Dual-Network QSAZ@VPH hydrogel-mediated verapamil treatment improved recovery of diabetic ulcer through inhibiting mitochondrial oxidative stress and enhancing angiogenesis
Background: Diabetic ulcer (DU) are severe complications of diabetes, characterized by persistent inflammation, oxidative stress, and impaired mitochondrial function. Verapamil, a calcium channel blocker, has shown potential in reducing oxidative stress and improving mitochondrial dysfunction, but i...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-08-01
|
| Series: | Materials & Design |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0264127525006720 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850164421112889344 |
|---|---|
| author | Bin Chen Hang Li Yuliang Sun Yuhua Li Parisa Anvari Ghazal Shokraneh Menglin Cong AmirMahdi Saeidi Hecheng Ma Tian Li Gang Wang Junhao Lin Zhijian Wei |
| author_facet | Bin Chen Hang Li Yuliang Sun Yuhua Li Parisa Anvari Ghazal Shokraneh Menglin Cong AmirMahdi Saeidi Hecheng Ma Tian Li Gang Wang Junhao Lin Zhijian Wei |
| author_sort | Bin Chen |
| collection | DOAJ |
| description | Background: Diabetic ulcer (DU) are severe complications of diabetes, characterized by persistent inflammation, oxidative stress, and impaired mitochondrial function. Verapamil, a calcium channel blocker, has shown potential in reducing oxidative stress and improving mitochondrial dysfunction, but its application in DU treatment remains unexplored. Methods: A dual-network QSAZ@VPH hydrogel was developed for local delivery and controlled release of verapamil. In vitro experiments evaluated its protective effects on HUVECs exposed to H2O2-induced mitochondrial dysfunction, including inflammatory marker expression, apoptosis inhibition, and angiogenesis promotion. In vivo studies used db/db mice and DU model rats to assess wound healing, granulation tissue formation, and neovascularization. Results: In vitro, QSAZ@VPH reduced mitochondrial dysfunction, lowered inflammatory markers, inhibited apoptosis, and promoted angiogenesis. In vivo, the hydrogel significantly improved wound healing in both models, reversing impaired healing and promoting granulation tissue formation and enhanced neovascularization. Conclusions: The QSAZ@VPH hydrogel presents a promising strategy for diabetic ulcer therapy by targeting mitochondrial dysfunction and promoting tissue regeneration. |
| format | Article |
| id | doaj-art-2e98e53970f945d5b210a3ed5a9e6887 |
| institution | OA Journals |
| issn | 0264-1275 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials & Design |
| spelling | doaj-art-2e98e53970f945d5b210a3ed5a9e68872025-08-20T02:21:59ZengElsevierMaterials & Design0264-12752025-08-0125611425210.1016/j.matdes.2025.114252Dual-Network QSAZ@VPH hydrogel-mediated verapamil treatment improved recovery of diabetic ulcer through inhibiting mitochondrial oxidative stress and enhancing angiogenesisBin Chen0Hang Li1Yuliang Sun2Yuhua Li3Parisa Anvari4Ghazal Shokraneh5Menglin Cong6AmirMahdi Saeidi7Hecheng Ma8Tian Li9Gang Wang10Junhao Lin11Zhijian Wei12Department of orthopedic, Department of hand and foot surgery, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of orthopedic, Department of spinal surgery, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of orthopedic, Department of hand and foot surgery, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of orthopedic, Department of spinal surgery, Qilu Hospital of Shandong University, Jinan, ChinaCheeloo College of Medicine, Shandong University, Jinan, ChinaCheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of orthopedic, Department of spinal surgery, Qilu Hospital of Shandong University, Jinan, ChinaCheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of orthopedic, Department of spinal surgery, Qilu Hospital of Shandong University, Jinan, ChinaTianjin Key Laboratory of Acute Abdomen Disease-Associated Organ Injury and ITCWM Repair, Institute of Integrative Medicine of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin Medical University, 8, Changjiang Avenue, Tianjin 300100, China; Corresponding authors.Department of orthopedic, Department of hand and foot surgery, Qilu Hospital of Shandong University, Jinan, China; Corresponding authors.Department of orthopedic, Department of hand and foot surgery, Qilu Hospital of Shandong University, Jinan, China; Corresponding authors.Department of orthopedic, Department of spinal surgery, Qilu Hospital of Shandong University, Jinan, China; Corresponding authors.Background: Diabetic ulcer (DU) are severe complications of diabetes, characterized by persistent inflammation, oxidative stress, and impaired mitochondrial function. Verapamil, a calcium channel blocker, has shown potential in reducing oxidative stress and improving mitochondrial dysfunction, but its application in DU treatment remains unexplored. Methods: A dual-network QSAZ@VPH hydrogel was developed for