The new platform, described in the journal Materials Today Bio, is built from hyaluronic acid, a naturally occurring polysaccharide already familiar from cosmetic and biomedical applications. The key insight lies in the chemistry of crosslinking. Hyaluronic acid, with its abundant carboxyl groups, readily coordinates with multivalent cations such as calcium ions, forming a three-dimensional hydrogel network reinforced by hydrogen bonds in humid conditions. But when the gel encounters tissue fluid rich in monovalent sodium and potassium ions, ligand exchange displaces the pre-chelated calcium and the network rapidly falls apart. This dynamic, switchable coordination network gives the microneedles a rare combination of properties: enough mechanical strength to pierce the oral epithelium when dry, and near-instant disintegration once exposed to the salty microenvironment of ulcerated tissue.

The design inspiration came from nematocysts, the microscopic harpoon-like organelles that jellyfish use to discharge venom in response to osmotic pressure. To mimic this triggered-release strategy, the researchers first constructed drug-loaded nanofibers from glycyrrhizic acid, a natural saponin that self-assembles into long-range ordered structures with internal hydrophobic domains. Using a low-frequency acoustic resonance technique operating at 55 hertz, they co-assembled glycyrrhizic acid with two complementary plant-derived therapeutics: baicalein, a flavonoid that disrupts bacterial cell walls and inhibits bacterial DNA synthesis, and astaxanthin, a potent carotenoid antioxidant that scavenges reactive oxygen species and promotes tissue repair. The resulting nanofibers measured just 3 to 4 nanometers in diameter but stretched up to 5 micrometers in length, an extraordinary aspect ratio of 1250, with surface zeta potentials exceeding 40 millivolts that keep the suspensions physically stable.

Encapsulation within the nanofibers solved one of the most stubborn problems in phytochemical medicine: poor water solubility. Free baicalein and astaxanthin barely dissolve in aqueous media, but once loaded into the glycyrrhizic acid fibers their apparent solubilities rose to 775.50 and 95.16 micrograms per milliliter, corresponding to enhancements of 127.5-fold and 213.7-fold respectively. Because the nanofibers carry abundant surface carboxyl groups, they behave like anionic polymers and can themselves participate in calcium-mediated gelation, becoming woven into the hyaluronic acid matrix rather than merely suspended within it. When calcium chloride solution was added, a stable, self-healing gel formed within one minute, confirmed by scanning electron microscopy and rheological testing that revealed the characteristic thixotropic behavior of an electrostatically crosslinked network.

The finished microneedle patch, designated GA@BA&Ast MNs, was cast in polydimethylsiloxane molds using vacuum centrifugal casting. Each 10 by 10 millimeter patch carries a 15 by 15 array of needles, 600 micrometers tall with 300-micrometer bases, dimensions chosen to match the anatomy of the oral epithelium so the tips cross the stratum corneum without damaging deeper tissue. Mechanical testing showed the composite needles were 1.56 times stronger than pure hyaluronic acid microneedles, comfortably exceeding the 0.15-newton threshold required for epithelial penetration. Confocal imaging of fluorescently labeled patches confirmed uniform drug distribution throughout the tips, and in rat tissue the needles delivered their cargo to depths of at least 220 micrometers, reaching the deep epithelial layers that topical formulations cannot access.

Once inserted, the transformation was dramatic. In dissolution experiments simulating the oral environment at 37 degrees Celsius and high humidity, the needle tips vanished within 2 minutes, and quantitative analysis showed that more than 85 percent of the microneedle volume had decomposed within 20 minutes, leaving minimal remnants. Spectroscopic analysis with ATR-FTIR and X-ray photoelectron spectroscopy traced the mechanism: sodium ions from the tissue fluid infiltrate the matrix and associate with the hyaluronic acid carboxylates, initiating network rearrangement, while hyperosmotic conditions further drive hydration, swelling and diffusion. Compared with chitosan-based microneedles, the release rates of astaxanthin and baicalein were enhanced by factors of 15.49 and 596.31 respectively. Crucially, the released nanofibers were then rapidly taken up by surrounding cells: within 30 minutes, the absolute amounts of astaxanthin and baicalein absorbed by oral tissue exceeded those from chitosan microneedles by 91.71-fold and 401.47-fold.

Laboratory assays revealed how the two drugs divide the therapeutic labor. In endothelial cell models, the combined nanofibers drove a scratch-wound closure rate of 87.8 percent within 24 hours, significantly outperforming astaxanthin alone at 56.4 percent, and promoted the formation of orderly tubular networks on Matrigel, indicating robust pro-angiogenic activity. The dual-drug formulation also showed the strongest scavenging of reactive oxygen species in inflamed macrophages. On the antimicrobial front, baicalein proved to be the core active component: plate assays confirmed that the released nanofibers killed and inhibited both Escherichia coli and Staphylococcus aureus, while neither hyaluronic acid nor glycyrrhizic acid alone had significant effect. In lipopolysaccharide-stimulated macrophages, the combination produced the greatest reductions in the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha among all tested groups.

