Innovative microneedle technology for penetration depth control

Over the last decade, significant advances in the biomanufacturing of microneedle-based devices (MNs) 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 has 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 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 ensured 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.