Black phosphorus thermosensitive hydrogels loaded with bone marrow mesenchymal stem cell-derived exosomes synergistically promote bone tissue defect repair.

The osteogenic function of mesenchymal stem cells (MSCs) is mainly attributed to the paracrine effect of extracellular vesicles. MSC-derived exosomes are interesting candidates as biopharmaceuticals for drug delivery and for the engineering of biologically functionalized materials, and have emerged as cell-free regenerative medicine in recent years. In this study, bone marrow mesenchymal stem cell (BMSC)-derived exosomes were loaded with photothermal material layered black phosphorus (BP) modified poly(N-isopropylacrylamide) (PNIPAAm) thermosensitive hydrogels to explore their effects on bone defect repair. In vitro, it was confirmed that the local high heat of nano-BP irradiated using a near-infrared (NIR) laser could trigger the reversible cascade reaction of hydrogels, and that the mechanical contraction of hydrogels led to the controllable release of a large number of exosomes along with the release of water molecules. Furthermore, in vitro investigations demonstrated that BP hydrogels loaded with BMSC-derived exosomes had favourable biocompatibility and could promote the proliferation and osteogenic differentiation of MSCs. Experiments conducted in vivo confirmed that this system significantly promoted bone regeneration. Therefore, the results of our study indicated that the nanoplatform based on BP thermosensitive hydrogels could provide a new clinical treatment strategy for controlled release and on-demand drug delivery, while the cell-free system composed of BMSC-derived exosomes had great application potential in bone tissue repair with the synergism of BP.

An optimized nonlinear generalized predictive control for steam temperature in an ultra supercritical unit.

The optimize control of the ultra supercritical (USC) unit has been a major concern in power industry. The intermediate point temperature process is a multi-variable system with strong nonlinearity, large scale and great delay, which greatly affects the safety and economy of the USC unit. Generally, it is difficult to realize effective control by using conventional methods. This paper presents a nonlinear generalized predictive control based on a composite weighted human learning optimization network (CWHLO-GPC) to improve the control performance of intermediate point temperature. Based on the characteristics of the onsite measurement data, the heuristic information is incorporated into the CWHLO network, and expressed by different local linear models. Then, global controller is elaborately constituted based on a scheduling program inferred from the network. Compared with classical generalized predictive control (GPC), the non-convex problem is effectively solved by introducing CWHLO models into the convex quadratic program (QP) routine of local linear GPC. Finally, detailed analysis on set point tracking and interference resisting via simulation is addressed to illustrate the efficiency of the proposed strategy.

Pyroptosis-related gene-based prognostic signature for predicting the overall survival of oral squamous cell carcinoma patients.

Purpose: Oral squamous cell carcinoma (OSCC) is the most common oral cancer worldwide. Pyroptosis is a type of programmed cell death mediated by caspase, accompanied by an inflammatory response, and plays an important role in cancer progression. The purpose of this study was to explore and identify potential biomarkers and further elucidate the potential role of cell pyroptosis in OSCC. Methods: We regarded the samples from The Cancer Genome Atlas database as a training dataset, screened differentially expressed genes (DEGs), and further screened out OSCC phenotypic characteristic genes by using weighted gene co-expression network analysis. The analysis of 42 known pyroptosis-related genes showed that Psuch genes were widely expressed, mutated, and methylated in OSCC samples. Results: Through correlation analysis, we identified our OSCC pyroptosis-related DEGs. To further evaluate the prognostic value of pyroptosis-related regulators, we constructed a seven gene-based prognostic signature using Cox univariate analysis and least absolute shrinkage and selection operator Cox regression analysis. Meanwhile, we found that patients in the low-risk group had higher immune infiltration. Moreover, our results also indicated significant differences in sensitivity to cisplatin and gefitinib between the high-risk and low-risk groups. Conclusion: Our study successfully constructed the pyroptosis-related prognostic signature, which might play a potential prediction role in OSCC prognosis. Our findings also suggested that pyroptosis-related regulators might be novel biomarkers for tumor diagnosis and treatment in OSCC.

Early loading of splinted implants in posterior mandible: Three-year results of a prospective multicenter study.

