David M. Knapp

Rheology of reconstituted type I collagen gel in confined compression

Collagen gels are used extensively for studying cell–matrix mechanical interactions and for making tissue equivalents, where these interactions lead to bulk deformation of the sparse network of long, highly entangled collagen fibrils and syneresis of the interstitial aqueous solution. We have used the confined compression test in conjunction with a biphasic theory to characterize collagen gel mechanics. A finite element method model based on our biphasic theory was used to analyze the experimental results. The results are qualitatively consistent with a viscoelastic collagen network, an inviscid interstitial solution, and significant frictional drag. Using DASOPT, a differential-algebraic equation solver coupled with an optimizing algorithm, the aggregate modulus for the collagen gel was estimated as 6.32 Pa, its viscosity as 6.6×104 Pa s, and its interphase drag coefficient as 6.4×109 Pa s m−2 in long-time (5 h) creep. Analysis of short-time (2 min) constant strain rate tests gave a much higher modulus (...

A dissolution-diffusion model for the TAXUS™ drug-eluting stent with surface burst estimated from continuum percolation

A two-layer dissolution-diffusion model is derived which incorporates a surface burst component that is estimated from continuum percolation models of overlapping Poisson distributed spheres. The model is shown to adequately describe the release properties of paclitaxel from a hydrophobic polymer matrix, including the surface burst and sustained release dependence on drug loading.

Biomaterial considerations for drug-eluting stents

The ultimate test for implant biomaterials is determined by the long-term, post-market clinical product performance. This is a key consideration in the initial design and development for drug-eluting stents. To insure this ultimate clinical success, a rigorous series of bench-top, preclinical and clinical evaluations must be performed. The factors in the biomaterial choice which are important for each stage in this development process include pharmaceutical, physical, and biological elements. This presentation will outline the steps taken by Boston Scientific in each of these stages to achieve the desired clinical end-points.

Day 1 wound fluid and PDGF-BB elicit similar fibroblast behavior in vitro

We utilized a novel in vitro assay to investigate factors that modulate the behavioral phenotype of fibroblasts during wound healing. Using the Isometric Cell Traction Assay (ICTA), we quantified simultaneously the migration and traction of rat dermal fibroblasts entrapped in a collagen gel immersed in cell culture medium. We found that the addition of 10% day 1 wound fluid to culture medium inhibited fibroblast-mediated gel compaction when compared to medium with 10% rat serum or 10% day 5 rat wound fluid. Similar results were obtained after addition of 5-50 ng/ml platelet-derived growth factor-BB (PDGF-BB)+10% serum. These results suggest that PDGF-BB, a growth factor released by platelets and in abundance in early wound fluid, is an important species in stimulating phenotype transition to a migrating (early) wound fibroblast versus a tissue contracting (late) wound fibroblast.