Sustained Release of Insulin-Like Growth Factor-1 from Bombyx mori L. Silk Fibroin Delivery for Diabetic Wound Therapy

The goals of this study are to develop a high purity patented silk fibroin (SF) film and test its suitability to be used as a slow-release delivery for insulin-like growth factor-1 (IGF-1). The release rate of the SF film delivering IGF-1 followed zero-order kinetics as determined via the Ritger and Peppas equation. The release rate constant was identified as 0.11, 0.23, and 0.09% h⁻¹ at 37 °C for SF films loaded with 0.65, 6.5, and 65 pmol IGF-1, respectively. More importantly, the IGF-1 activity was preserved for more than 30 days when complexed with the SF film. We show that the IGF-1-loaded SF films significantly accelerated wound healing in vitro (BALB/3T3) and in vivo (diabetic mice), compared with wounds treated with free IGF-1 and an IGF-1-loaded hydrocolloid dressing. This was evidenced by a six-fold increase in the granulation tissue area in the IGF-1-loaded SF film treatment group compared to that of the PBS control group. Western blotting analysis also demonstrated that IGF-1 receptor (IGF1R) phosphorylation in diabetic wounds increased more significantly in the IGF-1-loaded SF films group than in other experimental groups. Our results suggest that IGF-1 sustained release from SF films promotes wound healing through continuously activating the IGF1R pathway, leading to the enhancement of both wound re-epithelialization and granulation tissue formation in diabetic mice. Collectively, these data indicate that SF films have considerable potential to be used as a wound dressing material for long-term IGF-1 delivery for diabetic wound therapy.     

Silkworm Gut Fibres from Silk Glands of Samia cynthia ricini—Potential Use as a Scaffold in Tissue Engineering

High-performance fibroin fibres are ideal candidates for the manufacture of scaffolds with applications in tissue engineering due to the excellent mechanical properties and optimal biocompatibility of this protein. In this work, the manufacture of high-strength fibres made from the silk glands of Samia cynthia ricini is explored. The glands were subjected to soaking in aqueous dissolutions of acetic acid and stretched to manufacture the fibres. The materials produced were widely characterized, in terms of morphology, mechanical properties, crystallinity and content of secondary structures, comparing them with those produced by the standard procedure published for Bombyx mori. In addition, mechanical properties and biocompatibility of a braided scaffold produced from these fibres was evaluated. The results obtained show that the fibres from B. mori present a higher degree of crystallinity than those from S. c. ricini, which is reflected in higher values of elastic modulus and lower values of strain at break. Moreover, a decrease in the elongation values of the fibres from S. c. ricini was observed as the concentration of acetic acid was increased during the manufacture. On the other hand, the study of the braided scaffolds showed higher values of tensile strength and strain at break in the case of S. c. ricini materials and similar values of elastic modulus, compared to those of B. mori, displaying both scaffolds optimal biocompatibility using a fibroblast cell line.     

Decellularized Cartilage Extracellular Matrix Incorporated Silk Fibroin Hybrid Scaffolds for Endochondral Ossification Mediated Bone Regeneration

Tissue engineering strategies promote bone regeneration for large bone defects by stimulating the osteogenesis route via intramembranous ossification in engineered grafts, which upon implantation are frequently constrained by insufficient integration and functional anastomosis of vasculature from the host tissue. In this study, we developed a hybrid biomaterial incorporating decellularized cartilage extracellular matrix (CD-ECM) as a template and silk fibroin (SF) as a carrier to assess the bone regeneration capacity of bone marrow-derived mesenchymal stem cells (hBMSC’s) via the endochondral ossification (ECO) route. hBMSC’s were primed two weeks for chondrogenesis, followed by six weeks for hypertrophy onto hybrid CD-ECM/SF or SF alone scaffolds and evaluated for the mineralized matrix formation in vitro. Calcium deposition biochemically determined increased significantly from 4-8 weeks in both SF and CD-ECM/SF constructs, and retention of sGAG’s were observed only in CD-ECM/SF constructs. SEM/EDX revealed calcium and phosphate crystal localization by hBMSC’s under all conditions. Compressive modulus reached a maximum of 40 KPa after eight weeks of hypertrophic induction. μCT scanning at eight weeks indicated a cloud of denser minerals in groups after hypertrophic induction in CD-ECM/SF constructs than SF constructs. Gene expression by RT-qPCR revealed that hBMSC’s expressed hypertrophic markers VEGF, COL10, RUNX2, but the absence of early hypertrophic marker ChM1 and later hypertrophic marker TSBS1 and the presence of osteogenic markers ALPL, IBSP, OSX under all conditions. Our data indicate a new method to prime hBMSC’S into the late hypertrophic stage in vitro in mechanically stable constructs for ECO-mediated bone tissue regeneration.     

