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Although the continuous development of small-diameter vascular grafts (SDVGs) (

The present study focused on the combination of biphasic calcium phosphate (BCP) nanoparticles into the modified hyaluronic acid based injectable hydrogels for bone tissue engineering. Self-cross-l...

Polyurethanes are of great interest in tissue engineering because of their tunable mechanical and nontoxic properties. Various fabrication techniques have been adapted to design polyurethane scaffo...

The present study focused on the combination of biphasic calcium phosphate (BCP) nanoparticles into the modified hyaluronic acid based injectable hydrogels for bone tissue engineering. Self-cross-linked thiolated hyaluronic acid (HA-HS) injectable hydrogels loaded with biphasic calcium phosphate (BCP) nanoparticles were prepared by disulfide cross-linking to mimic the extracellular matrix as a potential material for bone treatment. Varying concentration of HA-HS ranging between 1 and 5w/v% was tested to optimize the optimum concentration and were further modified with varying BCP concentrations for final optimization. Physico-chemical characterizations of the prepared hydrogel such as SEM, EDS, FT-IR, and XRD confirmed that the BCP has effectively loaded and distributed homogeneously in the HA-HS hydrogel. The results showed that the 3% (w/v) HA-HS hydrogel exhibits the appropriate properties for injectable hydrogel system such as gelation times, swelling rate and

Teeth extraction is inevitable in the case of progressive or alveolar bone destructing chronic periodontitis. Unfortunately, the resulting bone defects may lead to many side effects. Here, we developed a novel dental-bone substitute to preserve the extraction socket for hemostasis and bone regeneration. Hyaluronic acid-gelatin hydrogel (HG) polymers, β-tricalcium phosphate (TCP), and biphasic calcium phosphate (BCP) ceramics were fabricated using freeze-drying methods. The HG/TCP/BCP plug was prepared to be easily applied by pouring the mixture of HG and TCP into the shell-shaped mold, followed by placing the sponge type of BCP in the core portion of the mold compared to HG/TCP and collagen plugs. In vitro studies showed that HG/TCP and HG/TCP/BCP plugs were cytocompatible and could promote osteogenesis by upregulating the expressions of bone-related genes COL1, RUNX2, ALP, and OPN. The rabbit-femur defect model revealed that the implanted HG/TCP/BCP plug, which showed excellent hemostatic property, promote bone regeneration with a high rate of collagen distribution along with ALP and OPN expressions more than could the HG/TCP plug at 3 months after implantation, whereas the collagen plugs just filled with chondrocytes for cartilages formation. The HG/TCP/BCP plug should be considered for potential dental applications for one-step socket preservation.

In this study, we investigated the effectiveness of poly (lactic-co-glycolic acid) (PLGA) porous scaffold in enhancing bone regeneration through surface modification with glycol chitosan (GCH) and bone morphogenetic protein-2(BMP-2). Immobilization of GCH on PLGA (PLGA-GCH) and simple immobilization of osteogenic BMP-2 on PLGA-GCH (PLGA-GCH-BMP-2) via EDC/NHS as crosslinker was highly efficient. The surface morphologies of the scaffolds were observed using a scanning electron microscopy (SEM). The immobilization of GCH and BMP-2 on PLGA was characterized using Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS), which confirmed the conjugation of GCH and BMP-2 peptides on PLGA. Human adipose derived stem cells (hADSCs) were cultured on the scaffolds to determine the effect of surface modification on mineralization and cell differentiation. PLGA-GCH-BMP-2 scaffold showed enhanced in-vitro calcium mineralization and osteogenic differentiation of hADSCs using osteogenic medium. The developed scaffold might be effective filler materials for enhancing osteogenesis in 3D printed vertebra spacers targeting the aged patients.

The aim of this study was to improve the osteogenic ability of 3D-printed porous titanium (Ti) intervertebral spacer with a Tri-calcium Phosphate (TCP) loaded Demineralized Bone Matrix Hydrogel (DBM). Microstructures and morphologies of Ti, DBM loaded Ti (Ti/DBM), and TCP and DBM loaded Ti (Ti/DBM/TCP) scaffolds were characterized by SEM and EDX. In-vitro studies showed that Ti/DBM/TCP scaffold was biocompatible and could promote osteogenesis by up-regulating the expression of bone-related genes. Furthermore, the results of in-vivo studies using rabbit-femur defect model revealed that the implanted Ti/DBM/TCP scaffold had superior bone regeneration. The TCP and DBM loading were an effective approach of inducing osteogenesis in 3D-printed Ti intervertebral spacer by providing favorable osteogenic differentiation conditions and promoting bone formation.