OBJECTIVE: To evaluate the clinical outcomes of an early loading protocol of splinted implants with a fluoride-modified nanostructure surface and a tapered apex design for the therapy of posterior partial edentulism of mandible. MATERIALS AND METHODS: One hundred and seven implants were placed in the mandible of 45 subjects at three centres in China. A minimum of two and a maximum of three implants were placed in an edentulous region using a one-stage protocol. Each subject received a screw-retained, splinted and fixed permanent prosthesis 6-8 weeks after surgery. Marginal bone level (MBL) change, implant survival and soft tissue health were assessed at 6, 12, 24 and 36 months after loading. A total of 92 implants from 40 subjects were recalled and investigated in this clinical trial. RESULTS: After three-year loading, the survival rate of implant was 100%. On a subject level, there was a mean (±SD) marginal bone gain of 0.23 ± 0.48 mm at 36-month recall and the change in MBL was statistically significant (p = .00061) compared with time of loading. On an implant level, the change in MBL was statistically significant (p = .03914, p = .01494, p = .00000) at 12, 24 and 36 months of loading compared with time of loading. CONCLUSION: Three-year data indicate that early loading protocol of splinted implants with a fluoride-modified nanostructure surface and a tapered apex design is feasible and safe for the therapy of partial edentulism in posterior mandible, which may contribute to bone gain when the suitable occlusal load and oral hygiene maintenance are kept.

Functionalization of Silk Fibroin Electrospun Scaffolds via BMSC Affinity Peptide Grafting through Oxidative Self-Polymerization of Dopamine for Bone Regeneration.

Electrospun scaffolds have been broadly studied to enhance bone regeneration because of the ability to simulate the structure and biological functions of the extracellular matrix. Polydopamine (PDA) is used to coat various surfaces at a slightly basic pH (8-8.5) and spontaneously reacts with nucleophilic functional groups. It is suitable for surface modifications of scaffolds correlated with bone formation. E7 is a newly discovered peptide with specific affinity for bone marrow mesenchymal stem cells (BMSCs). It can be useful for recruiting stem cells. Here, electrospun silk fibroin (SF) scaffolds were fabricated, and PDA was used for surface modification followed by grafting E7 (SF-PDA-E7). These composite SF-PDA-E7 electrospun scaffolds improved hydrophilicity, facilitated cell proliferation and adhesion, and boosted the osteogenic differentiation of BMSCs by creating osteoinduction conditions under the synergistic effects of PDA and E7. Moreover, the scaffolds showed high efficiency for recruiting BMSCs induced by E7 both in vitro and in vivo, which was associated with the SDF-1α/CXCR4 axis and the p38, extracellular signal-related kinase, and Akt signal transduction pathways. These functionalized electrospun scaffolds promoted regeneration of bone in the rat calvarial bone defect model. In general, this study verified that PDA could be a simple and efficient method for surface modification, and E7-grafted PDA-modified SF electrospun scaffolds were suitable for bone tissue engineering.

Enhanced bone regeneration of the silk fibroin electrospun scaffolds through the modification of the graphene oxide functionalized by BMP-2 peptide.

INTRODUCTION: Bone tissue engineering has become one of the most effective methods to treat bone defects. Silk fibroin (SF) is a natural protein with no physiological activities, which has features such as good biocompatibility and easy processing and causes minimal inflammatory reactions in the body. Scaffolds prepared by electrospinning SF can be used in bone tissue regeneration and repair. Graphene oxide (GO) is rich in functional groups, has good biocompatibility, and promotes osteogenic differentiation of stem cells, while bone morphogenetic protein-2 (BMP-2) polypeptide has an advantage in promoting osteogenesis induction. In this study, we attempted to graft BMP-2 polypeptide onto GO and then bonded the functionalized GO onto SF electrospun scaffolds through electrostatic interactions. The main purpose of this study was to further improve the biocompatibility of SF electrospun scaffolds, which could promote the osteogenic differentiation of bone marrow mesenchymal stem cells and the repair of bone tissue defects. MATERIALS AND METHODS: The successful synthesis of GO and functionalized GO was confirmed by transmission electron microscope, X-ray photoelectron spectroscopy, and thermogravimetric analysis. Scanning electron microscopy, atomic force microscopy, mechanical test, and degradation experiment confirmed the preparation of SF electrospun scaffolds and the immobilization of GO on the fibers. In vitro experiment was used to verify the biocompatibility of the composite scaffolds, and in vivo experiment was used to prove the repairing ability of the composite scaffolds for bone defects. RESULTS: We successfully fabricated the composite scaffolds, which enhanced biocompatibility, not only promoting cell adhesion and proliferation but also greatly enhancing in vitro osteogenic differentiation of bone marrow stromal cells using either an osteogenic or non-osteogenic medium. Furthermore, transplantation of the composite scaffolds significantly promoted in vivo bone formation in critical-sized calvarial bone defects. CONCLUSION: These findings suggested that the incorporation of BMP-2 polypeptide-functionalized GO into chitosan-coated SF electrospun scaffolds was a viable strategy for fabricating excellent scaffolds that enhance the regeneration of bone defects.