Electrospun Polycaprolactone/Silk Fibroin/Small Intestine Submucosa Composites for Biomedical Applications

Natural biomaterials were used to improve the biocompatibility of synthetic biopolymers. PCL was electrospun with natural biopolymers, silk fibroin, and small intestine submucosa. Due to increased electrical conductivity, the diameter of the composite fibers highly depended on the amount of SIS in the polymer solution. PCL/SF/SIS electrospun composites exhibited various synergistic effects, including enhanced mechanical properties and incredibly improved hydrophilicity compared to those of pure PCL and PCL/SF fibers. An initial cell attachment test demonstrated that the interactions between PC‐12 nerve cells and the PCL/SF/SIS composites were more favorable than those between PC‐12 cells and a PCL/SF composite.

     

Morphological and Biological Evaluations of Human Periodontal Ligament Fibroblasts in Contact with Different Bovine Bone Grafts Treated with Low-Temperature Deproteinisation Protocol

Several types of deproteinised bovine bone mineral (DBBM) are available on the market, and each one is obtained with a thermic and chemical process that can differ, achieving different results. Currently, several protocols using low temperature are suggested to reduce the possible particle crystallisation during the production process. This study aimed to evaluate the biomorphological reaction of periodontal fibroblast cultures in contact with different DBBM particles treated with a low-temperature protocol (Thermagen^®) and without exposure to sodium hydroxide (NaOH). Morphological evaluation was performed using light, confocal laser, and scanning electron microscopy, and the biological reaction in terms of proliferation was performed using an XTT proliferation assay at 24 h (T1), 72 h (T2), and 7 days (T3). The morphological analysis highlighted how the presence of the materials stimulated a change in the morphology of the cells into a polygonal shape, surface reactions with the thickening of the membrane, and expression of actin. In particular, the morphological changes were appreciable from T1, with a progressive increase in the considered morphological characteristics at T2 and T3 follow-ups. The proliferation assay showed a statistical significance between the different experimental materials and the negative control in T2 and T3 follow-ups. The post hoc analysis did not reveal any differences between the materials. In conclusion, the grafts obtained with the low-temperature extractions protocol and not exposed to NaOH solution showed positive morphological reactions with no differences in the sizes of particles.     

Cetyl Trimethyl Ammonium Bromide Modified Montmorillonite-Doped Tasar Silk Fibroin/Polyvinyl Alcohol Blend 3D Nanowebs for Tissue Engineering Applications

Cetyl trimethyl ammonium bromide (CTAB) modified montmorillonite (MMT) clay (CTAB-MT) doped, tasar silk fibroin-polyvinyl alcohol blend-based 3D nanowebs are generated through electrospinning technique. The morphological analysis reveals the formation of interlinked 3D nanoweb-like architecture and high surface roughness through scanning electron microscopy (SEM) and atomic force microscopy, respectively. The existence of CTAB-MT in nanowebs is confirmed by Fourier transform infrared and complete exfoliation of clay in the polymer blend matrix along with the altered crystallinity of samples is indicated in X-ray diffraction. The incorporation of CTAB-MT clay has shown the enhancement of thermal and mechanical properties of nanoweb samples while the water uptake capacity is reduced and enzymatic biodegradability is found to slow down. The samples present excellent biocompatibility with no cytotoxicity in the Alamar blue assay and high attachment as well as spreading of L929 fibroblast cells covering the entire surface as observed in SEM. The CTAB-MT clay has imparted the samples with good antimicrobial activity against E. coli and S. aureus bacterial strains. The aforementioned properties of these CTAB-MT clay doped 3D nanowebs direct toward their suitability as a potential candidate for tissue engineering applications in the biomedical field.     

