Nanocrystalline cellulose–hyaluronic acid composite enriched with GM-CSF loaded chitosan nanoparticles for enhanced wound healing

Abstract

In recent years, applications of biopolymers such as hyaluronic acid (HA) for wound dressing have attracted more attention. However, the poor mechanical properties of HA-based wound dressings limit their clinical applications. Incorporation of reinforcing agents such as nanocrystalline cellulose (CNC) in HA-based wound dressings can improve their mechanical properties. In addition, controlled delivery of growth factors to the wound site using nanoparticles can significantly improve the healing process. In this study, we focus on development and characterization of a novel CNC reinforced HA-based composite containing chitosan nanoparticles loaded with GM-CSF (CNC-HA/GM-CSF-Chi-NPs composite) as an effective wound dressing. CNC-HA/GM-CSF-Chi-NPs composite showed some physicochemical characteristics such as appropriate mechanical properties, high swelling capacity (swelling ratio: 2622.1% ± 35.2%) and controlled release of GM-CSF up to 48 h which make it an excellent candidate for wound dressing. In vivo investigation showed that, after 13 d, the wounds covered with CNC-HA/GM-CSF-Chi-NPs composite could reach to nearly full wound closure and complete re-epithelialization compared to the normal saline treated wounds which exhibited nearly 70% of wound size reduction. Furthermore, the CNC-HA/GM-CSF-Chi-NPs composite treated wounds exhibited significantly lower inflammatory reaction, enhanced re-epithelialization and improved granulation tissue formation compared with CNC-HA/Chi-NPs composite treated wound; it might be due to positive effects of GM-CSF on the wound healing process. Our results suggest that CNC-HA/GM-CSF-Chi-NPs composite can be potentially applied in clinical practice for wound treatment.

Recent trends on wound management: New therapeutic choices based on polymeric carriers

“…In addition, NP applied wounds showed sufficiently lower inflammatory reaction, improved re-epithelization as well as enhance granulation tissue formation. The results suggest that the prepared dressing can be potentially applied in clinical practice for wound treatment [83] .…”

Nanocellulose: From Fundamentals to Advanced Applications

“…The cell culture exhibited that NIH-3H3 cells can attached to, grow, and proliferate well on the GA-HA-CNC hydrogels, confirming their potential application in wound dressing field. Recently, Dehkordi et al prepared a novel CNC-reinforced hyaluronic acid composite containing nanochitosan loaded with granulocyte macrophage colony stimulating factor (GM-CSF) as an efficient candidate for wound healing (Dehkordi et al, 2019). The resulted composite exhibited interesting features such as high swelling capacity, suitable mechanical characteristics and controlled release of GM-CSF.…”

Progress in the Development of Chitosan-Based Biomaterials for Tissue Engineering and Regenerative Medicine

“…Furthermore, positively charged CS containing biomaterials could be loaded with growth factors and cytokines to improve their performance in the wound healing process. In a recent study, CS NPs prepared through ionotropic gelation with tripolyphosphate [49] were loaded with granulocyte-macrophage colony-stimulating factor (GM-CSF) as a part of a nanocrystalline cellulose-hyaluronic acid composite prepared by a freeze-drying method [50]. Loading efficiency of GM-CSF was as high as 97.4 ± 1.68% with sustained release of~100% over 48 h and in vivo experiments have shown that composites loaded with encapsulated GM-CSF in CS NPs induce greater wound closure compared to the composite alone [50].…”