Sprayable hydrogel sponge for neurovascular microenvironment reconstruction and inflammation modulation in diabetic wound healing
Diabetic wounds are characterized by chronic inflammation, vascular insufficiency, and peripheral neuropathy, which collectively disrupt the neurovascular microenvironment essential for coordinated tissue regeneration. However, strategies targeting neurovascular regeneration remain limited. Here, we...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2025-12-01
|
| Series: | Bioactive Materials |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X25003615 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849222595113648128 |
|---|---|
| author | Xiaozhen Zhou Pengchao Ma Yihao Liu Zhaojian Wang Shida Chen Zekun Cheng Songlu Tseng Hui Wu Mengdi Zhang Fengzhou Du Nanze Yu Xiao Long Jiuzuo Huang Xiumei Wang |
| author_facet | Xiaozhen Zhou Pengchao Ma Yihao Liu Zhaojian Wang Shida Chen Zekun Cheng Songlu Tseng Hui Wu Mengdi Zhang Fengzhou Du Nanze Yu Xiao Long Jiuzuo Huang Xiumei Wang |
| author_sort | Xiaozhen Zhou |
| collection | DOAJ |
| description | Diabetic wounds are characterized by chronic inflammation, vascular insufficiency, and peripheral neuropathy, which collectively disrupt the neurovascular microenvironment essential for coordinated tissue regeneration. However, strategies targeting neurovascular regeneration remain limited. Here, we developed a sprayable hydrogel sponge based on gelatin methacryloyl and methacrylamide-modified ε-poly-L-lysine (S-GPL), co-functionalized with VEGF-mimetic peptide (KLT) and BDNF-mimetic peptide (RGI). The sprayable format conforms to irregular wound geometries, while the pneumatic spraying technique generates high-pressure microbubbles that create a porous structure, thereby enhancing exudate absorption and sustained peptide release as a sponge dressing. Additionally, the incorporation of KLT and RGI facilitates the reconstruction of the neurovascular microenvironment. In vitro, KLT promoted endothelial cell maturation and cytokine secretion, whereas RGI enhanced Schwann cell activity. Notably, S-GPLKLT/RGI facilitated intercellular interactions between RSCs and HUVECs, highlighting the cellular mechanisms underlying neurovascular communication. In a full-thickness diabetic wound model in rats, the hydrogel accelerated wound closure, re-epithelialization, and matrix remodeling. These effects were accompanied by enhanced neovascularization and axonal regeneration, along with the formation of a spatially organized neurovascular niche, as evidenced by CD31+ capillaries closely aligned with PGP9.5+ nerve fibers. Building upon the intrinsic anti-inflammatory properties of S-GPL, transcriptomic and immunohistochemical analyses further revealed that S-GPLKLT/RGI treatment suppressed the IL-17 signaling pathway. However, the relationship between immunomodulation and neurovascular reconstruction warrants further investigation. Collectively, this study presents a sprayable antibacterial hydrogel that not only reconstructs the neurovascular microenvironment but also mitigates chronic inflammation, offering a clinically translatable strategy for diabetic wound management. |
| format | Article |
| id | doaj-art-f28a1477451d4369b867f638cadc5000 |
| institution | Kabale University |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-f28a1477451d4369b867f638cadc50002025-08-26T04:14:27ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-12-015435237010.1016/j.bioactmat.2025.08.008Sprayable hydrogel sponge for neurovascular microenvironment reconstruction and inflammation modulation in diabetic wound healingXiaozhen Zhou0Pengchao Ma1Yihao Liu2Zhaojian Wang3Shida Chen4Zekun Cheng5Songlu Tseng6Hui Wu7Mengdi Zhang8Fengzhou Du9Nanze Yu10Xiao Long11Jiuzuo Huang12Xiumei Wang13Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100032, China; 4+4 Medical Doctor Program, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China; Center for Regenerative Medicine & Plastic Surgery Research, Peking Union Medical College Hospital, Beijing, 10032, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China; Department of Orthopedics, The Fourth Medical Centre of Chinese PLA General Hospital, Beijing, 100089, ChinaDepartment of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100032, China; Center for Regenerative Medicine & Plastic Surgery Research, Peking Union Medical College Hospital, Beijing, 10032, China4+4 Medical Doctor Program, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, ChinaDepartment of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100032, China; Center for Regenerative Medicine & Plastic Surgery Research, Peking Union Medical College Hospital, Beijing, 10032, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, ChinaDepartment of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100032, China; Center for Regenerative Medicine & Plastic Surgery Research, Peking Union Medical College Hospital, Beijing, 10032, ChinaDepartment of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100032, China; Center for Regenerative Medicine & Plastic Surgery Research, Peking Union Medical College Hospital, Beijing, 10032, ChinaDepartment of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100032, China; Center for Regenerative Medicine & Plastic Surgery Research, Peking Union Medical College Hospital, Beijing, 10032, ChinaDepartment of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100032, China; Center for Regenerative Medicine & Plastic Surgery Research, Peking Union Medical College Hospital, Beijing, 10032, China; Corresponding author. Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100032, China.Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100032, China; Center for Regenerative Medicine & Plastic Surgery Research, Peking Union Medical College Hospital, Beijing, 10032, China; Corresponding author. Center for Regenerative Medicine & Plastic Surgery Research, Peking Union Medical College Hospital, Beijing, 10032, ChinaState Key Laboratory of New Ceramic Materials, Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China; Corresponding author.Diabetic wounds are characterized by chronic inflammation, vascular insufficiency, and peripheral neuropathy, which collectively disrupt the neurovascular microenvironment essential for coordinated tissue regeneration. However, strategies targeting neurovascular regeneration remain limited. Here, we developed a sprayable hydrogel sponge based on gelatin methacryloyl and methacrylamide-modified ε-poly-L-lysine (S-GPL), co-functionalized with VEGF-mimetic peptide (KLT) and BDNF-mimetic peptide (RGI). The sprayable format conforms to irregular wound geometries, while the pneumatic spraying technique generates high-pressure microbubbles that create a porous structure, thereby enhancing exudate absorption and sustained peptide release as a sponge dressing. Additionally, the incorporation of KLT and RGI facilitates the reconstruction of the neurovascular microenvironment. In vitro, KLT promoted endothelial cell maturation and cytokine secretion, whereas RGI enhanced Schwann cell activity. Notably, S-GPLKLT/RGI facilitated intercellular interactions between RSCs and HUVECs, highlighting the cellular mechanisms underlying neurovascular communication. In a full-thickness diabetic wound model in rats, the hydrogel accelerated wound closure, re-epithelialization, and matrix remodeling. These effects were accompanied by enhanced neovascularization and axonal regeneration, along with the formation of a spatially organized neurovascular niche, as evidenced by CD31+ capillaries closely aligned with PGP9.5+ nerve fibers. Building upon the intrinsic anti-inflammatory properties of S-GPL, transcriptomic and immunohistochemical analyses further revealed that S-GPLKLT/RGI treatment suppressed the IL-17 signaling pathway. However, the relationship between immunomodulation and neurovascular reconstruction warrants further investigation. Collectively, this study presents a sprayable antibacterial hydrogel that not only reconstructs the neurovascular microenvironment but also mitigates chronic inflammation, offering a clinically translatable strategy for diabetic wound management.http://www.sciencedirect.com/science/article/pii/S2452199X25003615Sprayable hydrogelHydrogel spongeDiabetic wound dressingNeurovascular microenvironmentInflammation modulation |
| spellingShingle | Xiaozhen Zhou Pengchao Ma Yihao Liu Zhaojian Wang Shida Chen Zekun Cheng Songlu Tseng Hui Wu Mengdi Zhang Fengzhou Du Nanze Yu Xiao Long Jiuzuo Huang Xiumei Wang Sprayable hydrogel sponge for neurovascular microenvironment reconstruction and inflammation modulation in diabetic wound healing Bioactive Materials Sprayable hydrogel Hydrogel sponge Diabetic wound dressing Neurovascular microenvironment Inflammation modulation |
| title | Sprayable hydrogel sponge for neurovascular microenvironment reconstruction and inflammation modulation in diabetic wound healing |
| title_full | Sprayable hydrogel sponge for neurovascular microenvironment reconstruction and inflammation modulation in diabetic wound healing |
| title_fullStr | Sprayable hydrogel sponge for neurovascular microenvironment reconstruction and inflammation modulation in diabetic wound healing |
| title_full_unstemmed | Sprayable hydrogel sponge for neurovascular microenvironment reconstruction and inflammation modulation in diabetic wound healing |
| title_short | Sprayable hydrogel sponge for neurovascular microenvironment reconstruction and inflammation modulation in diabetic wound healing |
| title_sort | sprayable hydrogel sponge for neurovascular microenvironment reconstruction and inflammation modulation in diabetic wound healing |
| topic | Sprayable hydrogel Hydrogel sponge Diabetic wound dressing Neurovascular microenvironment Inflammation modulation |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X25003615 |
| work_keys_str_mv | AT xiaozhenzhou sprayablehydrogelspongeforneurovascularmicroenvironmentreconstructionandinflammationmodulationindiabeticwoundhealing AT pengchaoma sprayablehydrogelspongeforneurovascularmicroenvironmentreconstructionandinflammationmodulationindiabeticwoundhealing AT yihaoliu sprayablehydrogelspongeforneurovascularmicroenvironmentreconstructionandinflammationmodulationindiabeticwoundhealing AT zhaojianwang sprayablehydrogelspongeforneurovascularmicroenvironmentreconstructionandinflammationmodulationindiabeticwoundhealing AT shidachen sprayablehydrogelspongeforneurovascularmicroenvironmentreconstructionandinflammationmodulationindiabeticwoundhealing AT zekuncheng sprayablehydrogelspongeforneurovascularmicroenvironmentreconstructionandinflammationmodulationindiabeticwoundhealing AT songlutseng sprayablehydrogelspongeforneurovascularmicroenvironmentreconstructionandinflammationmodulationindiabeticwoundhealing AT huiwu sprayablehydrogelspongeforneurovascularmicroenvironmentreconstructionandinflammationmodulationindiabeticwoundhealing AT mengdizhang sprayablehydrogelspongeforneurovascularmicroenvironmentreconstructionandinflammationmodulationindiabeticwoundhealing AT fengzhoudu sprayablehydrogelspongeforneurovascularmicroenvironmentreconstructionandinflammationmodulationindiabeticwoundhealing AT nanzeyu sprayablehydrogelspongeforneurovascularmicroenvironmentreconstructionandinflammationmodulationindiabeticwoundhealing AT xiaolong sprayablehydrogelspongeforneurovascularmicroenvironmentreconstructionandinflammationmodulationindiabeticwoundhealing AT jiuzuohuang sprayablehydrogelspongeforneurovascularmicroenvironmentreconstructionandinflammationmodulationindiabeticwoundhealing AT xiumeiwang sprayablehydrogelspongeforneurovascularmicroenvironmentreconstructionandinflammationmodulationindiabeticwoundhealing |