The decisive test came in a rat model of oral ulceration induced by acetic acid chemical burn. Over a seven-day treatment period, ulcers treated with the full microneedle system achieved 77.3 percent wound closure, compared with just 25.5 percent natural healing in untreated animals, 34.9 percent with blank microneedles and 54.3 percent with baicalein-only patches. Macroscopically, the treated ulcers regained a healthy pink color, a sign of rapid revascularization absent in the controls. Histological examination told the same story: while untreated animals remained at the early granulation stage, the combination-treated tissue showed a smooth, continuous epithelial layer covering the wound with minimal inflammatory infiltration, hallmarks of the final maturation and remodeling phase of healing. Masson’s trichrome staining revealed uniformly organized collagen fibers resembling normal mucosa, and immunohistochemistry showed collagen deposition enhanced by 41 percent and vascular endothelial growth factor expression boosted by 47 percent relative to model controls, alongside elevated phosphorylation of PI3K and Akt, suggesting the pro-angiogenic effect runs through this well-known signaling pathway.

Safety results were equally encouraging. Major organs from treated animals showed intact architecture without inflammation, necrosis or fibrosis, the hemolysis rate stayed below the 5 percent acceptance criterion, and endothelial cell viability remained above 90 percent after exposure to patch extracts. Because the formulation relies on plant-derived compounds rather than antibiotics or corticosteroids, it sidesteps the side effects and resistance concerns associated with conventional pharmacological treatments. The researchers position the platform as a universal delivery system for hydrophobic small-molecule drugs, one whose osmolality-triggered disintegration requires no external stimulus and is tailored specifically to the wet, hyperosmotic and mechanically active environment of the mouth. If the approach translates to the clinic, the humble jellyfish sting, refined over hundreds of millions of years of evolution, may offer relief to the millions of people who suffer each year from the raw, painful lesions of oral ulcers, and potentially to patients with oral fibrosis and oral cancer as well.

Subject of Research: Osmolality-responsive dissolving microneedles for oral ulcer drug delivery

Article Title: Hyaluronic acid-based osmolality-responsive immediate-release microneedles co-loading baicalein and astaxanthin for oral ulcer therapy

Article References: Yang, J., Shi, K., Wang, J., Liu, H., Zhang, Y., Guang, X., Wang, S., Lei, W., Wang, Y., Tan, M., Ma, X., & Wu, H. (2026). Hyaluronic acid-based osmolality-responsive immediate-release microneedles co-loading baicalein and astaxanthin for oral ulcer therapy. Materials Today Bio, 41, Article 103702. https://doi.org/10.1016/j.mtbio.2026.103702

Image Credits: AI Generated

DOI: 10.1016/j.mtbio.2026.103702

Keywords: microneedles, oral ulcers, hyaluronic acid, drug delivery, baicalein, astaxanthin, glycyrrhizic acid, nanofibers, biomimetic, osmolality-responsive, wound healing, anti-inflammatory

The material at the heart of the study comes from the sponge Haliclona sp., whose skeleton is built from spicules—slender, needle-shaped rods of biosilica. In earlier work, the same group showed that intact spicules, massaged briefly into the skin, create dense fields of nanometer-scale microchannels that boost penetration of small drugs. Those channels, however, proved too narrow for biomacromolecules, which typically range from a few to hundreds of kilodaltons. The researchers’ new idea was to etch the spicules themselves, dissolving away the tip and, unexpectedly, the entire axial core to leave a continuous hollow channel running the length of each needle. This transformation converts each spicule from a solid puncturing pin into something closer to a microscopic drinking straw embedded in the skin.

Manufacturing the hollow structures required careful optimization of an alkaline etching process. The team immersed purified spicules in sodium hydroxide solutions of varying concentration and duration, then evaluated how many spicules developed open tips, how large the resulting channels were, and whether the etched structures retained the mechanical strength needed to pierce skin. The harshest condition tested—2 molar sodium hydroxide for 72 hours—produced the widest openings and highest opening rates but visibly degraded structural integrity. The sweet spot turned out to be 2 molar NaOH for 48 hours, which maximized hollow-channel formation while preserving the spicules’ ability to withstand handling and skin insertion. Scanning electron microscopy of cross-sections taken at the tip, mid-shaft, and base revealed a continuous internal lumen, and confocal microscopy after Nile Red staining confirmed that the channels readily admit fluid and dissolved compounds.

