Cervical Tissue Engineering Using Silk Scaffolds and Human Cervical Cells

Abstract

Spontaneous preterm birth is a frequent complication of pregnancy and a common cause of morbidity in childhood. Obstetricians suspect abnormalities of the cervix are implicated in a significant number of preterm births. The cervix is composed of fibrous connective tissue and undergoes significant remodeling in preparation for birth. We hypothesized that a tissue engineering strategy could be used to develop three-dimensional cervical-like tissue constructs that would be suitable for investigating cervical remodeling. Cervical cells were isolated from two premenopausal women undergoing hysterectomy for a benign gynecological condition, and the cells were seeded on porous silk scaffolds in the presence or absence of dynamic culture and with 10% or 20% serum. Morphological, biochemical, and mechanical properties were measured during the 8-week culture period. Cervical cells proliferated in three-dimensions and synthesized an extracellular matrix with biochemical constituents and morphology similar to native tissue. Compared to static culture, dynamic culture was associated with significantly increased collagen deposition ( p < 0.05), sulfated glycosaminoglycan synthesis ( p < 0.05), and mechanical stiffness ( p < 0.05). Serum concentration did not affect measured variables. Relevant human tissue-engineered cervical-like constructs constitute a novel model system for a range of fundamental and applied studies related to cervical remodeling.

644: A silk-based injectable biomaterial as an alternative to cervical cerclage: an in-vitro study

“…27 Briefly, minced cervical tissue was cultured in Dulbecco Modified Eagle Medium, 10% fetal bovine serum, and antibiotics. After 10 days, cervical fibroblasts grew out from the explants.…”

Towards the development of a bioengineered uterus: Comparison of different protocols for rat uterus decellularization

“…Concerning the female internal genital tract, small patches of myometrial tissue were recently decellularized using a modified protocol that had been optimized for decellularization of blood vessels [22]. Other tissue engineering approaches for uterine tissue include the use of scaffolds of collagen/matrigel [23][24][25] or silk/collagen [26], as well as scaffolds made from blood clots [27]. Promising results using biodegradable polymer scaffolds for ''subtotal uterine tissue replacement'' in a rabbit model was recently reported in a review [28].…”

Biocompatibility of a Sonicated Silk Gel for Cervical Injection During Pregnancy: In Vivo and In Vitro Study

“…29 Informed consent was obtained, and institutional review board approval was obtained prior to study initiation. Cells were isolated using an explant culture method as described previously.…”