3D printed antibacterial herbal loaded alginate-pectin medical patch: Fabrication and characterization

Abstract

This thesis focuses on a comprehensive and multi-disciplinary approach to the development of an effective and sustainable wound dressing. The thesis consists of three main parts, each layer building upon the previous to create a final product that is both innovative and practical. In the first part, the necessary materials such as pectin was synthesized in order to serve as the base layer of the wound dressing. This involves careful selection and testing of materials to ensure that it meets the necessary requirements for strength, flexibility, and biocompatibility. In the second part of the thesis, the antibacterial agents from herbal extracts were prepared. These natural agents offer several advantages over synthetic alternatives, including reduced toxicity and improved biocompatibility. Also, natural and biocompatible nanoclay as a carrier for these agents were used to controlled release, with the assistance of synthesized cellulose which was extracted from waste fruits, expected effects were improved, and targeted delivery to the wound area. In the third and final part of the thesis, advanced 3D printing technology was used in two ways. Firstly, a skeleton was designed for the prepared hydrogels using 3D printing. This skeleton provides structure and support for the hydrogel while allowing for air flow and moisture control. Secondly, the polymers (pectin:alginate/gelatin and nanoclay loaded ones themselves were 3D printed using Fused Deposition Modeling (FDM). We also integrated the hydrogel and clay material to form more hydrophilic film patch that is both strong and flexible. The final product is an antibacterial wound dressing that combines advanced materials and technologies to promote healing and prevent infection. This innovative approach has the potential to revolutionize wound care and improve patient outcomes. As it has been demonstrated in literature, wound healing is a complex and intricate process that involves multiple stages and requires the right type of dressings to prevent infection and promote the regrowth of tissue. The ideal dressing should have several key properties, including the ability to keep the wound moist, allow air to flow through, protect the wound from external contaminants, absorb excess fluid, and be easy to remove without causing additional damage to the wound. Hydrogels are an excellent choice for wound dressings due to their unique physical and chemical properties. These materials are highly absorbent and can retain large amounts of water, which helps to keep the wound moist and promote healing. A hydrophilic wound dressing is necessary for rapid therapeutic effect and absorption of exudate. This characteristic also helps to maintain a moist environment, promote high blood absorption, and enhance erosion capability and it was measured with contact angles. They are also permeable to gases, allowing air to flow through and providing xx oxygen to the wound. Additionally, hydrogels can be formulated to have antimicrobial properties, which can help to fight against bacteria and prevent infection. In this thesis, pectin was synthesized from pomegranate and grapefruit peels using citric acid extraction and cellulose was synthesized from pomegranate peels, making the study sustainable and environmentally friendly. Also, the fallen fruits from the grapefruit trees in the faculty garden were collected and utilized in the study, emphasizing their significant contribution to the fruit industry and agricultural research. Additionally, the effect of grapefruit juice instead of citric acid was alternatively used during the process of pectin extraction with the aim of achieving zero waste. Malva sylvestris and Cichorium intybus L, two local Turkish herbs, were used as antibacterial agents. The extraction of these herbs was done using microwave-assisted extraction with ethanol and membrane-assisted purification methods. Additionally, dialysis tubes which are kind of membrane, were used during the purification of antibacterial herbal extracts and the resulted extracts were compared with traditional extraction methods. The synthesized extracts were analyzed using optical spectroscopy techniques such as UV-Vis Absorption Spectroscopy. Herbal extracts were loaded into Halloysite nanotubes (HNTs) and injected into the hydrogel pores in order to help with air flow in the hydrogel area. Glycerol also used as a plasticizer. The process of extracting materials from plants and fruit wastes was also carried out using microwave-assisted synthesis methods, which are low-cost and time-efficient. The effectiveness of Malva sylvestris and Cichorium intybus L against bacteria was examined using the disc diffusion method. Their antibacterial activities were tested against E. coli and S. aurous that are effective two common types of wound bacteria to create pectin/alginate-based hydrogel wound dressings. Disc diffusion tests confirmed the antibacterial activity of the chosen plant extracts against common wound bacteria. To improve the effect of nanotubes such as high water absorbency and elongation as fillers of reinforced hydrogels composites, cellulose was synthesized. Ash content tests and moisture level measurements of the synthesized pectin and cellulose confirmed their high purity. In the next stage of the thesis, biopolymers and HNTs were combined to form a composite that was used to formulate a hydrogel that could be used inside a 3D printed skeleton. To design an effective antibacterial patch, 3D FDM printer were used. A patch-shaped skeleton with several pins were designed using 3D printing technology to make the hydrogel porous masks. The pectin/alginate based composites were poured on top of a cross-linker solution to form the hydrogel on the mask surface. Then, the pectin/alginate based hydrogels were cross-linked with calcium chloride (CaCl2). In the final stage of the thesis, formulated layer from cellulose and HNTs composite were prepared. These nanoclays were designed to act as carriers for herbal extracts. The effectiveness of these hydrogels in preventing bacterial growth was also tested against common wound bacteria, E coli and S. aurous and the results were successful. Additionally, the ability of these hydrogels to absorb water was evaluated using a gelatin hydration test. The behavior of the hydrogels was also examined in detail. In conclusion, the results showed that hydrogels containing either Malva sylvestris or Cichorium intybus L plant extract have great potential as antibacterial patches for xxi wound dressing. However, further in vivo studies are necessary before any clinical application can be made.