Back to Search
Start Over
Development of alginate hydrogels for the treatment of diabetic foot ulcers
- Publication Year :
- 2022
- Publisher :
- Bangor University, 2022.
-
Abstract
- The focus of this thesis was to develop a novel hydrogel wound dressing from alginate, a biocompatible naturally occurring polysaccharide found primarily in green algae, to be administered through injection, gelling in-situ and removed as one entity for the treatment of chronic diabetic foot wounds. This thesis comprises of four chapters as described below: Chapter one offers an insight into the project through a systematic review from a medical and biological, and from a chemical perspective. Diabetes Mellitus, its complications and the onset of diabetic foot ulcers and the medical 'TIME' protocol of wound care and management are discussed which encompasses the precautions and challenges in wound healing. Diabetic foot ulcer wound therapeutics are reviewed. Dressing format and dressing materials are discussed with a short discussion of their advantages and disadvantages. This chapter leads onto general fundamentals and basic concepts of alginate polymer chemistry. Literature review of polymerisation techniques involving alginates related to this project are presented and hydrogels and its inclusion in diabetic wound therapy are also included herein. Chapter two describes the methodologies and equipment used as part of this project. In this chapter, the fundamentals of analytical techniques used for the presentation of data in this thesis will be presented and discussed. In this chapter, the scientific background to aid interpretation and comprehension of scientific data are included. This chapter concludes with details of full experimental procedures for the synthesis of hydrogel precursors, the preparation of alginate hydrogel via multi-modal crosslinks, and the characterisation of alginate gelation and post-gelation, including the in-situ rheological study of the gelation mechanism. Chapter three contains five subsections and focuses on the data obtained as part of this work. Discussions and arguments pertaining to the scientific findings are presented. An overview of the chapter is presented in section 1, along with the GPC profiles of the alginate raw materials. Section 2 details the synthesis of glycidyl acrylate from glycidol and acryloyl chloride, where yields upwards to 78 % and product purity of 88 % were obtained. Section 3 describes the acrylate modification of sodium alginate using glycidyl acrylate to synthesise the precursor for hydrogel preparation. The resultant material was characterised using 1H NMR to estimate the degree of substitution using anomeric proton signals where a maximum of 30 % substitution was recorded for mannuronate-rich alginates and the same reaction using guluronate-rich alginates afforded a maximum substitution of 33 %. In addition, the effects of time and temperature on the reaction step were studied. Section 4 describes the thiolate modification of sodium alginate using cysteine hydrochloride and cysteamine hydrochloride as the thiolation agent. 1H-NMR analyses using anomeric proton signals estimated a peak thiolation substitution of 12 %, with mass yields upwards to 78 % obtained. The thiol content of prepared alginate samples were quantified using Ellman's Assay and converted to present thiol density, where a theoretical maximum of 743 (μg thiol)/(g alginate) thiol density was calculated. The effects of pH on the thiolation step was investigated, and pH 4.0 was found to be the optimum pH during the chemical work-up. In section 5, an in-situ one-pot technique of hydrogel preparation via Michael-type addition is developed. Herein, alginate moieties underwent multiple techniques to form hydrogels, but with an emphasis on covalent crosslinking via Michael-type addition reaction. Ionotropic gelation using calcium chloride produced a stiff hydrogel instantaneously, and photo-gelation using Irgacure 2959 photoinitiator produced a robust hydrogel after 7 minutes of curing under a UV-β lamp. Covalent crosslinking was achieved between acrylate and thiol functional groups using acrylate modified alginate as the acrylate moiety and pentaerythritol tetrakis(3-mercaptopropionate) thiol crosslinker or thiol modified alginate as the thiol moiety. The observations and results from laboratory testing were compared with in-situ rheological experiment data, where the gelation times recorded were 1 hour for laboratory gelation and 50 minutes on the rheometer. Within this section, the results from materials testing would be included such as release studies, gelation studies, including in-situ rheological study of alginate gelation, and microscopy tests on dried alginate fibres and alginate hydrogels. A mini conclusion may be found at the end of each chapter sections. Chapter four summarises the research presented in this thesis and draws general conclusions. Herein, the reader will also see comments made by the author with regards to the research direction and future modifications to the project to retain its novelty for successive researchers.
- Subjects :
- Alginate
Diabetic foot ulcer
Hydrogel
Wound therapeutics
Subjects
Details
- Language :
- English
- Database :
- British Library EThOS
- Publication Type :
- Dissertation/ Thesis
- Accession number :
- edsble.856585
- Document Type :
- Electronic Thesis or Dissertation