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A Bio-Inspired Swellable Microneedle Adhesive for Mechanical Interlocking With Tissue

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A Bio-Inspired Swellable Microneedle Adhesive for Mechanical Interlocking With Tissue

Seung Yun Yang et al. Nat Commun.

Abstract

Achieving significant adhesion to soft tissues while minimizing tissue damage poses a considerable clinical challenge. Chemical-based adhesives require tissue-specific reactive chemistry, typically inducing a significant inflammatory response. Staples are fraught with limitations including high-localized tissue stress and increased risk of infection, and nerve and blood vessel damage. Here inspired by the endoparasite Pomphorhynchus laevis, which swells its proboscis to attach to its host's intestinal wall, we have developed a biphasic microneedle array that mechanically interlocks with tissue through swellable microneedle tips, achieving ~3.5-fold increase in adhesion strength compared with staples in skin graft fixation, and removal force of ~4.5 N cm(-2) from intestinal mucosal tissue. Comprising a poly(styrene)-block-poly(acrylic acid) swellable tip and non-swellable polystyrene core, conical microneedles penetrate tissue with minimal insertion force and depth, yet high adhesion strength in their swollen state. Uniquely, this design provides universal soft tissue adhesion with minimal damage, less traumatic removal, reduced risk of infection and delivery of bioactive therapeutics.

Figures

Figure 1
Figure 1. Concept and fabrication of the bio-inspired microneedle (MN) adhesive
a, Illustration showing mechanical interlocking of a water responsive shape-changeable microneedle following penetration into a tissue. b, Schematic showing the preparation of the double-layered MN array using a PDMS mold and showing the chemical structure of PS-b-PAA with PS weight fraction (wtPS) of 25% used for the swellable tip. c, Cartoon showing the inner structure of double-layered MN and reversible water responsiveness. A thin hydrophobic film comprising the PS block covered the outer surface of the MN, likely due to the presence of the hydrophobic PDMS mold. During fabrication of the of non-swellable PS core, PS chains likely entangle with the PS block at the interface (dashed line) between the swellable tip and PS core providing interfacial adhesion to prevent delamination. d-f, Cross-sectional optical images of hollow MN (without the PS core) with different PS-b-PAA filling fractions including (d) 20%, (e) 40%, and (f) 70% (height of PS-b-PAA layer compared to total MN height). These MNs were prepared by solvent-casting PS-b-PAA dissolved in DMF using different concentrations (d: 10 wt%, e: 18 wt%, and f:25wt%). g, Double-layered MN with a swellable tip (20% height fraction) following filling of the PS core. Scale bar, 200 µm. h, Photograph of the double-layered MN array with density of 10x10/cm2 showing high pattern fidelity. Scale bar is 1mm. The PS-b-PAA tip is clearly distinguishable from the PS core as shown in the inset (Scale bar, 500 µm).
Figure 2
Figure 2. Swelling of BCP MN following insertion into a hydrogel and muscle tissue
a, Time-dependent swelling of the BCP MNs (40% swellable tip height fraction) following insertion into a 1.4 wt% agarose hydrogel (0 s, 60 s, 600 s). b, OFDI images showing swelling of the same BCP MNs following insertion into muscle tissue (0 s, 120 s, 360 s, 600 s). Scale bar, 500 µm.
Figure 3
Figure 3. MN adhesive firmly adheres to skin
a, Normal adhesion strength for PS MN and BCP MN adhesives with 20% and 40% swellable tip height fractions following insertion into skin (2 min and 10 min). Flat PS and PS-b-PAA films were used as controls. b, Effect of swelling time within skin on adhesion for a BCP MN adhesive with a swellable tip height fraction of 40%. c, Representative force-displacement curve during BCP MN insertion into, and removal from pig skin. d, Photograph of flexible BCP MN adhesive (2cm × 2cm) prepared by using a thermoplastic elastomer as the base material (in place of PS). e, Adhesion on a dynamic surface. Flexible BCP MN adhesives applied to shaved skin on top of the pig wrist joint showed firm attachment during ~ 100 cycles of bending motion. All error bars represent standard deviation.
Figure 4
Figure 4. MN adhesive achieves effective fixation of skin grafts and resists bacterial infiltration
a-b, Comparison of the contact area between a skin graft and tissue-like hydrogel (4 wt% agarose gel) after (a) applying staples and (b) a BCP MN adhesive. Staples showed less contact area between the skin graft and underlying hydrogel and upon removal induced significant damage to the underlying hydrogel (region marked by arrow in Fig. 4a), while the BCP MN adhesive showed continuous contact ~ 100% with minimal damage to the hydrogel. c-d, Force displacement profiles and photographs acquired during pull-off tests of skin graft on muscle tissue fixed by c, staples and d, BCP MN adhesive. While the stapled skin graft was easily separated from the underlying muscle with a low pull-off strength, the BCP MN adhesive provided continuous contact between the skin graft and muscle tissue via mechanical interlocking with underlying muscle tissue. e-h,Comparison of the bacterial barrier property of incised skin grafts following application of (e,f) staples and (g,h) a BCP MN adhesive. e(i): Cartoon illustrating the primary site of bacterial infiltration through the gaps between staple legs and skin grafts. e(ii): a photograph showing stapled skin grafts after bacteria infiltration; cyanoacrylate glue was used to tightly seal the incised region (dark area outlined by dotted black line). f, GFP expressing E. coli colonies formed near deep staple holes (marked by red dots) where skin grafts did not appose the underlying agar layer (left, bright field image). The infiltration of E. coli through the staple holes was confirmed by green fluorescence (right, fluorescent image). g(i): Cartoon showing bacterial barrier resistance of the BCP MN adhesive resulting from tight sealing of holes by swollen MNs and g(ii): photograph of the BCP MN adhesive applied on the incised skin grafts. h, BCP adhesive prevented bacterial infiltration (left, bright field image) with minimal damage and (right, fluorescent image) no green fluorescence was detected on the agar plate. Scale bar, 1 mm.
Figure 5
Figure 5. MN adhesive firmly attaches to wet intestine tissue
a-b, Photographs from a, outer and b, inner (mucosal) surfaces of pig intestine tissue and corresponding depth profile showing topographical roughness. c, Adhesion strength for PS MN (non-swellable) and swellable BCP MN adhesives with a rigid and flexible base following insertion into mucosal and serosal intestine surfaces. The asterisk indicates statistical significance with p < 0.05 (ANOVA with post-hoc Tukey’s HSD test). Error bars represent standard deviation. d, Following penetration into the outer surface of intestine tissue and application of 60° or 100° of rotation, significant damage to PS MN was observed (broken MN), while BCP MN and Flex BCP MN exhibited significantly reduced MN breakage. e-g, Photographs for tilted view of MN arrays after torsion test of 100° rotation using (e) PS MN, (f) BCP MN, and (g) Flex BCP MN adhesives. The tips or entire PS MNs were broken by torsional stress (especially at the edges of the patch marked by arrow), yet BCP MN with rigid and flexible bases showed high resistance to torsional stress by bending in the direction of the shear force.

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