Biopolymer/Glycopolypeptide‐Blended Scaffolds: Synthesis,Characterization and Cellular Interactions

Three‐dimensional (3D) scaffolds formed from natural biopolymers gelatin and chitosan that are chemically modified by galactose have shown improved hepatocyte adhesion, spheroid geometry and functions of the hepatocytes. Galactose specifically binds to the hepatocytes via the asialoglycoprotein receptor (ASGPR) and an increase in galactose density further improves the hepatocyte proliferation and functions. In this work, we aimed to increase the galactose density within the biopolymeric scaffold by physically blending the biopolymers chitosan and gelatin with an amphiphlic β‐galactose polypeptide (PPO‐GP). PPO‐GP, is a di‐block copolymer with PPO and β‐galactose polypeptide, exhibits lower critical solution temperature and is entrapped within the scaffold through hydrophobic interactions. The uniform distribution of PPO‐GP within the scaffold was confirmed by fluorescence microscopy. SEM and mechanical testing of the hybrid scaffolds indicated pore size, inter connectivity and compression modulus similar to the scaffolds made from 100 % biopolymer. The presence of the PPO‐GP on the surface of the scaffold was tested monitoring the interaction of an analogous mannose containing PPO‐GP scaffold and the mannose binding lectin Con‐A. In vitro cell culture experiments with HepG2 cells were performed on GLN‐GP and CTS‐GP and their cellular response was compared with GLN and CTS scaffolds for a period of seven days. Within three days of culture the Hep G2 cells formed multicellular spheroids on GLN‐GP and CTS‐GP more efficiently than on the GLN and CTS scaffolds. The multicellular spheroids were also found to infiltrate more in GLN‐GP and CTS‐GP scaffolds and able to maintain their round morphology as observed by live/dead and SEM imaging.     

Genipin‐crosslinked gelatin hydrogel incorporated with PLLA‐nanocylinders as a bone scaffold: Synthesis,characterization, and mechanical properties evaluation

Nowadays, despite remarkable progress in developing bone tissue engineering products, the fabrication of an ideal scaffold that could meet the main criteria, such as providing mechanical properties and suitable biostability as well as mimicking the bone extracellular matrix, still seems challenging. In this regard, utilizing combinatorial approaches seems more beneficial. Here, we aim to reinforce the mechanical characteristics of gelatin hydrogel via a combination of Genipin‐based chemical cross‐linking and incorporation of the poly l ‐lactic acid (PLLA) nanocylinders for application as bone scaffolds. Amine‐functionalized nanocylinders are prepared via the aminolysis procedure and incorporated in gelatin hydrogel. The nanocylinder content (0, 1, 2, 3, and 4 wt%) and cross‐linking density (0.1, 0.5, and 1 wt/vol%) are optimized to achieve suitable morphology, swelling ratio, degradation rate, and mechanical behaviors. The results indicate that hydrogel scaffold cross‐linking by 0.5 wt% of Genipin shows optimized morphological feathers with a pore size of around 300 to 500 μm as well as an average degradation rate (40.09% ± 3.08%) during 32 days. Besides, the incorporation of 3 wt% PLLA nanocylinders into the cross‐linked gelatin scaffold provides an optimized mechanical reinforcement as compressive modulus, and compressive strength show a 4‐ and 2.6‐fold increase, respectively. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay indicates that the scaffold does not have any cytotoxicity effect. In conclusion, gelatin composite reinforced with 3 wt% PLLA nanocylinders cross‐linked via 0.5 wt/vol% Genipin is suggested as a potential scaffold for bone tissue engineering applications.     