A Carbodiimide Cross-Linked Silk Fibroin/Sodium Alginate Composite Hydrogel with Tunable Properties for Sustained Drug Delivery

Carbodiimide cross-linked silk fibroin (SF)/sodium alginate (SA) composite hydrogels with superior stability and tunable properties are developed by varying preparation parameters. SF/SA blend ratio modulation allows to achieve composite hydrogel gelation times of 18–65 min, and rheological analysis shows that the speed of gel formation, the hydrogel network's density, and the hydrogels’ compressive properties are closely related to the blend ratio. The G′ of different hydrogels varies substantially from 28 to 413 Pa, and the hydrogel with higher SF content has a greater stiffness. The composite hydrogels present appropriate porosity of 76.63–85.09% and pore size of 316–603 µm. Hydrogel stability improves significantly after cross-linking, and substantial swelling occurs due to the hydrophilicity of SA. The 7/3 and 6/4 SF/SA hydrogels are more resistant to degradation in PBS, and cytotoxicity testing confirmed their biocompatibility. For release studies in vitro, two model compounds are used as drug models, tetracycline hydrochloride, and bovine serum albumin (BSA). Different ratios of SF/SA have a greater influence on the release of BSA. This study provides a practical preparation method for flexible SF/SA composite hydrogels, which can help design hydrogels with specific physicochemical properties for different applications, especially drug delivery.     

Enhanced BMP-2-Mediated Bone Repair Using an Anisotropic Silk Fibroin Scaffold Coated with Bone-like Apatite

The repair of large bone defects remains challenging and often requires graft material due to limited availability of autologous bone. In clinical settings, collagen sponges loaded with excessive amounts of bone morphogenetic protein 2 (rhBMP-2) are occasionally used for the treatment of bone non-unions, increasing the risk of adverse events. Therefore, strategies to reduce rhBMP-2 dosage are desirable. Silk scaffolds show great promise due to their favorable biocompatibility and their utility for various biofabrication methods. For this study, we generated silk scaffolds with axially aligned pores, which were subsequently treated with 10× simulated body fluid (SBF) to generate an apatitic calcium phosphate coating. Using a rat femoral critical sized defect model (CSD) we evaluated if the resulting scaffold allows the reduction of BMP-2 dosage to promote efficient bone repair by providing appropriate guidance cues. Highly porous, anisotropic silk scaffolds were produced, demonstrating good cytocompatibility in vitro and treatment with 10× SBF resulted in efficient surface coating. In vivo, the coated silk scaffolds loaded with a low dose of rhBMP-2 demonstrated significantly improved bone regeneration when compared to the unmineralized scaffold. Overall, our findings show that this simple and cost-efficient technique yields scaffolds that enhance rhBMP-2 mediated bone healing.     

Recent Research Progress of Ionic Liquid Dissolving Silks for Biomedicine and Tissue Engineering Applications

Ionic liquids (ILs) show a bright application prospect in the field of biomedicine and energy materials due to their unique recyclable, modifiability, structure of cation and anion adjustability, as well as excellent physical and chemical properties. Dissolving silk fibroin (SF), from different species silkworm cocoons, with ILs is considered an effective new way to obtain biomaterials with highly enhanced/tailored properties, which can significantly overcome the shortcomings of traditional preparation methods, such as the cumbersome, time-consuming and the organic toxicity caused by manufacture. In this paper, the basic structure and properties of SF and the preparation methods of traditional regenerated SF solution are first introduced. Then, the dissolving mechanism and main influencing factors of ILs for SF are expounded, and the fabrication methods, material structure and properties of SF blending with natural biological protein, inorganic matter, synthetic polymer, carbon nanotube and graphene oxide in the ILs solution system are introduced. Additionally, our work summarizes the biomedicine and tissue engineering applications of silk-based materials dissolved through various ILs. Finally, according to the deficiency of ILs for dissolving SF at a high melting point and expensive cost, their further study and future development trend are prospected.     

