Search

Due to the lower regeneration capacity of the osteoporotic bone, the treatment of osteoporotic defects is extremely challenging in clinics. In this study, strontium-doped bioactive glass nanoparticles loaded with sodium alendronate (ALN), namely A-SrBG, were incorporated into the poly(ether-ether-ketone) matrix to fabricate a bioactive composite scaffold (ASP), which was expected to both inhibit bone resorption and promote bone regeneration. The results showed that such a composite scaffold with interconnected macropores (200-400 μm) could release Ca

Polymeric biocomposites display some advantages over metal or ceramic biomaterials, and are regarded as a promising candidate for artificial joint application. Herein, molybdenum disulfide (MD) nanosheets were prepared and incorporated into polyimide (PI) to form MD/PI composites with a MD content of 20 wt% (PM20) and 40 wt% (PM40). The results revealed that incorporation of MD nanosheets obviously improved the tribological performances, surface properties (

As an implantable biomaterial, polyetherketoneketone (PEKK) exhibits good mechanical strength but it is biologically inert while tantalum (Ta) possesses outstanding osteogenic bioactivity but has a high density and elastic modulus. Also, silicon nitride (SN) has osteogenic and antibacterial activity. In this study, a microporous surface containing both SN and Ta microparticles on PEKK (STP) exhibiting excellent osteogenic and antibacterial activity was created by sulfonation. Compared with sulfonated PEKK (SPK) without microparticles, the surface properties (roughness, surface energy, hydrophilicity and protein adsorption) of STP significantly increased due to the SN and Ta particles presence on the microporous surface. In addition, STP also exhibited outstanding antibacterial activity, which inhibited bacterial growth in vitro and prevented bacterial infection in vivo because of the presence of SN particles. Moreover, the microporous surface of STP containing both SN and Ta particles remarkably induced response (e.g., proliferation and differentiation) of rat bone mesenchymal stem (rBMS) cells in vitro. Furthermore, STP significantly improved new bone regeneration and osseointegration in vivo. Regarding the induction of cellular response in vitro and improvement of osseointegration in vivo, the microporous surface containing Ta was better than the surface with SN particles. In conclusion, STP with optimized surface properties activated cellular responses in vitro, enhanced osseointegration and prevented infection in vivo. Therefore, STP possessed the dual biofunctions of excellent osteogenic and antibacterial activity, showing great potential as a bone substitute., Graphical abstract Image 1, Highlights •Microporous surface containing SN/Ta microparticles on PEKK (STP) was created. •Surface performances (e.g., roughness) of STP were significantly increased. •STP exhibited antibacterial activity in vitro and prevented infection in vivo. •STP remarkably induced response of bone mesenchymal stem cells in vitro. •STP obviously improved bone regeneration and osseointegration in vivo.

BGNs-Man/Ag can target infected macrophages and kill intracellular S. aureus via activating their autonomous defense.

Polyetherketoneketone (PEKK) exhibits admirable biocompatibility and mechanical performances but bioinert while tantalum (Ta) possesses excellent osteogenesis and osseointegration but high elastic modulus and density, and processing is too difficult and expensive. In the present study, combining of the advantages of both PEKK and Ta, implantable composites of PEKK/Ta were fabricated by blending PEKK with Ta microparticles of 20 v% (PT20) and 40 v% (PT40) content. In comparison with PT20 and PEKK, the surface hydrophilicity, surface energy, roughness and proteins adsorption as well as mechanical performances of PT40 significantly increased because of the higher Ta particles content in PEKK. Furthermore, PT40 exhibited the mechanical performances (e.g., compressive strength and modulus of elasticity) close to the cortical bone of human. Compared with PT20 and PEKK, PT40 with higher Ta content remarkably enhanced the responses (including adhesion, proliferation and osteogenic differentiation) of MC3T3-E1 cells in vitro. Moreover, PT40 markedly improved bone formation as well as osseointegration in vivo. In short, incorporation of Ta microparticles into PEKK created implantable composites with improved surface performances, which played key roles in stimulating cell responses/bone formation as well as promoting osseointegration. PT40 might have great potential for bear-loading bone substitute., Graphical abstract Image 1, Highlights • Bioactive composites of PEKK/Ta (PT) were fabricated by melt blending. • Compressive strength, bending strength and elastic modulus significantly increased with Ta content increasing. • Hydrophilicity, surface energy, roughness and protein adsorption remarkably enhanced with Ta content increasing. • PT40 significantly promoted the responses (adhesion, proliferation and osteogenic differentiation) of MC3T3-E1 cells. • PT40 obviously accelerated osteogenesis and osseointegration in vivo.