Simulation of the bioadhesive gelatin‐alginate conjugate loaded with antibiotic drugs

In the present research, molecular modeling methods were used to study a novel bioadhesive composed of gelatin (protein) and alginate (polysaccharides), crosslinked with N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide hydrochloride (EDC) and N‐hydroxysuccinimide (NHS). Three antibiotic drugs were added to the bioadhesive: Vancomycin, Ofloxacin, and Clindamycin. Computational tools were applied to estimate the crosslinking degree and compare the effect of the antibiotics on the physical properties of the gelatin‐alginate conjugate. The crosslinking degree was estimated by calculating the enthalpy of mixing of gelatin with alginate and their interaction with the crosslinking agents. The calculations revealed that gelatin mixes well with alginate, which enables their crosslinking. Various ratios between EDC and NHS were examined, and an optimal ratio was found. The interaction of alginate‐gelatin conjugate with the antibiotics was correlated to the experimental results of bonding strength. The most significant interaction of the conjugate is with clindamycin. The gelatin part is responsible for the strong interaction with clindamycin, and alginate forms strong interaction with ofloxacin. Thus, the interaction of alginate‐gelatin conjugate with the antibiotics is governed by the proportion between gelatin and alginate in the conjugate. The degradation rate of gelatin‐alginate was related to its interaction with water. It was found that the conjugate is highly hydrophilic. Gelatin is more soluble in water than both alginate and alginate‐gelatin and is probably the part in the conjugate that governs the solubility and degradation rate. Therefore, the degradation rate of the conjugate can be controlled by changing the proportion between gelatin and alginate.     

Template‐free Fabrication of Hierarchical Macro‐/mesoporous N‐doped TiO2/graphene Oxide Composites with Enhanced Visible‐light Photocatalytic Activity

Hierarchical macro‐/mesoporous N‐doped TiO₂/graphene oxide (N‐TiO₂/GO) composites were prepared without using templates by the simple dropwise addition mixed solution of tetrabutyl titanate and ethanol containg graphene oxide (GO) to the ammonia solution, and then calcined at 350 °C. The as‐prepared samples were characterized by scanning electron microscopy (SEM), Brunauer‐Emmett‐Teller (BET) surface area, X‐ray diffraction (XRD), Raman spectroscopy, X‐ray photoelectron spectroscopy (XPS), and UV‐Vis absorption spectroscopy. The photocatalytic activity was evaluated by the photocatalytic degradation of methyl orange in an aqueous solution under visible‐light irradiation. The results show that N‐TiO₂/GO composites exhibited enhanced photocatalytic activity. GO content exhibited an obvious influence on photocatalytic performance, and the optimal GO addition content was 1 wt%. The enhanced photocatalytic activity could be attributed to the synergetic effects of three factors including the improved visible light absorption, the hierarchical macro‐mesoporous structure, and the efficient charge separation by GO.     

Electrospun core–sheath fibers for integrating the biocompatibility of silk fibroin and the mechanical properties of PLCL

In the process of preparing core–sheath fibers via coaxial electrospinning, the relative evaporation rates of core and sheath solvents play a key role in the formation of the core–sheath structure of the fiber. Both silk fibroin (SF) and poly(lactide‐co‐ε‐caprolactone) (PLCL) have good biocompatibility and biodegradability. SF has better cell affinity than PLCL, whereas PLCL has higher breaking strength and elongation than SF. In this work, hexafluoroisopropanol (HFIP)‐formic acid (volume ratio 8:2), HFIP and HFIP–dichloromethane (volume ratio 8:2) were used to dissolve PLCL as the core solutions, and HFIP was used to dissolve SF as the sheath solution. Then, core–sheath structured SF/PLCL (C‐SF/PLCL) fibers were prepared by coaxial electrospinning with the core and sheath solutions. Transmission electron microscopy images indicated the existence of the core–shell structure of the fibers, and energy dispersive X‐ray analysis results revealed that the fiber mat with the greatest content of core–shell structure fibers was obtained when the core solvent was HFIP–dichloromethane (volume ratio 8:2). Tensile tests showed that the C‐SF/PLCL fiber mat displayed improved tensile properties, with strength and elongation that were significantly higher than those of the pure SF mat. The C‐SF/PLCL fiber mat was further investigated as a scaffold for culturing EA.hy926 cells, and the results showed that the fiber mat permitted cellular adhesion, proliferation and spreading in a manner similar to that of the pure SF fiber mat. These results indicated that the coaxial electrospun SF/PLCL fiber mat could be considered a promising candidate for tissue engineering scaffolds for blood vessels. Copyright © 2014 John Wiley & Sons, Ltd.     

