Drug delivery across length scales

Over the last century, there has been a dramatic change in the nature of therapeutic, biologically active molecules available to treat disease. Therapies have evolved from extracted natural products towards rationally designed biomolecules, including small molecules, engineered proteins and nucleic acids. The use of potent drugs which target specific organs, cells or biochemical pathways, necessitates new tools which can enable controlled delivery and dosing of these therapeutics to their biological targets. Here, we review the miniaturisation of drug delivery systems from the macro to nano-scale, focussing on controlled dosing and controlled targeting as two key parameters in drug delivery device design. We describe how the miniaturisation of these devices enables the move from repeated, systemic dosing, to on-demand, targeted delivery of therapeutic drugs and highlight areas of focus for the future

Impingement and Stability of Total Hip Arthroplasty Versus Femoral Head Resurfacing Using a Cadaveric Robotics Model

We identified and compared the impingent-free range of motion (ROM) and subluxation potential for native hip, femoral head resurfacing (FHR), and total hip arthroplasty (THA). These constructs were also compared both with and without soft tissue to elucidate the role of the soft tissue. Five fresh-frozen bilateral hip specimens were mounted to a six-degree of freedom robotic manipulator. Under load-control parameters, in vivo mechanics were recreated to evaluate impingement free ROM, and the subluxation potential in two at risk positions for native hip, FHR, and THA. Impingement-free ROM of the skeletonized THA was greater than FHR for the anterior subluxation position. For skeletonized posterior subluxations, stability for THA and FHR constructs were similar, while a different pattern was observed for specimens with soft tissues intact. FHR constructs were more stable than THA constructs for both anterior and posterior subluxations. When the femoral neck is intact the joint has an earlier impingement profile placing the hip at risk for subluxation. However, FHR design was shown to be more stable than THA only when soft tissues were intact

The Contribution of the Acetabular Labrum to Hip Joint Stability: A Quantitative Analysis Using a Dynamic Three-Dimensional Robot Model

The acetabular labrum provides mechanical stability to the hip joint in extreme positions where the femoral head is disposed to subluxation. We aimed to quantify the isolated labrum\u27s stabilizing value. Five human cadaveric hips were mounted to a robotic manipulator, and subluxation potential tests were run with and without labrum. Three-dimensional (3D) kinematic data were quantified using the stability index (Colbrunn et al., 2013, Impingement and Stability of Total Hip Arthroplasty Versus Femoral Head Resurfacing Using a Cadaveric Robotics Model, J. Orthop. Res., 31(7), pp. 1108-1115). Global and regional stability indices were significantly greater with labrum intact than after total labrectomy for both anterior and posterior provocative positions. In extreme positions, the labrum imparts significant overall mechanical resistance to hip subluxation. Regional stability contributions vary with joint orientation

The Contribution of the Acetabular Labrum to Hip Joint Stability: A Quantitative Analysis Using a Dynamic Three-Dimensional Robot Model

The acetabular labrum provides mechanical stability to the hip joint in extreme positions where the femoral head is disposed to subluxation. We aimed to quantify the isolated labrum\u27s stabilizing value. Five human cadaveric hips were mounted to a robotic manipulator, and subluxation potential tests were run with and without labrum. Three-dimensional (3D) kinematic data were quantified using the stability index (Colbrunn et al., 2013, Impingement and Stability of Total Hip Arthroplasty Versus Femoral Head Resurfacing Using a Cadaveric Robotics Model, J. Orthop. Res., 31(7), pp. 1108-1115). Global and regional stability indices were significantly greater with labrum intact than after total labrectomy for both anterior and posterior provocative positions. In extreme positions, the labrum imparts significant overall mechanical resistance to hip subluxation. Regional stability contributions vary with joint orientation