Biomaterial-based models of the endometrium and trophoblast invasion to investigate early pregnancy

Zambuto, Samantha G.

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https://hdl.handle.net/2142/115872 Copy

Description

Title

Biomaterial-based models of the endometrium and trophoblast invasion to investigate early pregnancy

Author(s)

Zambuto, Samantha G.

Issue Date

2022-06-29

Director of Research (if dissertation) or Advisor (if thesis)

Harley, Brendan AC

Doctoral Committee Chair(s)

Harley, Brendan AC

Committee Member(s)

• Clancy, Kathryn BH
• Underhill, Gregory H
• Nowak, Romana A

Department of Study

Bioengineering

Discipline

Bioengineering

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• tissue engineering
• biomaterials
• women's health
• female reproductive health
• pregnancy
• trophoblast
• invasion' angiogenesis
• hydrogels
• gelatin

Abstract

Pregnancy is established once an invading blastocyst successfully implants into the lining of the uterus known as the endometrium. Cellular crosstalk between endometrial cells and trophoblast cells from the blastocyst coordinate the extent of invasion into the endometrium and defects in this crosstalk can lead to a spectrum of pregnancy conditions; however, implantation occurs 6-12 days into pregnancy which provides a difficult challenge to studying this process in humans. Initial blastocyst implantation into the endometrium has never been observed in humans and what we currently know is inferred from rare histological specimens. With complex, three-dimensional in vitro model systems, we have the unique opportunity to develop platforms to study this process in systems that replicate the in vivo tissue microenvironment. We demonstrated that methacrylamide-functionalized gelatin (GelMA) hydrogels are adaptable for studying dynamic endometrial processes, including vascular formation, hormone responsiveness, epithelial monolayer formation, and trophoblast invasion. We create and characterize a library of GelMA hydrogels with mechanical properties similar to the native endometrium and placenta, support the culture of an endometrial perivascular niche to study endometrial angiogenesis, provide biochemical cues to hormone-responsive cells (e.g., decidualization of endometrial stromal cells), establish epithelial monolayers overlaying GelMA hydrogels and have employed the GelMA platform for trophoblast invasion assays. These tools allow us to answer the following questions: How does cortisol influence endometrial function? How do biomolecular signals from stress influence trophoblast invasion?

Graduation Semester

2022-08

Type of Resource

Thesis

Copyright and License Information

Copyright 2022 Samantha Zambuto

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