Ultrahigh protein adsorption capacity and sustained release of nanocomposite scaffolds: implication for growth factor delivery systems

Abstract

Scaffolds that can load and deliver growth factors are promising for the regeneration of tissues. High loading and long-term delivery of the molecules are generally considered key aspects in optimizing the therapeutic outcome of the growth factor-delivering scaffolds. Here we report nanocomposite scaffolds incorporating nanoparticles that have exceptionally high capacity to load proteins/growth factors and release them in a sustainable manner. Bioactive glass nanoparticles (BGn) in a mesoporous form were added to a degradable polymer (polylactic acid; PLA) up to 200% (BGn/PLA by weight), which was formed into highly porous scaffolds. The specific surface area and hydrophilicity of the scaffolds were significantly enhanced by BGn incorporation. The BGn/PLA scaffolds adsorbed proteins at high quantities with respect to pure PLA scaffolds, ∼20 times for cytochrome C and ∼5 times for lysozyme, and the protein adsorption was largely charge-dependent (i.e., selectively adsorbed positively-charged proteins due to a negatively-charged BGn). The loaded protein was released from the BGn/PLA scaffolds in a highly sustainable manner over weeks, which was contrasted to the abrupt protein release (almost complete within one week) observed in pure PLA scaffolds. Fibroblast growth factor 2 (FGF2) was used as the representative growth factor that was involved in cell mitosis and tissue repair for biological efficacy. The FGF2 release continued over 4 weeks with an almost linear release pattern after the initial 3 days. The scaffolds that release FGF2 slowly demonstrated significantly stimulated proliferation of mesenchymal stem cells with respect to those without FGF2, with continuous biological effects over 3 weeks. The BGn/PLA nanocomposite scaffolds, proven to be effective in loading specific growth factors at high quantity and delivering sustainably over weeks to months, may be potentially useful in tissue repair and regeneration processes.