Xiaoling Liao

RETRACTED: Effect of nanostructure on osteoinduction of porous biphasic calcium phosphate ceramics

In order to evaluate the effect of the nanostructure of calcium phosphate ceramics on osteoinductive potential, porous biphasic calcium phosphate (BCP) ceramics with a nano- or submicron structure were prepared via microwave sintering and compared to conventional BCP ceramics. The selective protein adsorption of bovine serum albumin and lysozyme (LSZ) and the osteogenic differentiation of human mesenchymal stem cells in vitro was investigated. Porous BCP nanoceramics showed higher ability to adsorb proteins, especially low molecular weight protein of LSZ, than conventional BCP ceramics, and the BCP nanoceramics promoted bone sialoprotein expression more than conventional BCP did. Further in vivo study to investigate ectopic bone formation and bone repair efficiency proved the highly osteoinductive potential of nanostructured BCP ceramics. The results suggest that nanostructured BCP ceramics have the potential to become a new generation of bioceramics for bone tissue engineering grafts.

Preparation of bioactive β-tricalcium phosphate microspheres as bone graft substitute materials

In this study, β-tricalcium phosphate (Ca3PO4, β-TCP) microspheres with different diameters were fabricated via a solid-in-oil-in-water (S/O/W) emulsion method. After soaking in simulated body fluid (SBF), the fabricated β-TCP microspheres were fully covered with a new bone-like apatite layer; subsequent analysis suggested that the microspheres have excellent bioactivity properties, specifically in inducing apatite deposition. The calcium release profiles of the microspheres were tested in pH7.4 Tris-HCl buffer, and results demonstrated that the Ca2+ continually released from microspheres during the two-week test period. We then co-cultured bone marrow stem cells (BMSCs) in vitro with β-TCP microspheres, and performed SEM and confocal microscope analyses to find that β-TCP microspheres efficiently promoted BMSC attachment and bone-related gene expression. The co-cultured BMSCs and microspheres were successfully implanted subcutaneously into nude mice for 8weeks. The H&E neo-tissue staining results showed that abundant new bone-like structures had formed between the β-TCP microspheres, implying that β-TCP microspheres used as a cell carrier and bone graft substitute material show highly promising potential application for irregular-shaped bone defect regeneration.

PEG- b -PCL polymeric nano-micelle inhibits vascular angiogenesis by activating p53-dependent apoptosis in zebrafish

Micro/nanoparticles could cause adverse effects on cardiovascular system and increase the risk for cardiovascular disease-related events. Nanoparticles prepared from poly(ethylene glycol) (PEG)-b-poly(ε-caprolactone) (PCL), namely PEG-b-PCL, a widely studied biodegradable copolymer, are promising carriers for the drug delivery systems. However, it is unknown whether polymeric PEG-b-PCL nano-micelles give rise to potential complications of the cardiovascular system. Zebrafish were used as an in vivo model to evaluate the effects of PEG-b-PCL nano-micelle on cardiovascular development. The results showed that PEG-b-PCL nano-micelle caused embryo mortality as well as embryonic and larval malformations in a dose-dependent manner. To determine PEG-b-PCL nano-micelle effects on embryonic angiogenesis, a critical process in zebrafish cardiovascular development, growth of intersegmental vessels (ISVs) and caudal vessels (CVs) in flk1-GFP transgenic zebrafish embryos using fluorescent stereomicroscopy were examined. The expression of fetal liver kinase 1 (flk1), an angiogenic factor, by real-time quantitative polymerase chain reaction (qPCR) and in situ whole-mount hybridization were also analyzed. PEG-b-PCL nano-micelle decreased growth of ISVs and CVs, as well as reduced flk1 expression in a concentration-dependent manner. Parallel to the inhibitory effects on angiogenesis, PEG-b-PCL nano-micelle exposure upregulated p53 pro-apoptotic pathway and induced cellular apoptosis in angiogenic regions by qPCR and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay. This study further showed that inhibiting p53 activity, either by pharmacological inhibitor or RNA interference, could abrogate the apoptosis and angiogenic defects caused by PEG-b-PCL nano-micelles, indicating that PEG-b-PCL nano-micelle inhibits angiogenesis by activating p53-mediated apoptosis. This study indicates that polymeric PEG-b-PCL nano-micelle could pose potential hazards to cardiovascular development.

