Kitipong Kiti. Development of biopolymer wound dressings for the treatment of chronic wound. Doctoral Degree(Applied Chemistry). Mae Fah Luang University. Learning Resources and Educational Media Center. : Mae Fah Luang University, 2022.
Development of biopolymer wound dressings for the treatment of chronic wound
Abstract:
A chronic wound is a non-healing wound that demonstrates interruption of the wound healing process mainly caused by bacterial infection. The development of wound dressing for chronic wound treatment is recently focused on biomedical products. Consequently, the design and fabrication of biopolymer wound dressings are significant issues in biomedical fields. This dissertation reports the potential use of biopolymer wound dressing materials for the treatment of wounds, especially chronic wounds.
Firstly, we fabricated and characterized curcumin-β-cyclodextrin inclusion complex-loaded sodium alginate/chitosan (CMx-loaded SA/CS) bilayer hydrogels for use as wound dressing materials. Various concentrations of calcium chloride (CaCl2), including 0.05, 0.10, and 0.20% w/v were directly added to SA layer for crosslinking hydrogels. The morphology, Attenuated total reflection-Fourier transform infrared (ATR-FTIR) analysis, thermal properties, mechanical properties, moisture absorption, mucoadhesion, water swelling and weight loss, release characteristics, antibacterial activity, and indirect cytotoxicity of the bilayer hydrogels were investigated. The results showed that the SA and CS layers were successfully attached through electrostatic force. Increasing CaCl2 concentration caused the mechanical properties to increase, but the moisture absorption, water swelling, and weight loss to decrease. Moreover, the high content of CaCl2 tended to decrease maximum detachment force. For the release study, the hydrogels showed similar release behaviors of CM. The CMx-loaded SA/CS bilayer hydrogels exhibited inhibition against both Gram-negative (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). All CMxloaded SA/CS bilayer hydrogels were non-toxic to NCTC clone 929 cells and normal human dermal fibroblast (NHDF) cells.
Next, the cellulose sponges with curcumin-β-cyclodextrin inclusion complex (CMx) and chitosan (CS) were fabricated for use as wound dressings. 1-Allyl-3-methylimidazolium chloride (AMIMCl) ionic liquid as a green solvent was used for dissolving cellulose. Due to the low aqueous solubility and low bioavailability of curcumin, cyclodextrins (CDs) were applied and complexed with curcumin to obtain CMx. In addition, CS was incorporated into the cellulose sponges to improve the antibacterial activity of sponges. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) analysis, morphological appearances, mechanical properties, water retention and weight loss, release behaviors, antibacterial activity, indirect cytotoxicity, cell attachment, and cell proliferation of the CMx/CS-loaded cellulose sponges were investigated. From the results, the cellulose sponges showed a porous structure. Incorporating CMx and CS improved the mechanical properties compared to the neat cellulose sponges. Moreover, the addition of CS into the cellulose sponges exhibited antibacterial activity against E. coli and S. aureus. Furthermore, the indirect cytotoxicity of the CMx/CSloaded cellulose sponges was non-toxic and compatible with NCTC clone 929 and NHDF cells.
Last but not least, the treatment of chronic wounds requires good monitoring for wound infection. One of the indicators for the infected wound is the change in pH values around the wound area. Therefore, the visual pH sensor from Clitoria ternatea flower (CT) was used to indicate the pH value and evaluate the wound status. The CT extract contains anthocyanins which are pigments that appear in different colors depending on the pH values. The color of CT extract at pH values ranging from 2.0 to 12.0 was investigated by the UVvis spectrophotometer and the naked eye. The antioxidant activity, antibacterial activity, and cytotoxicity of CT extract were evaluated for its biological activities. The concentration of CT extract that can scavenge 50% of DPPH free radicals was 0.80 mg/mL. Besides, the CT extract showed non-toxic to NCTC clone 929 cells. However, the CT extract demonstrated low inhibition of S. aureus, E. coli, P. aeruginosa, and S. epidermidis bacteria. Also, the CT extract loaded in the paper showed the color changes in bacterial solutions. The color changed from blue- purple to blue-green in bacterial solutions indicating the wound infection.
Lastly, we fabricated the bilayer sponge based on sodium alginate-carboxymethyl cellulose (SA-CMC) incorporated with amoxicillin trihydrate (AMX) and quaternized chitosan (QCS) containing Clitoria ternatea extract (CT). The AMX-loaded SA-CMC/CT-loaded QCS bilayer sponges crosslinked with 0.25, 0.35, and 0.45% CaCl2 were fabricated to indicate wound infection and heal the wound. The morphology, ATR-FTIR analysis, mechanical properties, water retention, weight loss, color change, antibacterial activity, cytotoxicity, and in vitro cell migration of bilayer sponges were investigated. The high porous structure of bilayer sponges showed ability of water absorption. The porous structure patterns affected to the compressive strength, and maximum strength at 70% deformation. The bilayer sponges investigated the inhibition of S. aureus, E.coli, S. epidermidis, and S. pyogenes. Although the detection of color from the image demonstrated an unclear change of color, the color change on bacterial agar demonstrated a precise result. The blue-purple color of the bilayer changed to blue-green color with S. pyogenes bacteria. Moreover, these bilayer sponges showed non-toxic and improved the wound closure of NCTC clone 929 cells. Therefore, these bilayer sponges could indicate wound infection and heal the wound.