Youliang Hong

Preparation, bioactivity, and drug release of hierarchical nanoporous bioactive glass ultrathin fibers.

Hierarchical nanoporous bioactive glass ultrathin fibers with different pore diameters from 1.5-nm micropores up to 65-nm macropores are synthesized using P123-PEO co-templates and an electrospinning technique (see image). Experiments demonstrate that the prepared bioactive glass fibers are highly homogenous and bioactive and their nanopores can control drug release well.

A hierarchically graded bioactive scaffold bonded to titanium substrates for attachment to bone.

In this paper we report a Ti-based, hierarchical porous scaffold anchored to Ti substrates, prepared by synthesizing hydroxyapatite--calcium carbonate-Ti three--layer spheres and combining a modified plasma spraying process and an anodic oxidation treatment. The hierarchical porous scaffolds were composed of 100-350 μm interconnecting macropores, 0.2-90 μm pores and ~100 nm nanopores with >70% porosity. At the same time, the scaffolds also had the graded structures constructed by bioactive TiO(x) in surface transforming to metallurgy-bondable Ti in bottom. Mechanical property tests demonstrated that the porous scaffolds had similar Youngs modulus with natural bone and strong bonding strength with the Ti substrates. The simulate body fluid immersion showed that bone-like apatite layer could form rapidly at scaffold surface. The in vitro cell incubation demonstrated that the porous scaffolds had good cellular compatibility and could correctly regulate cascade gene expression of primary osteoblasts. The intramuscular implantations indicated the porous scaffolds had high osteoinductivity and the bone implantations demonstrated that the scaffolds could facilitate new bone growth and have strong bonding strength with surrounding bone.

Synthesis and protein adsorption of hierarchical nanoporous ultrathin fibers.

In this paper we describe hierarchical nanoporous ultrathin fibers, which are synthesized using an electrospinning technique and the surfactant-polymer cotemplates. Composite fibers with viscoelastic characters resulting from the driving force of surfactants are first organized by electrospinning a solution containing nanostructure-directing agents, nonionic triblock copolymer pluronic 123 and polyethylene oxide. Subsequently, the defined shrinkage and calcination of the composite fibers yielded the corresponding nanoporous fibers. The porous structure, size, and shape demonstrated are very sensitive to shrinkage, and nanopores from 3.8 nm mesopores up to approximately 450 nm macropores can be prepared in direct proportion to the fibrous shrinkage. Protein adsorption experiments demonstrate that the nanoporous fibers with large pores (40 nm) are favorable for the large-size bovine serum albumin (BSA) protein adsorption, where BSA can quickly enter the large pores. Therefore, the superlong large-pore fibers in the form of macroscopic macroporous membranes have potential applications for large-size protein separation.

APPLICATIONS OF CALCIUM PHOSPHATE NANOPARTICLES IN POROUS HARD TISSUE ENGINEERING SCAFFOLDS

To repair bone defects, an important approach is to fabricate tissue engineering scaffolds as substitutions to replace auto-/allologous bones. Currently, processing a biomaterial into three-dimensional porous scaffolds and incorporating the calcium phosphate (Ca–P) nanoparticles into scaffolds profile two main characteristics of bone tissue engineering scaffolds. Based on this fact, in this paper we describe the design principles of the Ca–P nanoparticle-based and porous bone tissue engineering scaffolds. Then we summarize a variety of the Ca–P nanoparticle-based scaffolds, including discussion of the integration of the Ca–P nanoparticles with ceramics and polymers, followed by introduction of safety of the Ca–P nanoparticles in scaffolds.

Reverse-biomineralization assembly of acid-sensitive biomimetic fibers for hard tissue engineering and drug delivery

Biomimetic design and fabrication of tissue-engineered bone scaffolds that not only resemble natural bone in structure and performance, but also are endowed with specific functions, e.g., for drug delivery, are always an exciting research area. Herein, we report a kind of doxorubicin hydrochloride-loaded biomimetic ultrathin fiber, which is synthesized by preparing a kind of nanoporous bioactive glass fiber as a drug/protein carrier and bio-template and combining them in a reverse-biomineralization reaction. Protein adsorption experiments demonstrate that bovine serum albumin can be hosted in open large nanopores of bioactive glass fibers and the adsorption mechanism follows the intraparticle diffusion process. Biomineralization shows that proteins and drugs can be integrated at the nanoscale into minerals to form biomimetic and drug-loaded fibers, and the formation of such fibers depends on the functional ion (Ca, P, and Si) release of bioactive glass fibers and electrostatic interaction among bioactive glass fibers, proteins, and drugs. The drug-loaded composite fibers demonstrate bare homogeneous solid matrices in the fiber interior and surfaces upon which amorphous carbonated apatite resides. The drug release profiles show that the as-synthesized fibers are acid-sensitive and drugs can be released at pH 5, but not at neutral pH 7.4. Because of their structural advantages and the characteristics of acid-sensitive drug release, the biomimetic fibers have potential applications for repairing the bone defects resulting from tumour extirpation.