Immobilization of heparin/poly-l-lysine microspheres on medical grade high nitrogen nickel-free austenitic stainless steel surface to improve the biocompatibility and suppress thrombosis

Thrombosis formation, restenosis, and delayed endothelium regeneration continue to be a challenge for coronary artery stent therapy. To improve the hemocompatibility of cardiovascular implants and to selectively direct vascular cell behavior, a novel heparin/poly-l-lysine microsphere was developed and immobilized on a dopamine-coated surface. We chose medical grade high nitrogen nickel-free austenitic stainless steel as the stent material since it has better biocompatibility. The stability and structural characteristics of the microspheres changed with the heparin: poly-l-lysine concentration ratio. Antithrombin III binding was significantly enhanced. Furthermore, for plasma coagulation tests, the activated partial thromboplastin time and thrombin time were prolonged and depended on the heparinfunction. The modified exhibited excellent stability and anticoagulant activity, and efficiently accelerated endothelialization and anticoagulation. This work has potential application for the design of coronary artery stent surfaces tailored for vascular cell behavior.

Biomaterials and bone tissue engineering

During the last decades, bone tissue repair and regeneration have been increasing interest in the clinical therapy scientific field, and with the development of materials, biology and tissue engineering, the bone tissue engineering has been as an efficient method to treat bone defects. This review summarizes several aspects related to bone tissue engineering for bone repair and regeneration: the biomaterials in the bone tissue engineering, the stem cell behavior in bone tissue engineering, and the development of biomaterials and bone tissue engineering. We also highlight several latest advancements in bone tissue engineering. Finally, a brief summary of the bone tissue engineering challenges in the field are provided with suggestions for future research directions.

Fabrication of superparamagnetic nanofibrous poly(l-lactic acid)/γ-Fe2O3 microspheres for cell carriers: FABRICATION OF SUPERPARAMAGNETIC NANOFIBROUS PLLA MICROSPHERES

Nanofibrous poly(l-lactic acid) (PLLA) microspheres are extensively studied to be used as cell carriers in the field of tissue engineering because the unique structure can promote cell proliferation and migration. But as injectable scaffold materials, PLLA microspheres easily run off to the soft tissue space because of the lack of cohesive force. It will affect the treatment efficiency and even cause additional inflammatory response. In order to overcome this disadvantage, superparamagnetic γ-Fe2 O3 nanoparticles assisted with oxidative polymerization of dopamine were used for surface modification of PLLA microspheres in this study. The results showed that this surface modification had no obvious cytotoxicity, and the modified microspheres possessed the ability to carry seed cells to controllably move to the defect sites with the guidance of magnetic field, which may be able to increase the repair efficiency. Moreover, the characteristic nanofibrous structure was not destroyed after modification, which was able to promote biological activity of cells. This work provides a novel way to produce superparamagnetic nanofibrous microspheres designed for cell microcarriers.

Fabrication and Characterization of Silk Microfiber-Reinforced Methacrylated Gelatin Hydrogel with Turnable Properties

Abstract Despite considerable research effort, the natural hydrogels presently available for tissue engineering suffer from several major drawbacks, one of the significant issue is their poor mechanical strength which are unable to satisfy some mechanical requirements for successful outcomes. Herein, to mimic the composition and structure of the natural extracellular matrix, the micron-sized silk fibers obtained by alkaline hydrolysis were used as a reinforcement phase in a GelMA hydrogel, resulting in a material with significantly greater stiffness than pure GelMA hydrogel alone. In addition, the hydrogel demonstrated tunable compressive strength, swelling capacity, and degradation properties based on the silk fiber length. Experiments with cells indicated that MC3T3-E1 pre-osteoblasts quickly adhered to and proliferated on the surface of the composite hydrogels, as revealed by FDA/PI staining and CCK-8 assays. In addition, various cellular responses, including cell adhesion, changes in cellular morphology and cell proliferation behavior, occurred on the composite hydrogel and varied with fiber length. Overall, this study introduces a series of fiber-reinforced, tunable composite hydrogels that could be useful for various tissue engineering applications.

The effect of biomaterial's properties on the bone cell functions

In the bone tissue engineering, the new bone tissue regeneration is managed by these bone cells under tightly controlled microenvironment including both chemical and mechanical stimuli. In this paper, we summarize an overview of published studies on the understandings of the cells response to environmental stimuli. Specific attention has been focused on the effect of biomaterials chemical and physical properties on the bone cell functions. Finally, we advance the fluorescent living cell imaging method is expected to reveal the interaction mechanisms between cells and materials and the osteogenic mechanisms of living stem cell at the molecular level, and we highlighted the directions for future research.