Abstract Microneedle arrays show many advantages in drug delivery applications due to their convenience and reduced risk of infection. Compared to other microscale manufacturing methods, 3D printing easily overcomes challenges in the fabrication of microneedles with complex geometric shapes and multifunctional performance. However, due to material characteristics and limitations on printing capability, there are still bottlenecks to overcome for 3D printed microneedles to achieve the mechanical performance needed for various clinical applications. The hierarchical structures in limpet teeth, which are extraordinarily strong, result from aligned fibers of mineralized tissue and protein‐based polymer reinforced frameworks. These structures provide design inspiration for mechanically reinforced biomedical microneedles. Here, a bioinspired microneedle array is fabricated using magnetic field‐assisted 3D printing (MF‐3DP). Micro‐bundles of aligned iron oxide nanoparticles (aIOs) are encapsulated by polymer matrix during the printing process. A bioinspired 3D‐printed painless microneedle array is fabricated, and suitability of this microneedle patch for drug delivery during long‐term wear is demonstrated. The results reported here provide insights into how the geometrical morphology of microneedles can be optimized for the painless drug delivery in clinical trials.
more »
« less
A Review of 3D-Printing of Microneedles
Microneedles are micron-sized devices that are used for the transdermal administration of a wide range of active pharmaceutics substances with minimally invasive pain. In the past decade, various additive manufacturing technologies have been used for the fabrication of microneedles; however, they have limitations due to material compatibility and bioavailability and are time-consuming and expensive processes. Additive manufacturing (AM), which is popularly known as 3D-printing, is an innovative technology that builds three-dimensional solid objects (3D). This article provides a comprehensive review of the different 3D-printing technologies that have the potential to revolutionize the manufacturing of microneedles. The application of 3D-printed microneedles in various fields, such as drug delivery, vaccine delivery, cosmetics, therapy, tissue engineering, and diagnostics, are presented. This review also enumerates the challenges that are posed by the 3D-printing technologies, including the manufacturing cost, which limits its viability for large-scale production, the compatibility of the microneedle-based materials with human cells, and concerns around the efficient administration of large dosages of loaded microneedles. Furthermore, the optimization of microneedle design parameters and features for the best printing outcomes is of paramount interest. The Food and Drug Administration (FDA) regulatory guidelines relating to the safe use of microneedle devices are outlined. Finally, this review delineates the implementation of futuristic technologies, such as artificial intelligence algorithms, for 3D-printed microneedles and 4D-printing capabilities.
more »
« less
- Award ID(s):
- 2116181
- PAR ID:
- 10383411
- Date Published:
- Journal Name:
- Pharmaceutics
- Volume:
- 14
- Issue:
- 12
- ISSN:
- 1999-4923
- Page Range / eLocation ID:
- 2693
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
null (Ed.)Drug delivery through the skin offers many advantages such as avoidance of hepatic first-pass metabolism, maintenance of steady plasma concentration, safety, and compliance over oral or parenteral pathways. However, the biggest challenge for transdermal delivery is that only a limited number of potent drugs with ideal physicochemical properties can passively diffuse and intercellularly permeate through skin barriers and achieve therapeutic concentration by this route. Significant efforts have been made toward the development of approaches to enhance transdermal permeation of the drugs. Among them, microneedles represent one of the microscale physical enhancement methods that greatly expand the spectrum of drugs for transdermal and intradermal delivery. Microneedles typically measure 0.1–1 mm in length. In this review, microneedle materials, fabrication routes, characterization techniques, and applications for transdermal delivery are discussed. A variety of materials such as silicon, stainless steel, and polymers have been used to fabricate solid, coated, hollow, or dissolvable microneedles. Their implications for transdermal drug delivery have been discussed extensively. However, there remain challenges with sustained delivery, efficacy, cost-effective fabrication, and large-scale manufacturing. This review discusses different modes of characterization and the gaps in manufacturing technologies associated with microneedles. This review also discusses their potential impact on drug delivery, vaccine delivery, disease diagnostic, and cosmetics applications.more » « less
-
Abstract 3D printing, also known as additive manufacturing, holds immense potential for rapid prototyping and customized production of functional health‐related devices. With advancements in polymer chemistry and biomedical engineering, polymeric biomaterials have become integral to 3D‐printed biomedical applications. However, there still exists a bottleneck in the compatibility of polymeric biomaterials with different 3D printing methods, as well as intrinsic challenges such as limited printing resolution and rates. Therefore, this review aims to introduce the current state‐of‐the‐art in 3D‐printed functional polymeric health‐related devices. It begins with an overview of the landscape of 3D printing techniques, followed by an examination of commonly used polymeric biomaterials. Subsequently, examples of 3D‐printed biomedical devices are provided and classified into categories such as biosensors, bioactuators, soft robotics, energy storage systems, self‐powered devices, and data science in bioplotting. The emphasis is on exploring the current capabilities of 3D printing in manufacturing polymeric biomaterials into desired geometries that facilitate device functionality and studying the reasons for material choice. Finally, an outlook with challenges and possible improvements in the near future is presented, projecting the contribution of general 3D printing and polymeric biomaterials in the field of healthcare.more » « less
-
Abstract Microneedles have recently emerged as a powerful tool for minimally invasive drug delivery and body fluid sampling. To date, high‐resolution fabrication of microneedle arrays (MNAs) is mostly achieved by the utilization of sophisticated facilities and expertise. Particularly, hollow microneedles have usually been manufactured in cleanrooms out of silicon, resin, or metallic materials. Such strategies do not support the fabrication of microneedles from biocompatible/biodegradable materials and limit the capability of multimodal drug delivery for the controlled release of different therapeutics through a combination of injection and sustained diffusion. This study implements low‐cost 3D printers to fabricate relatively large needle arrays, followed by repeatable shrink‐molding of hydrogels to form high‐resolution molds for solid and hollow MNAs with controllable sizes. The developed strategy further enables modulating surface topography of MNAs to tailor their surface area and instantaneous wettability for controllable drug delivery and body fluid sampling. Hybrid gelatin methacryloyl (GelMA)/polyethylene glycol diacrylate (PEGDA) MNAs are fabricated using the developed strategy that can easily penetrate the skin and enable multimodal drug delivery. The proposed method holds promise for affordable, controllable, and scalable fabrication of MNAs by researchers and clinicians for controlled spatiotemporal administration of therapeutics and sample collection.more » « less
-
null (Ed.)Microneedles provide a transdermal pathway for drug delivery, cosmetic infusion, vaccine administration, and disease diagnostics. Microneedle fabrication relies on the interplay of several variables which include design parameters, material properties, and processing conditions. In this research, our group explores the effect of design parameters and process variables for laser ablation of microneedles within a Polymethyl methacrylate (PMMA) mold. An Ytterbium laser (200W) was utilized to study the effect of five inputs factors (laser power, pulse width, number of repetitions, laser waveform, and interval time between laser pulses) on two output factors (diameter and height) of the fabricated microneedles. Polydimethylsiloxane (PDMS) polymer was cast within the PMMA microneedle mold. Scanning electron microscopy (SEM) was employed to image topographical features of the microneedles. Further, mechanical testing of the microneedles was conducted to evaluate the buckling load and deformation behavior of the microneedle array. A 20W pulse laser with trapezoidal waveform resulted in optimal microneedle topography with an aspect ratio of 1.2. ANOVA results (α = 0.05) depicted that laser power and number of repetitions were significant factors determining the geometrical features of the microneedle array. This research establishes a framework for the design and manufacturing of customized microneedles for precision medicine.more » « less
An official website of the United States government

