Browsing by Subject "Islet transplantation"

Now showing 1 - 3 of 3

Open Access
Bioactive peptide nanofibers for tissue regeneration
(2016-01) Uzunallı, Gözde
Defects in the tissues or organs caused by trauma or diseases can have detrimental effects on all aspects of patients’ life quality. During the last three decades, considerable developments have been made in tissue engineering and regenerative medicine in order to find alternative treatment methods to recover tissue function after injury. These methods are based on the development of materials that are uniquely suited to the specific requirements of the tissue type and the repair process itself. Consequently, the implanted biomaterial must be compatible with biological systems and capable of delivering the signals necessary to facilitate tissue repair. In the present thesis, peptide amphiphile molecules were used to meet these requirements and develop next-generation biomaterials that are able to enhance the repair process while minimally affecting the integrity of surrounding tissues. Peptide amphiphiles are molecules that naturally self-assemble into nanofibrous hydrogel structures that closely emulate the composition of the extracellular matrix. As peptide amphiphiles contain amino acid sequences, bioactive signals can also be integrated into their structure to create a biocompatible environment and enhance the survival and proliferation of the resident cell population. In the scope of the present thesis, peptide amphiphile systems were utilized in three distinct applications. The first chapter covers the fundamentals of regenerative medicine and tissue engineering, the interactions between biomaterials and cells and extracellular materials, and the materials that are commonly used for these applications. The second chapter details the use of fibronectin- and laminin-derived peptide amphiphiles for the regeneration of corneal injuries. The third chapter investigates the ability of heparin-mimetic peptide hydrogels to facilitate the survival of pancreatic islets in vitro and demonstrates that islets transplanted in tandem with peptide gels trigger a local angiogenic response, decrease blood glucose levels and retain these functionalities even after 28 days of observation. The fourth chapter concerns the application of heparin-mimetic peptide amphiphile molecules for the recovery of acute wound injuries through the establishment of a well-ordered collagen matrix and the enhancement of the re-epithelialization process. Distinct peptide amphiphiles bearing bioactive signals conductive to tissue development were developed and utilized in all three studies, and the use of these materials has been demonstrated to serve as an adequate means of enhancing tissue repair.
Open Access
Improving pancreatic islet in vitro functionality and transplantation efficiency by using heparin mimetic peptide nanofiber gels
(Elsevier, 2015) Uzunalli, Gözde; Tumtas, Yasin; Delibasi, T.; Yasa, Oncay; Mercan, S.; Güler, Mustafa O.; Tekinay, Ayse B.
Pancreatic islet transplantation is a promising treatment for type 1 diabetes. However, viability and functionality of the islets after transplantation are limited due to loss of integrity and destruction of blood vessel networks. Thus, it is important to provide a proper mechanically and biologically supportive environment for enhancing both in vitro islet culture and transplantation efficiency. Here, we demonstrate that heparin mimetic peptide amphiphile (HM-PA) nanofibrous network is a promising platform for these purposes. The islets cultured with peptide nanofiber gel containing growth factors exhibited a similar glucose stimulation index as that of the freshly isolated islets even after 7 days. After transplantation of islets to STZ-induced diabetic rats, 28 day-long monitoring displayed that islets that were transplanted in HM-PA nanofiber gels maintained better blood glucose levels at normal levels compared to the only islet transplantation group. In addition, intraperitoneal glucose tolerance test revealed that animals that were transplanted with islets within peptide gels showed a similar pattern with the healthy control group. Histological assessment showed that islets transplanted within peptide nanofiber gels demonstrated better islet integrity due to increased blood vessel density. This work demonstrates that using the HM-PA nanofiber gel platform enhances the islets function and islet transplantation efficiency both in vitro and in vivo.
Open Access
Three dimensional glycosaminoglycan mimetic peptide amphiphile hydrogels for regenerative medicine applications
(2015-05) Tümtaş, Yasin
Defects and impairments of tissues or organs affect millions of people, resulting in considerable losses in workforce and life quality. The treatment of major tissue injuries requires the development of advanced medical techniques that enhance the natural repair processes of the human body. Novel biomaterials can modulate the repair of organs and tissues by providing a suitable environment for the recruitment, proliferation and differentiation of stem and progenitor cells, allowing the recovery of degenerated or otherwise nonfunctional tissues. Peptide amphiphiles (PAs) serve as model biomaterials due to their capacity for self-assembly, which allows peptide monomers to form complex networks that approximate the structure and function of the natural extracellular matrix. Peptide networks can be further modified by the attachment of various epitopes and functional groups, allowing these materials to present bioactive signals to surrounding cells. Glycosaminoglycans (GAGs) are negatively charged, unbranched polysaccharides that constitute a substantial part of the ECM in various tissues and play an important role in maintaining tissue integrity. Therefore, mimicking GAGs presents a suitable means for modulating cell behavior and especially lineage commitment in stem cells. In this work, I describe the design and synthesis of several bioactive, three dimensional (3D) GAG-mimetic peptide amphiphile hydrogels for in vitro stem cell differentiation and in vivo pancreatic islet transplantation. In Chapter 1, I detail the extracellular environment of tissues and the importance of GAGs in maintaining cell and tissue function. In Chapter 2, I describe the in vitro experiments involving the effects of sulfonation and the presence of glucose units on the differentiation of mesenchymal stem cells. In Chapter 3, I utilize a heparin-mimetic PA to increase the survival of pancreatic islets transplanted into the rat omentum, and demonstrate that increased angiogenesis results in enhanced survival. Lastly, in Chapter 4, I summarize my results and describe the course of future experiments for the artificial regeneration of tissues through peptide amphiphile networks.