Collagen characterization soft tissues: structure-function relationships in cervical tissue

The mechanical integrity of the cervix and the timing of its softening prior to delivery are critical for successful pregnancies. During normal pregnancies, the cervix remains firm and closed during gestation and radically softens at the time of delivery through a microstructural remodeling process to allow the fetus passage. In contrast, in the preterm birth condition Cervical Insufficiency, the cervix prematurely and asymptomatically remodels, softens, and dilates, resulting in premature labor and preterm birth. To predict these processes, we quantify the microstructural properties of biopsies of cervical tissue for incorporation into multiscale FEMs of the cervix developed by collaborator Prof. Kristin Myers at Columbia University.

Key findings: The experimental work in our lab elucidates the mechanisms by which the microstructure of cervical tissue influences its material behavior, with the ultimate goal of predicting how the cervix deforms under the mechanical loads experienced during normal pregnancies and preterm births, using models developed by Prof. Myers. MS students Jia Hao and WB Ryan Harris used second harmonic generation imaging to compare the orientation and concentration of collagen in cervical tissue from patients with a history of preterm birth versus term deliveries. Our major findings showed that the microstructural alignment and distribution of collagen varies with anatomic location relative to proximity to the cervical canal, consistent with local anatomic differences in the mechanical properties and function of the cervix [11]. Furthermore, collagen alignment decreased with pregnancy and with parity in previously pregnant women. a critical strength of this study is that it provides important new information about pregnant and non-pregnant human cervical tissue from clinical specimens.

Second harmonic generation imaging quantifies region-specific properties of cervical microstructure that reflect local differences in loading and function. Tissue at the inner circumferential zone, cervical tissue in the outer zone was characterized by greater spatial heterogeneity of aligned collagen (G0) than that of the inner zone, reflecting an adaptive response to the local mechanical environment of the cervix. *p < 0.05 by student’s t test

Impact: This work provides important new information about pregnant and non-pregnant human cervical tissue from clinical specimens. Because most previous studies in cervical remodeling have been conducted on rodent cervices, our findings fill an important gap in knowledge about human cervical tissue in pregnancy. Our findings elucidate outstanding questions surrounding the underlying causes of cervical insufficiency and preterm birth by providing new descriptions of the microstructural cervical collagen in non-pregnant and pregnant women.

Future work: We will extend these studies by prospectively collecting tissue from patients with a history of preterm birth and gestational age-matched controls. Thelong-term goal is to develop functional diagnostic markers of preterm birth by identifying microstructural mechanisms that characterize normal and pathologic tissue remodeling events in the body.

Collaborators
Kristin Myers, Columbia University