Award Abstract # 1751050
CAREER: Determining the Dynamic Role of Elastic Fibers in Cervovaginal Adaptations

NSF Org: CMMI
Division of Civil, Mechanical, and Manufacturing Innovation
Recipient: THE ADMINISTRATORS OF TULANE EDUCATIONAL FUND
Initial Amendment Date: February 6, 2018
Latest Amendment Date: February 6, 2018
Award Number: 1751050
Award Instrument: Standard Grant
Program Manager: Wendy C. Crone
CMMI
 Division of Civil, Mechanical, and Manufacturing Innovation
ENG
 Directorate for Engineering
Start Date: July 1, 2018
End Date: June 30, 2024 (Estimated)
Total Intended Award Amount: $500,000.00
Total Awarded Amount to Date: $500,000.00
Funds Obligated to Date: FY 2018 = $500,000.00
History of Investigator:
  • Kristin Miller (Principal Investigator)
    kristin.miller@utdallas.edu
Recipient Sponsored Research Office: Tulane University
6823 SAINT CHARLES AVE
NEW ORLEANS
LA  US  70118-5665
(504)865-4000
Sponsor Congressional District: 01
Primary Place of Performance: Tulane University
1324 Tulane Avenue
New Orleans
LA  US  70112-2604
Primary Place of Performance
Congressional District:
02
Unique Entity Identifier (UEI): XNY5ULPU8EN6
Parent UEI: XNY5ULPU8EN6
NSF Program(s): CAREER: FACULTY EARLY CAR DEV,
BMMB-Biomech & Mechanobiology
Primary Program Source: 01001819DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 028E, 070Z, 1045, 9102, 9150
Program Element Code(s): 104500, 747900
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.041

ABSTRACT

This Faculty Early Career Development Program (CAREER) project will support an integrated research and education program to determine the role of elastic fibers in the soft tissues of the female reproductive system. Elastic fibers are present in most soft biological tissues and are critical to tissue function. Loss of elastic fibers may contribute to significant health problems of the female pelvic floor and lead to preterm birth and pelvic organ prolapse. This project will develop a computer model that can predict how elastic fibers in the soft tissues of the female reproductive system change in response to mechanical pressure. This will help to advance health by determining causes for changes in the tissue properties during pregnancy and during other normal events that change tissue mechanical pressure. The knowledge and new computer modeling tools could also be used to understand how other soft tissues containing elastic fibers such as the lungs, blood vessels, skin, and the digestive system change as the result of applied mechanical pressure. Research findings from this project will be incorporated into a mobile telephone game, teaching modules for K-12 education and into undergraduate and graduate biomedical engineering courses.

An experimentally-validated computational model will be used to determine why and how elastic fibers influence mechanobiological adaptations in biological tissues. This will be accomplished by: 1) Determining the role of elastic fibers in evolving biaxial mechanical properties and contractility in cervovaginal tissue in response to altered loads in situ using a mechanical loading tissue culture system; 2) Formulating a biomechanical growth and remodeling model that describes cervovaginal mechanical properties, contractility, and extracellular matrix composition with and without compromised elastic fibers; and 3) Validating the model by predicting the key features of cervovaginal adaptations in response to altered mechanical loading.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

