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The Development of Polymer Construct...

Murphy, Kendall.

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The Development of Polymer Constructs for Adipose Tissue Engineering Applications.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The Development of Polymer Constructs for Adipose Tissue Engineering Applications./
作者:	Murphy, Kendall.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
面頁冊數:	150 p.
附註:	Source: Dissertations Abstracts International, Volume: 82-02, Section: B.
Contained By:	Dissertations Abstracts International82-02B.
標題:	Chemical engineering. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=27832221
ISBN:	9798662435605

The Development of Polymer Constructs for Adipose Tissue Engineering Applications.
Murphy, Kendall.

The Development of Polymer Constructs for Adipose Tissue Engineering Applications. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 150 p.

Source: Dissertations Abstracts International, Volume: 82-02, Section: B.

Thesis (Ph.D.)--University of South Carolina, 2020.

This item must not be sold to any third party vendors.

The adipose tissue functions as the body's main energy reservoir and plays a central role in maintaining whole body energy homeostasis. The ability to modulate this tissue's inherent endocrine and metabolic functions has promising implications in treating disease associated with adipose tissue dysfunction. This work revolves around two diseases where adipose tissue inflammation and metabolic dysfunction drive the disease, obesity and cachexia. Both diseases impact a significant population of U.S. adults and substantially reduce patient quality of life. In this study, we first demonstrate the use of novel therapeutic platforms engineered to specifically target adipose tissue inflammation and lipid catabolism through localized drug delivery for the treatment of obesity. Specifically, we developed poly(lactide-co-glycolide) scaffolds loaded with resveratrol, a small molecule with promising anti-obesity and anti-inflammatory properties, but one that suffers from poor bioavailability. Implant into the epididymal fat of lean mice indicates that resveratrol augments an anti-inflammatory environment established by PLG scaffolds without drug. Furthermore, this strategy protected against inflammatory stimuli, such as mice fed a high fat diet and adipocytes treated with pro-inflammatory cytokines. Additionally, mice pre-treated with resveratrol loaded scaffolds and then fed a high fat diet gained significantly less body weight and adipose tissue mass compared to mice that received scaffolds without the drug. Collectively, this shows that PLG scaffolds are a promising platform for the treatment of metabolic diseases. Secondly, we characterize the impact of chemotherapy treatment on adipose tissue remodeling as a model for cancer associated cachexia. Here we report that a clinically relevant bolus of doxorubicin significantly reduces animal body weight and induces fibrosis in subcutaneous adipose tissue in female rats. Similar to cachexic patients, this response was associated with an increase in collagen 1 and a marker of activated fibroblasts. Finally, we indicate that the subcutaneous adipose tissue exhibited greater fibrosis compared to visceral adipose tissue. This work is expected to provide greater understanding of doxorubicin's potential role in promoting cancer-associated cachexia and provide insight for the development of future strategies to sustain adipose tissue health during chemotherapy treatment.

ISBN: 9798662435605Subjects--Topical Terms:

560457
Chemical engineering.
Subjects--Index Terms:

Polymer constructs

The Development of Polymer Constructs for Adipose Tissue Engineering Applications.
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300 $a 150 p.
500 $a Source: Dissertations Abstracts International, Volume: 82-02, Section: B.
500 $a Advisor: Gower, R. Michael.
502 $a Thesis (Ph.D.)--University of South Carolina, 2020.
506 $a This item must not be sold to any third party vendors.
520 $a The adipose tissue functions as the body's main energy reservoir and plays a central role in maintaining whole body energy homeostasis. The ability to modulate this tissue's inherent endocrine and metabolic functions has promising implications in treating disease associated with adipose tissue dysfunction. This work revolves around two diseases where adipose tissue inflammation and metabolic dysfunction drive the disease, obesity and cachexia. Both diseases impact a significant population of U.S. adults and substantially reduce patient quality of life. In this study, we first demonstrate the use of novel therapeutic platforms engineered to specifically target adipose tissue inflammation and lipid catabolism through localized drug delivery for the treatment of obesity. Specifically, we developed poly(lactide-co-glycolide) scaffolds loaded with resveratrol, a small molecule with promising anti-obesity and anti-inflammatory properties, but one that suffers from poor bioavailability. Implant into the epididymal fat of lean mice indicates that resveratrol augments an anti-inflammatory environment established by PLG scaffolds without drug. Furthermore, this strategy protected against inflammatory stimuli, such as mice fed a high fat diet and adipocytes treated with pro-inflammatory cytokines. Additionally, mice pre-treated with resveratrol loaded scaffolds and then fed a high fat diet gained significantly less body weight and adipose tissue mass compared to mice that received scaffolds without the drug. Collectively, this shows that PLG scaffolds are a promising platform for the treatment of metabolic diseases. Secondly, we characterize the impact of chemotherapy treatment on adipose tissue remodeling as a model for cancer associated cachexia. Here we report that a clinically relevant bolus of doxorubicin significantly reduces animal body weight and induces fibrosis in subcutaneous adipose tissue in female rats. Similar to cachexic patients, this response was associated with an increase in collagen 1 and a marker of activated fibroblasts. Finally, we indicate that the subcutaneous adipose tissue exhibited greater fibrosis compared to visceral adipose tissue. This work is expected to provide greater understanding of doxorubicin's potential role in promoting cancer-associated cachexia and provide insight for the development of future strategies to sustain adipose tissue health during chemotherapy treatment.
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