Development of an endometrial inspired biomaterial

Jacquelyn C. Pence
2016 · W2622633571
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This study developed an endometrial-inspired 3D vasculogenic culture in vitro using collagen scaffolds and gelatin hydrogels to improve nutrient transport in biomaterials by incorporating hormone-driven pro-angiogenic cues.

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This PhD dissertation studied how to create endometrial-inspired biomaterial systems that support pro-angiogenic processes by overcoming nutrient-transport limitations of vascularization in biomaterial cultures. Using porous collagen scaffolds and gelatin hydrogels, the author co-cultured endometrial epithelial and stromal cells with non-endometrial endothelial cells in vitro to monitor vascularization-related, pro-angiogenic events, and additionally tested combinations of traditional angiogenic cues (including vascular endothelial growth factor) with sex-hormone cues such as estradiol. A key finding described is that endometrial vascularization can be modeled in 3D with hormone- and growth-factor–informed biological cues, with the goal of improving the efficiency and mechanistic understanding of pre-vascularization. The dissertation’s stated scope is primarily in vitro modeling and biomaterial development rather than demonstrating functional integration of vascular networks in vivo. This paper is centrally about endometriosis — specifically, it uses endometrium-inspired vascularization mechanisms and hormone-driven cues (estradiol/progesterone biology) that are relevant to endometriosis-associated aberrant vascular growth within endometrial tissue contexts.

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Abstract

For regenerative medicine applications, a common limitation to biomaterial cultures and implants is nutrient transport. Unlike native tissue which contains a dense vascular network to provide nutrients and eliminate waste, biomaterials rely solely on diffusive transport which is often insufficient at maintaining cellular behavior of implants, diminishing their efficacy. Many strategies seek to prevascularize these de novo tissue constructs using traditional tissue engineering techniques such as including cocultures of pro-angiogenic cells or the delivery of angiogenic factors within the biomaterials to direct cellular behavior. These methods have not shown the capacity to recreate the complexity of neovascular processes. The work described in this thesis develops an angiogenic tissue model to improve general understanding of how native vascular processes translate to vascularization in an in vitro environment and to develop new techniques to efficiently pre-vascularize biomaterials. The intent of this model is to incorporate biological cues inspired by a physiological vascularization process that occurs within the endometrium, the lining of the uterus. Since endometrial vascularization is orchestrated by changes in sex hormones estradiol and progesterone in vivo, we chose to develop an endometrial inspired 3D vasculogenic culture in vitro. We culture endometrial epithelial and stromal cells with non-endometrial endothelial cells in both porous collagen scaffolds and gelatin hydrogel biomaterial environments in order to monitor pro-angiogenic processes. Additionally, we explore how traditional tissue engineering and nature-inspired methods can be combined to present not only traditional angiogenic driving cues (i.e. vascular endothelial growth factor) but additional pro-angiogenic cues such as estradiol within these biomaterial constructs to promote pro-angiogenic events.
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Withdraw Loading… Development of an endometrial inspired biomaterial Pence, Jacquelyn Loading… Permalink https://hdl.handle.net/2142/92736 Description - Title - Development of an endometrial inspired biomaterial - Author(s) - Pence, Jacquelyn - Issue Date - 2016-06-30 - Director of Research (if dissertation) or Advisor (if thesis) - Harley, Brendan A. - Doctoral Committee Chair(s) - Harley, Brendan A. - Committee Member(s) - Clancy, Kathryn B.H. - Nowak, Romana A. - Hammack, William S. - Department of Study - Chemical & Biomolecular Engr - Discipline - Chemical Engineering - Degree Granting Institution - University of Illinois at Urbana-Champaign - Degree Name - Ph.D. - Degree Level - Dissertation - Date of Ingest - 2016-11-10T17:49:58Z - Keyword(s) - scaffold - hydrogel - endometrium - vascularization - collagen - hormones - Abstract - For regenerative medicine applications, a common limitation to biomaterial cultures and implants is nutrient transport. Unlike native tissue which contains a dense vascular network to provide nutrients and eliminate waste, biomaterials rely solely on diffusive transport which is often insufficient at maintaining cellular behavior of implants, diminishing their efficacy. Many strategies seek to prevascularize these de novo tissue constructs using traditional tissue engineering techniques such as including cocultures of pro-angiogenic cells or the delivery of angiogenic factors within the biomaterials to direct cellular behavior. These methods have not shown the capacity to recreate the complexity of neovascular processes. The work described in this thesis develops an angiogenic tissue model to improve general understanding of how native vascular processes translate to vascularization in an in vitro environment and to develop new techniques to efficiently pre-vascularize biomaterials. The intent of this model is to incorporate biological cues inspired by a physiological vascularization process that occurs within the endometrium, the lining of the uterus. Since endometrial vascularization is orchestrated by changes in sex hormones estradiol and progesterone in vivo, we chose to develop an endometrial inspired 3D vasculogenic culture in vitro. We culture endometrial epithelial and stromal cells with non-endometrial endothelial cells in both porous collagen scaffolds and gelatin hydrogel biomaterial environments in order to monitor pro-angiogenic processes. Additionally, we explore how traditional tissue engineering and nature-inspired methods can be combined to present not only traditional angiogenic driving cues (i.e. vascular endothelial growth factor) but additional pro-angiogenic cues such as estradiol within these biomaterial constructs to promote pro-angiogenic events. - Graduation Semester - 2016-08 - Type of Resource - text - Permalink - http://hdl.handle.net/2142/92736 - Copyright and License Information - Copyright 2016 Jacquelyn C. Pence Owning Collections Graduate Dissertations and Theses at Illinois PRIMARY Graduate Theses and Dissertations at IllinoisManage Files Loading… Edit Collection Membership Loading… Edit Metadata Loading… Edit Properties Loading… Embargoes Loading…

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