Chip electrophoresis of gelatin‐based nanoparticles

Recently, biodegradable nanoparticles received increasing attention for pharmaceutical applications as well as applications in the food industry. With the current investigation we demonstrate chip electrophoresis of fluorescently (FL) labeled gelatin nanoparticles (gelatin NPs) on a commercially available instrument. FL labeling included a step for the removal of low molecular mass material (especially excess dye molecules). Nevertheless, for the investigated gelatin NP preparation two analyte peaks, one very homogeneous with an electrophoretic net mobility of μ = ?24.6 ± 0.3 × 10^?9 m²/Vs at the peak apex (n = 17) and another more heterogeneous peak with μ between approximately ?27.2 ± 0.2 × 10^?9 m²/Vs and ?36.6 ± 0.2 × 10^?9 m²/Vs at the peak beginning and end point (n = 11, respectively) were recorded. Filtration allowed enrichment of particles in the size range of approximately 35 nm (pore size employed for concentration of gelatin NPs) to 200 nm (pore size employed during FL labeling). This corresponded to the very homogeneous peak linking it to gelatin NPs, whereas the more heterogeneous peak probably corresponds to gelatin not cross‐linked to such a high degree (NP building blocks). Several further gelatin NP preparations were analyzed according to the same protocol yielding peaks with electrophoretic net mobilities between ?23.3 ± 0.3 × 10^?9 m²/Vs and ?28.9 ± 0.2 × 10^?9 m²/Vs at peak apexes (n = 15 and 6). Chip electrophoresis allows analyte separation in less than two minutes (including electrophoretic sample injection). Together with the high sensitivity of the FL detection – the LOD as derived for the first main peak of the applied dye from the threefold standard deviation of the background noise values 80 pM for determined separation conditions – this leads to a very promising high throughput separation technique especially for the analysis of bionanoparticles. For gelatin NP preparations, chip electrophoresis allows for example the comparison of preparation batches concerning the amount of NPs and gelatin building blocks as well as the indirect assessment of the degree of gelatin cross‐linking (from obtained FL signals).     

Sol–gel transition behavior of biodegradable three‐arm and four‐arm star‐shaped PLGA–PEG block copolymer aqueous solution

Two types of temperature‐sensitive biodegradable three‐arm and four‐arm star‐shaped poly(DL ‐lactic acid‐co‐glycolic acid‐b‐ethylene glycol) (3‐arm and 4‐arm PLGA–PEG) were successfully synthesized via the coupling reaction of 3‐arm and 4‐arm PLGA and α‐monocarboxyl‐ω‐monomethoxypoly(ethylene glycol) (CMPEG). In dilute aqueous solutions, star PLGA–PEGs showed the temperature‐ and concentration‐dependent formation and aggregation of micelles over specific concentration and specific temperature. With increasing the molecular weight and the relative hydrophobicity of hydrophobic PLGA block, critical micelle temperature (CMT) decreased. Aqueous solution of 4‐arm PLGA–PEG started to form micelles at lower temperature and showed sharper temperature‐dependent growth in micelle size. These results are due to the enhanced hydrophobicity of PLGA block. On the other hand, at high concentration, two types of 3‐arm and 4‐arm PLGA–PEG showed sol–gel–sol transition behavior as the temperature was increased. The 3‐arm and 4‐arm PLGA–PEG showed sol–gel transition at higher polymer concentrations (above 24 wt %) than the PEG–PLGA–PEG triblock copolymer. As the molecular weight and the relative hydrophobicity of PLGA block increased, the critical gel concentration (CGC) decreased. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 888–899, 2006     

Effect of PLGA block molecular weight on gelling temperature of PLGA‐PEG‐PLGA thermoresponsive copolymers