Implanted materials with both osteogenic and antibacterial functions are promising for facilitating osteointegration and preventing infection for orthopedic applications. In this work, we synthesized flower-like molybdenum disulfide (fMD) submicro-spheres containing nanosheets, which were incorporated onto the microporous surface of polyimide (PI)

Nanoporous tantalum pentoxide (NTP) particles with a pore size of about 10 nm were synthesized and blended with polyetheretherketone (PEEK) to fabricate a PEEK/NTP composite (PN). Subsequently, PN was treated by concentrated sulfuric acid to create a microporous surface (pore size of around 2 μm) on sulfonated PN (SPN), which formed a hierarchical micro & nanoporous surface. Compared with PN, the porous surface of SPN exhibited higher roughness, hydrophilicity, and surface energy. In addition, genistein (GT) was loaded into the porous surface of SPN (SPNG), which showed high GT loading capacity and sustained release of GT into phosphate buffered saline (PBS). Moreover, SPNG revealed excellent antibacterial activity, which inhibited bacterial (E. coli and S. aureus) growth in vitro due to the synergistic effects of both sulfonic acid (SO3H) groups and the sustained release of GT. Compared with PN, SPN significantly improved the adhesion, proliferation, and osteogenic differentiation of bone mesenchymal stem cells in vitro. Moreover, compared with SPN, SPNG further enhances the cell responses. Compared with PN, SPN remarkably improved bone formation and osteointegration in vivo. Furthermore, compared with SPN, SPNG further enhanced the osteointegration. In short, SPNG with a micro & nanoporous surface, SO3H groups, and the sustained release of GT exhibited antibacterial activity and accelerated osteointegration, which would have tremendous potential as drug-loaded implants for bone substitute.

Colon cancer is a common malignant tumor in the digestive tract, with relatively high rates of morbidity and mortality. It is the third most common type of tumor in the world. The effective treatment of advanced colon cancer is limited, so it is particularly important to study the new pathogenesis of colon cancer. Ferroptosis is a nonapoptotic regulated cell death mode driven by iron-dependent lipid peroxidation, a process which has been discovered in recent years. Autophagy involves lysosomal degradation pathways that promote or prevent cell death. High levels of autophagy are associated with ferroptosis, but a clear association has not yet been made between ferroptosis and autophagy in colon cancer. Through the analysis of transcriptome expression profiling data in colon cancer, we obtained the common upregulated genes and downregulated genes by recording the intersection of the differentially expressed genes in each dataset. Solute Carrier Family 2 Member 1 (SLC2A1) was identified by combining autophagy genes obtained from GeneCards and ferroptosis genes obtained from FerrDb. In order to explore the clinical significance and prognostic value of SLC2A1, we utilized massive databases to conduct an in-depth exploration of the methylation of SLC2A1, and we also investigated the differences in immune infiltration between tumor and normal tissues. We found that there are abundant methylation sites in SLC2A1 and that the methylation of SLC2A1 is correlated with the immunosuppression of tumor tissue. We discovered that during the induction of environmental factors, the transcription and methylation levels of SLC2A1 were greatly increased, autophagy and ferroptosis were inhibited, and the immune system was defective, resulting in a poor prognosis for patients. These results suggest that the autophagy and ferroptosis-related gene SLC2A1 is involved in the tumor immune regulation of colon cancer, and SLC2A1 may become a new therapeutic target for colon cancer.

Lymph node metastasis is an independent risk factor for survival of gastric cancer, but the underlying mechanism remains unclear. Adenosine (ADO) plays an immune regulation role through binding to adenosine receptors (ARs), especially A2AR. PD-L1 plays a key role in the immune escape of tumor. However, the expression of these two indicators in lymph nodes of gastric cancer has been rarely studied. Lymph node samples of 95 gastric cancer patients, including metastatic lymph nodes and matched non-metastatic lymph nodes were collected. Expression of A2AR and PD-L1 were detected with immunohistochemistry. The relationships among their expression with clinicopathological factors and prognostic parameters were analyzed as well. The expressions of A2AR and PDL-1 were both higher in metastatic lymph node than matched non-metastatic lymph node. The expression of A2AR in metastatic lymph nodes of gastric cancer was positively correlated with PD-L1. Positive expressions of A2AR and PDL-1 were associated with tumor N stage and prognostic parameters. There was no significant relationship with other clinicopathological characteristics. Our obtained data suggested that the high expressions of A2AR and PD-L1 were associated with the lymph node metastasis and a poor prognosis in gastric cancer, which may be a potential diagnostic and a therapeutic target for gastric cancer.

