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).