Thermoresponsive, biodegradable polymeric hydrogel networks are used widely in medicinal applications. Poly(d ,l ‐lactic acid‐co‐glycolic acid)‐b‐poly(ethylene glycol)‐b‐poly(d ,l ‐lactic acid‐co‐glycolic acid) (PLGA‐PEG‐PLGA) triblock copolymers exhibit a sol–gel transition upon heating. The effect of PLGA block and PEG chain molecular weights (MWs) on the gelling temperature of polymer aqueous solution (20% w/w) is described. All polymer solutions convert into a hard gel within 2 °C of the gelling temperature. The release properties of the gels were displayed using paracetamol as a representative drug. A linear relation is described between the gelling temperature and PLGA block MW. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 35–39     

Temperature Responsive Shape‐Memory Scaffolds with Circumferentially Aligned Nanofibers for Guiding Smooth Muscle Cell Behavior

Structural simulation of the smooth muscle layer plays an important role in tissue engineering of blood vessels for the replacement of damaged arteries. However, it is difficult to construct small‐diameter tubular scaffolds to homogenously locate and align smooth muscle cells (SMCs). In this work, novel temperature responsive shape‐memory scaffolds are designed for SMC culturing. The scaffolds are composed of an outer layer of poly(lactide–glycolide–trimethylene carbonate) (PLGATMC) for programming the deformation from planar to small‐diameter tubular shape and an inner layer of aligned nanofibrous membrane of poly(lactide–glycolide)/chitosan (PLGA/CS) to regulate cell adhesion, proliferation, and morphology. The SMC behaviors and functions are dependent on the PLGA/CS ratios of membranes, and the scaffold with PLGA/CS 7:3 membrane exhibits the most suitable ability to regulate SMC behavior. The PLGA/CS@PLGATMC scaffold can be deformed into a temporary planar at 20 °C for convenient seeding and attachment of SMCs and then immediately self‐rolled into 3D tube at 37 °C. The proposed strategy offers a practical approach for the development of small‐diameter vascular scaffolds from 2D planar into 3D tubular shape by self‐rolling.     

Fabrication of Transparent,Tough, and Conductive Shape‐Memory Polyurethane Films by Incorporating a Small Amount of High‐Quality Graphene

We report a mechanically strong, electrically and thermally conductive, and optically transparent shape‐memory polyurethane composite which was fabricated by introducing a small amount (0.1 wt%) of high‐quality graphene as a filler. Geometrically large (≈4.6 μm²), but highly crystallized few‐layer graphenes, verified by Raman spectroscopy and transmission electron microscopy, were prepared by the sonication of expandable graphite in an organic solvent. Oxygen‐ containing functional groups at the edge plane of graphene were crucial for an effective stress transfer from the graphene to polyurethane. Homogeneously dispersed few‐layered graphene enabled polyurethane to have a high shape recovery force of 1.8 MPa cm⁻³. Graphene, which is intrinsically stretchable up to 10%, will enable high‐performance composites to be fabricated at relatively low cost and we thus envisage that such composites may replace carbon nanotubes for various applications in the near future.     

Optimization of fibrin gelation for enhanced cell seeding and proliferation in regenerative medicine applications

In order to improve the cell seeding efficiency and cell compatibility inside porous tissue scaffolds, a method of fibrin gel‐mediated cell encapsulation inside the scaffold was optimized. Disc‐type poly(d ,l ‐glycolic‐co‐lactic acid) (PLGA) scaffolds without a dense surface skin layer were fabricated using an established solvent casting and particulate leaching method as a model porous scaffold, which showed high porosity ranging from 90 ± 2% to 96 ± 2%. The thrombin and fibrinogen concentration as precursors of fibrin gel was varied to control the gelation kinetics as measured by rheology analysis, and optimized conditions were developed for a uniform fibrin gel formation with the target cells inside the porous PLGA scaffold. The fibroblast cell seeding accompanied by a uniform fibrin gel formation at an optimized gelation condition inside the PLGA scaffold resulted in an increase in cell seeding efficiency, a better cell proliferation, and an increase in final cell density inside the scaffold. Scanning electron microscopy images revealed that cells were better spread and grown by fibrin gel encapsulation inside scaffold compared with the case of bare PLGA scaffold. Copyright © 2016 John Wiley & Sons, Ltd.     