Mineralized polymeric cryogels with interconnective macroporous structure have demonstrated their potential as promising scaffolding material in bone tissue engineering. However, their capability in inducing osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro and osteogenesis in vivo has not been explored yet. In this work, the roles of the mineralized cryogel on osteogenesis are systematically studied. Mineralized macroporous poly(ethylene glycol)-co-2-hydroxyethyl methacrylate cryogel promotes osteogenic differentiation of rat MSCs, particularly in upregulating the activity of alkaline phosphatase (ALP, ∼5.7-folds) and expression of related osteogenic gene markers (ALP ∼16-folds, osteocalcin ∼133-folds) at 14 days. In vivo implantation reveals that mineralized cryogels could promote fast osteogenesis and angiogenesis in critical-sized cranial bone defect of a Sprague-Dawley rat model in 4 weeks. The adsorption, entrapment, and concentration of osteogenic growth factors (bone morphogenetic protein 2) and angiogenesis growth factor (vascular endothelial growth factor [VEGF]) in the matrices in vivo may possibly participate in the process of osteogenesis and angiogenesis. Notably, the adsorption of larger amount of VEGF in nonmineralized cryogels facilitates obvious angiogenesis and comparable osteogenesis in bone defect in 8 weeks. Graphical abstract [Figure: see text] Impact Statement The current work reported the fabrication and characterization of a biomimicking mineralized polymeric cryogel as scaffolding material in bone regeneration. In addition to its three dimensional porous structure and the osteogenic potential, this biomimicking scaffold was also found to enhance the adsorption of biochemical cues, which in turn greatly promoted the angiogenesis as well as the tissue regeneration.

BackgroundIt has been reported that there are more than ten antimicrobial peptides (AMPs) belonging to the cecropin family inMusca domestica; however, few of them have been identified, and the functions of the other molecules are poorly understood.MethodsSequences of theM. domesticacecropin family of genes were cloned from cDNA template, which was reverse-transcribed from total mRNA isolated from third-instar larvae ofM. domesticathat were challenged with pathogens. Sequence analysis was performed using DNAMAN comprehensive analysis software, and a molecular phylogenetic tree of the cecropin family was constructed using the Neighbour-Joining method in MEGA v.5.0 according to the mature peptide sequences. Antibacterial activity of the syntheticM. domesticacecropin protein was detected and the minimum inhibitory concentration (MIC) values were determined using broth microdilution techniques. Time-killing assays were performed on the Gram-negative bacteria,Acinetobacter baumannii, at the logarithmic or stabilizing stages of growth, and its morphological changes when treated with Cec4 were assessed by scanning electron microscopy (SEM) and detection of leakage of 260 nm absorbing material.ResultsEleven cecropin family genes, namelyCec01,Cec02andCec1-9, show homology to the Cec form in a multigene family on the Scaffold18749 ofM. domestica. In comparing the encoded cecropin protein sequences, most of them have the basic characteristics of the cecropin family, containing 19 conservative amino acid residues. To our knowledge, this is the first experimental demonstration that most genes in the Cec family are functional. Cec02, Cec1, Cec2, Cec5 and Cec7 have similar antibacterial spectra and antibacterial effects against Gram-negative bacteria, while Cec4 displays a more broad-spectrum of antimicrobial activity and has a very strong effect onA. baumannii. Cec4 eliminatedA. baumanniiin a rapid and concentration-dependent manner, with antibacterial effects within 24 h at 1× MIC and 2× MIC. Furthermore, SEM analysis and the leakage of 260 nm absorbing material detection indicated that Cec4 sterilized the bacteria through the disruption of cell membrane integrity.ConclusionsAlthough there are more than ten cecropin genes related toM. domestica, some of them have no preferred antibacterial activity other than Cec4 againstA. baumannii.

Stomach adenocarcinoma(STAD) is one of the deadliest cancers in the world. The expression levels of family members of mex-3 RNA that bound MEX3A (member A) and MEX3B (member B) were high expressions in different cancers and interconnected to deficient prognosis. The present research assessed the potential regarding the expression of MEX3A and MEX3B in STAD by analysing the facts of STAD (viz. The Cancer Genome Atlas). TCGA, MEX3A and MEX3B in the cancers were analyzed using TIMER2.0, Kaplan Meier Plotter, and cBioPortal. The data was visualized using version 4.0.3 of R. We found MEX3A and MEX3B had various expressions regarding major cancer and relevant common tissues. Especially, high expression of MEX3A and MEX3B had relationships with the OS (namely overall survival) with deficiency and RFS (viz. relapse-free survival) concerning STAD. The expressions of MEX3B had correlations to T stage with P being 0.012 and to the race with P being 0.049. MEX3B was highly expressed in T3 and T4 stages, and was highly expressed in the white race. MEX3A mutation had a better survival without diseases, with P being 0.0205. However, the situation was different with non-overall survival, with P being 0.194, in comparison with the patients who did not have MEX3A change. MEX3A and MEX3B on tumor pathogenesis might be related to "RNA splicing" and "spliceosomal complex" and "single-stranded RNA binding". We further investigated the association between MEX3A and MEX3B and immune cells. The mast cells of the most connections to MEX3A (R=-0.300, P

