Characterizing short-term release and neovascularization potential of multi-protein growth supplement delivered via alginate hollow fiber devices.

Multi-protein (10-250 kDa) endothelial cell growth supplement (ECGS) contains growth factors of varying sizes resulting in advanced release rates from diffusion-based drug delivery devices. As a result, the biochemical stimulus provided by ECGS for neovascularization in the critical initial stages of cell transplantation in artificial organs may differ from that for single growth factor delivery. In this study, both in vitro and in vivo studies were conducted with ECGS to correlate in vitro release of multiple angiogenic growth factors to vascularization potential in vivo. The short-term release of ECGS from calcium alginate gels supported in the lumen of polypropylene (PP) hollow fibers was investigated in vitro for up to 142 h. The overall time constant increased from 2, 2.2 and 6.3 h as the alginate concentration was increased from 1.5%, 2% and 3%, respectively. However, time constants for individual species ranged from 1.5 to 77 h. The in vivo bioactivity of released ECGS was assessed for up to 21 days using a Lewis rat model implanted with 1.5% calcium alginate gels supported in PP and polysulfone hollow fibers. For the ECGS-releasing PP hollow fiber system, a two-fold increase in neovascularization with respect to the control was observed for the period between 7 and 17 days post-implantation at the device-tissue interface (p<0.05).

Mathematical modeling of myoglobin facilitated transport of oxygen in devices containing myoglobin-expressing cells.

Low pO(2) is perhaps the most significant factor in artificial pancreas failure. In these environments, not only is the beta cell production of insulin reduced, but the cell death rate is also significantly higher. Mathematical models are developed to test the feasibility of facilitated oxygen transport in enhancing O(2) flux to genetically engineered cells in a bioartificial device such as a pancreas. For this device, it is proposed that beta cells be genetically engineered to express myoglobin throughout the cell. In addition, the significance of including myoglobin throughout the alginate matrix present to provide immuno-protection for the transplanted cells is considered. The mathematical analysis predicts that myoglobin facilitated oxygen transport has the potential of increasing the oxygen concentration at the centre of a cluster of cells (islet) with an effective radius of 100 microm by 50%. These theoretical models for myoglobin facilitated oxygen transport with homogeneous Michaelis-Menten consumption also indicate that including myoglobin in the alginate gel would beneficially improve the flux of oxygen to the transplanted cells.