Biocompatible silk/calcium silicate/sodium alginate composite scaffolds for bone tissue engineering.

Scaffolds are crucial for bone tissue engineering since their compositions and properties could significantly affect the seeded cells' behavior. In this study, we developed an interpenetrating network hydrogel by utilizing Ca2+ from calcium silicate (CS) to simultaneously crosslink silk fibroin (SF) and sodium alginate (SA). Afterwards, the hydrogels were lyophilized to obtain scaffolds and systematically evaluated by physical characterizations, in vitro cytocompatibility and alkaline phosphatase (ALP) assay. We found that CS inside the porous structure of SF/CS/SA scaffolds could remarkably enhance hydrophilicity, degradation, compression resistance, bioactivity and pH of SF/CS/SA scaffolds. Scaffolds with CS concentrations of 25% and 12% (25/CS and 12/CS) could dominantly stimulate proliferation of bone marrow stromal cells (BMSCs). Besides, BMSCs cultured with 25/CS and 12/CS scaffolds showed high ALP activity, respectively. Consequently, this study suggested SF/CS/SA scaffolds possess potential in non-loading bone tissue engineering application.

Time-Phase Sequential Utilization of Adipose-Derived Mesenchymal Stem Cells on Mesoporous Bioactive Glass for Restoration of Critical Size Bone Defects.

The effective transportation of oxygen, nutrients, and metabolic wastes through new blood vessel networks is key to the survival of engineered constructs in large bone defects. Adipose-derived mesenchymal stem cells (ADSCs), which are regarded as excellent candidates for both bone and blood vessel engineering, are the preferred option for the restoration of massive bone defects. Therefore, we propose to induce ADSCs into osteogenic and endothelial cells differently. A modified hierarchical mesoporous bioactive glass (MBG) scaffold with an enhanced compressive strength was constructed and prevascularized by seeding with endothelial-induced ADSCs (EI-ADSCs). The prevascularized scaffolds were combined with osteogenically induced ADSCs (OI-ADSCs) to repair critical-size bone defects. To validate the angiogenesis of the prevascularized MBG scaffolds in vivo, green fluorescent protein (GFP) was used to label EI-ADSCs. The labeled EI-ADSCs were demonstrated to survive and participate in vascularization at day 7 after subcutaneous implantation in nude mice by double immunofluorescence staining of CD31 and GFP. Regarding the restoration of critical size bone defects, early angiogenesis of rat femur plug defects was evaluated by perfusion of Microfil after 3 weeks. Compared to nonvascularized MBG carrying OI-ADSCs (MBG/OI-ADSCs) and non-cell-seeded MBG scaffolds, the prevascularized MBG carrying OI-ADSCs (Pv-MBG/OI-ADSCs) showed enhanced angiogenesis on the surface and interior. Through dynamic bone formation analysis with sequential fluorescent labeling and Van Gieson's picro-fuchsin staining, we found that the Pv-MBG/OI-ADSCs exhibited the highest mineral deposition rate after surgery, which may be contributed by rapid vascular anastomosis facilitating increased survival of the seeded OI-ADSCs and by the recruitment function for bone mesenchymal stem cells. Therefore, the strategy of time-phase sequential utilization of ADSCs on MBG scaffolds is a practical design for the repair of massive bone defects.