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Akintunde, Akinjide R. and Robison, Kathryn M. and Capone, Daniel J. and Desrosiers, Laurephile and Knoepp, Leise R. and Miller, Kristin S. "Effects of Elastase Digestion on the Murine Vaginal Wall Biaxial Mechanical Response" Journal of Biomechanical Engineering , v.141 , 2019 10.1115/1.4042014 Citation Details
Clark, Gabrielle L. and Pokutta-Paskaleva, Anastassia P. and Lawrence, Dylan J. and Lindsey, Sarah H. and Desrosiers, Laurephile and Knoepp, Leise R. and Bayer, Carolyn L. and Gleason, Rudolph L. and Miller, Kristin S. "Smooth muscle regional contribution to vaginal wall function" Interface Focus , v.9 , 2019 10.1098/rsfs.2019.0025 Citation Details
Clark-Patterson, Gabrielle L. and Buchanan, Lily M. and Ogola, Benard O. and Florian-Rodriguez, Maria and Lindsey, Sarah H. and De Vita, Raffaella and Miller, Kristin S. "Smooth muscle contribution to vaginal viscoelastic response" Journal of the Mechanical Behavior of Biomedical Materials , v.140 , 2023 https://doi.org/10.1016/j.jmbbm.2023.105702 Citation Details
Clark-Patterson, Gabrielle L. and McGuire, Jeffrey A. and Desrosiers, Laurephile and Knoepp, Leise R. and De Vita, Raffaella and Miller, Kristin S. "Investigation of Murine Vaginal Creep Response to Altered Mechanical Loads" Journal of Biomechanical Engineering , v.143 , 2021 https://doi.org/10.1115/1.4052365 Citation Details
Clark-Patterson, Gabrielle L. and Roy, Sambit and Desrosiers, Laurephile and Knoepp, Leise R. and Sen, Aritro and Miller, Kristin S. "Role of fibulin-5 insufficiency and prolapse progression on murine vaginal biomechanical function" Scientific Reports , v.11 , 2021 https://doi.org/10.1038/s41598-021-00351-1 Citation Details
Conway, Cassandra K. and Qureshi, Hamna J. and Morris, Victoria L. and Danso, Elvis K. and Desrosiers, Laurephile R. and Knoepp, Leise J. and Goergen, Craig S. and Miller, Kristin "Biaxial biomechanical properties of the nonpregnant murine cervix and uterus" Journal of Biomechanics , v.94 , 2019 10.1016/j.jbiomech.2019.07.011 Citation Details
Conway, Cassandra K. and Varghese, Asha and Mahendroo, Mala and Miller, Kristin S. "The Role of Biaxial Loading on Smooth Muscle Contractility in the Nulliparous Murine Cervix" Annals of Biomedical Engineering , 2021 https://doi.org/10.1007/s10439-021-02778-z Citation Details
Jennings, Christian_M and Markel, Andrew_C and Domingo, Mari_J_E and Miller, Kristin_S and Bayer, Carolyn_L and Parekh, Sapun_H "Collagen organization and structure in FBLN5-/- mice using label-free microscopy: implications for pelvic organ prolapse" Biomedical Optics Express , v.15 , 2024 https://doi.org/10.1364/BOE.518976 Citation Details
White, Shelby E. and Conway, Cassandra K. and Clark, Gabrielle L. and Lawrence, Dylan J. and Bayer, Carolyn L. and Miller, Kristin S. "Biaxial Basal Tone and Passive Testing of the Murine Reproductive System Using a Pressure Myograph" Journal of Visualized Experiments , 2019 10.3791/60125 Citation Details

PROJECT OUTCOMES REPORT

Disclaimer

This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.

The primary outcome of this project was to better understand how elastic fibers, an important protein in biological soft tissues, contributes to how tissues resist changes in shape while being subjected to loads in the human body. For example, pressures within the abdominal region change throughout the day and during physiologic events such as pregnancy. In this project, we characterized how disruption of elastic fibers changed the shape and resistance to biomechanical loads in the mouse cervix and vagina. To accomplish this, we developed engineering biomechanics tools to measure both contractile and non-contractile properties in the cervix and vagina while keeping their original shape.  In both organs, we demonstrated that disruptions or malformation of elastic fibers significantly affect the structural integrity and ability of these organs to resist changes in shape under biomechanical pressures. Interestingly, we identified that disruption of elastic fibers causes different results in the cervix and vagina despite their close proximity and coordinated functions during pregnancy. In the vagina, we identified a larger resistance to changes in shape (increased stiffness) following elastic fiber disruption, whereas in the cervix, stiffness decreased. We also showed that disrupted elastic fiber formation decreased contractile behavior of the smooth muscle cells in both the vagina and cervix. Results from these studies could improve the development of diagnostic and therapeutic methods for health issues involving the vagina and the cervix such as pelvic organ prolapse or preterm birth. 

 

As for our broader impacts outside of the laboratory, our group led workshops on tissue engineering at Girls in STEM at Tulane and Boys at Tulane in STEM. These workshops were geared towards increasing enthusiasm for and interest in STEM education and careers. Emphasis was placed on providing opportunities for underrepresented minorities and girls to meet and work with role models in engineering. The workshops included a short lecture about engineering design principles and biological applications, followed by hands-on activities to encourage creativity and critical thinking. Participants were surveyed before and after the workshop and we quantified increased science identity and role model identity. Altogether, the workshops improved general public knowledge of biomedical engineering, engineering applications, and attitudes toward identifying as a scientist. Furthermore, women’s reproductive health has historically been underfunded and understudied. As such, there is a general lack of understanding of how different proteins and cells contribute to vaginal and cervical structural stability. This leads to controversial and ineffective treatments and interventions for common conditions such as pelvic organ prolapse and preterm birth. The methods and results from this project are expected to serve as the foundation for future studies to inform efforts first to better understand the causes of pelvic floor and pregnancy-related disorders and second to guide targeted research efforts in treating such disorders.


Last Modified: 10/04/2024
Modified by: Kristin S Miller

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