Osteogenic commitment of mesenchymal stem cells in apatite nanorod-aligned ceramics.

It is significant to process the clinically used biomaterials into a scaffold with specific nanotopographies, which can act as physical cues to regulate the osteogenic commitment of mesenchymal stem cells. In this study, hydroxyapatite (HAP) was considered as the processed objective and a facile, hydrothermal method was developed to grow the vertically oriented HAP nanorods in porous HAP ceramics. Experiments demonstrated that the formation of the HAP nanorods in porous ceramics was decided by a novel epitaxial growth mechanism and length of nanorods could be well-controlled by the growth time. Cell experiments demonstrated that such novel stereotopographical cues could regulate bone marrow mesenchymal stem cells to differentiate into the osteogenic lineage, thereby displaying that the porous ceramics with the HAP nanorods-aligned stereotopographies have a good prospect for applications in regenerative medicine of hard tissues.

Preparation and biological effects of apatite nanosheet-constructed porous ceramics

The design and processing of bioceramics into specific architectures (especially with micro-/nanoscale specific architectures) to improve their biological performances or extend their applications are always the cutting-edge research of bioceramics. Herein, we designed a kind of apatite nanosheet-constructed porous ceramics (AN-PCs), which were fabricated by foam moulding, high heat sintering, and then water soaking the α-tricalcium phosphate (hydroxyapatite - contained porous biphasic calcium phosphate ceramics). Experiments demonstrated that such stereo-nanotopographies had excellent cytocompatibility, and could regulate mesenchymal stem cells (MSCs) to differentiate into osteogenic lineages. And an in vivo ectopic-implant showed that the AN-PCs possessed osteoinductivity. Thus, the AN-PCs reported herein show improved biological performances to repair hard tissues.

Rapid osteogenic differentiation of mesenchymal stem cells on hydroxyapatite nanocrystal clusters-oriented nanotopography

Although it has been well demonstrated that specific nanotopographies alone can direct the fate decision of stem cells, there is still a huge gap, and at the same time, denotes a large challenge to translate this concept into clinical trials. Herein, we reported on using a kind of clinically relative biomaterial, hydroxyapatite, to prepare a kind of specific nanotopography constructed by the randomly oriented hydroxyapatite nanocrystal clusters, through high temperature water vapour treatment of the plasma-sprayed hydroxyapatite slices. Cell experiments demonstrated that bone-marrow mesenchymal stem cells could exert a strong adhesive tension on the nanocrystal clusters-oriented topography, and the formed strong intracytoskeletal stress in turn promoted cells to osteogenic differentiation rapidly; the differentiation process was associated with, but faster than, the model of osteoblastic differentiation. Therefore, our work reported here extremely shortened the gap from the concepts of mechanotransduction, i.e., extracellular physical forces sponsored from materials features can induce mechanochemical conversion to alter the fate decision of stem cells, to the clinical trials.

Biological effects of apatite nanoparticle-constructed ceramic surfaces in regulating behaviours of mesenchymal stem cells

Although calcium phosphate (CaP) ceramics have been originally defined as bioactive materials because a biologically active hydroxycarbonate apatite (HCA) layer can form on their surfaces, the biological effects of the as-grown HCA layers are far from understood. In particular, it is unclear whether the as-grown HCA nanotopography can mediate the osteogenic commitment of mesenchymal stem cells (MSCs). In this study, a systematic investigation was performed to investigate the formation and biological effects of HCA nanotopography on CaP ceramic surfaces. Experiments demonstrate that the hydroxyapatite phase-containing CaP ceramics tend to grow HCA nanoparticle-constructed nanotopography, which can mediate bone marrow MSCs to condensate and spontaneously differentiate toward osteogenic lineage. In addition, the biological evolution of MSCs adhered on such nanotopography is similar to intramembranous ossification. Our findings provide support for applications of wurtzite phase-containing CaP ceramics in regenerative medicine for hard tissues.