Surrogate post-coital testing for contraceptive efficacy against human sperm activity in the ovine vaginal model†.

High unintended pregnancy rates are partially due to lack of effective nonhormonal contraceptives; development of safe, effective topical vaginal methods will address this need. Preclinical product safety and efficacy assessment requires in vivo testing in appropriate models. The sheep is a good model for the evaluation of vaginally delivered products due to its close similarities to humans. The study objective was to develop an ovine model for efficacy testing of female nonhormonal contraceptives that target human sperm. Fresh human semen was pooled from male volunteers. Nonpregnant female Merino sheep were treated with control or vaginal contraceptive product (IgG antibody with action against sperm or nonoxynol-9 [N9]). Pooled semen was added to the sheep vagina and mixed with product and vaginal secretions. Microscopic assessment of samples was performed immediately and progressive motility (PM) of sperm was compared between treatments. Cytokines CXCL8 and IL1B were assessed in vaginal fluid after instillation of human semen. No adverse reactions or elevations in proinflammatory cytokines occurred in response to human semen. N9 produced signs of acute cellular toxicity while there were no cellular changes after IgG treatment. N9 and IgG had dose-related effects with the highest dose achieving complete sperm immobilization (no sperm with PM). Surrogate post-coital testing of vaginally administered contraceptives that target human semen was developed in an ovine model established for vaginal product preclinical testing. This expanded model can aid the development of much needed nonhormonal topical vaginal contraceptives, providing opportunities for rapid iterative drug development prior to costly, time-intensive human testing.

Fabrication of High-Aspect-Ratio 3D Hydrogel Microstructures Using Optically Induced Electrokinetics.

We present a rapid hydrogel polymerization and prototyping microfabrication technique using an optically induced electrokinetics (OEK) chip, which is based on a non-UV hydrogel curing principle. Using this technique, micro-scale high-aspect-ratio three-dimensional polymer features with different geometric sizes can be fabricated within 1⁻10 min by projecting pre-defined visible light image patterns onto the OEK chip. This method eliminates the need for traditional photolithography masks used for patterning and fabricating polymer microstructures and simplifies the fabrication processes. This technique uses cross-link hydrogels, such as poly(ethylene glycol) (PEG)-diacrylate (PEGDA), as fabrication materials. We demonstrated that hydrogel micropillar arrays rapidly fabricated using this technique can be used as molds to create micron-scale cavities in PDMS (polydimethylsiloxane) substrates. Furthermore, hollow, circular tubes with controllable wall thicknesses and high-aspect ratios can also be fabricated. These results show the potential of this technique to become a rapid prototyping technology for producing microfluidic devices. In addition, we show that rapid prototyping of three-dimensional suspended polymer structures is possible without any sacrificial etching process.