PLGA film/Titanium nanotubues as a sustained growth factor releasing system for dental implants.

Ti-based implants sometimes fail to integrate with surrounding bone tissue due to insufficiency of new bone formation and surface bonding. To overcome this problem, this research focused on establishing a sustained bone growth factor delivery system by applying anodized TiO2 nanotube arrays and PLGA film on the titanium implant surface. TiO2 nanotube arrays were made by anodic oxidation method, and were then filled with rhBMP2 by vacuum freeze-drying. Next, PLGA was deposition on the surface of this material. The designed system was characterized, pharmacokinetic release rate of rhBMP2 was determined. Adhesion, proliferation, and differentiation activity of osteoblasts cultured on the new surfaces and traditional titanium surfaced were compared. SEM showed that a surface of TiO2 nanotube arrays were successfully generated. PLGA membranes of 50 nm, 250 nm, 800 nm thickness were successfully deposited on the surfaces of TiO2 nanotube layers by using 1%, 3%, 10% PLGA solutions. PLGA film of 250 nm thickness showed ideally controlled release of rhBMP2, lasting for 4 weeks. Furthermore, 250 nm thickness PLGA film improved osteoblast adhesion, proliferation, and levels of alkaline phosphatase. In conclusion, the PLGA film / TiO2 nanotube growth factor delivery system can effectively sustain the release of rhBMP-2, and promote proliferation and differentiation of MC3T3-E1 osteoblasts.

Alendronate delivery on amino modified mesoporous bioactive glass scaffolds to enhance bone regeneration in osteoporosis rats.

The regeneration capacity of osteoporotic bones is generally lower than that of normal bones. Nowadays, alendronate (AL) are orally administrated for osteoporosis due to the inhibition of bone resorption. However, systemic administration of AL is characterized by extremely low bioavailability and high toxicity. In this study, the amino-modified mesoporous bioactive glass scaffolds (N-MBGS) were fabricated by a simple powder processing technique as a novel drug-delivery system for AL. The effects of AL on the osteogenic differentiation of bone mesenchymal stem cells derived from ovariectomized rats (rBMSCs-OVX) were first estimated. The loading efficiency and release kinetics of AL on N-MBGS were investigated in vitro and the osteogenesis of AL-loaded N-MBGS in rat calvarial defect model was detected by micro-CT measurements and the histological assay. Our results revealed that proper concentration of AL significantly promoted osteogenic differentiation of rBMSCs-OVX. The amount and delivery rate of AL were greatly improved through amino modification. Additionally, scaffolds with AL showed better bone formation in vivo, especially for the N-MBGS group. Our results suggest that the novel amino-modified MBGS are promising drug-delivery system for osteoporotic bone defect repairing or regeneration. The experimental schematic of the novel amino-modified MBGS as a promising drug-delivery system for osteoporotic bone regeneration.

The osteoimmunomodulatory properties of MBG scaffold coated with amino functional groups.

Mesoporous bioactive glass (MBG) is a good scaffold for bone regeneration. In this study, amino functionalized MBG (N-MBG) was used as a model scaffold to examine the effect of the scaffold to bone marrow stromal cells (BMSCs) and macrophages. The MTT results revealed that the proliferation of BMSCs from ovariectomized rabbits was enhanced by N-MBG. Compared to the control group, the expression of osteogenic genes was significantly enhanced by N-MBG, which was related to CaSR pathway. Meanwhile, the anti-inflammatory cytokines (interleukin-10 and arginase-1) were also upregulated by N-MBG stimulation compared with MBG. Furthermore, the amino functionalization of MBG resulted in an increase in the pH value of the material extract. Interestingly, the formation of TRAP+ multinuclear cells was inhibited by the slightly alkaline extract to a certain extent, which reasonably explained the increase in TRAP+ multinuclear cells after adjusting the pH value of N-MBG extract. In vivo, the areas of new bone formation in the maxillary sinus floor elevation were increased in the N-MBG/BMSCs group with less TRAP+ multinuclear cells compared with the MBG/BMSCs group. These findings provided valuable insight that the osteogenic ability of MBG scaffold could be enhanced by amino functionalization due to coordinate BMSCs and macrophages differentiation.