Fabrication of graphene‐silver/polyurethane nanofibrous scaffolds for cardiac tissue engineering

The graphene‐based nanocomposites are considered as great candidates for enhancing electrical and mechanical properties of nonconductive scaffolds in cardiac tissue engineering. In this study, reduced graphene oxide‐silver (rGO‐Ag) nanocomposites (1 and 2 wt%) were synthesized and incorporated into polyurethane (PU) nanofibers via electrospinning technique. Next, the human cardiac progenitor cells (hCPCs) were seed on these scaffolds for in vitro studies. The rGO‐Ag nanocomposites were studied by X‐ray diffraction (XRD), Raman spectroscopy, and transmission electron microscope (TEM). After incorporation of rGO‐Ag into PU nanofibers, the related characterizations were carried out including scanning electron microscope (SEM), TEM, water contact angle, and mechanical properties. Furthermore, PU and PU/nanocomposites scaffolds were used for in vitro studies, wherein hCPCs showed good cytocompatibility via 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay and considerable attachment on the scaffold using SEM studies. Real‐time polymerase chain reaction (PCR) and immunostaining studies confirmed the upregulation of cardiac specific genes including GATA‐4, T‐box 18 (TBX 18), cardiac troponin T (cTnT), and alpha‐myosin heavy chain (α‐MHC) in the PU/rGO‐Ag scaffolds in comparison with neat PU ones. Therefore, these nanofibrous rGO‐Ag–reinforced PU scaffolds can be considered as suitable candidates in cardiac tissue engineering.     

Mechanical properties and degradation studies of poly(D,L‐lactide‐co‐glycolide) 50:50/graphene oxide nanocomposite films

Poly(D,L‐lactide‐co‐glycolide) 50:50 (PLGA)/graphene oxide (GO) nanocomposite films were prepared with various GO weight fractions. A significant enhancement of mechanical properties of the PLGA/GO nanocomposite films was obtained with GO weight fractions. The incorporation of only 5 wt% of GO resulted in an ~2.5‐fold and ~4.7‐fold increase in the tensile strength and Young's modulus of PLGA, respectively. The thermomechanical behaviors of composite films were investigated by dynamic mechanical analysis. Results indicated that the values of T_g and storage moduli of the PLGA/GO composites were higher than those of the pristine PLGA. The improvement in oxygen barrier properties of composites was presumably attributed to the filler effect of the randomly dispersed GO throughout the PLGA matrix. In this work, we also studied in vitro biodegradation behavior. PLGA/GO composite films were hydrolyzed at 37°C for periods up to 49 days. Because of the presence of GO nanosheets, degradation of composite films took place more slowly with increasing GO amounts. Copyright © 2013 John Wiley & Sons, Ltd.     

A hybrid scaffold of poly(lactide-<Emphasis Type="Italic">co</Emphasis>-glycolide) sponge filled with fibrin gel for cartilage tissue engineering

The poly(lactide-co-glycolide)(PLGA) sponge fabricated by a gelatin porogen leaching method was filled with fibrin gel to obtain a hybrid scaffold for chondrocytes culture in vitro.The fibrin gel evenly distributed in the hybrid scaffold with visible fibrinogen fibers after drying.In vitro culture it was found that in the hybrid scaffold the chondrocytes distributed more evenly and kept a round morphology as that in the normal cartilage.Although the chondrocytes seeded in the control PLGA sponges showed similar proliferation behavior with that in the hybrid scaffolds,they were remarkably elongated,forming a fibroblast-like morphology.Moreover,a larger amount of glycosaminoglycans was secreted in the hybrid scaffolds than that in the PLGA sponges after in vitro culture of chondrocytes for 4 weeks.The results suggest that the fibrin/PLGA hybrid scaffold may be favorably applied for cartilage tissue engineering.     

