טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentOrtal Yom-Tov
SubjectThe Use of Emulsions Encapsulated within
Poly Ethylene Glycol Hydrogels for Biomedical
Applications
DepartmentDepartment of Biotechnology
Supervisors Full Professor Bianco-Peled Havazelet
Professor Seliktar Dror
Full Thesis textFull thesis text - English Version


Abstract

Poly(ethylene glycol) (PEG) hydrogels are a prime example for biocompatible hydrogels that are used in biomedical applications. The current research uses encapsulated emulsions as a tool to control the structure and properties of PEG-based hydrogels. Emulsion-templated PEG-based hydrogels were utilized as injectable porous hydrogels for tissue engineering, and as hydrogel tablets for floating drug delivery systems (FDDS). Further, in order to avoid the use of photo-crosslinking, which is comprised of many difficulties in polymerizing cloudy solutions, a novel method for the polymerization of PEG-based hydrogels was investigated.

The experimental work presented in this thesis is comprised of three projects; the first project focuses on the development and investigation of a novel method for the synthesis of injectable porous hydrogels with in situ pore formation. The use of injectable porous hydrogels is of great interest in biomedical applications, due to their biocompatibility, excellent permeability, and easy integration into sites of surgical procedures. By implementing a method that incorporates in situ pore formation with controllable porosity and pore size, the synthesis of hydrogels tailor-made for specific biomedical applications is realized. An emulsion-templating technique is used to encapsulate oil droplets, which are subsequently leached out of the hydrogel to create the porous structure. Pore size and porosity were manipulated by changing oil-to-water ratios and the surfactant concentrations. The relationship between porosity, pore size, and the hydrogel’s physical and mechanical characteristics was analyzed, and the potential of this material as a protein drug delivery system was demonstrated. 

The second project focuses on the use of buoyant or floating hydrogel tablets as a means to sustain the release of drugs in the stomach. In this study, we synthesized bioactive hydrogels that have sustainable release rates for drugs in the stomach based on a hydrogel preparation technique that employs emulsifying surfactants. The emulsion gelation technique, which encapsulates oil droplets within the hydrogels during crosslinking, was used to decrease their specific gravity in aqueous environments, resulting in floating drug release depots. Properties such as swelling, buoyancy, density and drug release were manipulated by changing the polymer concentrations, surfactant percentages and the oil:polymer ratios. The relationship between these properties and the hydrogel’s floating lag time was documented.

A number of cross-linking chemistries have been reported to create hydrogel networks of PEG-Thiol hydrogels, with Michael-type addition reactions and acrylate polymerization being the most commonly utilized. The third project of this thesis involves the investigation of hydrogels composed of PEGDA and 4-arm PEG-Thiol (PEG-4SH) with equimolar ratios between acrylates and thiols. The polymer solutions of PEG-4SH were mixed for different time intervals prior to their mixing with PEGDA solutions. Swelling experiments, rheology testing and Young's modulus measurements were performed in order to study structure and properties of the resultant hydrogels. The manipulation of architecture and properties was achieved by alterations in the preparation procedure. Consequently, this methodology, which gives further insights into the impact of the polymerization mechanism on PEG-Thiol based hydrogel properties, can be readily applied to develop hydrogel biomaterials that are tailor-made for specific biomedical applications.