Kendini iyileştirebilen biyopolimer katkılı hidrojel esaslı yara örtüsü malzemesi geliştirilmesi
Development of self-healing biopolymer added hydrogel based wound dressing material
Yazar: AHMET KAŞAĞICI
Danışman: PROF. DR. MAHMUT ÖZACAR
Sakarya Üniversitesi / Fen Bilimleri Enstitüsü / Biyomedikal Mühendisliği Ana Bilim Dalı
Derece: Yüksek Lisans, 2023
Konu: Biyomühendislik = Bioengineering ; Kimya = Chemistry ; Mühendislik Bilimleri = Engineering Sciences

Özet:
Yara örtüleri genel olarak yaradan kaynaklanan istenmeyen etkileri azaltmak ve yara iyileşmesini desteklemek için gereklidir. Etkili bir yara bakımının sağlanması açısından yara örtüsü malzemesi seçimi çok önemlidir. Yara örtüsü malzemesinin en iyi tasarımı, yara örtüsü malzemesinin yarayı hızlı iyileştirmesi, yara iyileşmesi için gerekli olan en iyi koşulları sağlaması, nemli ortamı koruması, şişme özelliklerinin iyi olması ve antibakteriyel özelliklerinin iyi olması ile gerçekleşebilir. Hidrojel malzemelerin elastik yapıya sahip olması ve yumuşak özellikte bulunması yaranın iyileşmesinden sonra herhangi bir zarar görmeden kolay bir şekilde uygulanmasına ve çıkarılabilmesine olanak sağlar. Ayrıca hidrojeller çok çeşitli yaraların tedavisinde kullanılabilecek yara örtüsü malzemesi geliştirilmesi için tercih edilebilir. Doku mühendisliği ve ilaç salım uygulamalarında da hidrojeller çok sık tercih edilmektedir. Polivinil alkol, suda çözünürlüğü, toksik olmaması, biyouyumlu olması ve çok iyi mekanik özelliklere sahip olması nedeni ile hidrojel hazırlamada çok sık kullanılan polimerlerden birisidir. Doğal polisakkaritlerden birisi olan kitosan ise sağlıklı yaşam formülasyonlarında sık olarak kullanılmaktadır. Kitosan, biyomedikalde en çok kullanılan polimerlerden birisi olarak karşımıza çıkar. Gliserol ise iyi bir plastikleştiricidir, geniş bir kullanım alanına sahiptir ve biyouyumluluk özelliğine sahiptir. Yapılan çalışmada polivinil alkol ve kitosan polimerleri kullanılarak hidrojel malzemeler hazırlanmıştır. Hazırlanan bu hidrojellerde ilaç, zeytin yaprağı ekstraktı ve borik asit katkı maddesine bağlı olarak yara iyileşmesinde önemli olabilecek bazı karakteristik özellikleri ile kendi kendini iyileştirme özelliklerindeki değişimler incelenmiştir. Polivinil alkol, kitosan ve gliserol ile oluşturulan hidrojellerle aynı formülasyona sahip olan ancak içerisine katkı maddesi ilave edilen hidrojellerin özellikleri birbirleri ile karşılaştırılmıştır. Üretilen hidrojellerin antibakteriyel özelliğe katkısı, şişme özellikleri, su tutma özellikleri, kendi kendini iyileştirme özellikleri, temas açısı özellikleri, ilaç salımı, FTIR analizleri ve SEM analizleri yapılmıştır. Üretilen bütün hidrojel malzemelerde katkı maddelerinin hidrojel yapısını bozmadığı düşünülmektedir. Ayrıca katkı maddesi ilave edilen hidrojel malzemelerin saf hidrojel malzemelerden daha üstün özelliklere sahip olduğu düşünülmektedir. Katkı maddesi ve ilaç ilave edilen hidrojel yara örtüsü malzemelerinin, yara örtüsü kullanımı açısından kapsamlı araştırmalar için potansiyel göstereceği düşünülmektedir.

