The enhancement of osteogenesis by nano-fibrous scaffolds incorporating rhBMP-7 nanospheres

Abstract

It is advantageous to incorporate controlled growth factor delivery into tissue engineering strategies. The objective of this study was to develop a three-dimensional (3D) porous tissue engineering scaffold with the capability of controlled releasing recombinant human bone morphogenetic protein-7 (rhBMP-7) for enhancement of bone regeneration. RhBMP-7 was first encapsulated into poly(lactic-co-glycolic acid) (PLGA) nanospheres (NS) with an average diameter of 300 nm. Poly (L-lactic acid) (PLLA) scaffolds with interconnected macroporous and nano-fibrous architectures were prepared using a combined sugar sphere template leaching and phase separation technique. A post-seeding technique was then utilized to immobilize rhBMP-7 containing PLGA nanospheres onto prefabricated nano-fibrous PLLA scaffolds with well maintained 3D structures. In vitro release kinetics indicated that nanosphere immobilized scaffold (NS-scaffold) could release rhBMP-7 in a temporally controlled manner, depending on the chemical and degradation properties of the nanospheres which were immobilized onto the scaffold. In vivo, rhBMP-7 delivered from NSscaffolds induced significant ectopic bone formation throughout the scaffold while passive adsorption of rhBMP-7 into the scaffold resulted in failure of bone induction due to either the loss of rhBMP-7 biological function or insufficient duration within the scaffold. We conclude that the interconnected macroporous architecture and the sustained, prolonged delivery of bioactive rhBMP-7 from NS immobilized nano-fibrous scaffolds actively induced new bone formation throughout the scaffold. The approach offers a new delivery method of BMPs and a novel scaffold design for bone regeneration.

Biomimetic materials for tissue engineering

“…Four scaffolds (without cells) were implanted subcutaneously onto the dorsum of each rat. After 6 weeks, H & E staining indicates that there was significant bone formation in the BMP7-NS containing scaffold (Figure 11 A), but only fibrous tissue in the scaffold without BMP7 (Figure 11 B), or in the same scaffold pre-soaked in a BMP7 solution (Figure 11 C) [140]. This result was also supported by von Kossa staining and radiographic measurements [140].…”

“…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).…”

“…After 6 weeks, H & E staining indicates that there was significant bone formation in the BMP7-NS containing scaffold (Figure 11 A), but only fibrous tissue in the scaffold without BMP7 (Figure 11 B), or in the same scaffold pre-soaked in a BMP7 solution (Figure 11 C) [140]. This result was also supported by von Kossa staining and radiographic measurements [140]. The results indicated that incorporation of BMP7 into nanospheres, which were then immobilized onto a scaffold, preserved the biological activity of BMP7 and could prolong the duration to induce ectopic bone formation.…”

Silk fibroin microparticles as carriers for delivery of human recombinant BMPs. Physical characterization and drug release

“…In fact, as we have observed the silk fibroin microparticles exhibited a slow rate of degradation. The release amounts during this phase were such that they could meet the concentrations of growth factor required in most in vitro and in vivo applications (in the range of few hundreds of nanograms to a few micrograms), by choosing a specific amount of BMP during the loading process (Kenley et al, 1994;Hosseinkhani et al, 2007;Wei et al, 2007;Bessa et al, 2009).…”

“…Several different microparticulated systems have been investigated for the delivery of BMPs, most based on polylactic-co-glycolic acid (PLGA) (Lee et al, 1994;Phillips et al, 2006;Wei et al, 2007), on collagen (Wang et al, 2003, Itoh et al, 2004 or on dextran (Chen et al, 2006. Silk is an attractive choice as a material for bone tissue engineering, due to being biocompatible, slowly biodegradable and possessing excellent mechanical properties such as tensile strength and rigidity which are highly desirable for a potential use as a scaffold for bone tissue engineering (Scheibel 2006).…”