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Introduction: Designing footwear for comfort is vital for preventing foot injuries and promoting foot health. This study explores the impact of auxetic structured shoe soles on plantar biomechanics and comfort, motivated by the integration of 3D printing in footwear production and the superior mechanical properties of auxetic designs. The shoe sole designs proposed in this study are based on a three-dimensional re-entrant auxetic lattice structure, orthogonally composed of re-entrant hexagonal honeycombs with internal angles less than 90 degrees. Materials fabricated using this lattice structure exhibit the characteristic of a negative Poisson's ratio, displaying lateral expansion under tension and densification under compression., Methods: The study conducted a comparative experiment among three different lattice structured (auxetic 60°, auxetic 75° and non-auxetic 90°) thermoplastic polyurethane (TPU) shoe soles and conventional polyurethane (PU) shoe sole through pedobarographic measurements and comfort rating under walking and running conditions. The study obtained peak plantar pressures (PPPs) and contact area across seven plantar regions of each shoe sole and analyzed the correlation between these biomechanical parameters and subjective comfort., Results: Compared to non-auxetic shoe soles, auxetic structured shoe soles reduced PPPs across various foot regions and increased contact area. The Auxetic 60°, which had the highest comfort ratings, significantly lowered peak pressures and increased contact area compared to PU shoe sole. Correlation analysis showed that peak pressures in specific foot regions (hallux, second metatarsal head, and hindfoot when walking; second metatarsal head, third to fifth metatarsal head, midfoot, and hindfoot when running) were related to comfort. Furthermore, the contact area in all foot regions was significantly associated with comfort, regardless of the motion states., Conclusion: The pressure-relief performance and conformability of the auxetic lattice structure in the shoe sole contribute to enhancing footwear comfort. The insights provided guide designers in developing footwear focused on foot health and comfort using auxetic structures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Lu, Yang, Liu, Guo and Wang.)