The etching pattern itself has an elegant biological explanation. Siliceous sponge spicules are built around a proteinaceous axial filament, and the alkaline treatment appears to preferentially dissolve along this central core, carving out the hollow channel along a pre-existing biological template. This means the manufacturing process exploits the sponge’s own architecture rather than fighting it—a rare example of a natural biomaterial being upgraded through a one-step chemical modification into something functionally analogous to an engineered hollow microneedle array, but without any of the cleanroom microfabrication that synthetic microneedles demand.

With the hollow spicules in hand, the researchers benchmarked them against a formidable lineup of competitors in Franz diffusion cell experiments using fresh porcine skin: intact spicules, conventional microneedle patches, dermaroller devices, iontophoresis, and plain subcutaneous injection. For sodium fluorescein, a small hydrophilic tracer, hollow spicules alone achieved total skin absorption of roughly 24 percent, rising to nearly 43 percent when paired with a 15-minute course of low-current iontophoresis. The combination produced a synergistic index of 1.44, meaning the two techniques together outperformed the sum of their individual effects. For larger fluorescent dextrans of 20, 40, and 150 kilodaltons, the gap widened dramatically. With the 20-kilodalton dextran, hollow spicules plus iontophoresis pushed absorption to about 35 percent with a synergistic index of 3.29, while intact spicules combined with iontophoresis showed no synergy at all—clear evidence that the hollow channels, not merely the puncture sites, were doing the heavy lifting.

Dose dependence and distribution uniformity emerged as two further advantages. When the team varied the amount of hollow spicules applied, penetration of the 150-kilodalton dextran scaled accordingly, giving clinicians a tunable knob for dosing. More striking was the spatial pattern: biomacromolecules delivered through spicule-treated skin spread evenly across the entire treated area, with no significant concentration differences among randomly sampled sites. Subcutaneous injection, by contrast, produced a hot spot at the needle entry point with essentially no detectable drug 5 millimeters or 1 centimeter away. For depot drugs, that pooling is sometimes desirable, but for vaccines and immunotherapies meant to engage skin-resident immune cells, uniform distribution could translate into more consistent uptake and fewer local adverse effects.

The platform’s most clinically resonant demonstration involved an antibody fragment. The team compared hollow spicules against laboratory-fabricated dissolving microneedle patches—10-by-10 arrays of quadrangular pyramidal needles, each about 820 micrometers tall and mechanically robust enough to withstand roughly 0.8 newtons of compressive force—for delivering a shark-derived anti-PD-L1 variable new antigen receptor, a model antibody-like therapeutic. The hollow spicules achieved total skin absorption of about 25 percent, roughly doubling the microneedle patch result of 11.5 percent and more than quadrupling the untreated control. Because antibody drugs represent one of the fastest-growing classes of biologics yet remain almost entirely injection-bound, a topical route that outperforms microneedles would be a meaningful advance for patients who self-administer these therapies.

To test whether the effect matters biologically, not just chemically, the researchers delivered ovalbumin, a classic model antigen, to guinea pigs over consecutive days and tracked immune activation. Both the injection group and the hollow-spicule group showed visible immune reactions by day 2, and by day 8 the spicule group’s responses, while milder than injection, remained significantly stronger than controls and intact-spicule groups. Blood analysis told the same quantitative story: ovalbumin-specific IgE levels were markedly elevated in the spicule group, and interleukin-4 concentrations showed no significant difference from the injection group. In other words, a topical massage of sponge-derived microneedles provoked an immune response functionally comparable to a needle in the flesh—a result with obvious implications for needle-free vaccination.

Safety data were encouraging but appropriately caveated. Mild redness and swelling after application resolved within 48 to 72 hours, and histological counts of immune cells in treated skin spiked to roughly 550 cells per analyzed region at 24 and 48 hours before falling back to baseline levels by day 10, statistically indistinguishable from untreated controls. Repeated application produced no chronic inflammatory infiltration, and examination of major organs revealed no abnormalities. The authors are candid, however, about a longer-term concern: silica is a recognized granulomatogenic material, and cutaneous silica granulomas can appear months or even years after exposure. Their 10-day observation window cannot rule out such delayed reactions, and the team calls for extended follow-up studies, including polarized-light assessment for birefringent particles, before the platform moves toward human use.

