventional carbonate-bicarbonate (CBC) and phosphate-buffered saline (PBS) methods. Our comparative analysis demonstrated that the new buffer maintains exceptional pH stability throughout the methacrylation reaction, even at a larger reaction volume. GelMA gels synthesized using the new buffer system exhibited significantly improved storage and loss modulus compared to materials produced with CBC and PBS buffers, while maintaining equivalent degrees of substitution as verified by NMR analysis. Circular dichroism measurements revealed enhanced triple helix formation in GelMA produced with the new buffer system, contributing to its superior mechanical properties. These findings establish our buffer as an optimal approach for producing high-strength GelMA scaffolds with enhanced mechanical integrity and consistent quality across variable production scales. Notably, this same approach has been successfully applied to synthesize GelMA nanoparticles with consistently reproducible results.
