Kinsenoside‐Loaded Microneedle Accelerates Diabetic Wound Healing by Reprogramming Macrophage Metabolism via Inhibiting IRE1α/XBP1 Signaling Axis
Abstract Continuously bacterial infection, undue oxidative stress, and inflammatory responses in the skin tissue microenvironment determine the delayed healing outcome of diabetic wounds, which remain a tough clinical challenge and need multifaceted therapeutic strategies. In this work, HA‐ADH/HA‐QA...
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Wiley
2025-07-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202502293 |
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| author | Li Lu Jiewen Liao Chao Xu Yuan Xiong Juan Zhou Guangji Wang Ze Lin Kangkang Zha Chuanlu Lin Ruiyin Zeng Guandong Dai Qian Feng Bobin Mi Guohui Liu |
| author_facet | Li Lu Jiewen Liao Chao Xu Yuan Xiong Juan Zhou Guangji Wang Ze Lin Kangkang Zha Chuanlu Lin Ruiyin Zeng Guandong Dai Qian Feng Bobin Mi Guohui Liu |
| author_sort | Li Lu |
| collection | DOAJ |
| description | Abstract Continuously bacterial infection, undue oxidative stress, and inflammatory responses in the skin tissue microenvironment determine the delayed healing outcome of diabetic wounds, which remain a tough clinical challenge and need multifaceted therapeutic strategies. In this work, HA‐ADH/HA‐QA‐ALD‐based hydrogel microneedle (HAQA‐MN) with antimicrobial and antioxidative activities incorporating kinsenoside (KD) coated with macrophage membrane (M‐KD) targeting inflammation relief is developed to improve the cutaneous micro‐niche. KD is observed to trigger trimethylamine N‐oxide‐irritated proinflammatory macrophages repolarization from M1 state to anti‐inflammatory M2 phenotype, and the underlying mechanism is due to drug‐induced IRE1α/XBP1/HIF‐1α pathway suppression, accompanied by diminution of glycolysis and enhancement of oxidative phosphorylation, resulting in proinflammatory cascade inhibition and anti‐inflammatory signaling enhancement. The hydrazone cross‐linked HAQA‐MN possesses favorable biocompatibility, self‐healing, controlled release of M‐KD and excellent mechanical properties. Moreover, the MN patch remarkedly restrains the survival of E. coli and S. aureus and eliminates hydrogen peroxide to preserve cellular viability. Notably, M‐KD@HAQA‐MN array effectively ameliorates cutaneous inflammation and oxidative stress and facilitate angiogenesis and collagen deposition, thereby accelerating tissue regeneration of diabetic mice with a full‐thickness skin defect model. Collectively, this study highlights a multifunctional MN platform as a promising candidate in clinical application for the treatment of diabetic wounds. |
| format | Article |
| id | doaj-art-133d01f6f2b9400baba15fdc6fb9e1fb |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-133d01f6f2b9400baba15fdc6fb9e1fb2025-08-20T03:36:45ZengWileyAdvanced Science2198-38442025-07-011226n/an/a10.1002/advs.202502293Kinsenoside‐Loaded Microneedle Accelerates Diabetic Wound Healing by Reprogramming Macrophage Metabolism via Inhibiting IRE1α/XBP1 Signaling AxisLi Lu0Jiewen Liao1Chao Xu2Yuan Xiong3Juan Zhou4Guangji Wang5Ze Lin6Kangkang Zha7Chuanlu Lin8Ruiyin Zeng9Guandong Dai10Qian Feng11Bobin Mi12Guohui Liu13Department of Orthopedics Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Orthopedics Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaKey Laboratory of Biorheological Science and Technology Ministry of Education College of Bioengineering Chongqing University Chongqing 400044 ChinaDepartment of Orthopedics Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 ChinaDepartment of Cardiology Hubei Provincial Hospital of Traditional Chinese Medicine Wuhan 430073 ChinaDepartment of Cardiology The Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science and Technology Wuhan 430073 ChinaDepartment of