Controlled release of analgesic drugs from porous bioresorbable structures for various biomedical applications

Pain is one of the most common patient complaints encountered by health professionals and remains the number one cause of absenteeism and disability. In the current study, analgesic-eluting bioresorbable porous structures prepared using the freeze-drying of inverted emulsions technique were developed and studied. These drug-eluting structures can be used for coating fibers or implants, or for creating standalone films. They are ideal for forming biomedically important structures that can be used for various applications, such as wound dressings that provide controlled release of analgesics to the wound site in addition to their wound dressing role. Our investigation focused on the effects of the inverted emulsion's parameters on the shell microstructure and on the resulting drug-release profile of ibuprofen and bupivacaine. The release profiles of ibuprofen formulations exhibited a diffusion-controlled pattern, ranging from several days to 21 days, whereas bupivacaine formulations exhibited an initial burst release followed by a three-phase release pattern over a period of several weeks. Higher organic to aqueous phase ratios and higher polymer contents reduced the burst release of both drugs and prolonged their release due to lower porosity. Overall, the drug-eluting porous structures loaded with either ibuprofen or bupivacaine demonstrated a promising potential for use in various applications that require pain relief

Internal Mechanics of a Subject-Specific Wrist in the Sagittal versus Dart-Throwing Motion Plane in Adult and Elder Models: Finite Element Analyses

Introduction: Most of the wrist motions occur in a diagonal plane of motion, termed the dart-throwing motion (DTM) plane; it is thought to be more stable compared with movement in the sagittal plane. However, the effect of the altered carpus motion during DTM on the stress distribution at the radiocarpal joint has yet to be explored. Aim: To calculate and compare the stresses between the radius and two carpal bones (the scaphoid and the lunate) in two wrist positions, extension and radial extension (position in DTM), and between an adult and an elder model. Methods: A healthy wrist of a 40-year-old female was scanned using Magnetic Resonance Imaging in two wrist positions (extension, radial extension). The scans were transformed into three-dimensional models and meshed. Finite element (FE) analyses in each position of the wrist were conducted for both adult and elder models, which were differentiated by the mechanical properties of the ligaments. The distal surfaces of the carpal bones articulating with the metacarpals were loaded by physically accurate tendon forces for each wrist position. Results: The von Mises, shear stresses and contact stresses were higher in the extension model compared with the radial-extension model and were higher for the radius-scaphoid interface in the adult model compared with the elder model. In the radius-scaphoid interface, the stress differences between the two wrist positions were smaller in the elder model (11.5% to 22.5%) compared with the adult model (33.6–41.5%). During radial extension, the contact area at the radius-lunate interface was increased, more so in the adult model (222.2%) compared with the elder model (127.9%), while the contact area at the radius-scaphoid was not affected by the position of the wrist in the adult model (100.9%) but decreased in the elder model (50.2%) during radial extension. Conclusion: The reduced stresses during radial extension might provide an explanation to our frequent use of this movement pattern, as the reduced stresses decrease the risk of overuse injury. Our results suggest that this conclusion is relevant to both adults and elder individuals

FITC-Dextran Release from Cell-Embedded Fibrin Hydrogels

Fibrin hydrogel is a central biological material in tissue engineering and drug delivery applications. As such, fibrin is typically combined with cells and biomolecules targeted to the regenerated tissue. Previous studies have analyzed the release of different molecules from fibrin hydrogels; however, the effect of embedded cells on the release profile has yet to be quantitatively explored. This study focused on the release of Fluorescein isothiocyanate (FITC)-dextran (FD) 250 kDa from fibrin hydrogels, populated with different concentrations of fibroblast or endothelial cells, during a 48-h observation period. The addition of cells to fibrin gels decreased the overall release by a small percentage (by 7–15% for fibroblasts and 6–8% for endothelial cells) relative to acellular gels. The release profile was shown to be modulated by various cellular activities, including gel degradation and physical obstruction to diffusion. Cell-generated forces and matrix deformation (i.e., densification and fiber alignment) were not found to significantly influence the release profiles. This knowledge is expected to improve fibrin integration in tissue engineering and drug delivery applications by enabling predictions and ways to modulate the release profiles of various biomolecules

FITC-Dextran Release from Cell-Embedded Fibrin Hydrogels

Fibrin hydrogel is a central biological material in tissue engineering and drug delivery applications. As such, fibrin is typically combined with cells and biomolecules targeted to the regenerated tissue. Previous studies have analyzed the release of different molecules from fibrin hydrogels; however, the effect of embedded cells on the release profile has yet to be quantitatively explored. This study focused on the release of Fluorescein isothiocyanate (FITC)-dextran (FD) 250 kDa from fibrin hydrogels, populated with different concentrations of fibroblast or endothelial cells, during a 48-h observation period. The addition of cells to fibrin gels decreased the overall release by a small percentage (by 7–15% for fibroblasts and 6–8% for endothelial cells) relative to acellular gels. The release profile was shown to be modulated by various cellular activities, including gel degradation and physical obstruction to diffusion. Cell-generated forces and matrix deformation (i.e., densification and fiber alignment) were not found to significantly influence the release profiles. This knowledge is expected to improve fibrin integration in tissue engineering and drug delivery applications by enabling predictions and ways to modulate the release profiles of various biomolecules

Media 1: Continuous wide-field characterization of drug release from skin substitute using off-axis interferometry

Originally published in Optics Letters on 15 August 2013 (ol-38-16-3017