From saccharides to synthetics: exploring biomaterial scaffolds as cell transduction enhancers.

Dry, transduction biomaterial scaffolds (Drydux) represent a novel platform for enhancing viral transduction, achieving drastic improvements in transduction efficiency (from ∼10% to >80%) while simplifying production of potent genetically engineered cells. This technology addresses a critical bottleneck in cell therapy manufacturing, where conventional methods require complex protocols and often yield suboptimal results. However, the underlying material science driving Drydux-enhanced transduction remains unclear. Here, we comprehensively assess biomaterial properties that influence viral transduction enhancement through systematic testing of polysaccharides, proteins, elastin-like polypeptides (ELPs), and synthetic polymers. Our findings reveal that surface porosity and liquid absorption are primary drivers of transduction enhancement, while polymer charge and flexibility play secondary roles. Negatively charged and flexible materials-particularly gelatin, hyaluronan, and alginate-demonstrated superior performance. Notably, despite promising material characteristics, synthetic polymers failed to enhance transduction, highlighting the unique advantages of specific biomaterial compositions. By elucidating these structure-function relationships, this work establishes design principles for optimizing biomaterial-enhanced transduction and expands the Drydux platform's potential for transforming cell therapy manufacturing, regenerative medicine, and beyond.