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Glucose-triggered in situ forming keratin hydrogel for the treatment of diabetic wounds
- Source :
- Acta Biomaterialia. 125:208-218
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- The development of protein-based in situ forming hydrogel remains a big challenge due to the limited chemical groups in proteins. Keratins are a group of cysteine-rich structural protein found abundant in skin and skin appendant. Recently, our lab has established a disulfide shuffling strategy to prepare keratin hydrogels via oxygen (O2) oxidation. However, such hydrogel still needed to be molded in advance. In this work, inspired by the fact that glucose commonly exists in body fluids, a glucose-triggered in situ forming keratin hydrogel was developed based on the disulfide shuffling strategy via a higher oxidation force of hydrogen peroxide (H2O2). The hydrogel precursor solution consisted of keratin, cysteine and glucose oxidase (GOD), which could generate H2O2 in an indirect and mild way via GOD-catalyzed oxidation of glucose in body fluids. Our findings demonstrated that the GOD-catalyzed oxidation method not only shortened the gelation time but improved the mechanical strength of the hydrogel by comparison with O2 oxidation and direct addition of H2O2 solution methods, and realized in situ gelation within 3 min on a full-thickness wound bed in normal mice. Moreover, the in situ forming keratin hydrogel was applied as a drug depot for wound repair, and the deferoxamine-loaded one accelerated healing in the full-thickness wounds of streptozotocin-induced diabetic rats, notably by promoting angiogenesis and neovascularization in wounds. STATEMENT OF SIGNIFICANCE: Studies show that keratin hydrogels possess tissue regeneration capacity, especially in skin wound repair. However, most of the reported keratin hydrogels needed to be molded in advance and cannot fit irregular wound shape. This work describes a glucose-triggered in situ forming keratin hydrogel via a disulfide shuffling strategy under the oxidation of hydrogen peroxide. Of note, the hydrogen peroxide was supplied indirectly by glucose oxidase-catalyzed oxidation of glucose in wound fluids, and this method needed no additional crosslinking agents or chemical modifications on keratins. Our findings showed that this hydrogel realized in situ gelation within 3 min on a full-thickness wound bed and enabled an injectable mode with good filling ability toward irregular wounds. Moreover, this hydrogel could be applied as a drug depot for the treatment of diabetic wounds.
- Subjects :
- In situ
Skin wound
0206 medical engineering
Biomedical Engineering
macromolecular substances
02 engineering and technology
Biochemistry
Diabetes Mellitus, Experimental
Biomaterials
Mice
chemistry.chemical_compound
Keratin
Animals
Glucose oxidase
Hydrogen peroxide
Molecular Biology
chemistry.chemical_classification
Wound Healing
integumentary system
biology
technology, industry, and agriculture
Structural protein
Hydrogels
Hydrogen Peroxide
General Medicine
021001 nanoscience & nanotechnology
020601 biomedical engineering
Rats
Glucose
chemistry
Self-healing hydrogels
Biophysics
biology.protein
Keratins
0210 nano-technology
Biotechnology
Cysteine
Subjects
Details
- ISSN :
- 17427061
- Volume :
- 125
- Database :
- OpenAIRE
- Journal :
- Acta Biomaterialia
- Accession number :
- edsair.doi.dedup.....e036ac1da87ca94391e7a643784422a6
- Full Text :
- https://doi.org/10.1016/j.actbio.2021.02.035