The accumulation of adenosine in the tumor microenvironment is associated with tumor progression in many cancers. However, whether adenosine is involved in gastric cancer (GC) metastasis and progression, and the underlying molecular mechanism, is largely unclear. In this study, we find that GC tissues and cell lines had higher A2aR levels than nontumor gastric tissues and cell lines. A2aR expression correlated positively with TNMstage, and associated with poor outcomes. Adenosine enhanced the expression of the stemness and epithelial–mesenchymal transition-associated genes by binding to A2aR. A2aR expression on GC cells promoted metastasis in vivo. The PI3K-AKT-mTOR signaling pathway was involved in adenosine-stimulated GC cell migration and invasion. Our results indicate that adenosine promotes GC cell invasion and metastasis by interacting with A2aR to enhance PI3K–AKT–mTOR pathway signaling.

Background A case of Acinetobacter baumannii (A. baumannii), known as gram-negative bacteria, causes a range of nosocomial infections. Due to the continuous detection of multi-drug resistant A. baumannii in the clinic, there is an urgent need to find alternative therapies, including broad-spectrum antibacterial peptides (AMP). Recently it has been found that the peptide Cec4 has good antibacterial activity against A. baumannii, but the antibacterial mechanism remains elusive. Materials and methods The basic structure of Cec4 was analyzed by circular dichroism (CD) spectroscopy, and the potential antibacterial mechanism of Cec4 was detected by flow cytometry, transmission electron microscopy, fluorescence and confocal microscopy. The minimum inhibitory concentration (MIC) of antimicrobial peptides against various A. baumannii was determinated with broth microdilution techniques. The biofilm formation and the sensitivity detection of biofilms to antimicrobial peptides were detected by crystal violet staining. Results In this study, the main secondary structure of the antibacterial peptide Cec4 is α-helix (99.7%) in the hydrophobic environment. Furthermore, after the treatment with Cec4, an amount of leakage of A. baumannii and the destruction of its cell membrane were detected. Moreover, it was observed that FITC-Cec4 can enter the cell, and more cells were held in the G1 phase with peptide Cec4. However, the DNA binding assay of the peptide Cec4 indicates that the peptide does not target DNA. In addition, peptide Cec4 was superior in reducing adherent biofilms of A. baumannii compared to conventional antibiotics and has no cytotoxicity. Conclusion It is apparent that the antibacterial peptide Cec4 may achieve rapid sterilization by multi-target interaction and presents an attractive therapeutic option for the prevention and control of A. baumannii infections.

The purpose of this study was to investigate the influences of drying methods on the risperidone (RIS) release profiles of RIS-loaded PLGA microspheres. These microspheres were fabricated with an O/W emulsion solvent evaporation method. The wet microspheres were dried with freeze drying and vacuum drying methods. The microspheres were mono-dispersed spheres with an average diameter of 100 μm. Studies found that drying methods had great influence on the porosity, morphology, and release profiles of RIS-loaded PLGA microspheres. Specifically, the freeze-dried microspheres had higher porosity (78.46 ± 1.64%) than those vacuum-dried ones (52.45 ± 2.68%), and they showed higher RIS release rates (p

Recent years have witnessed surging demand for bone repair/regeneration implants due to the increasing number of bone defects caused by trauma, cancer, infection, and arthritis worldwide. In addition to bone autografts and allografts, biomaterial substitutes have been widely used in clinical practice. Personalized implants with precise and personalized control of shape, porosity, composition, surface chemistry, and mechanical properties will greatly facilitate the regeneration of bone tissue and satiate the clinical needs. Additive manufacturing (AM) techniques, also known as 3D printing, are drawing fast growing attention in the fabrication of implants or scaffolding materials due to their capability of manufacturing complex and irregularly shaped scaffolds in repairing bone defects in clinical practice. This review aims to provide a comprehensive overview of recent progress in the development of materials and techniques used in the additive manufacturing of bone scaffolds. In addition, clinical application, pre-clinical trials and future prospects of AM based bone implants are also summarized and discussed.

