Kurkumin Yüklü Üç Boyutlu Poli(ε-kaprolakton)/Kitosan Nanofibröz Yara Örtü Malzemelerinin Geliştirilmesi

Abstract

This study was financially supported by Hacettepe University Scientific Research Projects Coordination Unit with a career initiation project titled “Development of Curcumin Loaded Macroporous Antibacterial Three-Dimensional Nanofibrous Wound Dressing Materials” (FKB-2022-19592). The main goal of this thesis is to develop curcumin loaded macroporous three-dimensional (3D) wound dressing materials that can be manufactured in desired shapes and sizes. Firstly, poly(ε-caprolactone)/chitosan (PCL-Chi) nanofibrous matrices and curcumin loaded PCL-Kit-Kur5 (5 wt% curcumin) and PCL-Kit-Kur10 (10 wt% curcumin) nanofibrous matrices are produced with traditional electrospinning method. Then, these matrices are dispersed by using a homogenizer and poured into molds of various shapes and sizes. After freeze-drying, 3D nanofibrous wound dressing materials are successfully produced. These 3D nanofibrous wound dressing materials were characterized in detail by various physical and chemical methods. First of all, the chemical structures of the wound dressings were verified using ATR-FTIR analysis. Water contact angles of the 3D nanofibrous wound dressings were measured as 54° ± 7°, 51° ± 14° and 57° ± 9° for the PCL-Kit, PCL-Kit-Kur5, PCL-Kit-Kur10 groups respectively; the water uptake capacities of the wound dressing materials were above 400% for the groups. In vitro biodegradation tests were performed over 28 days and ~3-4% mass reduction is observed for all groups. According to the mechanical compression tests, the elastic modulus were found as 7,6 ± 1,2 kPa, 15,8 ± 1,5 kPa and 6,6 ± 3,0 kPa for PCL-Kit, PCL-Kit-Kur5, PCL-Kit-Kur10 groups, respectively. The structures of the 3D nanofibrous wound dressings are characterized by micro-computed tomography and the total porosity is found to be ~90% or over for all the groups. Loading efficiency and drug release studies were conducted for the curcumin loaded 3D nanofibrous wound dressing materials. Encapsulation efficiency is calculated as 60,8 ± 2,5% for PCL-Kit-Kur5 group and 72,5 ± 2,8% for PCL-Kit-Kur10 group. To analyze the curcumin release kinetics from the 3D wound dressing materials, drug release profiles are fitted to mathematical kinetic models. The highest correlation was achieved with the Higuchi model for PCL-Kit-Kur5 and with the zero-order kinetic model for PCL-Kit-Kur10. Lastly, cell culture studies were carried out and no cytotoxic effects are observed for any nanofibrous wound dressing materials. In addition, it was observed that cells in 3D nanofibrous wound dressing materials containing curcumin had much higher mitochondrial activity compared to other groups, especially during the first 7 days of culture. Scanning electron microscopy imaging is conducted and successful cell adhesion and migration was observed on the 2D nanofibrous materials; however, these were limited to only the surface of matrices. On the contrary, in 3D nanofibrous wound dressing materials, it was observed that cells adhered and spread around macropores even at material depths, and cell-material and cell-cell interactions were successfully formed. In conclusion, 3D nanofibrous dressing materials with macroporosity in different sizes and shapes were successfully produced with the production method used, and they supported cell adhesion, migration, and proliferation. It is thought that the 3D wound dressing materials developed in this thesis study can be used clinically in the field of skin tissue engineering after being developed with future studies and examined in detail with in vivo studies.