论聚丙烯高熔融指数（MFR）产品的生产工艺

介绍了聚丙烯高熔融指数产品的三种生产工艺及其对应的产品性能，比较了工艺的优缺点，确定了一种最佳的生产方法。     

Porous composites of hydroxyapatite‐filled poly[ethylene‐co‐(vinyl acetate)] for tissue engineering

A novel porous composite of hydroxyapatite/poly[ethylene‐co‐vinyl acetate)] (HAP/EVA) having better osteointegration was fabricated by gas foaming technique using a non toxic gas blowing agent intended for bone replacement applications. Combined techniques of scanning electronic microscopy (SEM) and X‐ray microcomputed tomography (µCT) analysis showed that the pore size and pore volume of the porous composite decrease with the increase of HAP content. The gravimetric analysis evidenced for good pore interconnectivity within the porous composites. Energy dispersive X‐ray analysis (EDX) studies inveterated the even scattering of Ca ions which in turn indicate the uniform dispersion of HAP particles in the composites. The significant gradation in Ca ion concentration seen in EDX studies is well accordance with the amount of HAP loading in the sample. Mechanical properties of the porous composite having different HAP content were measured to have the compressive strength varying from 1.06 to 2.2 MPa. Non‐cytotoxic character of the material was observed by the cytocompatibility studies. The metabolic activity of L929 cells seeded on the material assessed by [3‐(4,5‐dimethylthiazol)‐2‐yl]‐2,5‐diphenyltertrazolium bromide (MTT) assay was found to be 91.8%. The adhesion and migration of the cells inside the pore walls were visualized by confocal microscopy. Copyright © 2010 Society of Chemical Industry     

部分氧化法生产高等级道路沥青的工艺设计

介绍了广州石油化工总厂依托溶剂脱沥青装置建成一套规模为30万t／a的“沥青部分氧化装置”的工艺设计。该装置工艺简单，投资少，选用恰当的原油进行分输、分储、分炼可以生产出符合GB／T15180—94国家标准的高等级道路沥青。     

Suitability of Chitosan Scaffolds with Carbon Nanotubes for Bone Defects Treated with Photobiomodulation

Biomaterials have been investigated as an alternative for the treatment of bone defects, such as chitosan/carbon nanotubes scaffolds, which allow cell proliferation. However, bone regeneration can be accelerated by electrotherapeutic resources that act on bone metabolism, such as low-level laser therapy (LLLT). Thus, this study evaluated the regeneration of bone lesions grafted with chitosan/carbon nanotubes scaffolds and associated with LLLT. For this, a defect (3 mm) was created in the femur of thirty rats, which were divided into 6 groups: Control (G1/Control), LLLT (G2/Laser), Chitosan/Carbon Nanotubes (G3/C+CNTs), Chitosan/Carbon Nanotubes with LLLT (G4/C+CNTs+L), Mineralized Chitosan/Carbon Nanotubes (G5/C+CNTsM) and Mineralized Chitosan/Carbon Nanotubes with LLLT (G6/C+CNTsM+L). After 5 weeks, the biocompatibility of the chitosan/carbon nanotubes scaffolds was observed, with the absence of inflammatory infiltrates and fibrotic tissue. Bone neoformation was denser, thicker and voluminous in G6/C+CNTsM+L. Histomorphometric analyses showed that the relative percentage and standard deviations (mean ± SD) of new bone formation in groups G1 to G6 were 59.93 ± 3.04a (G1/Control), 70.83 ± 1.21b (G2/Laser), 70.09 ± 4.31b (G3/C+CNTs), 81.6 ± 5.74c (G4/C+CNTs+L), 81.4 ± 4.57c (G5/C+CNTsM) and 91.3 ± 4.81d (G6/C+CNTsM+L), respectively, with G6 showing a significant difference in relation to the other groups (a ≠ b ≠ c ≠ d; p < 0.05). Immunohistochemistry also revealed good expression of osteocalcin (OC), osteopontin (OP) and vascular endothelial growth factor (VEGF). It was concluded that chitosan-based carbon nanotube materials combined with LLLT effectively stimulated the bone healing process.     