Institutional investors, especially public funds, play an important role in governing listed firms as they grow in Chinese stock markets. We classify each fund as “dedicated,” “transient,” ...

Surface characteristics of the biomaterials have significant effects on response of osteoblast and formation of new bone tissue. In this study, to improve the bio-performance of polyimide (PI) as an implantable material for bone substitute, concentrated sulfuric acid suspension with tantalum (V) oxide (vTO) submicro-particles of 10w% (PIST10) and 15w% (PIST15) was utilized to modify PI surface. After sulfonation, microporous coatings including vTO particles were created on PI (PIST10 and PIST15) while microporous coating without vTO particles was also created on PI (PIS). Results showed that surface roughness, hydrophilicity and protein adsorption of PIST15 was remarkably higher than PIST10 and PIS. Furthermore, after soaking into simulated body fluid (SBF), no apatite mineralization on PIS was found, while PIST15 with high vTO content exhibited better apatite mineralization compared with PIST10. Moreover, PIS showed low antibacterial property, while PIST15 with high vTO content revealed better antibacterial property compared with PIST10. In addition, cellular response (such as adhesion, proliferation and alkaline phosphatase activity) of bone marrow stromal cells (BMSC) of rat to PIST15 was higher than PIST10 and PIS. In conclusion, the microporous coating of PIST15 including vTO submicro-particles possessed good antibacterial property and bioactivity, which significantly promoted the responses of BMSC. Therefore, PIST15 has potential application prospects for bone substitute.

Using a large sample of firm‐level media reports data, we examine whether and how media reports affect the probability of stock price crash in China. We find that positive media reports reduce the probability of stock price crash, while the relationship between negative reports and the probability of price crash is U‐shaped. The probability of stock price crash is more sensitive to the media reports in SOEs and large firms. Furthermore, we find evidence to support the media management behaviour of institutional investors. Such behaviour significantly changes the probability of stock price crash. However, we only observe the media management behaviour of institutional investors in firms held by non‐block institutions, in support of the notion that transient investors behave opportunistically and reap short‐term investment gains through media management.

The aim of this study was to fabricate different risperidone (RIS)–loaded poly(lactic-co-glycolic acid) microspheres (PLGA MS) with various viscosity of PLGA polymers and investigate the RIS release profiles. Risperidone-loaded PLGA MS were fabricated via an oil/water–type emulsion solvent evaporation method, using ethyl acetate and benzil alcohol as the dispersed solvents. The PLGA (75:25) with the viscosity of 0.82, 0.93, and 1.10 dL/g was used in the fabrication. The morphology and the degradation of the RIS-PLGA MS were investigated with a scanning electron microscope. The distribution states of RIS in the PLGA MS were studied with differential scanning calorimetry. The residual of ethyl acetate and benzil alcohol in the resulting MS was monitored with gas chromatography. The in vitro release profiles of RIS from PLGA MS were also studied. Scanning electron microscope photographs illustrated that the obtained PLGA MS were monodisperse spheres with an average diameter of 100 μm. Gas chromatography results suggested that no residual ethyl acetate was left in the final RIS-PLGA MS, and the residue amount of benzil alcohol was about 1%. In vitro drug release profiles from the microsphere showed a substantially sigmoidal pattern of negligible initial burst up to 24 hours and minimal release (time lag) for 14 days. After the lag phase, slow release took a place up to 30 days, and then rapid release occurred sharply for about 2 weeks. The RIS release reached equilibrium around day 50. All release profiles showed the similar trend, and no significant difference was observed among these release profiles (P > .05). This phenomenon indicated that RIS-loaded PLGA MS with the viscosity of 0.82 to 0.93 dL/g showed the optimal release behavior. However, no obvious differences were found among the MS obtained from the viscosity of 0.82 to 1.10 dL/g. These studies provided basis for the quality control in the industrial production of PLGA MS.

Background. Programmed cell death ligand 1 (PD-L1) is a key inhibitor to the immune response by binding to the specific receptor PD-1. Adenosine receptor 2 (A2aR) can play an immunosuppressive role in tumor microenvironment by binding to its ligand adenosine (ADO). However, the expression of these two markers has been rarely studied in colorectal cancer simultaneously.Materials and Methods. We, respectively, collected tumor and adjacent nontumor tissue specimens of 204 patients with colorectal cancer. The expressions of PD-L1 and A2aR were detected by immunohistochemistry. The association among their expressions with clinicopathological characteristics and prognostic parameters were analyzed as well.Results. The expressions of PD-L1 and A2aR in tumor tissues were both higher than those in matched adjacent nontumor tissues. PD-L1 expression was significantly correlated with lymph node metastasis and tumor TNM stage. A2aR expression was significantly correlated with tumor size, depth of tumor invasion, and TNM stage. Univariate analysis showed that the high expressions of PD-L1 and A2aR were inversely correlated with the overall survival, respectively. Multivariate analysis further confirmed that both of them were independent prognostic markers for patients.Conclusion. The results of this study suggested that the high expressions of PD-L1 and A2aR were associated with a poor prognosis of colorectal cancer. Coinhibition of these two proteins may be a new breakthrough in the treatment of this disease.

