University of Kentucky
Cross-Linking of Polymeric Micelles in Bulk Solution for Regenerative Medicinal Applications
Institution
University of Kentucky
Faculty Advisor/ Mentor
Sundar Authimoolam; David Puleo; Thomas Dziubla
Abstract
Mucin is a lubricating, protective barrier that coats most of the human body’s epithelial barriers. The exact function of mucin varies greatly from surface to surface (e.g. GI tract, mouth, eye, etc.), and is highly dependent upon the structural, chemical, and mechanical properties. Changes to these properties can lead to a variety of complex and debilitating pathologies, including dry mouth, increased risk of infection, and colitis. In our current work, we proposed development of a synthetic mucin network that could serve as a biomimetic barrier capable of treating those specific pathologies through targeted tissue adhesion. It has been previously shown that methoxy-poly(ethylene glycol)-poly(lactic acid), an amphiphilic diblock copolymer, is capable of forming micelles with different structural morphologies (i.e., spherical or filamentous). Utilizing the unique structure of the worm-like micelles, it is possible to produce a 3-dimensional mucin mimicking network. In our previous research, biotinylated worm micelles were surfacedeposited forming networks via a layer-by-layer deposition approach, utilizing high affinity biotin-avidin linkages. In order to form a thixotropic network that can be applied in a single thick coat, we studied the ability to bulk crosslink filomicelles into a continuous gel. By adjusting the solution properties, including, density, viscosity and micelle concentration, we demonstrate the ability to formulate crosslinked micelles leading towards a practical bulk synthetic mucin. Changing the micelle concentration allowed us to control the porosity and degree of crosslinking within the networks. On the other hand, varying the viscosity and density of the bulk solution allowed us to control stability of network suspension as well as cross-linking duration. Therefore, tuning the reaction parameters allowed the achievement of optimal conditions for network formation with a porous, uniform, gel-like structure mimicking that of natural mucin found in the body.
Cross-Linking of Polymeric Micelles in Bulk Solution for Regenerative Medicinal Applications
Mucin is a lubricating, protective barrier that coats most of the human body’s epithelial barriers. The exact function of mucin varies greatly from surface to surface (e.g. GI tract, mouth, eye, etc.), and is highly dependent upon the structural, chemical, and mechanical properties. Changes to these properties can lead to a variety of complex and debilitating pathologies, including dry mouth, increased risk of infection, and colitis. In our current work, we proposed development of a synthetic mucin network that could serve as a biomimetic barrier capable of treating those specific pathologies through targeted tissue adhesion. It has been previously shown that methoxy-poly(ethylene glycol)-poly(lactic acid), an amphiphilic diblock copolymer, is capable of forming micelles with different structural morphologies (i.e., spherical or filamentous). Utilizing the unique structure of the worm-like micelles, it is possible to produce a 3-dimensional mucin mimicking network. In our previous research, biotinylated worm micelles were surfacedeposited forming networks via a layer-by-layer deposition approach, utilizing high affinity biotin-avidin linkages. In order to form a thixotropic network that can be applied in a single thick coat, we studied the ability to bulk crosslink filomicelles into a continuous gel. By adjusting the solution properties, including, density, viscosity and micelle concentration, we demonstrate the ability to formulate crosslinked micelles leading towards a practical bulk synthetic mucin. Changing the micelle concentration allowed us to control the porosity and degree of crosslinking within the networks. On the other hand, varying the viscosity and density of the bulk solution allowed us to control stability of network suspension as well as cross-linking duration. Therefore, tuning the reaction parameters allowed the achievement of optimal conditions for network formation with a porous, uniform, gel-like structure mimicking that of natural mucin found in the body.