Researchers have been exploring the potential of gelatin, chitosan, and polycaprolactone (GCP) nanofiber mats for enhancing skin wound healing. Their focus has been on improving these mats by incorporating silver nanoparticle-coated carbon quantum dots (Ag-CQDs) and trisodium citrate, aiming to create a more effective wound healing material.
Background
Nanofibers are widely utilized in tissue engineering due to their unique properties, which make them highly effective for wound healing applications. These fibers are typically synthesized using the electrospinning process, which produces materials with a large surface area, an interconnected pore network, and high porosity. These characteristics are crucial for optimal cell seeding, oxygen and nutrient transfer, matrix production, fluid drainage, and vascularization at wound sites, all while limiting bacterial penetration.
Due to these properties, nanofibers serve as excellent scaffold materials for wound healing. They support tissue regeneration, facilitate the delivery of active therapeutic agents, and help retain moisture at the wound site. Moreover, the flexibility of the electrospinning process allows for the co-electrospinning of polymers with various therapeutic agents, enhancing the functionality of the resulting nanofibers.
During the healing process, the pH of the wound environment shifts from alkaline to neutral and eventually to acidic. An acidic environment is particularly beneficial for wound healing as it promotes vascularization and epithelization, enhances oxygen release, modulates protease activity, reduces bacterial products and infection, and boosts antibacterial activity. As a result, the topical application of acids such as citric and ascorbic acid has shown positive therapeutic effects on various types of wounds.
Importance of CQDs
Nanoparticles, defined as particles ranging from 1 to 100 nm with a high surface-to-volume ratio, are increasingly used in wound healing and tissue engineering research. Among these, carbon quantum dots (CQDs) are zero-dimensional (0D) nanoparticles smaller than 10 nm that exhibit unique stability, optical properties, and excellent biocompatibility.
CQDs are chemically inert, inexpensive, and possess low toxicity, making them suitable for biomedical applications. Their antioxidant and antibacterial properties, along with their ability to stimulate angiogenesis, further enhance their potential in wound healing. By combining CQDs with traditional wound healing agents, researchers can develop innovative solutions to address the challenges of acute wound care, offering new approaches to enhance healing and improve patient outcomes.
The Proposed Approach
In this study, researchers developed a biodegradable nanofiber scaffold for wound healing by electrospinning a blend of synthetic and natural polymers, including polycaprolactone, gelatin, and chitosan. To enhance the wound healing capacity of the scaffold, they incorporated citrate and Ag-CQDs. TheCQDs were synthesized from thiourea and citrate salt using a hydrothermal method.
The resulting nanoscaffolds were designated based on their composition: the scaffold containing gelatin, chitosan, polycaprolactone, and Ag-CQDs was labeled as GCP-Q, while the scaffold incorporating citrate along with the other components was labeled as GCP-QC. The researchers thoroughly characterized the physicochemical properties of these fabricated scaffolds and evaluated their wound-healing efficacy in an animal model.
Various techniques were employed to characterize the nanofibers and CQDs, including Fourier transform infrared (FTIR) spectroscopy, electron microscopy, contact angle analysis, ultraviolet-visible (UV–Vis) spectroscopy, photoluminescence spectroscopy, X-ray diffraction, as well as assessments of degradability, porosity, and histopathology.
To assess the antibacterial properties of the Ag-CQDs and CQDs, the researchers used Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as test organisms. They determined the minimum bactericidal concentration (MBC) and minimum inhibitory concentration (MIC) for these nanoparticles.
The CQDs were synthesized by using thiourea and citrate as carbon sources. Specifically, 0.1 g of thiourea, 75 ml of distilled water, and 2 g of tri-ammonium citrate were mixed and stirred magnetically. This mixture was then heated for 6 hours at 175 °C in an autoclave. After cooling the mixture to room temperature, undissolved particles were removed using a 0.2-micron filter, and the filtered CQDs were stored at 5 ± 3 °C.
To prepare the Ag-CQDs, a chemical reduction method was used. The process involved mixing 1.0 ml of 0.01 M silver nitrate with 3.0 ml of CQDs and 0.05 g of sodium borohydride, a strong reducing agent. The reaction mixture was then incubated for 3 hours at room temperature. The resulting yellow Ag-CQD nanocomposite solution was found to be stable for one month when stored at 5 ± 3 °C.
This study provides a comprehensive approach to developing and characterizing advanced nanofiber scaffolds for wound healing, highlighting the potential of Ag-CQDs and citrate in enhancing the therapeutic efficacy of wound dressings.
Importance of this Work
The successful fabrication of CQDs and Ag-CQDs using the hydrothermal and chemical reduction methods, respectively, marks a significant advancement in the development of materials for wound healing. The CQDs demonstrated notable antibacterial activity against both S. aureus and E. coli, with the silver nanoparticle coating playing a critical role in enhancing the MBC and MIC of CQDs against these gram-positive and gram-negative bacteria.
The integration of citrate and CQDs into the GCP nanofibers resulted in increased hydrophilicity, degradability, and porosity—key properties that are highly favorable for wound healing applications. SEM revealed that the GCP-QC, GCP-Q, and GCP nanofibers exhibited porous, fibrous structures, which are essential for effective wound dressings.
Interestingly, the incorporation of Ag-CQDs reduced the fiber diameter in GCP-Q compared to the unmodified GCP nanofibers, with a further reduction observed when citrate was added in GCP-QC. This reduction in nanofiber thickness is significant because it leads to an increased hydrolysis rate of the nanofibers, which is beneficial for controlled degradation in wound healing applications.
Degradation studies confirmed that the GCP-QC and GCP-Q nanofibers exhibited faster degradation rates compared to GCP alone, underscoring the role of citrate and Ag-CQDs in enhancing biodegradability. Additionally, the porosity of the nanofibers was measured at 88 % for GCP-QC, 87 % for GCP-Q, and 85 % for GCP, further supporting their suitability for wound healing, as high porosity facilitates better fluid management and cell infiltration.
Hematoxylin and eosin staining provided visual confirmation of accelerated wound closure with the use of GCP-QC and GCP-Q nanofibers compared to GCP alone, highlighting the superior performance of these modified nanofibers in promoting tissue regeneration.
In conclusion, the findings of this study demonstrate the potential of GCP-QC and GCP-Q nanofibers as effective materials for skin tissue engineering and wound healing. These nanofibers present a promising alternative to conventional wound dressings and scaffolds, offering enhanced antibacterial properties, improved biodegradability, and superior wound healing outcomes. This work lays the groundwork for further exploration and optimization of nanofiber-based wound dressings in clinical applications.
Journal Reference
Partovi, A., Khedrinia, M., Arjmand, S., Ranaei Siadat, S. O. (2024). Electrospun nanofibrous wound dressings with enhanced efficiency through carbon quantum dots and citrate incorporation. Scientific Reports, 14(1), 1-12. DOI: 10.1038/s41598-024-70295-9, https://www.nature.com/articles/s41598-024-70295-9
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