Additional file 1: Table S1. Primer sequences used for cloning in this study.

Bioactive scaffolds of magnesium silicate (m-MS)/poly(butylene succinate) (PBSu) composites were fabricated by a solvent casting–particulate leaching method for bone regeneration. The scaffolds had a hierarchical porous structure with interconnected macropores (300–500 μm), micropores (1–10 μm) and mesopores (∼5 nm). In addition, the composite scaffolds were degradable in Tris-HCl solution and formed apatite on their surfaces in simulated body fluid, indicating good degradability and bioactivity in vitro. Compared with PBSu scaffolds, the composite scaffolds improved the in vitro attachment, proliferation and osteogenic differentiation of MC3T3-E1 cells, revealing good cytocompatibility. Furthermore, the model of rabbit femur cavity defects was used to evaluate the in vivo osteogenesis of the composite scaffolds. The results of synchrotron radiation-based mCT (SRmCT) imaging, histological analysis and immunohistochemistry showed that the composite scaffolds were gradually degraded and replaced by new bone, and the scaffolds with 40 wt% m-MS (C40) almost completely disappeared after 12 weeks of implantation, indicating that the scaffolds containing m-MS enhanced new bone formation. The results demonstrated that the bioactive m-MS/PBSu composite scaffolds with good biocompatibility, degradability, bioactivity and osteogenesis are promising biomaterials for bone repair.

Recently, honeycomb-patterned polymeric films have been fabricated through breath-figure method to mimic the topographical feature of the basement membrane and this topography was demonstrated to enhance osteoblast functions including adhesion, spreading, proliferation, and differentiation. However, honeycomb-patterned films incorporated with other components benefiting osteoblast functions have not been reported yet. In this study, we report the fabrication of nano-hydroxyapatite (nHA) (3 wt%, 5 wt%, and 7 wt%) incorporated honeycomb poly(L-lactide) (PLLA) films to evaluate the effect of nHA on the self-assembly of honeycomb pores in PLLA films. Scanning electron microscopy (SEM) images demonstrated that 5 wt% nHA in PLLA resulted in the most regular honeycomb pores. Water contact angle test and protein adsorptions including fibronectin (FN) and serum were performed on 5 wt% nHA incorporated honeycomb PLLA films (H-PLLA/nHA), as well as the controls, flat PLLA films (F-PLLA), honeycomb PLLA films (H-PLLA), and flat HA films (F-HA). Honeycomb pores in H-PLLA films enhanced hydrophobicity compared with F-PLLA films, whereas nHA particles in H-PLLA/nHA films lowered the hydrophobicity compared with H-PLLA. Both the FN and serum protein adsorptions were increased on H-PLLA films compared with F-PLLA, but decreased significantly on H-PLLA/nHA films compared with H-PLLA films. Further, MC3T3-E1 mouse newborn calvaria preosteoblasts were employed to investigate the cell functions in terms of cell adhesion, spreading, proliferation, and differentiation on those films. The results strongly indicated that those cell functions were promoted on honeycomb films, especially H-PLLA/nHA films, compared with F-PLLA films and they did not show a significant difference between H-PLLA films and F-HA films.

Advanced technology has enabled us to investigate cell functions in biomimetic honeycomb films or macroporous inorganic scaffolds to tentatively seek more powerful engineered biomaterials for bone regeneration. However, to date, the cell functions of honeycomb-patterned 3-dimensional scaffolds have not been studied. Herein, we report a facile and novel approach to fabricate photo-crosslinked hierarchically honeycomb-patterned/macroporous calcium phosphate cement (CH-CPC) scaffolds and their biological impact on MC3T3-E1 cells. The CH-CPC scaffolds together with controls, photo-crosslinked calcium phosphate cement scaffolds without honeycomb pores (CW-CPC) and calcium phosphate cement (CPC) scaffolds, were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), energy dispersive spectroscopy (EDS), gel fraction measurement, thermogravimetric analysis (TGA), Brunauer–Emmett–Teller (BET) tests, and mechanical testing. The CH-CPC scaffolds were fully covered with a honeycomb layer with a pore diameter of 1.5–3.7 μm on the scaffold surface and the inside of the CH-CPC scaffolds was also covered with a honeycomb layer, but with poorer coverage and regularity in terms of pore size. The crosslinked networks in CW-CPC and CH-CPC scaffolds enhanced their compressive strength. The surface area and water adsorption in CH-CPC scaffolds were significantly higher than those of CPC and CW-CPC scaffolds due to the formation of honeycomb pores, which also promoted fibronectin (FN) adsorption on CH-CPC scaffolds. MC3T3-E1 cells were seeded on these scaffolds to study the cell response. The results clearly suggested that, in comparison with CPC and CW-CPC scaffolds, cell adhesion, spreading, proliferation, and differentiation were enhanced on CH-CPC scaffolds.

