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A microengineered model of the human cervix

Description:

3D biomimetic cervical model for studying reproductive medicine, pregnancy, and cervical infection

 

Inventor

Dan Dongeun Huh, Wilf Family Term Chair and Assistant Professor of Bioengineering

 

Problem

The cervix is an essential component of the female reproductive system that provides a protective barrier and structural support to the uterus, playing a key role in maintaining pregnancy to term.  During pregnancy, the cervix undergoes extensive tissue remodeling in a highly orchestrated process to enable cervical distensibility and dilation in preparation for birth.  Premature cervical dilation due to errors in tissue remodeling is a key clinical event preceding preterm labor.  Preterm birth is the leading cause of perinatal morbidity and mortality, affecting over 10% of pregnancies worldwide.  Despite the prevalence of preterm delivery, the main causes and underlying mechanisms remain poorly understood, hindering the identification of therapeutic targets and intervention strategies.  Cervical infection accounts for the largest fraction of preterm birth (25-40%).  Although prophylactic antimicrobial treatment has been proposed by clinicians, this approach has been ineffective in reducing preterm birth rates, suggesting more complex disease mechanisms than invasion by bacterial pathogens.  In particular, much remains to be learned about how cervical infection induces premature remodeling of the cervix.

 

Solution

Researchers in the Huh lab have expanded their organs-on-a-chip capabilities to design and fabricate cervix-on-a-chip, with demonstrated co-culturing of human cervical epithelial cells, uterine fibroblasts, and uterine smooth muscle cells in a compartmentalized microdevice.  The dynamic interactions between these tissue types within the cervix can be precisely controlled and examined to mimic conditions of pregnancy, preterm birth, cervical cancer, and cervical infection.  The combined use of microfluidics and microfabrication technologies yields 3D biomimetic structures that provide new capabilities for precise spatiotemporal control of cells and their microenvironment in a physiologically relevant manner, circumventing the challenge of recreating abnormal tissue remodeling and other relevant pathophysiology with conventional cell culture methods.  Infection-induced disrupted barrier function, increased permeability of the cell layer, and elevated secretion of inflammatory cytokines from the cervical cells after treatment with pathogens have been demonstrated.