The study also contributes a quantitative framework for predicting how drugs will behave under spicule treatment. Because hollow spicules remain embedded in skin during use, they generate annular channels rather than the funnel-shaped perforations left by removable microneedles. Building on established microporous-skin permeability models, the researchers derived and fitted an equation capturing the dependence of permeability on molecular weight and oil-water partitioning across six test compounds, with the expected inverse relationship to molecular weight dominating the tested range. The team notes that validation in ex vivo human skin and clinical studies will be essential, since animal skin differs from human skin in barrier structure and immune responsiveness. Still, the combination of natural abundance, batch-to-batch dimensional consistency, low manufacturing cost, tunable dosing, uniform drug spread, and demonstrated vaccine-grade immune activation makes hollow sponge spicules one of the more compelling entries yet in the race to retire the hypodermic needle.

Subject of Research: Transdermal delivery of biomacromolecules using hollowed marine sponge spicules as natural microneedles

Article Title: Enhanced skin delivery of biomacromolecules using hollow sponge spicules

Article References: Mou, D., Yang, M., Jia, M., Liu, Y., Chen, J., Xiao, X., & Chen, M. (2026). Enhanced skin delivery of biomacromolecules using hollow sponge spicules. Bioengineering & Translational Medicine, 11(5), Article e70149. https://doi.org/10.1002/btm2.70149

Image Credits: AI Generated

DOI: 10.1002/btm2.70149

Keywords: drug delivery, microneedles, sponge spicules, transdermal, biomacromolecules, vaccination, biologics, iontophoresis, biosilica, skin barrier, antibody delivery, marine biotechnology

The problem the team set out to solve is well known among environmental analysts. Conventional Fourier transform infrared (FTIR) spectroscopy, the workhorse technique for identifying plastics, struggles badly with particles smaller than about 50 micrometers, because the infrared absorption cross-section of such tiny targets is simply too weak. Irregularly shaped fragments, which are exactly what environmental weathering produces, scatter incident light and generate artifacts, background signals, and ambiguous interpretations. Raman spectroscopy has partly filled the gap and is now more intensively used for microplastic identification than FTIR, but it too suffers from low sensitivity and diffraction-limited spatial resolution, and particles smaller than roughly 20 micrometers are often considered non-detectable in the standard Raman microscopy format.

Surface-enhanced infrared absorption offers a way around these limits. The technique exploits resonant electron oscillations, or plasmons, within metallic nanoantennas to dramatically boost the magnitude of infrared signals from molecules close to the metal surface. The catch has been that gold nanorods, the most commonly used plasmonic nanoantennas, naturally resonate in the visible to near-infrared range, not the mid-infrared where the characteristic vibrational fingerprints of polymers live. Achieving genuine plasmonic enhancement in the mid-IR has been rare, hampered by intrinsic noise, the limitations of mid-infrared light emitters, and the need for sophisticated waveguide-based light control. Previous successes required painstaking lift-off lithography or meta-films with stringent lattice fabrication to create short-range-ordered gold nanostructures under sub-wavelength gaps.

The Korean team, led by Hyun Ho Lee of Myongji University together with Jonghoon Choi of Chung-Ang University, took a deliberately looser approach. Instead of precisely patterning nanostructures, they allowed gold nanorods to randomly stack and cluster at the tips of polymeric microneedles during a simple imprint fabrication process. When packed closely together at sub-wavelength spacings, these short-range-ordered clusters act as nanoresonators capable of exciting both plasmon and phonon resonances in the mid-infrared. The random light confinement created by the tightly packed rods, combined with the reflection prism of the ATR setup, proved sufficient to evoke strong signal enhancement without any elaborate nanofabrication.

The microneedles themselves were made by a soft-lithography stamping method. For conical-shaped arrays, the researchers engraved molds directly into polydimethylsiloxane (PDMS) using a carbon dioxide laser, varying laser intensity and speed to control the tip geometry. For pyramidal arrays, they used a commercially available polycarbonate microneedle patch as a master to create PDMS molds. A drop of Norland Optical Adhesive 63, a UV-curable polymer, was cast onto the mold, drawn into every recess under vacuum, and stamped onto glass before being cured with ultraviolet light for 25 minutes and baked at 70 degrees Celsius. Critically, the gold nanorod solution was applied to the mold first, so that the rods became concentrated and embedded precisely at the tip end of each needle as the adhesive cured around them.

Selectivity came from chemistry rather than geometry. The researchers functionalized the exposed nanorods with a short oligopeptide called polystyrene binding peptide, or PSBP, a seven-amino-acid sequence (HWGMWSY) with a terminal thiol group that anchors it efficiently to gold surfaces. This peptide binds strongly and specifically to polystyrene, so any polystyrene microplastic drifting near a needle tip gets captured right where the plasmonic hotspots are concentrated. Before conjugation, the team used a plasma treatment to oxidize the needle tips and expose the gold nanorods that had been passivated by the adhesive during stamping, confirming the exposure with energy-dispersive X-ray spectroscopy. The microneedles were then incubated in the peptide solution, rinsed thoroughly, and dipped into samples containing polystyrene fragments at concentrations ranging from 0.1 to 100 milligrams per milliliter.