Fabrication of large-pore mesoporous Ca-Si-based bioceramics for bone regeneration.

Our previous study revealed that mesoporous Ca-Si-based materials exhibited excellent osteoconduction because dissolved ions could form a layer of hydroxycarbonate apatite on the surface of the materials. However, the biological mechanisms underlying bone regeneration were largely unknown. The main aim of this study was to evaluate the osteogenic ability of large-pore mesoporous Ca-Si-based bioceramics (LPMSCs) by alkaline phosphatase assay, real-time PCR analysis, von Kossa, and alizarin red assay. Compared with large-pore mesoporous silica (LPMS), LPMSCs had a better effect on the osteogenic differentiation of dental pulp cells. LPMSC-2 and LPMSC-3 with higher calcium possessed better osteogenic abilities than LPMSC-1, which may be related to the calcium-sensing receptor pathway. Furthermore, the loading capacity for recombinant human platelet-derived growth factor-BB was satisfactory in LPMSCs. In vivo, the areas of new bone formation in the calvarial defect repair were increased in the LPMSC-2 and LPMSC-3 groups compared with the LPMSC-1 and LPMS groups. We concluded that LPMSC-2 and LPMSC-3 possessed both excellent osteogenic abilities and satisfactory loading capacities, which may be attributed to their moderate Ca/Si molar ratio. Therefore, LPMSCs with moderate Ca/Si molar ratio might be potential alterative grafts for craniomaxillofacial bone regeneration.

The response of human osteoblasts, epithelial cells, fibroblasts, macrophages and oral bacteria to nanostructured titanium surfaces: a systematic study.

Nanotopography modification is a major focus of interest in current titanium surface design; however, the influence of the nanostructured surface on human cell/bacterium behavior has rarely been systematically evaluated. In this study, a homogeneous nanofiber structure was prepared on a titanium surface (Nano) by alkali-hydrothermal treatment, and the effects of this Nano surface on the behaviors of human MG-63 osteoblasts, human gingival epithelial cells (HGECs) and human gingival fibroblasts (HGFs) were evaluated in comparison with a smooth titanium surface (Smooth) by polishing and a micro-rough titanium surface (Micro) by sandblasting and acid etching. In addition, the impacts of these different surface morphologies on human THP-1 macrophage polarization and Streptococcus mutans attachment were also assessed. Our findings showed that the nanostructured surface enhanced the osteogenic activity of MG-63 cells (Nano=Micro>Smooth) at the same time that it improved the attachment of HGECs (Nano>Smooth>Micro) and HGFs (Nano=Micro>Smooth). Furthermore, the surface with nanotexture did not affect macrophage polarization (Nano=Micro=Smooth), but did reduce initial bacterial adhesion (Nano

Functionalized mesoporous bioactive glass scaffolds for enhanced bone tissue regeneration.

Mesoporous bioactive glass (MBG), which possesses excellent bioactivity, biocompatibility and osteoconductivity, has played an important role in bone tissue regeneration. However, it is difficult to prepare MBG scaffolds with high compressive strength for applications in bone regeneration; this difficulty has greatly hindered its development and use. To solve this problem, a simple powder processing technique has been successfully developed to fabricate a novel type of MBG scaffold (MBGS). Furthermore, amino or carboxylic groups could be successfully grafted onto MBGSs (denoted as N-MBGS and C-MBGS, respectively) through a post-grafting process. It was revealed that both MBGS and the functionalized MBGSs could significantly promote the proliferation and osteogenic differentiation of bMSCs. Due to its positively charged surface, N-MBGS presented the highest in vitro osteogenic capability of the three samples. Moreover, in vivo testing results demonstrated that N-MBGS could promote higher levels of bone regeneration compared with MBGS and C-MBGS. In addition to its surface characteristics, it is believed that the decreased degradation rate of N-MBGS plays a vital role in promoting bone regeneration. These findings indicate that MBGSs are promising materials with potential practical applications in bone regeneration, which can be successfully fabricated by combining a powder processing technique and post-grafting process.

Selective responses of human gingival fibroblasts and bacteria on carbon fiber reinforced polyetheretherketone with multilevel nanostructured TiO2.