Orthopedics Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Orthopedics Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Orthopedics Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Orthopedics Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Orthopaedics Pingshan District People's Hospital of Shenzhen Pingshan General Hospital of Southern Medical University Shenzhen Guangdong 518118 ChinaKey Laboratory of Biorheological Science and Technology Ministry of Education College of Bioengineering Chongqing University Chongqing 400044 ChinaDepartment of Orthopedics Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Orthopedics Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaAbstract Continuously bacterial infection, undue oxidative stress, and inflammatory responses in the skin tissue microenvironment determine the delayed healing outcome of diabetic wounds, which remain a tough clinical challenge and need multifaceted therapeutic strategies. In this work, HA‐ADH/HA‐QA‐ALD‐based hydrogel microneedle (HAQA‐MN) with antimicrobial and antioxidative activities incorporating kinsenoside (KD) coated with macrophage membrane (M‐KD) targeting inflammation relief is developed to improve the cutaneous micro‐niche. KD is observed to trigger trimethylamine N‐oxide‐irritated proinflammatory macrophages repolarization from M1 state to anti‐inflammatory M2 phenotype, and the underlying mechanism is due to drug‐induced IRE1α/XBP1/HIF‐1α pathway suppression, accompanied by diminution of glycolysis and enhancement of oxidative phosphorylation, resulting in proinflammatory cascade inhibition and anti‐inflammatory signaling enhancement. The hydrazone cross‐linked HAQA‐MN possesses favorable biocompatibility, self‐healing, controlled release of M‐KD and excellent mechanical properties. Moreover, the MN patch remarkedly restrains the survival of E. coli and S. aureus and eliminates hydrogen peroxide to preserve cellular viability. Notably, M‐KD@HAQA‐MN array effectively ameliorates cutaneous inflammation and oxidative stress and facilitate angiogenesis and collagen deposition, thereby accelerating tissue regeneration of diabetic mice with a full‐thickness skin defect model. Collectively, this study highlights a multifunctional MN platform as a promising candidate in clinical application for the treatment of diabetic wounds.https://doi.org/10.1002/advs.202502293diabetic woundinflammationkinsenosidemacrophagemetabolic reprogrammingmicroneedle |
| spellingShingle | Li Lu Jiewen Liao Chao Xu Yuan Xiong Juan Zhou Guangji Wang Ze Lin Kangkang Zha Chuanlu Lin Ruiyin Zeng Guandong Dai Qian Feng Bobin Mi Guohui Liu Kinsenoside‐Loaded Microneedle Accelerates Diabetic Wound Healing by Reprogramming Macrophage Metabolism via Inhibiting IRE1α/XBP1 Signaling Axis Advanced Science diabetic wound inflammation kinsenoside macrophage metabolic reprogramming microneedle |
| title | Kinsenoside‐Loaded Microneedle Accelerates Diabetic Wound Healing by Reprogramming Macrophage Metabolism via Inhibiting IRE1α/XBP1 Signaling Axis |
| title_full | Kinsenoside‐Loaded Microneedle Accelerates Diabetic Wound Healing by Reprogramming Macrophage Metabolism via Inhibiting IRE1α/XBP1 Signaling Axis |
| title_fullStr | Kinsenoside‐Loaded Microneedle Accelerates Diabetic Wound Healing by Reprogramming Macrophage Metabolism via Inhibiting IRE1α/XBP1 Signaling Axis |
| title_full_unstemmed | Kinsenoside‐Loaded Microneedle Accelerates Diabetic Wound Healing by Reprogramming Macrophage Metabolism via Inhibiting IRE1α/XBP1 Signaling Axis |
| title_short | Kinsenoside‐Loaded Microneedle Accelerates Diabetic Wound Healing by Reprogramming Macrophage Metabolism via Inhibiting IRE1α/XBP1 Signaling Axis |
| title_sort | kinsenoside loaded microneedle accelerates diabetic wound healing by reprogramming macrophage metabolism via inhibiting ire1α xbp1 signaling axis |
| topic | diabetic wound inflammation kinsenoside macrophage metabolic reprogramming microneedle |
| url | https://doi.org/10.1002/advs.202502293 |
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