Polylactide (PLA) and its copolymers have been widely used for bone tissue regeneration. In this study, a bioactive composite of ordered mesoporous calcium–magnesium silicate (m-CMS) and poly( l -lactide) (PLLA) was fabricated by melt blending method. The results indicated that the m-CMS particles were entrapped by polymer phase, and crystallinity of PLLA significantly decreased while the thermal stability of the m-CMS/PLLA composites was not obviously affected by addition of the m-CMS into PLLA. In addition, compared to PLLA, incorporation of the m-CMS into PLLA significantly improved the hydrophilicity, in vitro degradability and bioactivity (apatite-formation ability) of the m-CMS/PLLA composite, which were m-CMS content dependent. Moreover, it was found that incorporation of the m-CMS into PLLA could neutralize the acidic degradation by-products and thus compensated for the decrease of pH value. In cell culture experiments, the results showed that the composite enhanced attachment, proliferation and alkaline phosphatase activity (ALP) of MC3T3-E1 cells, which were m-CMS content dependent. The results indicated that the addition of bioactive materials to PLLA could result in a composite with improved properties of hydrophilicity, degradability, bioactivity and cytocompatibility.

Zhaoying Wu,1 Quan Li,2 Yongkang Pan,1 Yuan Yao,1 Songchao Tang,1 Jiacan Su,2 Jung-Woog Shin,3 Jie Wei,1 Jun Zhao4,5 1Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, 2Department of Orthopaedics Trauma, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China; 3Department of Biomedical Engineering, Inje University, Gimhae, Republic of Korea; 4Department of Orthodontics, 5Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People’s Republic of China Abstract: Bioactive composite macroporous scaffold containing nanoporosity was prepared by incorporation of nanoporous magnesium silicate (NMS) into poly(butylene succinate) (PBSu) using solvent casting–particulate leaching method. The results showed that the water absorption and in vitro degradability of NMS/PBSu composite (NMPC) scaffold significantly improved compared with magnesium silicate (MS)/PBSu composite (MPC) scaffold. In addition, the NMPC scaffold showed improved apatite mineralization ability, indicating better bioactivity, as the NMPC containing nanoporosity could induce more apatite and homogeneous apatite layer on the surfaces than MPC scaffold. The attachment and proliferation of MC3T3-E1 cells on NMPC scaffold increased significantly compared with MPC scaffold, and the alkaline phosphatase (ALP) activity of the cells on NMPC scaffold was expressed at considerably higher levels compared with MPC scaffold. Moreover, NMPC scaffold with nanoporosity not only had large drug loading (vancomycin) but also exhibited drug sustained release. The results suggested that the incorporation of NMS into PBSu could produce bioactive composite scaffold with nanoporosity, which could enhance water absorption, degradability, apatite mineralization and drug sustained release and promote cell responses. Keywords: nanocomposite, degradability, apatite mineralization, cell behaviors, drug release

The surfaces of nano-calcium silicate (n-CS)/polyetheretherketone (PK) composites were treated with abrasive paper and sand-blasting, and the surfaces performances of the as-treated composites were studied. The results showed that the surface roughness, hydrophilicity and mineralization of the simulated body fluid (SBF) of the composites surfaces were significantly improved, and the properties of the composites treated by with sand-blasting were better than those treated with abrasive paper. Moreover, the treated composites significantly promoted osteoblasts responses, such as cell attachment, spreading, proliferation and alkaline phosphatase (ALP) activity, compared to un-treated composites, and the cellular responses to the composites treated with sand-blasting were better than those treated with abrasive paper. The results suggested that surface treatment with sand-blasting was an effective method to greatly improve the surface bioperformances of the n-CS/PK composite, and this treated composite with improved bioactivity and cytocompatibility might be a promising implant material for orthopedic applications.