Abstract:
Wound dressings are generally necessary to reduce undesirable effects from the wound and to promote wound healing. There are many methods of bandages, dressings and targeted drug application for wound treatment. Methods such as dressings, cream and ointment dressings to prevent wounds help to accelerate wound healing, prevent mechanical damage and prevent contamination. The choice of dressing material is very important in terms of providing effective wound care. The best design of the dressing material can be achieved if the dressing material heals the wound quickly, provides the best conditions necessary for wound healing, maintains a moist environment, has good swelling properties and has good antibacterial properties. There are many new approaches to modern dressing design. It is recommended to use biopolymers and synthetic polymer materials to overcome the disadvantages of conventional dressings and to develop new dressing materials to be combined with different plant extracts. Medicines used for wounds are also very important to provide or assist wound healing. One of the materials that can be used as a wound dressing material is hydrogels. In modern wound dressing designs, hydrogels can be preferred because of their many superior properties. Hydrogels are interesting materials due to their ability to absorb fluids produced in the wound bed and to create a moist environment in the problematic part. Due to their three-dimensional structure, hydrogels support tissue regeneration and provide a suitable environment for cell proliferation.The elastic structure and soft nature of hydrogel materials allow easy application and removal without any damage after the wound has healed. In addition, hydrogels can be preferred for the development of dressing material that can be used in the treatment of a wide variety of wounds. Hydrogels are also frequently preferred in tissue engineering and drug release applications. Polyvinyl alcohol is one of the most frequently used polymers in hydrogel preparation due to its water solubility, non-toxicity, biocompatibility and very good mechanical properties. Chitosan, one of the natural polysaccharides, is frequently used in healthy life formulations. Chitosan is one of the most widely used polymers in biomedicine. Glycerol, on the other hand, is a good plasticizer, has a wide range of uses and has biocompatibility. In the study, it was aimed to prepare hydrogel materials using polyvinyl alcohol and chitosan polymers. Drug, boric acid and olive leaf extract were added as additives to other hydrogel samples to be prepared apart from the basic materials, and the effects of additives on the hydrogel structure and the changes in the properties of the additives, hydrogel materials, according to the materials formed were investigated. Boric acid, a type of boron, can be added to drug prescriptions during the wound healing process due to its antifungal properties, antibacterial potential, antiinflammatory properties and antioxidant properties. Studies have shown that boric acid shortens the time spent in intensive care and is beneficial for the healing of deep wounds. Olive leaf extract is frequently used as traditional anti-inflammatory drugs in Mediterranean medicine because it contains many polyphenolic compounds that are effective in the treatment of inflammation. In addition, olive leaves are used to heal various wounds. The properties of the hydrogels, which have the same formulation with the hydrogels formed with polyvinyl alcohol, chitosan and glycerol, but with added additives, were compared with each other. The contribution of the produced hydrogel dressing materials to the antibacterial properties, swelling properties, water retention properties, self-healing properties, contact angle properties, drug release, fourier transform infrared spectroscopy analyzes and scanning electron microscopy analyzes were made. Escherichia coli and staphylococcus aureus bacteria were selected to examine the antibacterial properties of hydrogel dressing materials. Bacteria and hydrogel sample samples cut in certain sizes were placed in the petri dish, the bottom of which was covered with agar, and the antibacterial properties of the hydrogel samples were examined and the results were interpreted. In order to examine the swelling and water retention properties of the obtained hydrogel dressing materials, samples were cut from each sample in certain proportions and all equal. The cut samples were weighed using precision scales and their initial weights were obtained. Then, for the swelling test, these samples were kept in distilled water and their swelling degrees were determined by weighing them again at certain hour intervals. For the water retention test, the cut samples were kept at room temperature and their water holding capacity was determined by weighing them at certain hour intervals. Both test results are important in terms of the healing processes of the wounds and the properties of the wound dressings, and the data obtained as a result of both tests were compared with the samples with additive material and the results were interpreted. The scratch test was used to examine the self-healing properties of hydrogel dressing materials. For the scratch test, each sample was cut in certain proportions, and the cut samples were scratched from one end to the other. Then, these samples were kept at room temperature for certain hours, and at the end of certain hours, all samples were taken to the freezer. The condition of the scratches was then examined under an optical microscope. The self-healing properties of hydrogel dressing materials were interpreted according to the closure of the scratches. Contact angle measurement, scanning electron microscopy analyzes and fourier transform infrared spectroscopy analyzes were performed to examine the character properties of the obtained hydrogel dressing materials. Because of the potential biomedical applications of the hydrogel dressing material developed in modern wound dressings, it is important to determine the behavior that will occur after contact with water of such materials. The tests were carried out using the devices in the laboratory and the results were interpreted. Drug release studies were performed with in vitro tests and the calibration curve was determined using ultraviolet-visible spectroscopy before the tests were performed. Phosphate buffer solution was prepared to carry out drug release tests, and the medicated samples were kept in this solution and the samples taken at the specified hours were calculated using an ultraviolet-visible spectroscopy device. When all the hydrogel dressing materials produced as a result of all the tests were examined, it was observed that the additives added to the hydrogels did not disrupt the hydrogel structure. In addition, it is thought that hydrogel samples with added boric acid and olive leaf extract have superior properties when compared to samples without additives. It has been observed that different percentages of chitosan used in hydrogels contribute to the antibacterial activity. As a result, samples with a high percentage of chitosan were selected and other tests after the antibacterial test were performed on these samples. In addition, it was observed that the hydrogel dressing samples with added additives did not show any negative effects on drug release. As a result, considering the positive properties of boric acid and olive leaf extract, it is thought that it can contribute to wound healing, and therefore, it is thought that the additives will contribute to the hydrogel dressing to be formed. It is thought that the investigation of the usability of the hydrogel dressing material developed by in vivo tests, which will be carried out apart from this study, will improve the studies to be done and show potential for future studies in terms of its use as a wound dressing.