Nano-fibrous scaffold for controlled delivery of recombinant human PDGF-BB

Abstract

The localized and temporally controlled delivery of growth factors is key to achieving optimal clinical efficacy. In sophisticated tissue engineering strategies, the biodegradable scaffold is preferred to serve as both a three-dimensional (3-D) substrate and a growth factor delivery vehicle to promote cellular activity and enhance tissue neogenesis. This study presents a novel approach to fabricate tissue engineering scaffolds capable of controlled growth factor delivery whereby growth factor containing microspheres were incorporated into 3-D scaffolds with good mechanical properties, wellinterconnected macroporous and nano-fibrous structures. The microspheres were uniformly distributed throughout the nano-fibrous scaffold and their incorporation did not interfere the macro-, micro-, and nanostructures of the scaffold. The release kinetics of platelet-derived growth factor-BB (PDGF-BB) from microspheres and scaffolds was investigated using poly(lactic-co-glycolic acid) (PLGA50) microspheres with different molecular weights (6.5 and 64kDa, respectively) and microsphere-incorporated poly(L-lactic acid) (PLLA) nano-fibrous scaffolds. Incorporation of microspheres into scaffolds significantly reduced the initial burst release. Sustained release from several days to months was achieved through different microspheres in scaffolds. Released PDGF-BB was demonstrated to possess biological activity as evidenced by stimulation of human gingival fibroblast DNA synthesis in vitro. The successful generation of 3-D nano-fibrous scaffold incorporating controlled-release factors indicates significant potential for more complex tissue regeneration.

Biomimetic materials for tissue engineering

“…We have recently developed technologies to immobilize nano-spheres onto the pore surface of scaffolds, such as the macro-porous and nano-fibrous scaffolds [140,141]. Single or multiple biological factors can be released in a spatially and temporally controlled fashion ( Figure 9).…”

“…Similarly, platelet-derived growth factor (PDGF) incorporated in PLGA nanospheres was released in a controlled fashion [141]. The released PDGF was demonstrated to be biologically active in vitro [141].…”

“…The released PDGF was demonstrated to be biologically active in vitro [141]. After implanted in Spague-Dawley rats, angiogenesis was evaluated using Factor VIII staining and hematoxylin counterstaining.…”

Biodegradable elastomeric scaffolds with basic fibroblast growth factor release

“…Incorporation of angiogenic growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), among others, into scaffolds for controlled release has been shown to promote local angiogenesis. [10,13] There are many methods to incorporate growth factors into synthetic scaffolds, such as absorbing growth factor to the scaffold, [14] blending growth factor containing microspheres into the scaffold, [10,15] or directly mixing growth factor containing protein powder into the scaffold during processing. [16,17] Adsorbing growth factor onto the scaffold has the drawback of low loading efficiencies and rapid release.…”

Cell and biomolecule delivery for regenerative medicine

“…Similarly, platelet-derived growth factor-BB (PDGF-BB) was released from PLGA microspheres in PLLA nano-fibrous scaffolds [42]. Sustained release was controlled through differing the molecular weight of the microspheres.…”