Polyurethane foam (PUF) composites are of great interest in various polymer applications due to their tunable mechanical and stretchable properties, and easy fabrication. In this study, flexible, biocompatible, and electroconductive PUF composites (PUF-graphene oxide (GO), PUF-polypyrrole (PPy)-GO, and PUF-poly(3,4-ethylenedioxythiophene) (PEDOT)-GO) were synthesized using a sequential procedure of vapor phase polymerization (VPP) and GO impregnation. First, hydroxyl groups in polytetramethylene ether glycol (PTMEG) and diisocyanate functional groups in polymeric methylene diphenyl diisocyanate (PMDI) underwent a reaction to generate urethane bonds. Then, by adding water, CO2 gas was used during the reaction of isocyanate to generate bubbles creating a porous interconnected foam. Conductive polymers (CPs) such as PPy and PEDOT were vapor-phased polymerized on the synthesized PUF matrix. Then, these composites were integrated with GO by impregnation on the surface of PUF-conductive polymers (CP). The flexible, and electroconductive PUF composites were analyzed and compared with respect to pore size distribution, mechanical, thermal, and electrical properties. Indirect biocompatibility and cell proliferation with PUF composites were also evaluated for 7 days. Among the PUF composites, the PUF-PPy-GO was further investigated as an NH3 gas sensing material and showed high values in sensitivity coefficients as well as the selectivity coefficients, demonstrating the sensor's utility in determining NH3 gas incidence.

In this study, a novel TEMPO-oxidized cellulose nanofiber (TOCN)-silk fibroin scaffold was prepared using a cost effective freeze drying method. Fundamental physical characterizations were carried out by scanning electron microscopy (SEM), pore diameter determination, FT-IR. PBS uptake behavior of the scaffold showed that, silk fibroin can enhance the swelling capacity of TOCN. L929 primary fibroblast cell was selected for in vitro studies, which showed that the scaffolds facilitated growth of cells. In vivo evaluation of TOCN, TOCN-silk fibroin composites was examined using critical sized rat skin excisional model for one and two weeks. The results of rat wound model revealed that, compared to only TOCN scaffold, TOCN-silk fibroin scaffold successfully promoted wound healing by the expression of wound healing markers. TOCN-silk fibroin 2% has the fastest wound healing capacity. Thus, it appears that TOCN-silk fibroin composite scaffolds can be useful as wound healing material in clinical applications.

The objective of this study was to fabricate multichannel biphasic calcium phosphate (BCP) and β-tricalcium phosphate (TCP) bone substitutes and compare their long-term biodegradation and bone regeneration potentials. Multi-channel BCP and TCP scaffolds were fabricated by multi-pass extrusion process. Both scaffolds were cylindrical with a diameter of 1-mm, a length of 1-mm, and seven interconnected channels. Morphology, chemical composition, phase, porosity, compressive strength, ion release behavior, and in-vitro biocompatibility of both scaffolds were studied. In-vivo biodegradation and bone regeneration efficacies of BCP and TCP were also evaluated using a rabbit model for 1 week, 1 month, and 6 months. BCP exhibited superior compressive strength compared to TCP scaffold. TCP showed higher release of both calcium ions and phosphorous ions than BCP in SBF solution. Both scaffolds showed excellent in-vitro biocompatibility and upregulated the expression of osteogenic markers of MC3T3-E1 cells. In-vivo studies revealed that both cylindrical TCP and BCP scaffolds were osteoconductive and supported new bone formation. Micro-CT data showed that the bone-regeneration efficacy of TCP was higher at one month and at six months after implantation. Histological examination confirmed that TCP degraded faster and had better bone regeneration than BCP after 6 months.