Corrosion behavior of tantalum alloying on γ‐TiAl by double‐glow plasma surface metallurgy technique

The Ta coating with corrosion resistance is grown on the γ‐TiAl substrate by double‐glow plasma surface metallurgy technique, followed by the electrochemical test in 10 wt%, 20 wt% HCl and 10 wt%, 40 wt% H₂SO₄ solution. The data of nanohardness and elastic modulus are collected by the nanoindention test. The adhesion strength of Ta coating is investigated by means of the scratch test. The study of corrosion resistance is performed using potentiodynamic polarization and electrochemical impedance spectroscopy and measured by SEM and X‐ray diffraction. Results highlight that the Ta coating is tightly bonded to the γ‐TiAl substrate, consisting of the deposition layer and diffusion layer. Experimental data indicate that the Ta coating presents excellent corrosion resistance, which is confirmed by the high values of polarization resistance (R_p) and the low values of corrosion current density (i_corr). The surface nanohardness of the Ta coating is improved from 3.41 to 7.29 GPa, nearly twice of that of the substrate. The Ta₂O₅ formed on the coating is able to hold back the penetration of adverse ions inwardly, owing to its dense structure and adhesion effect. Copyright © 2017 John Wiley & Sons, Ltd.     

Novel Thermoreversible Gelation of Biodegradable PLGA‐block‐PEO‐block‐PLGA Triblock Copolymers in Aqueous Solution

The BAB‐type triblock copolymers composed of a central poly(ethylene oxide) (PEO, M̄_nPEO = 1 000) block and two poly[(D ,L ‐lactic acid)‐co‐(glycolic acid)] end blocks with molecular weights between 900 and 1 600 exhibited an interesting phase transition behavior. The copolymer aqueous solution can form micelles with PLGA loops in the core and a PEO shell and groups of micelles because of bridging between micelles caused by the PLGA blocks with raising temperature. A possible micellar gelation mechanism was suggested.     

Preparation of rapidly curable hydrogels from gelatin and poly (carboxylic acid) and their adhesion to skin

Papidly curable hydrogels were prepared through chemical crosslinking of gelatin with poly(carboxylic acid)s including poly (L-glutamic acid) (PLGA), hyaluronic acid (HA), and poly (acrylic acid) (PAA) by use of water-soluble carbodiimide (WSC). The effects of the nature of added poly (carboxylic acid)s on gelation of mixed gelatinpoly (carboxylic acid) aqueous solutions and adhesion of the resulting hydrogels to the mouse skin were evaluated. The addition of poly (carboxylic acid) s reduced the gelation time of gelatin aqueous solutions except for HA. Mixed gelatin-PLGA solutions were cured more rapidly than other mixed solutions and the gelation time was shortened with the increasing PLGA molecular weight. The resulting gelatin-PLGA hydrogels exhibited stronger adhesion to the mouse skin than gelatin-HA and gelatin-PAA hydrogels. The bonding strength increased with the increase in PLGA molecular weight up to 83,000 and thereafter decreased. The longer gelation time and lower adhesion of the gelatin-PAA hydrogels than the gelatin-PLGA hydrogels seem to be due to poorer compatibility of gelatin with PAA than with PLGA. The mixed gelatin-PLGA solution underwent phase separation when the concentration and molecular weight of PLGA became higher than a threshold. The insignificant or suppressive effect of HA addition might be ascribed to the HA-WSC reaction which was the least effective in hydrogel formation.     

