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Naturally-occurring bacterial cellulose-hyperbranched cationic polysaccharide derivative/MMP-9 siRNA composite dressing for wound healing enhancement in diabetic rats
- Source :
- Acta biomaterialia. 102
- Publication Year :
- 2019
-
Abstract
- The anomalous high expression of matrix metalloproteinase 9 (MMP-9) is one important factor that impedes diabetic wound healing. Therefore, inhibition of MMP-9 expression in a diabetic wound could be a feasible method to promote wound healing. In this study, we studied the possibility of self-therapy using wound dressings that contain bacterial cellulose-hyperbranched cationic polysaccharide (BC-HCP) derivatives that encapsulate siRNA (BC-HCP/siMMP-9) and have controlled release properties. Herein, we used four HCPs (Gly-DMAPA, Gly-D4, Amyp-DMAPA, Amyp-D4) as gene carriers. Our results showed that all HCP derivatives were minimally toxic to cells in vitro, while the cationic properties of HCP could be used as a complexation agent for MMP-9 siRNA (siMMP-9). Upon exposure to bacterial cellulose (BC), the BC slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein levels of MMP-9 in a human immortalized epithelial cell line (HaCAT) and in diabetic rat wounds. Inhibition of MMP-9 in the wounds of diabetic rats resulted in a significant enhancement of wound healing, suggesting that the BC-HCP/siMMP-9 composite dressing could be used as a safe and effective dressing to promote wound healing in diabetic rats. STATEMENT OF SIGNIFICANCE: In this work, we evaluated the possibility of using bacterial cellulose-hyperbranched cationic polysaccharide derivatives (BC-HCP) as a self-therapeutic wound dressing with siRNA encapsulated and controlled release properties. Our results showed that the BC-HCP/siMMP-9 composite dressing slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein level of MMP-9 in human immortalized epithelial cell line and in the wound of diabetic rats. The BC-HCP/siMMP-9 composite dressing promoted diabetic wound healing by the unique nanostructure of BC and by releasing siMMP-9 for specific MMP-9 inhibition. Therefore, it could be used as a safe and effective dressing to promote wound healing in diabetic rats. This is the first evidence on the study of using BC as a dressing composite by encapsulating HCP/siRNA complexes for efficient RNAi gene silencing for better wound healing in diabetic rats.
- Subjects :
- Male
Dendrimers
0206 medical engineering
Biomedical Engineering
02 engineering and technology
Pharmacology
Matrix metalloproteinase
Polysaccharide
Biochemistry
Diabetes Mellitus, Experimental
Biomaterials
Rats, Sprague-Dawley
chemistry.chemical_compound
Gene silencing
Animals
HaCaT Cells
Humans
RNA, Small Interfering
Cellulose
Molecular Biology
chemistry.chemical_classification
Wound Healing
integumentary system
Chemistry
General Medicine
021001 nanoscience & nanotechnology
020601 biomedical engineering
Controlled release
Bandages
In vitro
HaCaT
Matrix Metalloproteinase 9
Bacterial cellulose
0210 nano-technology
Wound healing
Biotechnology
Subjects
Details
- ISSN :
- 18787568
- Volume :
- 102
- Database :
- OpenAIRE
- Journal :
- Acta biomaterialia
- Accession number :
- edsair.doi.dedup.....8639fbc9b8598ef74b5ad74e76fde4f7