The long-term success of dental implants relies not only on stable osseointegration but also on the integration of implant surfaces with surrounding soft tissues. In our previous work, titanium plasma immersion ion implantation (PIII) technique was applied to modify the carbon-fiber-reinforced polyetheretherketone (CFRPEEK) surface, constructing a unique multilevel TiO2 nanostructure thus enhancing certain osteogenic properties. However, the interactions between the modified surface and soft-tissue cells are still not clear. Here, we fully investigate the biological behaviors of human gingival fibroblasts (HGFs) and oral pathogens on the structured surface, which determine the early peri-implant soft tissue integration. Scanning electron microscopy (SEM) shows the formation of nanopores with TiO2 nanoparticles embedded on both the sidewall and bottom. In vitro studies including cell adhesion, viability assay, wound healing assay, real-time PCR, western blot and enzyme-linked immunosorbent assay (ELISA) disclose improved adhesion, migration, proliferation, and collagen secretion ability of HGFs on the modified CFRPEEK. Moreover, the structured surface exhibits sustainable antibacterial properties towards Streptococcus mutans, Fusobacterium nucleatum and Porphyromonas gingivalis. Our results reveal that the multilevel TiO2 nanostructures can selectively enhance soft tissue integration and inhibit bacterial reproduction, which will further support and broaden the adoption of CFRPEEK materials in dental fields.

Large-pore mesoporous Ca-Si-based bioceramics with high in vitro bioactivity and protein adsorption capability for bone tissue regeneration.

Mesoporous Ca-Si-based bioceramics represented by mesoporous bioactive glasses (MBG) have attracted much attention in the field of bone tissue regeneration due to their excellent bioactivity, biocompatibility and osteoconductivity. However, the small mesopores (<7 nm) have greatly hindered their ability to encapsulate macromolecular proteins with ability to significantly induce bone growth. To solve this problem, a novel type of large-pore mesoporous silica (LPMS) was first synthesized using a simple one-step method at high temperatures. Solid reactions were then carried out to synthesize large-pore mesoporous Ca-Si-based bioceramics (LPMSCs) using LPMS as both the template and silicon source, and Ca(NO3)2 as the calcium source. The prepared LPMSCs not only displayed large-diameter (>15 nm) mesopores, but also high in vitro bioactivities. Bovine serum albumin (BSA) was used as a model protein to evaluate the adsorption capacity and release properties of our synthesized products for proteins. The results demonstrated that BSA could be encapsulated into the LPMSCs, with a slow and sustained release behaviour. Furthermore, in vitro cell tests showed the LPMSCs to have a favourable effect on proliferation and osteogenetic differentiation. These findings indicate that LPMSCs could be used as a bioactive protein adsorption and release system for preparation of bone implant materials.

Dynamic model for controller design of condensate throttling systems.

Improving the load adjustment rate of coal-fired power plants in China is very important because of grid load fluctuations and the construction of new large-scale power plants connected to the country's power grid. In this paper, a new application of condensate throttling system for rapid load adjustment is proposed on the basis of the characteristics of turbine-stored energy. To ensure effective and safe operation of the condensate throttling system, a non-linear control model is derived through reasonable simplifications of fundamental physical laws, and the model parameters are identified using experimental data from a 660 MW supercritical coal-fired power plant. The model outputs are compared with actual measured data for different unit loads. Results show that the established model's responses strongly correlate with the actual unit's responses and can be used for controller design.

Strontium delivery on topographical titanium to enhance bioactivity and osseointegration in osteoporotic rats.

