Hydrogels are three dimensional, insoluble, porous and crosslinked polymer networks. Due to their high water content, they have great resemblance to natural tissues, and therefore, demonstrate high biocompatibility. The porous structure provides an aqueous environment for the cells and also allows influx of nutrients needed for cellular viability. In this study, a natural biodegradable material, agarose (Aga), was used and semi-interpenetrating networks (semi-IPN) were prepared with polymers having different charges, such as positively charged chitosan (Ch) and negatively charged alginate (Alg). Hydrogels were obtained by the thermal activation of agarose with the entrapment of Ch or Alg in the Aga hydrogel structures. Chemical composition of hydrogels were determined by ATR-FTIR examinations, mechanical properties of hydrogels were examined through compression tests, morphologies were confirmed by scanning electron microscopy (SEM) and confocal microscopy, thermal properties were evaluated by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Moreover, swelling ratios, water contact angles and surface free energies (SFE) were determined. Cell proliferation and cell migration within these hydrogels were examined by using L929 fibroblast cell line. MTS assays were carried out to observe the cell proliferation on hydrogels. Confocal microscopy was used in order to examine the cell behavior such as cell attachment and cell migration towards the hydrogels. It was observed that addition of positively charged Ch into agarose increased the ultimate compressive strength (UCS), decreased elastic modulus (E), increased the thermal stability and hydrophobicity of the semi-IPN hydrogels. On the other hand, addition of negatively charged Alg into agarose decreased UCS, E, thermal stability and hydrophilicity. Cell-material interaction results showed that Aga hydrogels in tissue engineering applications was improved by adding different charged polyelectrolytes. Cell migration within Aga hydrogels was enhanced by adding Ch, and hindered by addition of Alg. Maximum cell proliferation and maximum penetration of the cells were obtained with the Ch/Aga hydrogels most probably due to attraction between the negatively charged cell surface and the positively charged Ch/Aga hydrogel surface. It was shown that cell interaction of agarose hydrogel scaffolds could be enhanced by introducing chitosan within the agarose hydrogels and obtained structures could be candidates for tissue engineering applications.

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 200-224). Also available in print.

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 200-224). Also available online.

Thesis (Ph. D.)--University of Missouri--Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 95-113). Also available on the Internet.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2009. / Härtill 3 uppsatser.

Dissertation (Ph.D.)--University of South Florida, 2009. / Title from PDF of title page. Document formatted into pages; contains 91 pages. Includes vita. Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010.

Thesis (M. Phil.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 79-95). Also available in print.

Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 142-175). Also available in print.

Introduction: Stroke is caused from the occlusion of any cerebral artery leading to cerebral ischemia, brain damage and consequent neurological impairments and disability. The primary causes of mortality in western populations is stroke. Diabetes type 2 is a high risk factor for stroke. Stroke leads to an observable increase of neural stem cell proliferation in the subventricular zone and enhances neurogenesis in the adult rodent and human brain which suggest a mechanism contributing to stroke recovery. Neurogenesis in type 2 diabetes patients is impaired. However, whether stroke-induced neurogenesis is impaired in diabetes has not been studied. Exendin-4 is a drug for clinical treatment of type 2 diabetes which has been shown to have neuroprotective properties in animal studies. However whether Exendine-4 leads to increased neurogenesis after  stroke in the diabetic brain has not been previously studied.  Aims: The specific aims of this project were to determine whether stroke-induced stem cell proliferation is impacted by diabetes in the mouse, and if Exendine-4 regulates stroke-induced stem cell proliferation in normal and diabetic mice. Material and Methods: Aged obese/type 2 diabetic mice were subjected to stroke. The Exendin-4 treatment was started 1.5 hours thereafter. Treatment was continued for one week before animals were sacrificed. Brains were isolated and the neurons were immunostained using the specific proliferation marker Ki67. Neural stem cell proliferation was quantified by counting Ki67+ cells in the ipsilateral (subventricular zone in stroke hemisphere).The estimation was assessed by stereological counts of proliferating stem cell in the subventricular zone.  Results: The number of proliferating stem cell after stroke was statistically significantly higher in the normal mice versus diabetic mice. The effect was present in both sides (control and stroke) of the subventricular zone. Exendine-4 treatment induced statistically significant increased of  stem cell proliferation in normal mice but not in diabetic mice.   Conclusions: The result of this study shows that type 2 diabetes decreased the proliferation of neural stem cell in the subventricular zone and that Exendin-4 enhanced the subventricular proliferation in a preclinical model of clinical relevance. The data suggest that the Exendin-4 treatment could be administered to normal patients suffering from stroke in the ambulance or in the emergency room although more studies are needed.