Over the past decade, significant advances have been made in the biofabrication of microneedle-based devices (MNs), highlighting their potential for a range of therapeutic applications. However, ensuring that these micronanos penetrate to the correct depth to work effectively without causing harm has been an ongoing challenge. Researchers are now solving this problem, paving the way for more precise and safer treatments. A team led by Dr. Maryam Mobed-Miremadi of Santa Clara University in California, USA, successfully developed a new method to control the penetration depth of hollow MN arrays. A plug above the tip limits penetration to a target depth of 150 µm, ensuring precision within the epidermal layer. The work, published in the journal Applied Mechanics, uses a stop mechanism to ensure precise targeting while maintaining the structural integrity of the 3D printing device under mechanical loads.
MN is fabricated using stereolithography (SLA) technology, utilizing biocompatible photoresin with a resolution of 25-50 µm. Post-curing shrinkage was quantitatively assessed using transmission microscopy and imaging analysis. Thin sterile cross-linked alginate hydrogel sheets were used as skin analogues to mimic the biomechanical properties of the epidermis. Mechanical testing of these biocompatible hydrogels confirmed the ability of MN to achieve uniform penetration. Profile measurement analysis further validated the plug’s efficacy in maintaining consistent depth across the various tests. The density of the hydrogel film before and after puncture was measured using pycnometry to confirm the relationship between mass redistribution and material loss during microneedle indentation.
Extensive testing on hydrogel models showed that MNs are able to withstand forces in excess of those typically required for epidermal penetration. Measurements of peak penetration force, hardness and viscoelasticity ensure that the design meets the necessary standards for practical applications. The role of plugs in enhancing puncture uniformity and reducing variability was a significant finding.
COMSOL software was used for simulation, and the experimentally determined phantom properties and shrinkage parameters were used to simulate the stress distribution and deformation during device insertion. Density results are not simulated directly but provide material property input to computational models. These in silico experiments complement the empirical results, providing insights into areas of mechanical performance and potential design optimization. Stress relaxation curves and insertion force trends correlate closely with experimental results, enhancing the robustness of the device test design and integration process.
The methods and results of this study lay the foundation for advancing the development of MN technology in precision medicine applications. The researchers aimed to improve the reproducibility and scalability of the nozzle-to-nozzle penetration process. Design flexibility is achieved by adjusting the size of the stopper to accommodate the insertion depth initially used for microencapsulated cell delivery, extending its potential use to applications such as transdermal drug delivery and biomarker detection, thereby minimizing discomfort and Maximize treatment effectiveness.
Journal reference
DeFelippi, KM; Kuang, AYS; Little Apple, JR; Altay, R. Matheny, MB; Dubus, MM; Erebus, LM; Mobed-Miremadi, M. “A comprehensive approach to controlling penetration depth of 3D printed hollow microneedles.” application. Mecha.2024, 5233-259. https://doi.org/10.3390/applmech5020015
About the author
To celebrate 100 years of women in engineering, a biography of the author follows:
Dr. Mariam Mobed Mirmadi is a teaching professor in the Department of Bioengineering at Santa Clara University. Her current research interests include simulation, optimization and statistical validation of biomaterial-related platforms across multiple scales, including sustainable energy applications.
Kendall DeFelippi Graduated from Santa Clara University in December 2023 with a master’s degree in bioengineering. In addition to working on medical applications of microneedles (MN), she also studies microneedle scaling in bioprocessing applications. Kendall currently works as an Associate Scientist at Neurocrine Biosciences in San Diego, California.
Kristy Kwong is a bioengineering major pursuing a five-year bachelor’s/master’s degree at Santa Clara University and working as a part-time engineer at Stryker Medical. She continues to study the quantitative puncture properties of soft materials.
julia applegate is an electrical engineering student at Santa Clara University, pursuing a master’s degree. A recipient of the Claire Booth Undergraduate Scholarship, her research in bioengineering focuses on exploiting the mechanical and electrical properties of tetrafunctional hydrogel networks in biomedical devices and bioenergy applications.
Rana Altay is a doctoral student in Dr. Araci’s laboratory at Santa Clara University. Her research involves the intersection of microfluidics and wearable technologies. She studied mechatronics engineering at Sabanci University in Türkiye before attending Santa Clara University.
Maya Matheny is a first-year MD candidate at the Keck School of Medicine of USC. She earned a bachelor’s degree in bioengineering from Santa Clara University, where she became interested in biofabrication. Maya is passionate about advancing health care equity and combining technical expertise with compassionate patient care.
Maggie Dubs is a first-year MD student at the University of Colorado School of Medicine. She earned her bachelor’s degree in bioengineering from Santa Clara University, where she developed her translational research skills. Maggie has dedicated her entire medical career to integrating translational research with high-quality, compassionate patient care.
Lily Erebus Works as an engineer at Microchip Technology Inc. in Arizona. She earned a bachelor’s degree in bioengineering from Santa Clara University, where she worked as a healthcare innovation fellow and researcher.