Osseointegration remains a major clinical challenge in osteoporotic patients. Strontium (Sr) has been shown to be a significant therapy to favor bone growth by both increasing new bone formation and reducing bone resorption. In this study, we attempt to chemically functionalize Ti implants by micro-arc oxidation, alkali treatment and ion exchange. This functionalized Ti surface possessed a hierarchical topography with Sr incorporation, which can release Sr ions at a slow rate. To our knowledge, this work is the first to use this type of Sr-doped Ti surface to address osteoporotic bone mesenchymal stem cells (BMSCs) in the dual directions of bone regeneration, bone formation and bone resorption. The modified surface was demonstrated to remarkably enhance the adhesion, spreading, and osteogenic differentiation of BMSCs in vitro. The effect of the wash-out solution from various groups on osteoporotic BMSCs was also investigated. The Sr-doped group can improve the ALP activity and osteogenic gene expression. Moreover, the Sr-doped group and the wash-out solution show the most inhibition in osteoclast formation and maturation. Furthermore, the increased bioactivity of the hierarchical structure was also confirmed with the ovariectomized rat femur model in vivo. The outcome of fluorescence labeling, histology and histomorphometric analysis demonstrated a significant promotion of osseointegration in ovariectomized rats. Altogether, the experimental data indicate that the fabrication of a Sr-doped hierarchical Ti surface is a meaningful attempt to incorporate the Sr nutrient element into Ti-based implants, and it is expected to be exploited in developing better osseointegration for osteoporotic patients.

Effect of nano-structured bioceramic surface on osteogenic differentiation of adipose derived stem cells.

Tissue engineering strategies to construct vascularized bone grafts potentially revolutionize the treatment of massive bone loss. The surface topography of the grafts plays critical roles on bone regeneration, while adipose derived stem cells (ASCs) are known for their capability to promote osteogenesis and angiogenesis when applied to bone defects. In the present study, the effects of hydroxyapatite (HAp) bioceramic scaffolds with nanosheet, nanorod, and micro-nano-hybrid (the hybrid of nanorod and microrod) surface topographies on attachment, proliferation and osteogenic differentiation, as well as the expression of angiogenic factors of rat ASCs were systematically investigated. The results showed that the HAp bioceramic scaffolds with the micro-/nano-topography surfaces significantly enhanced cell attachment and viability, alkaline phosphatase (ALP) activity, and mRNA expression levels of osteogenic markers and angiogenic factors of ASCs. More importantly, the biomimetic feature of the hierarchical micro-nano-hybrid surface topography showed the highest stimulatory effect. The activation in Akt signaling pathway was observed in ASCs cultured on HAp bioceramics with nanorod, and micro-nano-hybrid surface topographies. Moreover, these induction effects could be repressed by Akt signaling pathway inhibitor LY294002. Finally, the in vivo bone regeneration results of rat critical-sized calvarial defect models confirmed that the combination of the micro-nano-hybrid surface and ASCs could significantly enhance both osteogenesis and angiogenesis as compared with the control HAp bioceramic scaffold with traditional smooth surface. Our results suggest that HAp bioceramic scaffolds with micro-nano-hybrid surface can act as cell carrier for ASCs, and consequently combine with ASCs to construct vascularized tissue-engineered bone.

rhPDGF-BB promotes proliferation and osteogenic differentiation of bone marrow stromal cells from streptozotocin-induced diabetic rats through ERK pathway.

Management of nonunion fracture and massive segmental bone defects in diabetes remains a challenging clinical problem. Bone marrow stromal cells (BMSCs) are crucial for bone remodeling and hold promise for bone regeneration. However, we have showed previously that diabetes can affect the proliferation and osteogenic potential of BMSCs adversely and a strategy to attenuate the impaired functions of BMSCs is required. Platelet-derived growth factor-BB (PDGF-BB) plays an important role in bone formation. However, little information is available about its effect on diabetic BMSCs. In this study, BMSCs were isolated from streptozotocin-induced diabetic rats. After treatment with recombinant human PDGF-BB (rhPDGF-BB), diabetic BMSCs demonstrated enhanced cell proliferation and osteogenic differentiation based on increased expressions of osteogenic genes (Runx2, alkaline phosphatase, and osteocalcin) and Runx2 protein, as well as upregulated alkaline phosphatase activity and mineralization. Furthermore, blocking extracellular signal regulated kinase (ERK) pathway by inhibitor PD98059 repressed the enhanced proliferation and osteogenic differentiation in diabetic BMSCs induced by rhPDGF-BB. Together, these results indicated that rhPDGF-BB stimulates proliferation and osteogenic differentiation partially through ERK pathway in diabetic BMSCs. Therefore, modulation of diabetic BMSCs could augment BMSCs function affected by diabetes and holds significance for future strategies to treat diabetic bone complications.