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4D Printing of a Bioinspired Microneedle Array with
Backward-Facing Barbs for Enhanced Tissue Adhesion
Daehoon Han, Riddish S. Morde, Stefano Mariani, Antonino A. La Mattina,
Emanuele Vignali, Chen Yang, Giuseppe Barillaro,* and Howon Lee*
Microneedle (MN), a miniaturized needle with a length-scale of hundreds of
micrometers, has received a great deal of attention because of its minimally
invasive, pain-free, and easy-to-use nature. However, a major challenge for
controlled long-term drug delivery or biosensing using MN is its low tissue
adhesion. Although microscopic structures with high tissue adhesion are
found from living creatures in nature (e.g., microhooks of parasites, barbed
stingers of honeybees, quills of porcupines), creating MNs with such complex
microscopic features is still challenging with traditional fabrication methods.
Here, a MN with bioinspired backward-facing curved barbs for enhanced
tissue adhesion, manufactured by a digital light processing 3D printing
technique, is presented. Backward-facing barbs on a MN are created by
desolvation-induced deformation utilizing cross-linking density gradient in a
photocurable polymer. Barb thickness and bending curvature are controlled
by printing parameters and material composition. It is demonstrated that
tissue adhesion of a backward-facing barbed MN is 18 times stronger than
that of barbless MN. Also demonstrated is sustained drug release with
barbed MNs in tissue. Improved tissue adhesion of the bioinspired MN
allows for more stable and robust performance for drug delivery, biofluid
collection, and biosensing.
DOI: 10.1002/adfm.201909197
Dr. D. Han, R. S. Morde, C. Yang, Prof. H. Lee
Department of Mechanical and Aerospace Engineering
Rutgers University-New Brunswick
98 Brett Road, Piscataway, NJ 08854, USA
E-mail: howon.lee@rutgers.edu
Dr. S. Mariani, A. A. La Mattina, E. Vignali, Prof. G. Barillaro
Department of Information Engineering
University of Pisa
via G. Caruso 16, 56122 Pisa, Italy
E-mail: g.barillaro@iet.unipi.it
The ORCID identification number(s) for the author(s) of this article
can be found under https://doi.org/10.1002/adfm.201909197.
ideally suited for delivery over extended
periods. In addition, professional training
is required for proper administration and
a potential risk of infection also exists
due to the large puncture on tissue after
use.[3] Microneedles (MNs) have gained
increasing attention as “pain-free” alter-
natives because they are short and thin
enough to reduce pain and the risk of
infection.[4] However, it is challenging
to use MNs for long-term and controlled
drug delivery which requires MN to
remain attached to soft tissue for a long
time. It is primarily because typical micro-
manufacturing techniques for MN fabrica-
tion yield a smooth and plain side profile
of MNs, which inevitably results in weak
tissue adhesion.
Some living creatures in nature have
developed interesting solutions to achieve
strong tissue adhesion in the micro-
scopic length-scale. Mosquitoes have stiff
jagged shafts on the sides of the feeding
duct. They serve as an anchorage system,
resulting in strong tissue adhesion during
the feeding process.[5] Endoparasitic
worms use swellable proboscis to attach to its host’s intestinal
wall. The swollen proboscis facilitates mechanical interlocking
with tissue to improve the adhesion.[6] Honeybees have micro-
scopic backward-facing barbs at their stinger.[7] The barbs are
mechanically interlocked with the tissue to enhance adhesion
to tissue when inserted. Recent studies have shown that a
barbed stinger exhibits about 70 times stronger adhesion force
than a barbless acupuncture needle.[8] Similarly, a natural quill
of North American porcupine having microscopic backward-
facing deployable barbs shows three times higher tissue adhe-
sion compared to its barbless counterpart.[9]
Inspired by these unique shapes and functions, much effort
has been made to enhance tissue adhesion of MN with jagged
shapes[10] and swellable structures.[6,11] However, conventional
manufacturing techniques for MNs such as micromolding,
laser cutting, and lithography draw significant limitation to
fabrication of elaborate microfeatures on MNs. Recently, a
honeybee-inspired MN having backward-facing barbs has
been created using a magnetorheological drawing lithog-
raphy technique, but its manufacturing process is still com-
plex, expensive, and time-consuming.[12] Here, we present a
4D printing approach (3D printing with a programmed shape
1. Introduction
Hypodermic needles have been in widespread use for liquid
drug injection and biofluid collection as an effective medical
device for centuries.[1] However, they cause significant pain
to patients during insertion due to their invasive nature.[2] It
is unavoidable to cause tissue damage and touch nerve end-
ings in the lower layers of the skin and, therefore, they are not
Adv. Funct. Mater. 2020, 30, 1909197