The evidence that the system works came from multiple directions. Scanning electron microscopy showed polystyrene particles attached specifically to the needle tips and nowhere else, with captured particles spanning sizes from about 10 to 100 micrometers despite the sieving step used to prepare the samples, which targeted fragments between 75 and 106 micrometers. The samples themselves were made to mimic real environmental debris: polystyrene litter was cryo-ground into irregularly shaped fragments rather than using the smooth spherical beads common in laboratory studies. The fact that nanoscale particles were also identified at the tips suggests the platform reaches down into the nanoplastic regime, where toxicity concerns are most acute.

The spectroscopic results were the centerpiece. When the peptide-functionalized, particle-capturing microneedles were pressed face-down against the flat surface of an ATR-FTIR spectrometer, characteristic polystyrene peaks appeared at 1450, 1700, and 1750 wavenumbers, amplified more than a hundredfold compared with controls. Those controls told a convincing story: needles carrying only the peptide showed no plastic peaks, and needles incubated in plastic solution without the peptide, allowing only weak physical adsorption, showed nothing detectable either. Because the adhesive itself is a benzene-containing polymer similar to polystyrene, the team checked whether the enhanced peaks might simply be background from the needle material, but the bare adhesive produced no strong signals at the characteristic positions. The enhancement, they concluded, arises from the plasmon polariton resonance of the clustered nanorods.

Raman measurements added a complementary dimension, though with an important caveat about geometry. Direct top illumination of the needles with a 532-nanometer laser failed to produce enhanced peaks, apparently because the needle apexes shadowed the signal. When the team tilted the samples and optimized the angle on a position-gauged stage, side illumination revealed surface-enhanced Raman scattering peaks, including a highlighted band near 2900 wavenumbers that distinguished tip-captured particles from bulk polystyrene powder, which instead shows its strongest aromatic carbon-hydrogen stretch at 3058 wavenumbers. That shift between the powder spectrum and the tip-captured spectrum is itself evidence of the plasmonic effect at work, and the finite number of nanorods exposed at each tip confers a moderate spatial resolution that ordinary Raman microscopy cannot match.

Beyond the raw sensitivity, the microneedle format brings practical advantages that could matter for field deployment. The needle array acts as a physical sieve during sampling, capturing particles while letting much of the background matrix wash away, which reduces interfering signals and substitutes for the filtration steps that conventional Raman workflows require. The high surface energy of the needles also lets aqueous samples dry quickly, and the arrays are cheap to replicate, with a single PDMS mold surviving three to five stamping cycles without mechanical failure. The researchers suggest that with further development of portable infrared measurement tools, the platform could enable rapid point-of-care style testing for environmental microplastic contamination, turning a laboratory-bound spectroscopic technique into something closer to a field instrument for tracking one of the defining pollutants of the plastic age.

Subject of Research: Surface-enhanced infrared spectroscopy using gold nanorod clusters on microneedle tips for detecting microplastics and nanoplastics

Article Title: Enhanced mid-IR detection characteristics of microplastics and nanoplastics using gold nanorods cluster at microneedle tips

Article References: Hur, H., Kim, C., Jo, A., Kim, G., Choi, J., & Lee, H. H. (2025). Enhanced mid-IR detection characteristics of microplastics and nanoplastics using gold nanorods cluster at microneedle tips. Advances in Industrial and Engineering Chemistry, 1(1), Article 9. https://doi.org/10.1007/s44405-025-00008-x

Image Credits: AI Generated

DOI: 10.1007/s44405-025-00008-x

Keywords: microplastics, nanoplastics, gold nanorods, SEIRA, microneedles, infrared spectroscopy, ATR-FTIR, SERS, polystyrene binding peptide, plasmonics, environmental monitoring, nanotechnology

The motivation comes from a growing recognition that skin diseases are not uniform across depth. Using spatial transcriptomics, the research team mapped bleomycin-induced fibrotic skin and found sharply stratified pathology. In the subcutaneous layer, the adipocyte marker Fabp4 progressively declined, reflecting fat loss and metabolic dysfunction. In the dermis, the senescence marker Cdkn1a steadily rose, pointing to an accumulation of aged, inflammation-secreting fibroblasts. Histological examination of clinical specimens from patients with localized scleroderma confirmed the same architecture: disorganized dermal collagen and fibrotic replacement of the subdermal adipose compartment. Immunofluorescence co-staining revealed senescent fibroblasts clustered in the dermis and adipocyte-to-myofibroblast transition, known as AMT, in the subcutis.