Phosphate glass fibers (PGF) have emerged as promising building blocks for constructing bone scaffolds. In this study, fibrous scaffolds (PGFS) were fabricated using a facile binding method at room temperature. PGFS exhibited an extracellular matrix-like morphology and were composed of PGF as matrix and chitosan as the natural binding glue. They showed an interconnected porous structure with a porosity of ~87% and pore size of 100-500 µm. PGFS exhibited the typical compressive stress-strain behaviour of highly porous, low-density, open-cell scaffolds. Their yield stress and modulus were ~0.38 and ~2.84 MPa, respectively, with the strength being higher than the lower bound of the compressive strength of cancellous bone. PGFS were degradable and the weight loss was about 25% after immersion in stimulated body fluid (SBF) for 28 days. In addition, the yield stress and the modulus decreased with increasing immersion time in SBF. Apatite formation could be detected on the surface of PGFS within 7 days of immersion in SBF. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay indicated that PGFS were non-cytotoxic against bone marrow stromal cells (bMSCs) after culture for up to 72 h. These results suggest that PGFS could be promising scaffolds for bone regeneration applications.

Xingtao Chen,1 Guoyue Lv,1 Jue Zhang,2 Songchao Tang,2 Yonggang Yan,1 Zhaoying Wu,2 Jiacan Su,2 Jie Wei2 1College of Physical Science and Technology, Sichuan University, Chengdu, 2Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, People’s Republic of China Abstract: A multi-(amino acid) copolymer (MAC) based on ω-aminocaproic acid, γ-aminobutyric acid, L-alanine, L-lysine, L-glutamate, and hydroxyproline was synthetized, and MAC microspheres encapsulating bovine serum albumin (BSA) were prepared by a double-emulsion solvent extraction method. The experimental results show that various preparation parameters including surfactant ratio of Tween 80 to Span 80, surfactant concentration, benzyl alcohol in the external water phase, and polymer concentration had obvious effects on the particle size, morphology, and encapsulation efficiency of the BSA-loaded microspheres. The sizes of BSA-loaded microspheres ranged from 60.2 µm to 79.7 µm, showing different degrees of porous structure. The encapsulation efficiency of BSA-loaded microspheres also ranged from 38.8% to 50.8%. BSA release from microspheres showed the classic biphasic profile, which was governed by diffusion and polymer erosion. The initial burst release of BSA from microspheres at the first week followed by constant slow release for the next 7 weeks were observed. BSA-loaded microspheres could degrade gradually in phosphate buffered saline buffer with pH value maintained at around 7.1 during 8 weeks incubation, suggesting that microsphere degradation did not cause a dramatic pH drop in phosphate buffered saline buffer because no acidic degradation products were released from the microspheres. Therefore, the MAC microspheres might have great potential as carriers for protein delivery. Keywords: poly (amino acid) copolymer, release, degradation

Mesoporous magnesium silicate (m-MS) was synthesized, and the in vitro degradability, bioactivity and primary cell responses to m-MS were investigated. The results suggested that the m-MS with mesoporous channels of approximately 5 nm possessed the high specific surface area of 451.0 m(2)/g and a large specific pore volume of 0.41 cm(3)/g compared with magnesium silicate (MS) without mesopores of 75 m2/g and 0.21 cm(3)/g, respectively. The m-MS was able to absorb a large number of water, with water absorption of 74% compared with 26% for MS. The m-MS was also degradable in a Tris-HCI solution, with a weight loss ratio of 40 wt% after a 70-day immersion period. The m-MS exhibited good in vitro bioactivity, inducing apatite formation on its surfaces after soaking in simulated body fluid (SBF) at a faster rate than observed for MS. The m-MS surface clearly promoted the proliferation and differentiation of MC3T3-E1 cells, and their normal cell morphology indicated excellent cytocompatibility. This study suggested that mesoporous magnesium silicate with a high specific surface area and pore volume had suitable degradability and good bioactivity and biocompatibility, making it an excellent candidate biomaterial for the induction of bone regeneration. (C) 2014 Elsevier B.V. All rights reserved.

The regenerative treatment of large osseous defects remains a formidable challenge in today. In the present study, we have synthesized biodegradable magnesium calcium phosphate biocement (MCPB) scaffolds with interconnected macroporous structure (100-600 mu m), as well as good bioactivity, biocompatibility and proper degradatibility. The results revealed that the porosity increased from 52% to 80% of MCPB scaffolds while the compressive strength decreased from 6.1MPa to 1.2MPa. We further assessed the effects of scaffolds on the rabbit femur cavity defect model in vivo by using synchrotron radiation X-ray microCT and microCT imaging, indicating that the MCPB scaffolds underwent gradually degradation and promoted the extensive neo-bone formation.