ArticleMaterials today. Bio2026
Bionic intelligent responsive barbed microneedles synergistically remodel the microenvironment for the treatment of refractory pigmentation disorders (melasma).
Article in Materials today. Bio, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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14 authors.
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Abstract
Clinically refractory melasma remains difficult to treat because it is driven by a multidimensional pathological microenvironment that includes melanocyte hyperactivity, aberrant vascular growth, oxidative stress and chronic inflammation. Single-pathway therapies therefore often produce incomplete or transient responses. To remodel this microenvironment more broadly, we developed a bioinspired, stimulus-responsive co-delivery microneedle platform (TXA/Exo@HAMA-PBA MNs). Inspired by the backward-curved barbs on the tick hypostome, the microneedles were engineered with outward-facing barbs to improve anchoring within skin tissue. Chemically, adipose-derived stem cell exosomes (ADSC-Exos) acted as bioactive crosslinking nodes. They were coupled to the HAMA-PBA matrix through ROS-sensitive dynamic boronate ester bonds, while tranexamic acid (TXA) was physically co-encapsulated. After insertion into ROS-rich melasma-like lesions, oxidative cleavage of carbon-boron bonds accelerated matrix degradation and promoted on-demand release of both payloads. Mechanistically, this platform produced an asymmetric but coordinated blockade of the pathological microenvironment: ADSC-Exos mainly scavenged local ROS, including ·OH, whereas TXA preferentially disrupted abnormal capillary networks. Together, they suppressed melanogenesis through the MITF/TYRP1 cascade and shifted macrophages from a pro-inflammatory M1 phenotype towards a tissue-reparative M2 phenotype. In a UV/progesterone-induced mouse model of melasma validated by bulk RNA sequencing, the system produced multidimensional microenvironmental regulation and visible depigmentation. This bioinspired, spatiotemporally responsive co-delivery microneedle platform integrates complementary and synergistic therapeutic actions and offers a translational strategy for complex, multifactorial hyperpigmentary disorders.
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