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<p>Pathological scars, resulting from abnormal collagen metabolism during wound healing, pose clinical challenges due to the high recurrence rates of conventional treatments. Therefore, early-stage modulation of the wound healing process is emerging as a pivotal strategy for preventing and treating pathological scars, necessitating precise coordination of vascular regeneration, inflammation regulation, cell migration, and collagen remodeling. Here, we developed a 3D-printed tower-shaped microneedle system (BSEVs@VA-HP MNs) loaded with vitamin A (VA)-containing Bletilla striata vesicles (BSEVs@VA) for functionally staged effects supported by release kinetics in scarless wound healing. The BSEVs@VA-HP MNs demonstrate exceptional mechanical strength, making them highly effective in penetrating the skin, adhering to tissues, and enzyme-responsive degradation. In rat wound models and rabbit ear scar models, the BSEVs@VA-HP MNs gradually dissolve and release BSEVs, which passively target and are internalized by cells. These BSEVs reprogram macrophages toward an M2 phenotype, mediating anti-inflammatory effects while simultaneously promoting angiogenesis and cell migration. Upon cellular internalization, lysosomes degrade BSEVs, liberating VA, which regulates the type I/III collagen balance during tissue remodeling, thereby suppressing myofibroblast activation and facilitating scarless wound healing. This study integrates natural plant-derived vesicles with 3D-printed bioinspired microneedle technology to establish a synergistic, stage-coordinated therapeutic strategy for scarless wound healing.</p> Graphical abstract <p></p>

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Tower-shaped super-adhesive microneedles loaded with vitamin A-containing Bletilla striata vesicles: temporally regulated Inflammation resolution and ECM remodeling for scarless wound healing

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月28日

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  • Shixing Edi,
  • Guopeng Tao,
  • Quluo Mupo,
  • Jiahong Hu,
  • Huan Gu,
  • Kaijun Gou,
  • Ping Zhou,
  • Jijun Zhou,
  • Xiao Wang,
  • Rui Zeng

摘要

Pathological scars, resulting from abnormal collagen metabolism during wound healing, pose clinical challenges due to the high recurrence rates of conventional treatments. Therefore, early-stage modulation of the wound healing process is emerging as a pivotal strategy for preventing and treating pathological scars, necessitating precise coordination of vascular regeneration, inflammation regulation, cell migration, and collagen remodeling. Here, we developed a 3D-printed tower-shaped microneedle system (BSEVs@VA-HP MNs) loaded with vitamin A (VA)-containing Bletilla striata vesicles (BSEVs@VA) for functionally staged effects supported by release kinetics in scarless wound healing. The BSEVs@VA-HP MNs demonstrate exceptional mechanical strength, making them highly effective in penetrating the skin, adhering to tissues, and enzyme-responsive degradation. In rat wound models and rabbit ear scar models, the BSEVs@VA-HP MNs gradually dissolve and release BSEVs, which passively target and are internalized by cells. These BSEVs reprogram macrophages toward an M2 phenotype, mediating anti-inflammatory effects while simultaneously promoting angiogenesis and cell migration. Upon cellular internalization, lysosomes degrade BSEVs, liberating VA, which regulates the type I/III collagen balance during tissue remodeling, thereby suppressing myofibroblast activation and facilitating scarless wound healing. This study integrates natural plant-derived vesicles with 3D-printed bioinspired microneedle technology to establish a synergistic, stage-coordinated therapeutic strategy for scarless wound healing.

Graphical abstract