An injectable ibuprofen sustained-release composite hydrogel system effectively accelerates diabetic wound healing via anti-inflammatory effects and angiogenesis
Open accessAbstract
Purpose: Excessive inflammation in diabetic wounds, driven by hyperglycemia, prolongs healing, increases the risk of non-healing ulcers, and can lead to severe complications such as amputation or life-threatening infections. Recurrent wound infections and prolonged treatment impose significant economic and psychological burdens, drastically reducing patients' quality of life. Modulating the inflammatory response is a promising strategy to accelerate diabetic wound healing. Ibuprofen (IBU), a widely used anti-inflammatory and analgesic agent, has the potential to promote healing by mitigating excessive inflammation and alleviating wound-associated pain. However, its clinical application is hindered by poor water solubility and a short half-life. Therefore, a controlled and sustained-release system for IBU could enhance its therapeutic efficacy in diabetic wound management. Materials and Methods: ) via ion crosslinking, photocrosslinking, and Schiff-base reactions. Results: The optimized hydrogel formulation was synthesized at 35°C, with a P/A molar ratio of 2 and an methacrylamide(MA) volume fraction of 20%. Physicochemical and biocompatibility analyses demonstrated that the IBU-loaded composite hydrogel exhibits enhanced mechanical strength, favorable biocompatibility, tunable degradation, and injectability. This system effectively addresses IBU's solubility and absorption challenges while conforming to wounds of varying shapes and sizes, enabling controlled and sustained drug release. Cellular and animal studies confirmed that the hydrogel continuously and uniformly releases IBU, exerting anti-inflammatory effects while promoting angiogenesis and fibroblast migration. This leads to enhanced granulation tissue formation, collagen deposition, and epidermal regeneration, significantly accelerating wound closure within 14 days. Conclusion: By simultaneously suppressing inflammation and stimulating tissue regeneration through controlled IBU release, this hydrogel system offers a highly effective strategy for diabetic wound healing and holds strong potential for clinical application.
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The combination of 90% amino substitution degree GelMA and 10% w/v concentration (GM90-10%) was selected for its optimal mechanical properties, biocompatibility, and photocrosslinking efficiency, which has become the mainstream choice for tissue engineering, 3D printing, and cell culture.
“For GelMA hydrogel preparation, the combination of 90 % amino substitution degree GelMA and 10 % w/v concentration (GM90-10 %) was selected for its optimal mechanical properties, biocompatibility, and photocrosslinking efficiency, which has become the mainstream choice for tissue engineering, 3D printing, and cell culture [47,48].”
From Hydrogel scaffold encapsulating MSC-Exos and ZIF-8 promotes bone regeneration via coordinating osteogenesis and immunomodulation (2025) · cites this paper as [48]
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“This observed cytotoxic effect can be attributed specifically to the released ibuprofen rather than the hydrogel matrix, consistent with established drug-release behaviour [30,111].”
Influential
- Authors
- Li, Z., Dong, H., Yang, S., Wang, X., & Li, Z.
- Affiliations
- First Affiliated Hospital of Zhengzhou University (CN)
- Corresponding author
- Li, Zhen
- Venue
- International Journal of Nanomedicine
- Publisher
- Informa UK Limited
- Published
- 2025-04
- Volume
- Volume 20
- Pages
- 4535-4550
- ISSN
- 1176-9114 (ISSN-L)
- 1178-2013
- PMC
- PMC11998958
- OpenAlex
- W4409367188
- Cited by
- 12
- References
- 58
- Citations by year
- 2026: 6 · 2025: 6
- FWCI
- 4.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Nanomedicine (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetic Foot Ulcer Assessment and Management
- Keywords
- ibuprofen, diabetic wound healing, composite hydrogels, sustained drug release, anti-inflammatory therapy, angiogenesis, ionic crosslinking, photocrosslinking, Schiff base, injectable hydrogel, fibroblast migration, collagen deposition, epidermal regeneration, hyperglycemia
- MeSH terms
- Angiogenesis, Alginates, Animals, Anti-Inflammatory Agents, Delayed-Action Preparations, Diabetes Mellitus, Experimental, Gelatin, Humans, Ibuprofen, Male, Wound Healing, Neovascularization, Physiologic, Hydrogels, beta-Cyclodextrins, Mice, Rats, Drug Liberation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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