Apatite-Polymer Composites for the Controlled Dual Delivery of BMP-2 and BMP-6 for Bone Tissue Engineering

The release of growth factors from tissue engineering scaffolds provides signals that influence the migration, differentiation, and proliferation of cells. The incorporation of a drug delivery platform that is capable of tunable release will give tissue engineers greater versatility in the direction of tissue regeneration. We have prepared a novel composite of two biomaterials with proven track records - apatite and poly(lactic-co-glycolic acid) (PLGA) – as a drug delivery platform with promising controlled release properties. These composites have been tested in the delivery of a model protein, bovine serum albumin (BSA), as well as therapeutic proteins, recombinant human bone morphogenetic protein-2 (rhBMP-2) and rhBMP-6. The controlled release strategy is based on the use of a polymer with acidic degradation products to control the dissolution of the basic apatitic component, resulting in protein release. Therefore, any parameter that affects either polymer degradation or apatite dissolution can be used to control protein release. We have modified the protein release profile systematically by varying the polymer molecular weight, polymer hydrophobicity, apatite loading, apatite particle size, and other material and processing parameters. Biologically active rhBMP-2 was released from these composite microparticles over 100 days, in contrast to conventional collagen sponge carriers, which were depleted in approximately 2 weeks. The released rhBMP-2 was able to induce elevated alkaline phosphatase and osteocalcin expression in pluripotent murine embryonic fibroblasts. To augment tissue engineering scaffolds with tunable and sustained protein release capabilities, these composite microparticles can be dispersed in the scaffolds in different combinations to obtain a superposition of the release profiles. We have loaded rhBMP-2 into composite microparticles with a fast release profile, and rhBMP-6 into slow-releasing composite microparticles. An equi-mixture of these two sets of composite particles was then injected into a collagen sponge, allowing for dual release of the proteins from the collagenous scaffold. The ability of these BMP-loaded scaffolds to induce osteoblastic differentiation in vitro and ectopic bone formation in a rat model is being investigated. We anticipate that these apatite-polymer composite microparticles can be extended to the delivery of other signalling molecules, and can be incorporated into other types of tissue engineering scaffolds.

Exploring Vision-Based Interfaces: How to Use Your Head in Dual Pointing Tasks

The utility of vision-based face tracking for dual pointing tasks is evaluated. We first describe a 3-D face tracking technique based on real-time parametric motion-stereo, which is non-invasive, robust, and self-initialized. The tracker provides a real-time estimate of a ?frontal face ray? whose intersection with the display surface plane is used as a second stream of input for scrolling or pointing, in paral-lel with hand input. We evaluated the performance of com-bined head/hand input on a box selection and coloring task: users selected boxes with one pointer and colors with a second pointer, or performed both tasks with a single pointer. We found that performance with head and one hand was intermediate between single hand performance and dual hand performance. Our results are consistent with previously reported dual hand conflict in symmetric pointing tasks, and suggest that a head-based input stream should be used for asymmetric control.

On the Behavior of the Homogeneous Self-Dual Model for Conic Convex Optimization

There is a natural norm associated with a starting point of the homogeneous self-dual (HSD) embedding model for conic convex optimization. In this norm two measures of the HSD model’s behavior are precisely controlled independent of the problem instance: (i) the sizes of ε-optimal solutions, and (ii) the maximum distance of ε-optimal solutions to the boundary of the cone of the HSD variables. This norm is also useful in developing a stopping-rule theory for HSD-based interior-point methods such as SeDuMi. Under mild assumptions, we show that a standard stopping rule implicitly involves the sum of the sizes of the ε-optimal primal and dual solutions, as well as the size of the initial primal and dual infeasibility residuals. This theory suggests possible criteria for developing starting points for the homogeneous self-dual model that might improve the resulting solution time in practice

The Influence of Adjacent Segment on the Reliability of Cu Dual Damascene Interconnects

Three terminal ‘dotted-I’ interconnect structures, with vias at both ends and an additional via in the middle, were tested under various test conditions. Mortalities (failures) were found in right segments with jL value as low as 1250 A/cm, and the mortality of a dotted-I segment is dependent on the direction and magnitude of the current in the adjacent segment. Some mortalities were also found in the right segments under a test condition where no failure was expected. Cu extrusion along the delaminated Cu/Si₃N₄ interface near the central via region was believed to cause the unexpected failures. From the time-to-failure (TTF), it is possible to quantify the Cu/Si₃N₄ interfacial strength and bonding energy. Hence, the demonstrated test methodology can be used to investigate the integrity of the Cu dual damascene processes. As conventionally determined critical jL values in two-terminal via-terminated lines cannot be directly applied to interconnects with branched segments, this also serves as a good methodology to identify the critical effective jL values for immortality.