The objective of the present work was to investigate the in-vitro and in-vivo performance of strontium doped calcium phosphate (Ca-Sr-P) coatings on ZK60 magnesium (Mg) alloy for bone applications. A chemical immersion technique was employed to develop Ca-Sr-P coating on biodegradable Mg alloy. Surface morphology, chemical composition, phase, mechanical properties, wettability, in-vitro corrosion, cytocompatability, in-vivo degradation and biocompatibility of Ca-Sr-P coatings were studied. The Ca-Sr-P coating (~20 µm) exhibited a dense, crystalline, uniform, and crack-free surface. In-vitro studies revealed that the coating improved the corrosion resistance of Mg alloy and enhanced bioactivity. The surface coating also promoted the adhesion, proliferation, and osteogenic markers expression of MC3T3-E1 cells. The coating lowered the degradation rate in-vivo compared with Mg alloy. Higher bone formation and better ossteointegration was found around the coating than the Mg alloy after 4 weeks of implantation in a rabbit model. Thus, the Ca-Sr-P coating with a reduced degradation and improved biocompatibility could be used in Mg-based orthopedic implant applications.

The objective of this study was to present an effective injectable adhesion barrier comprised of TEMPO-oxidized cellulose nanofiber (TOCN), methyl cellulose, carboxymethyl cellulose, and polyethylene glycol. Hydrogels with different concentrations (0.2, 0.5, 0.8, 1% w/v) of bio compatible TOCN were investigated to determine their abilities to prevent post-surgical peritoneal adhesion using a rat cecal wall abrasion model. Sol-gel transition at body temperature (37 °C) was optimized by adjusting concentration of sodium ions (Na+), with a gelation time of 45 ± 7 s. These TOCN containing hydrogels showed non cytotoxicity to rat bone marrow mesenchymal stem cells (RBMSCs) and L929 fibroblast cells as cell models during in vitro assessment. Degradation studies revealed that, TOCN concentration in hydrogel was inversely proportional to hydrolytic degradation rate. From in vivo evaluations, TOCN 0.2 hydrogel significantly reduced peritoneal adhesion in rat (n = 8) compared to untreated controls based on gross observation, histological analysis, and expression analysis of marker proteins. By taking advantages of thermo gelling, high stability, non-invasive way of application and rapid recovery potential, TOCN containing bio compatible hydrogel could be used as a cost-effective barrier to efficiently inhibit post-surgical peritoneal adhesions.

The present work addresses the performance of polycaprolactone (PCL) coating on fluoride treated (MgF2) biodegradable ZK60 magnesium alloy (Mg) for biomedical application. MgF2 conversion layer was first produced by immersing Mg alloy substrate in hydrofluoric acid solution. The outer PCL coating was then prepared using dip coating technique. Morphology, elements profile, phase structure, roughness, mechanical properties, invitro corrosion, and biocompatibility of duplex MgF2/PCL coating were then characterized and compared to those of fluoride coated and uncoated Mg samples. The invivo degradation behavior and biocompatibility of duplex MgF2/PCL coating with respect to ZK60 Mg alloy were also studied using rabbit model for 2 weeks. SEM and TEM analysis showed that the duplex coating was uniform and comprised of porous PCL film (~3.3 μm) as upper layer with compact MgF2 (~2.2 μm) as inner layer. No significant change in microhardness was found on duplex coating compared with uncoated ZK60 Mg alloy. The duplex coating showed improved invitro corrosion resistance than single layered MgF2 or uncoated alloy samples. The duplex coating also resulted in better cell viability, cell adhesion, and cell proliferation compared to fluoride coated or uncoated alloy. Preliminary invivo studies indicated that duplex MgF2/PCL coating reduced the degradation rate of ZK60 Mg alloy and exhibited good biocompatibility. These results suggested that duplex MgF2/PCL coating on magnesium alloy might have great potential for orthopedic applications.

