Intravaginal flux controlled pump for sustained release of macromolecules.

PURPOSE: To design a flux controlled pump (FCP) capable of 30-day, controlled release of macromolecules to the vaginal mucosa. METHODS: The FCP is composed of a single chamber fabricated from a rigid thermoplastic with orifices and encloses a pellet of water-swellable polymer containing the drug substance. We performed testing both in vitro and in rabbits. To ensure vaginal retention in the rabbit, we designed and attached an oval shape-memory polyether urethane retainer to the FCP allowing for long-term intravaginal evaluation of a solid dosage form without invasive surgical implantation. RESULTS: The orifices and swelling properties of the polymer pellet control water entry for polymer hydration and expansion, and subsequent extrusion of the drug-containing gel from the orifice. A FCP device containing a pellet composed of hydroxypropyl cellulose compounded with a model macromolecule, achieved controlled in vitro release for 30 days with an average release rate of 24 ± 2 µg/day (mean ± SD) and range of 16 to 42 µg/day. We observed a slightly lower average release rate in vivo of 20 ± 0.6 µg/day (mean ± SD). CONCLUSIONS: The size of the orifice and nature of the swelling polymer controls the hydration rate and thereby macromolecule release rate and duration from this FCP.

Single shot quantitative polarized light imaging system for rapid planar biaxial testing of soft tissues.

Quantitative Polarized Light Imaging (QPLI) is an established technique used to compute the orientation of collagen fibers based on their birefringence. QPLI systems typically require rotating linear polarizers to obtain sufficient data to estimate orientation, which limits acquisition speeds and is not ideal for its application to mechanical testing. In this paper, we present a QPLI system designed with no moving parts; a single shot technique which is ideal to characterize collagen fiber orientation and kinematics during mechanical testing. Our single shot QPLI system (ssQPLI) sorts polarized light into four linear polarization states that are collected simultaneously by four cameras. The ssQPLI system was validated using samples with known orientation and retardation, and we demonstrate its use with planar biaxial testing of mouse skin. The ssQPLI system was accurate with a mean orientation error of 1.35° ± 1.58°. Skin samples were tested with multiple loading protocols and in each case the mean orientation of the collagen network reoriented to align in the direction of primary loading as expected. In summary, the ssQPLI system is effective at quantifying collagen fiber organization, and, when combined with mechanical testing, can rapidly provide pixel-wise measures of fiber orientation during biaxial loading.

Skin Structure-Function Relationships and the Wound Healing Response to Intrinsic Aging.

Significance: Chronic wounds, such as diabetic foot ulcers, venous stasis ulcers, and pressure ulcers affect millions of Americans each year, and disproportionately afflict our increasingly older population. Older individuals are predisposed to wound infection, repeated trauma, and the development of chronic wounds. However, a complete understanding of how the attributes of aging skin affect the wound healing process has remained elusive. Recent Advances: A variety of studies have demonstrated that the dermal matrix becomes thinner, increasingly crosslinked, and fragmented with advanced age. These structural changes, as well as an increase in cell senescence, result in altered collagen fiber remodeling and increased stiffness. Studies combining mechanical testing with advanced imaging techniques are providing new insights into the relationships between these age-related changes. Emerging research into the mechanobiology of aging and the wound healing process indicate that the altered mechanical environment of aged skin may have a significant effect on age-related delays in healing. Critical Issues: The interpretation and synthesis of clinical studies is confounded by the effects of common comorbidities that also contribute to the development of chronic wounds. A lack of quantitative biomarkers of wound healing and age-related changes makes understanding structure-function relationships during the wound healing process challenging. Future Directions: Additional work is needed to establish quantitative and mechanistic relationships among age-related changes in the skin microstructure, mechanical function, and the cellular responses to wound healing.