Permeability studies in biomimetic glycosaminoglycan-hydrogel membranes

The rates of water and solute transport tend to be lower in fibrous materials than in bulk solution. This phenomenon of "hindered transport" is caused by steric, hydrodynamic, and electrostatic interactions between the solvent, the solute, and the fibers. In this research the effect of these interactions were studied using charged, fibrous agarose-glycosaminoglycan (GAG) membranes. The work was motivated by current research into the role of the glomerular capillary wall (GCW) in ultrafiltering blood plasma, which is the first step in the processing of blood by the kidney. The GCW is composed of three layers in series: an endothelium, a basement membrane, and an epithelium. Intreasing evidence from experimental results and theoretical models of the GCW indicate that the endothelial layer and its associated glycocalyx may significantly limit the transport of macromolecules across the glomerular barrier. The glycocalyx is primarily composed of proteoglycans, a fibrous mixtures of proteins and anionic GAG. GAG fibers are present in many other biological materials, such as basement membranes and cartilage, making the current studies in agarose-GAG relevant to a variety of biological systems. Agarose-GAG membranes were synthesized by using 1-cyano-4-(dimethylamino)pyridinium tetrafluoroborate (CDAP) to create reactive sites in thin agarose hydrogels. Chondroitin sulfate GAG was then covalently bound to the reactive sites via their terminal amine group. By manipulating the temperature and duration of key reaction steps, the synthesis was optimized to provide high bound GAG yields and a spatially uniform distribution of GAG throughout the membrane. Models of the coupling reaction were developed to guide the synthesis conditions, resulting in 70-115 [mu]m-thick membranes composed of 2-4 v% agarose and 0-0.4 v% GAG.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemical Engineering

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2008

Author dc:creator

• Mattern, Kristin J. (Kristin Julie)

Advisor dc:contributor.advisor

• William M. Deen.

• Chemical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/42940

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/42940