These findings suggest that the dermis and subcutis follow separate pathogenic programs, with the dermis driven by inflammation and cellular senescence and the fat layer driven by metabolic failure and fibrotic remodeling. Conventional delivery approaches cannot respect that geography. Subcutaneous injections and electroporation tend to leave mRNA stranded in the superficial dermis, while standard microneedle patches struggle to reach beyond the upper skin compartments. The stratum corneum, the skin’s tough outer barrier, remains a formidable obstacle for nucleic acid therapeutics, and controlling delivery depth has been an persistent challenge in cutaneous mRNA medicine.

The new platform builds on the team’s earlier threaded microneedle technology, in which continuous spiral grooves are etched into a stainless-steel needle roughly 4 millimeters long with an outer diameter of 230 micrometers. The grooves serve as protective channels that guide nanoformulated cargo along the insertion tract, reducing shear stress and tissue damage while enabling layer-resolved deposition. In prior work, the platform delivered neurotrophic factors for nerve repair and penetrated cartilage’s subchondral region for joint repair. For the skin application, the distal 1.5 millimeters of the threaded region carries the therapeutic payload.

The two therapeutic modules were engineered with complementary release behaviors. The first is SRT1720@HA, a hyaluronic acid hydrogel loaded with SRT1720, a SIRT1 agonist chosen after spatial transcriptomic analysis identified SIRT1 as a target in the epidermal and superficial dermal regions. Rheological testing confirmed a stable viscoelastic network, and in vitro release experiments showed roughly 80 percent cumulative SRT1720 release over 96 hours. The second module is PGC1α@LNP, lipid nanoparticles encapsulating messenger RNA encoding PGC-1α, a master regulator of mitochondrial metabolism identified as a target in the dermal-subcutaneous transitional zone. The nanoparticles measured about 108 nanometers in diameter, achieved an encapsulation efficiency of 92.6 percent, and released approximately 65 percent of their mRNA payload over 96 hours. Confocal imaging demonstrated time-dependent endosomal escape, and the formulation survived lyophilization and one month of storage without losing its ability to drive PGC1α expression in cells.

When the two modules were combined on a single threaded needle, fluorescence tracing in simulated skin and in living mice revealed a striking spatial division of labor. The hydrogel coating, sitting on the needle’s exterior, was preferentially wiped off during insertion and retained in the dermis, much like a conventional coated needle. The groove-embedded nanoparticles, protected from premature displacement, were carried along the full insertion tract and deposited from the dermis into the subcutaneous layer, particularly during rotational manipulation. Each microneedle carried roughly 44 nanograms of encapsulated PGC1α mRNA and about 15 nanograms of SRT1720, quantified by batch weighing and liquid chromatography-tandem mass spectrometry.

Safety and localization data supported the design. CCK-8 assays, EdU proliferation tests, and live-dead staining showed that both carriers were well tolerated by L929 fibroblasts and differentiated 3T3-L1 adipocytes across the tested concentration ranges. After microneedle application, exogenous PGC1α mRNA was detected only in treated dorsal skin, declining over time, while SRT1720 remained below the limit of quantification in plasma, lymph nodes, liver, and spleen. The system delivered its payloads locally with no measurable systemic exposure.

In cell models, each module addressed its layer-specific pathology. In senescent fibroblasts, SRT1720@HA reduced β-galactosidase positivity, restored migratory capacity in scratch assays, and dampened expression of senescence markers CDKN2A and CDKN1A along with SASP cytokines including IL-6 and IL-1β. In an AMT model where TGF-β1 pushed adipocytes toward a myofibroblast-like state, PGC1α@LNP preserved lipid droplets, upregulated adipocyte genes such as PPARγ, Perilipin, and Adiponectin, and downregulated fibrotic markers including α-SMA and Col1a1 at both the RNA and protein levels.

The decisive test came in bleomycin-induced skin fibrosis mice treated every other day for two weeks. All microneedle-based interventions improved fibrotic features, but the dual-loaded system performed best, markedly reducing dermal thickness, collagen deposition, and elastic fiber destruction. Layer-specific mechanisms were confirmed by immunostaining: the hydrogel module cut the proportion of senescent dermal fibroblasts, while the nanoparticle module suppressed AMT in the subcutaneous fat, and only the combination achieved both. Transcriptomic sequencing showed that combined treatment silenced p53 signaling, inflammatory genes, and matrix-remodeling pathways while reactivating lipid biosynthesis, mitochondrial electron transport, and PPAR-dependent metabolic programs.

