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Evaluation of an injectable polymeri...

Rocker, Adam John.

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Evaluation of an injectable polymeric delivery system for controlled and localized release of biological factors to promote therapeutic angiogenesis.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Evaluation of an injectable polymeric delivery system for controlled and localized release of biological factors to promote therapeutic angiogenesis./
Author:	Rocker, Adam John.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2016,
Description:	88 p.
Notes:	Source: Masters Abstracts International, Volume: 56-03.
Contained By:	Masters Abstracts International56-03(E).
Subject:	Biomedical engineering. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10247789
ISBN:	9781369472356

Evaluation of an injectable polymeric delivery system for controlled and localized release of biological factors to promote therapeutic angiogenesis.
Rocker, Adam John.

Evaluation of an injectable polymeric delivery system for controlled and localized release of biological factors to promote therapeutic angiogenesis. - Ann Arbor : ProQuest Dissertations & Theses, 2016 - 88 p.

Source: Masters Abstracts International, Volume: 56-03.

Thesis (M.S.)--University of Colorado at Denver, 2016.

Cardiovascular disease remains as the leading cause of death worldwide and is frequently associated with partial or full occlusion of coronary arteries. Currently, angioplasty and bypass surgery are the standard approaches for treating patients with these ischemic heart conditions. However, a large number of patients cannot undergo these procedures. Therapeutic angiogenesis provides a minimally invasive tool for treating cardiovascular diseases by inducing new blood vessel growth from the existing vasculature. Angiogenic growth factors can be delivered locally through gene, cell, and protein therapy. Natural and synthetic polymer growth factor delivery systems are under extensive investigation due their widespread applications and promising therapeutic potential. Although biocompatible, natural polymers often suffer from batch-to-batch variability which can cause unpredictable growth factor release rates. Synthetic polymers offer advantages for growth factor delivery as they can be easily modified to control release kinetics. During the angiogenesis process, vascular endothelial growth factor (VEGF) is necessary to initiate neovessel formation while platelet-derived growth factor (PDGF) is needed later to help stabilize and mature new vessels. In the setting of myocardial infarction, additional anti-inflammatory cytokines like IL-10 are needed to help optimize cardiac repair and limit the damaging effects of inflammation following infarction. To meet these angiogenic and anti-inflammatory needs, an injectable polymer delivery system created from a sulfonated reverse thermal gel encapsulating micelle nanoparticles was designed and evaluated. The sulfonate groups on the thermal gel electrostatically bind to VEGF which controls its release rate, while the micelles are loaded with PDGF and are slowly released as the gel degrades. IL-10 was loaded into the system as well and diffused from the gel over time. An in vitro release study was performed which demonstrated the sequential release capabilities of the polymer system. The ability of the polymer system to induce new blood vessel formation was analyzed in vivo using a subcutaneous injection mouse model. Histological assessment was used to quantify blood vessel formation and an inflammatory response which showed that the polymer delivery system demonstrated a significant increase in functional and mature vessel formation while significantly reducing inflammation.

ISBN: 9781369472356Subjects--Topical Terms:

535387
Biomedical engineering.

Evaluation of an injectable polymeric delivery system for controlled and localized release of biological factors to promote therapeutic angiogenesis.
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300 $a 88 p.
500 $a Source: Masters Abstracts International, Volume: 56-03.
500 $a Adviser: Daewon Park.
502 $a Thesis (M.S.)--University of Colorado at Denver, 2016.
520 $a Cardiovascular disease remains as the leading cause of death worldwide and is frequently associated with partial or full occlusion of coronary arteries. Currently, angioplasty and bypass surgery are the standard approaches for treating patients with these ischemic heart conditions. However, a large number of patients cannot undergo these procedures. Therapeutic angiogenesis provides a minimally invasive tool for treating cardiovascular diseases by inducing new blood vessel growth from the existing vasculature. Angiogenic growth factors can be delivered locally through gene, cell, and protein therapy. Natural and synthetic polymer growth factor delivery systems are under extensive investigation due their widespread applications and promising therapeutic potential. Although biocompatible, natural polymers often suffer from batch-to-batch variability which can cause unpredictable growth factor release rates. Synthetic polymers offer advantages for growth factor delivery as they can be easily modified to control release kinetics. During the angiogenesis process, vascular endothelial growth factor (VEGF) is necessary to initiate neovessel formation while platelet-derived growth factor (PDGF) is needed later to help stabilize and mature new vessels. In the setting of myocardial infarction, additional anti-inflammatory cytokines like IL-10 are needed to help optimize cardiac repair and limit the damaging effects of inflammation following infarction. To meet these angiogenic and anti-inflammatory needs, an injectable polymer delivery system created from a sulfonated reverse thermal gel encapsulating micelle nanoparticles was designed and evaluated. The sulfonate groups on the thermal gel electrostatically bind to VEGF which controls its release rate, while the micelles are loaded with PDGF and are slowly released as the gel degrades. IL-10 was loaded into the system as well and diffused from the gel over time. An in vitro release study was performed which demonstrated the sequential release capabilities of the polymer system. The ability of the polymer system to induce new blood vessel formation was analyzed in vivo using a subcutaneous injection mouse model. Histological assessment was used to quantify blood vessel formation and an inflammatory response which showed that the polymer delivery system demonstrated a significant increase in functional and mature vessel formation while significantly reducing inflammation.
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