Mallory Micah, Johnson Emma Grace, Saha Soumen, Pandit Sanika, McCune Joshua T, Dennis Mengnan, Gluck Jessica M, Duvall Craig L, Brown Ashley C, Chilkoti Ashutosh, Brudno Yevgeny
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA.
Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA.
Biomater Sci. 2025 May 16. doi: 10.1039/d4bm01588f.
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.
干燥转导生物材料支架（Drydux）是一种用于增强病毒转导的新型平台，在提高转导效率方面取得了显著进步（从约10%提高到>80%），同时简化了高效基因工程细胞的生产。该技术解决了细胞治疗制造中的一个关键瓶颈，传统方法需要复杂的方案且往往产生不理想的结果。然而，驱动Drydux增强转导的基础材料科学仍不清楚。在此，我们通过对多糖、蛋白质、弹性蛋白样多肽（ELP）和合成聚合物进行系统测试，全面评估了影响病毒转导增强的生物材料特性。我们的研究结果表明，表面孔隙率和液体吸收是转导增强的主要驱动因素，而聚合物电荷和柔韧性起次要作用。带负电荷且具有柔韧性的材料——特别是明胶、透明质酸和藻酸盐——表现出卓越的性能。值得注意的是，尽管具有有前景的材料特性，但合成聚合物未能增强转导，凸显了特定生物材料组成的独特优势。通过阐明这些结构-功能关系，这项工作确立了优化生物材料增强转导的设计原则，并扩展了Drydux平台在变革细胞治疗制造、再生医学及其他领域的潜力。
