No 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.

Scaffolds are crucial to tissue engineering/regeneration. In this work, a technique combining a unique phase-separation process with a novel sugar sphere template leaching process has been developed to produce three-dimensional scaffolds. The resulting scaffolds possess high porosities, well connected macropores, and nanofibrous pore walls. The technique advantageously controls macropore shape and size by sugar spheres, interpore opening size by assembly conditions (time and temperature of heat treatment), and pore wall morphology by phase-separation parameters. The bioactivity of a macroporous and nanofibrous poly(L-lactic acid) (PLLA) scaffold was demonstrated by the bone-like apatite deposition throughout the scaffold in a simulated body fluid (SBF). Preincorporation of nanosized hydroxyapatite eliminated the induction period and facilitated the apatite growth in the SBF. Interestingly, the apatite growth primarily occurred on the surface of the pores (internal and external) but not the interior of the nanofibrous network away from the pore surface. It was also noticed that the macropore size did not affect the apatite growth rate, while the interpore opening size did. The compressive modulus also increased substantially when a continuous apatite layer was formed on the pore walls of the scaffold. The resulting composite scaffold mimics natural bone matrix with the combination of an organic phase (a polymer such as PLLA) and an inorganic apatite phase. The demonstrated bioactivity of apatite layer, together with well-controlled macroporous and nanofibrous structures, makes the novel nanocomposite scaffolds desirable for bone tissue engineering.

Biomaterials play a pivotal role in regenerative medicine, which aims to regenerate and replace lost/ dysfunctional tissues or organs. Biomaterials (scaffolds) serve as temporary 3D substrates to guide neo tissue formation and organization. It is often beneficial for a scaffolding material to mimic the characteristics of extracellular matrix (ECM) at the nanometer scale and to induce certain natural developmental or/and wound healing processes for tissue regeneration applications. This article reviews the fabrication and modification technologies for nanofibrous, nanocomposite, and nanostructured drug-delivering scaffolds. ECM-mimicking nanostructured biomaterials have been shown to actively regulate cellular responses including attachment, proliferation, differentiation and matrix deposition. Nano-scaled drug delivery systems can be successfully incorporated into a porous 3D scaffold to enhance the tissue regeneration capacity. In conclusion, nano-structured biomateials are a very exciting and rapidly expanding research area, and are providing new enabling technologies for regenerative medicine.

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.