Over the last decade, significant advances in the biomanufacturing of microneedle-based devices (MN)s have emerged highlighting their potential over a range of therapeutic applications. However, ensuring that these MNs penetrate just the right depth to work effectively without causing harm has been a persistent challenge. Researchers are now tackling this issue, paving the way for more precise and safer treatments. A new approach to controlling the penetration depth of an array of hollow MNs have been successfully developed by a team led by Dr. Maryam Mobed-Miremadi of Santa Clara University, CA, USA. Incorporation of a stopper above the tip limited penetration to a target depth of 150 µm, ensuring precision within the epidermal layer. This work, published in the journal of Applied Mechanics, uses a stopper mechanism to ensure precise targeting while maintaining structural integrity of the 3D-printed device under mechanical load.
MNs were fabricated using stereolithography (SLA), leveraging a biocompatible photoresin with a 25–50 µm resolution. Shrinkage was quantitatively assessed post-curing using transmission microscopy and imaging analyses. Thin sterilized cross-linked alginate hydrogel slabs were used as skin analogs to mimic the biomechanical properties of the epidermis. Mechanical testing on these biocompatible hydrogels confirmed the MNs ability to achieve uniform penetration. Profilometry analyses further validated the efficacy of the stopper in maintaining consistent depth across various tests. Pycnometry was used to measure the density of hydrogel films before and after puncture to confirm mass redistribution versus material loss during microneedle indentation.
Extensive testing of the hydrogel phantoms revealed the MNs ability to withstand forces exceeding those typically required for epidermal penetration. Measurements of peak puncture forces, hardness and viscoelastic properties ensure that the design met the necessary standards for practical applications. The stopper’s role in enhancing uniformity and reducing variability in puncture was a significant finding.
Simulations using COMSOL software were conducted to model stress distributions and deformation during device insertion with the experimentally-determined properties of the phantoms and shrinkage parameters. Density findings were not directly simulated but were informed material property inputs for the computational model. These in silico experiments complemented the empirical results, providing insights into the mechanical performance and areas for potential design optimization. Stress relaxation profiles and insertion force trends closely aligned with experimental results reinforcing the robustness of the design and integrated process for device testing.
This study’s methodology and findings provide a foundation for advancing MN technology in precision medical applications. The researchers aim to refine the process for nozzle-to-nozzle penetration reproducibility and scalability. Design flexibility enabled by adapting the stopper’s dimension to insertion depth originally intended for microencapsulated cell delivery expands the potential use to applications such as transdermal drug delivery and biomarker detection, minimizing discomfort and maximizing therapeutic outcomes.
Journal Reference
Defelippi, K.M.; Kwong, A.Y.S.; Appleget, J.R.; Altay, R.; Matheny, M.B.; Dubus, M.M.; Eribes, L.M.; Mobed-Miremadi, M. “An Integrated Approach to Control the Penetration Depth of 3D-Printed Hollow Microneedles.” Appl. Mech.2024, 5, 233-259. https://doi.org/10.3390/applmech5020015
About the Authors
Celebrating 100 years of Women in Engineering the authors biographies are:
Dr. Maryam Mobed-Miremadi is a Teaching Professor in the Department of Bioengineering at Santa Clara University. Her current research interests include simulation, optimization, and statistical validation across multiscale biomaterials-related platforms, including sustainable energy applications.
Kendall DeFelippi graduated from Santa Clara University in December 2023 with an MS in Bioengineering. In addition to working on medical applications of microneedles (MNs), she has researched microneedle scaling for bioprocessing applications. Kendall currently works as an Associate Scientist at Neurocrine Biosciences in San Diego, CA.
Allyson Kwong is a bioengineering student pursuing a five-year BS/MS degree at Santa Clara University and working as a part-time engineer at Stryker Medical. She continues to research quantitative puncture characterization in soft materials.
Julia Appleget is an Electrical Engineering student pursuing an MS degree at Santa Clara University. As a recipient of the Clare Boothe undergraduate grant, her research in bioengineering focused on leveraging the mechanical and electrical properties of tetrafunctional hydrogel networks in biomedical device and bioenergy applications.
Rana Altay is a PhD student in Dr. Araci’s lab at Santa Clara University. Her research lies at the intersection of microfluidics and wearable technologies. Prior to attending Santa Clara University, she studied Mechatronics Engineering at Sabancı University in Turkey.
Maya Matheny is a first-year MD candidate at the Keck School of Medicine at the University of Southern California. She earned her bachelor’s degree in Bioengineering from Santa Clara University, where she developed an interest in biofabrication. Maya is passionate about advancing healthcare equity and combining technical expertise with compassionate patient care.
Maggie Dubus 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 is committed to integrating translational research with high-quality, compassionate patient care throughout her medical career.
Lily Eribes works as an engineer for Microchip Technology Inc. in Arizona. She earned her bachelor’s degree in Bioengineering from Santa Clara University, where she served as a Healthcare Innovation Fellow and researcher.
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