Phenomenological characterization of blood's intermediate shear rate: a new concept for hemorheology.

The phenomena of aggregation, breakdown, and disaggregation of the rouleaux of red blood cells (RBCs) in addition to deformability affect the human blood viscosity at different shear rates. In this study, the intermediate shear rate is introduced and defined when the effect of aggregation on the change of blood viscosity is diminished; and afterwards, the alteration in the blood viscosity is dominantly affected by the deformation of RBCs. With this respect, modeling the effective parameters on the blood shear-thinning behavior including hematocrit and plasma viscosity was performed for the two different shear regions discriminated by the proposed intermediate shear rates. The presented rheological model reflects a phenomenological approach to assess the human blood viscosity with an average error of ± 5% compared to experimental data for hematocrits between 0.299 and 0.702, subjected to various shear rates from 0.2 to 680 1/s. The temperature changes as well as biochemical effects on whole blood viscosity are characterized by the introduced plasma viscosity-dependent model. The presented comprehensive model could be used for better understanding of blood flow hemodynamics and analyzing the shear dependence of aggregation and deformability behaviors of RBCs.

Elimination of Induced Hypoxic Regions in Depth of 3D Porous Silk Scaffolds by the Introduction of Channel Configuration.

Development of large, clinically sized tissue constructs with efficient mass transport is a tremendous need in tissue engineering. One major challenge in large tissue-engineered constructs is to support homogeneous delivery of oxygen and nutrients throughout the tissue scaffold while eliminating induced hypoxic regions in depth. To address this goal, we introduced an especial channeled architecture on porous silk-based tissue scaffolds to improve supplying of oxygen to the cells in central regions of the scaffolds. Oxygen gradients were measured and evaluated in three scaffold prototypes, namely, one unchanneled and two channeled scaffolds with different channel diameters (500 µm and 1000 µm). The channels were introduced into the constructs using stainless-steel rods arranged uniformly in stainless-steel mold, a fabrication method that enables precise control over channel diameter and the distance between channels. During 2-week culture of G292 cells, the 1000 µm channeled scaffolds demonstrated higher oxygen concentration at the center compared to 500 µm channeled prototype; however, the oxygen concentration approached the same level around the last days of culture. Nevertheless, homogenous oxygen distribution throughout the 1000 µm channeled constructs and the consequence of higher cell proliferation at day 14 postseeding corroborate the efficient elimination of induced hypoxic regions; and therefore, it holds promise for clinically relevant sized scaffold especially in bone tissue engineering.

Development of Hormonal Intravaginal Rings: Technology and Challenges.

Intravaginal rings (IVRs) are minimally invasive polymeric devices specifically designed to be used for the sustained and prolonged release of various type of drugs such as hormones. One of the benefits of using topical drug delivery systems (e.g., IVRs) is the fact that systemic drug delivery may cause drug resistance due to elevated drug levels. Topical drug delivery also provides higher concentrations of the drug to the target site and has fewer side effects. In addition, when a drug is administered vaginally, the hepatic first-pass effect is avoided, resulting in higher absorption. Contraception and treatments for specific diseases such as endometriosis and hormone deficiencies can be improved by the administration of hormones via an IVR. This article aims to classify and compare various designs of commercially available and non-commercial hormonal IVRs and to analyze their performance. Current challenges affecting the development of IVRs are investigated, and proposed solutions are discussed. A comprehensive search of publications in MEDLINE/PubMed and of commercial product data of IVRs was performed, and the materials, designs, performance, and applications (e.g., contraception, endometriosis, estrogen deficiency and urogenital atrophy) of hormonal IVRs were thoroughly evaluated. Most hormonal IVRs administer female sex hormones, i.e., estrogen and progestogens. In terms of material, IVRs are divided into 3 main groups: silicone, polyurethane, and polyethylene-co-vinyl acetate IVRs. As regards their design, there are 4 major designs for IVRs which strongly affect their performance and the timing and rate of hormone release. Important challenges include reducing the burst release and maintaining the bioavailability of hormones at their site of action over a prolonged period of administration as well as lowering production costs. Hormonal IVRs are a promising method which could be used to facilitate combination therapies by administering multiple drugs in a single IVR while eliminating the side effects of conventional drug administration methods. IVRs could considerably improve women's quality of life all over the world within a short period of time.

Sustained subconjunctival drug delivery systems: current trends and future perspectives.

PURPOSE: One of the challenges of ocular drug delivery systems is sustainable delivery of the intended drug to the posterior segment of the eye. Periocular routes of drug delivery are a promising method to bridge this challenge. The purpose of this study is to investigate the recent advances and potentials of subconjunctival route and its pros and cons in comparison with other ocular drug delivery routes. METHODS: In this literature review, the comprehensive search of publications was performed in MEDLINE/PubMed indicating investigations on subconjunctival drug delivery systems using relevant keywords. RESULTS: Based on the resultant detailed criteria to choose an appropriate ocular drug delivery route, it is revealed that most of these routes are either highly invasive and/or provide low bioavailability of drug to the target tissue. Nevertheless, subconjunctival drug delivery could be considered as one of the less invasive and easily accessible routes for delivering various drugs to both anterior and posterior segments of the eye. However, most of such researches are at the stage of animal study in their pipelines. CONCLUSION: Periocular route of drug delivery is one of the most efficient routes for delivering the drugs to both anterior and posterior segments of the eye. Subconjunctival sustained drug delivery is highly effective and less invasive compared to other periocular routes. This makes subconjunctival implants and injections one of the most proper ways of treating various ranges of ocular diseases and disorders, e.g., diabetic retinopathy, dry eye syndrome, glaucoma, etc.