The authors caution that the mouse model does not fully recapitulate human fibrosis, that dose-matched free-drug controls are still needed to separate cargo effects from the platform itself, and that long-term durability and recurrence after treatment cessation remain open questions. Even so, the study demonstrates a versatile blueprint for layer-specific intervention in skin disease, one that could extend beyond fibrosis to any condition whose pathology is written differently in the dermis than in the fat beneath it.

Subject of Research: Layer-specific dermal and subcutaneous drug and mRNA delivery using a modular LNP-hydrogel threaded microneedle platform for treating skin fibrosis

Article Title: Layer‐Specific Dermal and Subcutaneous Delivery via Modular LNP–Hydrogel‐Integrated Threaded Microneedles

Article References: Xie, F., Zhang, Y., Ling, S., Huang, Y., Wei, Y., Fu, R., He, J., Liu, B., Zhou, L., Huo, K., Wang, Y., Li, Q., Du, Y., Cui, W., & Xie, Y. (2026). Layer‐Specific Dermal and Subcutaneous Delivery via Modular LNP–Hydrogel‐Integrated Threaded Microneedles. Advanced Science, Article e77624. https://doi.org/10.1002/advs.77624

Image Credits: AI Generated

DOI: 10.1002/advs.77624

Keywords: microneedles, mRNA therapy, lipid nanoparticles, skin fibrosis, spatial transcriptomics, SIRT1, PGC-1α, hydrogel, senescence, adipocyte-to-myofibroblast transition, drug delivery, Advanced Science

The central argument of the review is that modern wound care needs materials that do more than cover. Biomaterial-based polymeric patches are designed to combine three functions in a single platform: structural support for fragile new tissue, controlled delivery of therapeutic agents, and direct regenerative activity. Achieving that combination requires careful attention to a set of design determinants that the authors lay out systematically. Biocompatibility ensures the material does not provoke an immune attack; biodegradability allows the patch to be absorbed as the wound heals rather than requiring painful removal; mechanical integrity keeps the patch intact under the stresses of movement; and the polymer’s origin, whether natural or synthetic, shapes degradation rates, cell interactions, and regulatory pathways. Increasingly, researchers are also incorporating bioactive secondary metabolites, plant-derived compounds and other natural molecules with documented anti-inflammatory, antimicrobial, and pro-regenerative effects, to give the patch genuine pharmacological punch.

Among the most versatile platforms are hydrogels, three-dimensional polymer networks that can hold large quantities of water while remaining soft and tissue-like. Hydrogels maintain the moist environment that wound healing requires, and their crosslinked structure can be tuned to release drugs over hours or days. The review highlights natural polymer hydrogels based on alginate, chitosan, and carboxymethyl cellulose, which have shown anti-inflammatory and healing-accelerating effects in both in vitro and in vivo studies. Photo-crosslinkable gelatin methacryloyl hydrogels allow researchers to pattern the material with light, creating scaffolds that mimic the extracellular matrix. Injectable hydrogel formulations are pushing further, offering targeted control of oxidative stress, one of the key biochemical culprits that keeps diabetic wounds locked in a chronic, non-healing state. Conductive hydrogel patches add yet another dimension, using bioelectric stimulation to encourage cell migration and regeneration while doubling as wearable sensors.

Electrospun nanofiber scaffolds represent a second major architectural family. By drawing polymer solutions through an electric field, manufacturers can produce mats of fibers with diameters in the nanometer range, closely resembling the fibrous architecture of the natural extracellular matrix. This biomimetic topology encourages cells to attach, proliferate, and migrate across the wound bed. The review cites work on polycaprolactone-zinc scaffolds coated with fibroblast-derived extracellular matrix, which enhanced cell proliferation, migration, and fibroblast differentiation, and on radially oriented berberine-loaded PHBV nanofiber dressings designed to accelerate diabetic wound closure. Electrospun dressings loaded with carbon quantum dots and citrate have demonstrated improved antibacterial efficiency, and the technology has begun to appear in real-world clinical evaluation, with commercial systems such as Spincare being assessed for practical wound coverage.

Microneedle arrays are perhaps the most visually striking of the new architectures. These patches studded with microscopic needles, often tens to hundreds of micrometers tall, can painlessly penetrate the tough, dead surface layer of a chronic wound and deposit drugs, growth factors, or biomolecules directly into viable tissue below. The review describes bioinspired wearable polymer microneedle patches developed specifically for diabetic wound therapy, as well as multifunctional designs such as a kangfuxin-chitosan-fucoidan complex patch that enabled full-thickness wound healing in preclinical models, and ROS-scavenging microneedle patches that mop up the reactive oxygen species implicated in chronic inflammation. Because microneedles can be engineered from dissolving or biodegradable polymers, they can leave no sharps waste and release their payload as they dissolve, combining delivery, mechanical debridement of the wound surface, and safety in one device.