Apoptosis or programmed cell death plays an essential role in chemotherapy-induced tumor cell killing, and inducers of apoptosis are commonly used in cancer therapy. Treatment with Zelkova serrata extracts was performed in human gingival fibroblast (HGF), mouth epidermoid carcinoma cell (KB), lower gingival squamous cancer cell (YD38) and tongue mucoepidermoid carcinoma cells (YD15). We observed that extract prepared from Zelkova serrata twig selectively inhibited proliferation of various oral cancer cells, but not normal gingival fibroblasts, in a dose-dependent manner. Caspase-8-mediated apoptosis was induced by treatment with the extract only in mouth epidermoid carcinoma and not in other types of cancer cells, including lower gingival squamous cell carcinoma. The selective apoptotic effect of Zelkova serrata twig extract in mouth epidermoid carcinoma was dependent on normal p53 status. Apoptosis was not remarkably induced by treatment with the extract in either lower gingival squamous or tongue mucoepidermoid carcinoma cells, both of which contain abnormalities of p53. Upon treatment with Zelkova serrata twig extract, mouth epidermoid carcinoma cells accumulated in S phase by activation of p21. These data indicate that Zelkova serrata twig extract exerted a cancer type-specific, p53-dependent apoptotic effect and disturbed the cell cycle, which suggests that herbal medicine could be a treatment for specific types of cancers.

Accumulation of β-amyloid (Aβ) and resultant inflammation are critical pathological features of Alzheimer disease (AD). Microglia, a primary immune cell in brain, ingests and degrades extracellular Aβ fibrils via the lysosomal system. Autophagy is a catabolic process that degrades native cellular components, however, the role of autophagy in Aβ degradation by microglia and its effects on AD are unknown. Here we demonstrate a novel role for autophagy in the clearance of extracellular Aβ fibrils by microglia and in the regulation of the Aβ-induced NLRP3 (NLR family, pyrin domain containing 3) inflammasome using microglia specific atg7 knockout mice and cell cultures. We found in microglial cultures that Aβ interacts with MAP1LC3B-II via OPTN/optineurin and is degraded by an autophagic process mediated by the PRKAA1 pathway. We anticipate that enhancing microglial autophagy may be a promising new therapeutic strategy for AD.

Polo-like kinase-1 (Plk1) is phosphorylated on Thr210 for activation during mitosis. Here, we investigated the question of which kinase(s) is the specific upstream kinase of mitotic Plk1. Upstream kinases of Plk1 were purified from mitotic cell extracts through column chromatography procedures, and identified by mass spectrometry. Candidates for Plk1 kinase included p21-activated kinase, aurora A, and mammalian Ste20-like kinases. Immunoprecipitates of these proteins from mitotic cell extracts phosphorylated Plk1 on Thr210. Even if the activity of Aurora A was blocked with a specific inhibitor, Plk1 phosphorylation still occurred, suggesting that function of Plk1 could be controlled by these kinases for proper mitotic progression, as well as by Aurora A in very late G2 phase for the beginning of mitosis.Structured abstractMINT-7996332: PAK1(uniprotkb:Q13153)physically interacts(MI:0915) withPLK1(uniprotkb:P53350) bypull down(MI:0096)MINT-7996345: PAK3(uniprotkb:O75914)physically interacts(MI:0915) withPLK1(uniprotkb:P53350) bypull down(MI:0096)

Background Amyloid precursor protein (APP) is cleaved by β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) to produce β-amyloid (Aβ), a critical pathogenic peptide in Alzheimer’s disease (AD). Aβ generation can be affected by the intracellular trafficking of APP or its related secretases, which is thus important to understanding its pathological alterations. Although sorting nexin (SNX) family proteins regulate this trafficking, the relevance and role of sorting nexin-4 (SNX4) regarding AD has not been studied yet. Methods In this study, human brain tissue and APP/PS1 mouse brain tissue were used to check the disease relevance of SNX4. To investigate the role of SNX4 in AD pathogenesis, several experiments were done, such as coimmunoprecipitation, Western blotting, immunohistochemistry, and gradient fractionation. Results We found that SNX4 protein levels changed in the brains of patients with AD and of AD model mice. Overexpression of SNX4 significantly increased the levels of BACE1 and Aβ. Downregulation of SNX4 had the opposite effect. SNX4 interacts with BACE1 and prevents BACE1 trafficking to the lysosomal degradation system, resulting in an increased half-life of BACE1 and increased production of Aβ. Conclusions We show that SNX4 regulates BACE1 trafficking. Our findings suggest novel therapeutic implications of modulating SNX4 to regulate BACE1-mediated β-processing of APP and subsequent Aβ generation. Electronic supplementary material The online version of this article (doi:10.1186/s13195-016-0232-8) contains supplementary material, which is available to authorized users.