与胶原特异性结合的BMP2模拟肽/PLGA 3D打印复合支架的制备及成骨诱导活性

将胶原绑定结构域(CBD)多肽序列与骨形态发生蛋白2模拟肽(BMP2-MP)序列连接制备具有胶原绑定能力的CBD-BMP2-MP, 再将CBD-BMP2-MP与聚丙交酯-乙交酯/胶原(PLGA/COL)3D打印支架相结合, 以支架表面的胶原成分为媒介, 将CBD-BMP2-MP更有效地固定于骨修复材料上, 达到对其进行改性的目的. 利用扫描电子显微镜(SEM)、 电子万能试验机和接触角测量仪对复合支架表面形貌、 力学强度和亲水性等材料学性能进行评价. 用荧光成像法评测 CBD-BMP2-MP及BMP2-MP与支架材料的结合能力. 在各组支架材料表面接种MC3T3-E1细胞进行体外培养, 采用CCK-8、 鬼笔环肽荧光染色、 茜素红染色及qPCR综合评价细胞在材料表面的黏附、 增殖和成骨分化等细胞行为, 研究CBD-BMP2-MP修饰的3D多孔PLGA/COL复合支架的生物学性能. 研究结果表明, 利用3D打印技术制备的多孔支架具有形貌可控的孔隙结构, 为细胞生长创造更有利的细胞微环境, 支架表面胶原成分的加入提高了支架材料的亲水性, 同时对支架材料本身的力学性能无任何影响, 提高了复合支架本身的生物相容性. 与普通BMP2-MP相比, CBD-BMP2-MP具有更好的胶原绑定能力, 与复合支架的结合更稳定, 提高了PLGA/COL复合支架对BMP2-MP的负载能力. 支架表面负载CBD-BMP2-MP后具有极强的促细胞成骨分化能力. MC3T3-E1细胞表现出更高的钙沉积能力, 并且成骨分化相关基因Runx2, ALP, COL-I及OPN等水平也有了明显提升. 表明CBD-BMP2-MP多孔复合支架具有良好的生物相容性和成骨诱导活性, 在骨组织修复领域具有良好的应用前景.     

Microfluidic chip-based fabrication of PLGA microfiber scaffolds for tissue engineering

In this paper, we have developed a method to produce poly(lactic- co-glycolic acid) (PLGA) microfibers within a microfluidic chip for the generation of 3D tissue engineering scaffolds. The synthesis of PLGA fibers was achieved by using a polydimethylsiloxane (PDMS)-based microfluidic spinning device in which linear streams of PLGA dissolved in dimethyl sulfoxide (DMSO) were precipitated in a glycerol-containing water solution. By changing the flow rate of PLGA solution from 1 to 50 microL/min with a sheath flow rate of 250 or 1000 microL/min, fibers were formed with diameters that ranged from 20 to 230 microm. The PLGA fibers were comprised of a dense outer surface and a highly porous interior. To evaluate the applicability of PLGA microfibers generated in this process as a cell culture scaffold, L929 fibroblasts were seeded on the PLGA fibers either as-fabricated or coated with fibronectin. L929 fibroblasts showed no significant difference in proliferation on both PLGA microfibers after 5 days of culture. As a test for application as nerve guide, neural progenitor cells were cultured and the neural axons elongated along the PLGA microfibers. Thus our experiments suggest that microfluidic chip-based PLGA microfiber fabrication may be useful for 3D cell culture tissue engineering applications.     

Cell‐Free HA‐MA/PLGA Scaffolds with Radially Oriented Pores for In Situ Inductive Regeneration of Full Thickness Cartilage Defects

A bioactive scaffold with desired microstructure is of great importance to induce infiltration of somatic and stem cells, and thereby to achieve the in situ inductive tissue regeneration. In this study, a scaffold with oriented pores in the radial direction is prepared by using methacrylated hyaluronic acid (HA‐MA) via controlled directional cooling of a HA‐MA solution, and followed with photo‐crosslinking to stabilize the structure. Poly(lactide‐co‐glycolide) (PLGA) is further infiltrated to enhance the mechanical strength, resulting in a compressive modulus of 120 kPa. In vitro culture of bone marrow stem cells (BMSCs) reveals spontaneous cell aggregation inside this type of scaffold with a spherical morphology. In vivo transplantation of the cell‐free scaffold in rabbit knees for 12 w regenerates simultaneously both cartilage and subchondral bone with a Wakitani score of 2.8. Moreover, the expression of inflammatory factor interleukin‐1β (IL‐1β) is down regulated, although tumor necrosis factor‐α (TNF‐α) is remarkably up regulated. With the anti‐inflammatory, bioactive properties and good restoration of full thickness cartilage defect in vivo, the oriented macroporous HA‐MA/PLGA hybrid scaffold has a great potential for the practical application in the in situ cartilage regeneration.