2024 AIChE Annual Meeting
Extrusion of Double-Layer Alginate Constructs for Cellular Hormone Therapy
The onset of menopause in women is associated with health risks due to the loss of ovarian hormone production. One of the effects of changing systemic hormone levels is an increased risk of osteoporosis that, in turn, increases vulnerability to bone fracture. One way to combat this is to use pharmacological hormone therapy (pHT) consisting of estrogen alone or in combination with progesterone. However, pHT has been associated with an increased risk of cancer and cardiovascular disease and is, therefore, not currently a first-line approach to preventing osteoporosis. Our approach to potentially enhancing both safety and efficacy of hormone-based therapies is cell-based hormone therapy (cHT). We have used a biomimetic approach in which granulosa and theca cells are encapsulated in a two-compartment alginate system. This construct has the granulosa cells in the interior compartment while the theca cells are in the outer compartment of the construct, providing the juxtaposition of these cell types needed for the paracrine effects seen in native ovaries. We have previously reported the use of this cHT approach in rat models of ovarian failure. The goal of this work is to standardize the procedures used to create the double-layered cHT constructs. We use a syringe-based approach for extrusion of solution-phase alginate into bivalent cations for the formation of spherical particles for the inner compartment followed by a second extrusion of the particles suspended in solution-phase alginate into bivalent cations to form the outer compartment. By standardizing the procedure, the goal is to have greater control over the two-compartment cHT construct diameters so that they can be modified in future tests.