Polyphase Ceramic for Consolidating Nuclear Waste Compositions with High Zr-Cd-Na Content

The development of dense polyphase tailored ceramic forms for the immobilization of high-level nuclear wastes has been extended to an Idaho Chemical Processing Plant Fluorinel composition. The ceramic was designed to maximize waste loading and subsequent waste volume reduction without sacrificing chemical durability in aqueous environments. The ceramic, fabricated by hot isostatic pressing, consists of four main crystalline phases, calcium fluoride, zirconia, an apatite-structured solid-solution phase, and sphene. The form also contains a designed borosilicate glass phase, a Ni-Cd alloy, and a minor amount of crystalline zircon. The crystalline apatite solid-solution phase is the major host for incorporating the actinide simulants U, Ce, and Y, while the glass phase contains Cs and Sr. The calcium fluoride and sphene phases provide microstructural isolation of the radionuclide-containing phases. Since the glass and crystalline components of the ceramic are not phase compatible at all temperatures, the exact phase content is determined by the tailoring additives, consolidation temperature, and oxidation state control during processing. The simulated HLW ceramic has a density of 3.3 g/cm³ at a waste loading of 73 wt%.     

Antiosteoporotic Nanohydroxyapatite Zoledronate Scaffold Seeded with Bone Marrow Mesenchymal Stromal Cells for Bone Regeneration: A 3D In Vitro Model

Background: Bisphosphonates are widely employed drugs for the treatment of pathologies with high bone resorption, such as osteoporosis, and display a great affinity for calcium ions and apatitic substrates. Here, we aimed to investigate the potentiality of zoledronate functionalized hydroxyapatite nanocrystals (HAZOL) to promote bone regeneration by stimulating adhesion, viability, metabolic activity and osteogenic commitment of human bone marrow derived mesenchymal stromal cells (hMSCs). Methods: we adopted an advanced three-dimensional (3D) in vitro fracture healing model to study porous scaffolds: hMSCs were seeded onto the scaffolds that, after three days, were cut in halves and unseeded scaffolds were placed between the two halves. Scaffold characterization by X-ray diffraction, transmission and scanning electron microscopy analyses and cell morphology, viability, osteogenic differentiation and extracellular matrix deposition were evaluated after 3, 7 and 10 days of culture. Results: Electron microscopy showed a porous and interconnected structure and a uniform cell layer spread onto scaffolds. Scaffolds were able to support cell growth and cells progressively colonized the whole inserts in absence of cytotoxic effects. Osteogenic commitment and gene expression of hMSCs were enhanced with higher expressions of ALPL, COL1A1, BGLAP, RUNX2 and Osterix genes. Conclusion: Although some limitations affect the present study (e.g., the lack of longer experimental times, of mechanical stimulus or pathological microenvironment), the obtained results with the adopted experimental setup suggested that zoledronate functionalized scaffolds (GHAZOL) might sustain not only cell proliferation, but positively influence osteogenic differentiation and activity if employed in bone fracture healing.     

Acetanilide-loaded injectable hydrogels with enhanced bioactivity and biocompatibility for potential treatment of periodontitis