local delivery and controlled release of verapamil. In vitro experiments evaluated its protective effects on HUVECs exposed to H2O2-induced mitochondrial dysfunction, including inflammatory marker expression, apoptosis inhibition, and angiogenesis promotion. In vivo studies used db/db mice and DU model rats to assess wound healing, granulation tissue formation, and neovascularization. Results: In vitro, QSAZ@VPH reduced mitochondrial dysfunction, lowered inflammatory markers, inhibited apoptosis, and promoted angiogenesis. In vivo, the hydrogel significantly improved wound healing in both models, reversing impaired healing and promoting granulation tissue formation and enhanced neovascularization. Conclusions: The QSAZ@VPH hydrogel presents a promising strategy for diabetic ulcer therapy by targeting mitochondrial dysfunction and promoting tissue regeneration.http://www.sciencedirect.com/science/article/pii/S0264127525006720Diabetic ulcersVerapamilHydrogel deliveryWound healingMitochondrial |
| spellingShingle | Bin Chen Hang Li Yuliang Sun Yuhua Li Parisa Anvari Ghazal Shokraneh Menglin Cong AmirMahdi Saeidi Hecheng Ma Tian Li Gang Wang Junhao Lin Zhijian Wei Dual-Network QSAZ@VPH hydrogel-mediated verapamil treatment improved recovery of diabetic ulcer through inhibiting mitochondrial oxidative stress and enhancing angiogenesis Materials & Design Diabetic ulcers Verapamil Hydrogel delivery Wound healing Mitochondrial |
| title | Dual-Network QSAZ@VPH hydrogel-mediated verapamil treatment improved recovery of diabetic ulcer through inhibiting mitochondrial oxidative stress and enhancing angiogenesis |
| title_full | Dual-Network QSAZ@VPH hydrogel-mediated verapamil treatment improved recovery of diabetic ulcer through inhibiting mitochondrial oxidative stress and enhancing angiogenesis |
| title_fullStr | Dual-Network QSAZ@VPH hydrogel-mediated verapamil treatment improved recovery of diabetic ulcer through inhibiting mitochondrial oxidative stress and enhancing angiogenesis |
| title_full_unstemmed | Dual-Network QSAZ@VPH hydrogel-mediated verapamil treatment improved recovery of diabetic ulcer through inhibiting mitochondrial oxidative stress and enhancing angiogenesis |
| title_short | Dual-Network QSAZ@VPH hydrogel-mediated verapamil treatment improved recovery of diabetic ulcer through inhibiting mitochondrial oxidative stress and enhancing angiogenesis |
| title_sort | dual network qsaz vph hydrogel mediated verapamil treatment improved recovery of diabetic ulcer through inhibiting mitochondrial oxidative stress and enhancing angiogenesis |
| topic | Diabetic ulcers Verapamil Hydrogel delivery Wound healing Mitochondrial |
| url | http://www.sciencedirect.com/science/article/pii/S0264127525006720 |
| work_keys_str_mv | AT binchen dualnetworkqsazvphhydrogelmediatedverapamiltreatmentimprovedrecoveryofdiabeticulcerthroughinhibitingmitochondrialoxidativestressandenhancingangiogenesis AT hangli dualnetworkqsazvphhydrogelmediatedverapamiltreatmentimprovedrecoveryofdiabeticulcerthroughinhibitingmitochondrialoxidativestressandenhancingangiogenesis AT yuliangsun dualnetworkqsazvphhydrogelmediatedverapamiltreatmentimprovedrecoveryofdiabeticulcerthroughinhibitingmitochondrialoxidativestressandenhancingangiogenesis AT yuhuali dualnetworkqsazvphhydrogelmediatedverapamiltreatmentimprovedrecoveryofdiabeticulcerthroughinhibitingmitochondrialoxidativestressandenhancingangiogenesis AT parisaanvari dualnetworkqsazvphhydrogelmediatedverapamiltreatmentimprovedrecoveryofdiabeticulcerthroughinhibitingmitochondrialoxidativestressandenhancingangiogenesis AT ghazalshokraneh dualnetworkqsazvphhydrogelmediatedverapamiltreatmentimprovedrecoveryofdiabeticulcerthroughinhibitingmitochondrialoxidativestressandenhancingangiogenesis AT menglincong dualnetworkqsazvphhydrogelmediatedverapamiltreatmentimprovedrecoveryofdiabeticulcerthroughinhibitingmitochondrialoxidativestressandenhancingangiogenesis AT amirmahdisaeidi dualnetworkqsazvphhydrogelmediatedverapamiltreatmentimprovedrecoveryofdiabeticulcerthroughinhibitingmitochondrialoxidativestressandenhancingangiogenesis AT hechengma dualnetworkqsazvphhydrogelmediatedverapamiltreatmentimprovedrecoveryofdiabeticulcerthroughinhibitingmitochondrialoxidativestressandenhancingangiogenesis AT tianli dualnetworkqsazvphhydrogelmediatedverapamiltreatmentimprovedrecoveryofdiabeticulcerthroughinhibitingmitochondrialoxidativestressandenhancingangiogenesis AT gangwang dualnetworkqsazvphhydrogelmediatedverapamiltreatmentimprovedrecoveryofdiabeticulcerthroughinhibitingmitochondrialoxidativestressandenhancingangiogenesis AT junhaolin dualnetworkqsazvphhydrogelmediatedverapamiltreatmentimprovedrecoveryofdiabeticulcerthroughinhibitingmitochondrialoxidativestressandenhancingangiogenesis AT zhijianwei dualnetworkqsazvphhydrogelmediatedverapamiltreatmentimprovedrecoveryofdiabeticulcerthroughinhibitingmitochondrialoxidativestressandenhancingangiogenesis |