Controlled Release of IGF-1 and HGF from a Biodegradable Polyurethane Scaffold

Abstract

Purpose Biodegradable elastomers, which can possess favorable mechanical properties and degradation rates for soft tissue engineering applications, are more recently being explored as depots for biomolecule delivery. The objective of this study was to synthesize and process biodegradable, elastomeric poly(ester urethane)urea (PEUU) scaffolds and to characterize their ability to incorporate and release bioactive insulin-like growth factor–1 (IGF-1) and hepatocyte growth factor (HGF). Methods Porous PEUU scaffolds made from either 5 or 8 wt% PEUU were prepared with direct growth factor incorporation. Long-term in vitro IGF-1 release kinetics were investigated in saline or saline with 100 units/ml lipase to simulate in vivo degradation. Cellular assays were used to confirm released IGF-1 and HGF bioactivity. Results IGF-1 release into saline occurred in a complex multi-phasic manner for up to 440 days. Scaffolds generated from 5 wt% PEUU delivered protein faster than 8 wt% scaffolds. Lipase-accelerated scaffold degradation lead to delivery of >90% protein over 9 weeks for both polymer concentrations. IGF-1 and HGF bioactivity in the first 3 weeks was confirmed. Conclusions The capacity of a biodegradable elastomeric scaffold to provide long-term growth factor delivery was demonstrated. Such a system might provide functional benefit in cardiovascular and other soft tissue engineering applications.

IGF2: an endocrine hormone to improve islet transplant survival

“…Significant work in this area has been undertaken using the sister compound IGF1 (Jaklenec et al 2008, Chen et al 2009, Sun et al 2011, Kim et al 2012. In one example, Nelson et al (2011) used porous poly(ester urethane)urea scaffolds to demonstrate the long-term delivery of bioactive IGF1 in vitro. Likewise, the Meinel group showed that IGF1 releasing silk fibroin scaffolds initiated chondrogenesis from human mesenchymal stem cells in vitro (Uebersax et al 2008).…”

The Pharmacology of Regenerative Medicine

“…hepatocyte growth factor, which may aid in the regenerative process (Nelson et al, 2011), and suggests the next generation of drug delivery in cardiovascular applications beyond drug-eluting stents.…”

Joint Cartilage Tissue Engineering and Pre-Clinical Safety and Efficacy Testing

“…The simplest version of delivery system is a direct attachment of growth factor to the surface of the scaffold material by soaking the scaffold in growth factor suspension (Kanematsu et al, 2004), or incorporation of the growth factors and cytokines into biodegradable scaffolds, usually hydrogels (Yamamoto et al, 2001;Nelson et al, 2011). The factors are then released passively from the surface of the scaffold or as the scaffold degrades.…”