Multilayered composite dressings take a different approach to the same problem: rather than one material doing everything, they assign each layer a job. A typical bilayer or trilayer patch might feature a tough, bacteria-blocking outer film, a middle layer that stores and slowly releases therapeutics, and a soft, adhesive inner layer that conforms to the wound. The review points to examples including gelatin-chitosan bilayer patches loaded with medicinal plant extracts, tri-layer dressings combining zinc oxide nanoparticles with insulin-like growth factor 1 for full-thickness skin injuries, and pollen-integrated hydrogel patches with hierarchical structures that release active compounds in a spatio-temporally controlled fashion. This architectural sophistication mirrors the layered structure of skin itself and allows formulators to reconcile requirements, such as moisture retention and mechanical strength, that would otherwise conflict within a single material.

The most futuristic entries in the review are the smart, responsive patches that merge wound care with diagnostics. Hydrogel-based electronic-skin patches have been demonstrated that both accelerate healing and monitor the state of the wound in real time. Conducting polymer arrays with multiplex sensing and drug-delivery capabilities form the basis of next-generation smart bandages, while a negative-pressure smart patch has been reported that can both sense wound conditions and apply therapy on demand. Wearable platforms built on hydrogels are being designed to track biomarkers such as pH, temperature, uric acid, and moisture, parameters that correlate with infection and healing progress, and to trigger therapeutic release only when needed. The authors note that artificial intelligence is beginning to enter this space, with machine-learning approaches proposed for interpreting sensor data and personalizing treatment, turning the humble dressing into a closed-loop therapeutic system.

Underpinning all of these architectures is a growing appreciation of wound biology. The review situates material design within the cellular choreography of repair: the inflammatory phase dominated by macrophages whose plasticity determines whether healing proceeds or stalls, the proliferative phase in which fibroblasts lay down new matrix and new blood vessels form, and the remodeling phase that determines final scar quality. In diabetic and chronic wounds, elevated oxidative stress, persistent infection, and dysregulated inflammation derail this sequence. Bioactive metabolites from plants, marine peptides, and even microbial sources are being explored as natural modulators that can nudge the wound environment back toward regeneration, and polymer chemists are learning to embed these molecules without destroying their activity.

Yet the review’s most sobering contribution is its assessment of translation. Despite an impressive laboratory literature, the number of advanced polymeric patches that have reached routine clinical use remains small. The authors identify a cluster of recurring barriers: manufacturing scalability, since processes like electrospinning and microneedle molding are difficult to reproduce at industrial scale with consistent quality; product standardization, because natural polymers vary batch to batch; regulatory approval pathways that were not designed for combination products blending drug, device, and biological functions; cost-effectiveness in health systems already strained by chronic wound care; and, above all, the scarcity of large-scale clinical validation. Registered clinical trials of advanced patches, including nitric oxide-releasing patches for diabetic foot ulcers and hemostatic patches for surgery, exist but remain limited in number and scope relative to the volume of preclinical publications. The review also flags the poor quality of many animal studies and calls for better standardized reporting, citing newly proposed guidelines for wound-healing research.

The overall picture that emerges is of a field at an inflection point. The material science has arguably outpaced the clinical science: researchers can now build patches that sense, deliver, stimulate, and regenerate, but the pathway from elegant prototype to approved, affordable, widely available product remains bottlenecked by economics, regulation, and evidence. By integrating advances in material design with an honest appraisal of translational and clinical considerations, Nandi and colleagues offer a framework intended to help the next generation of patches cross that gap. For the millions of patients whose wounds will not heal, the promise is real, but so, the review makes clear, is the distance still to travel.

Subject of Research: Bioactive polymeric patches and advanced dressing architectures for chronic wound healing and their translational challenges

Article Title: Next-generation bioactive polymeric patches for chronic wound healing: from advanced architectures to translational challenges

Article References: Nandi, A., Ahmed, R. K., & Chakrabarti, S. (2026). Next-generation bioactive polymeric patches for chronic wound healing: from advanced architectures to translational challenges. Polymer Bulletin, 83(12), Article 643. https://doi.org/10.1007/s00289-026-06697-8

Image Credits: AI Generated

DOI: 10.1007/s00289-026-06697-8

Keywords: chronic wounds, wound healing, biomaterials, hydrogels, electrospun nanofibers, microneedles, smart dressings, drug delivery, tissue regeneration, polymers, diabetic ulcers, clinical translation