Chronic periodontitis poses long-term challenges in dentistry, requiring the development of innovative dental composites with biocompatibility, bone regeneration, and antibacterial properties. This study focuses on synthesis of novel injectable thermoresponsive hydrogels composed of chitosan, sodium bicarbonate, bioactive glass (20 and 40% w/w), and acetanilide drug (0.3 and 0.6% w/w). These hydrogels exhibit a sol–gel transition at 37°C, addressing periodontal challenges with reduced gelation time. The smooth flow characteristic was evaluated through 17-22 gauge syringe needles at low temperature. Rheological studies demonstrated pseudoplastic behavior, with viscosity decreasing as shear rate increases. Fourier transform infrared and x-ray diffraction analysis confirmed the bioactivity of hydrogels, forming a bone-like apatite layer in simulated body fluid. The drug-loaded hydrogels demonstrated promising in vitro antibacterial properties against dental pathogens, specifically Staphylococcus aureus and Pseudomonas aeruginosa. Drug dissolution analysis revealed relatively high release rate at 37°C, highlighting its role in rapidly eliminating bacterial colonies at the target site, while the subsequent sustained release contributes to the prevention of infection recurrence. Finally, biocompatibility was assessed with fibroblast, where the cells were observed anchoring into the polymeric chains of hydrogel through extended filopodia.     

2D MoS2 Nanosheet-Based Polyimide Nanocomposite with High Energy Density for High Temperature Capacitor Applications

With the development of electrical vehicles and power electronics, the demand for high-temperature energy storage capacitors with high energy density has grown rapidly. In this investigation, 2D MoS₂ nanosheets are coated with a thin layer of poly(methyl methacrylate) and then mixed with polyimide (PI) solution to fabricate nanocomposites. The dielectric constant of MoS₂-g-PMMA/PI (MPP-3%) reaches 4.2, which is 20% higher than that of a pristine PI film. The energy density of the MPP-3% nanocomposite reaches 8.6 J cm⁻³, which is 40% higher than the highest energy density of a pristine PI film. In addition, the electric breakdown field of the MPP-3% composite is 50% higher than that of the MoS₂/PI nanocomposite without a surface coating. Furthermore, it is found that the highest energy density of MoS₂-g-PMMA/PI reaches 3.92 J cm⁻³, which is 47.9% higher than that of the PI film at 150 °C. The charge–discharge efficiency of the nanocomposite film reaches 61.7% at 150 °C. This result is much higher than the previously reported research results for high-temperature capacitor applications. The MoS₂-g-PMMA/PI-based nanocomposite shows great promise for use in high-temperature capacitor applications.     

加氢降凝组合工艺技术

抚顺石油化工研究院开发的生产低凝清洁柴油加氢降凝组合工艺,集加氢精制与临氢降凝工艺技术优点于一体,具有工艺流程简单、精制及降凝效果好、柴油收率高、原料适应能力强、产品方案灵活等特点,已在哈尔滨等炼油厂得到工业应用.     

A New Method for Producing High Melt Strength Poly(propylene) with a Reactive Extrusion

Summary: A new class of melt blend material was prepared by extruding a mixture of 3‐aminopropyltriethoxysilane (APTES), maleic anhydride‐grafted poly(propylene) (PP‐g‐MA) with different molecular weight and MA content and poly(propylene) powder produced with a TiCl₃‐based catalyst (PP‐A). A suitable selection of PP‐g‐MA provided extremely high melt strength (MS) of resultant blend materials. Such a superior melt property was caused by the synergy between the present melt reaction and the higher molecular weight portion containing PP‐A. The gel content measurements of typical blend materials and PP‐g‐MA/APTES blends indicated that an excessive amount of inert PP suppresses the formation of gels. The reaction between PP‐g‐MA and APTES was then investigated by analyzing crystalline polymer fractions separated from the atactic PP/PP‐g‐MA/APTES and atactic PP/PP‐g‐MA blends. The FT‐IR analysis of the fractions revealed that the NH₂ group in APTES readily reacts with MA grafted on PP and the reaction leads to the formation of imide linkage. Moreover, the GPC analysis of the fraction showed that higher molecular weight polymers were formed in the presence of APTES. Since a trace amount of water surely produces in the vicinity of active silyltriethoxy groups during the reactive extrusion, such polymers were formed by the condensation between hydrolyzed APTES‐grafted polymer chains. These results led us to the conclusion that long‐chain‐branched PP (LCB‐PP) was certainly produced and its formation is essential for the increase in MS of the present blend materials.

Relationship between log(MS) and log(MFR) for PP/PP‐g‐MA/APTES and commercial PP resins.