An advanced model-based strategy to optimize the microbial production of biodegradable polymers under fed-batch conditions

Polyhydroxyalkanoates (PHAs), a class of microbially produced and completely biodegradable polymers with excellent mechanical properties, have the potential of partially replacing currently used synthetic polymers (e.g., polypropylene, etc.) in several applications.1,2 Despite the fact that their fermentative production is well known and demonstrated, their commercial development is still impeded by their high production cost, low productivity, high separation cost and the inability to efficiently control their molecular properties.1 To overcome the above limitations, an integrated mathematical model, consisting of metabolic, polymerization and macroscopic sub-models, was developed in this work to simulate and optimize the fermentative production of polyhydroxybutyrate (PHB, i.e., the first that was discovered and most studied PHA).2 This multi-scale mathematical model was validated against a series of statistically design experimental data, using a robust wild-type PHB producer, namely, Azohydromonas lata bacteria. Please click Additional Files below to see the full abstract

Multi-Scale, Multi-Phase Modelling of a Slurry-Phase Catalytic Ziegler-Natta HDPE Continuous Process

Continuous slurry-phase polymerization, in the presence of a heterogeneous Ziegler–Natta (Z–N) catalyst, is one of the most commonly employed processes in the production of polyolefins, including high-density polyethylene (HDPE), isotactic polypropylene (IPP) as well as their copolymers with higher olefins. Polymerization in a series of reactors is often employed to control comonomer distribution, which is important for resin grades such as pipe applications that require excellent environmental stress crack resistance. The slurry HDPE process technology employs two or more stirred-tank reactors in series and utilizes a Z-N catalyst system composed of a titanium chloride compound and an alkyl aluminum cocatalyst. The process uses hydrogen as a chain-termination agent to control the molecular weight of the product and a comonomer to control the density of the polyethylene grade. The process operates in a continuous mode in a cascade of two or three autoclave-type vessels. Each reactor can operate under a different hydrogen partial pressure, thereby allowing the control of the molecular weight distribution. Typical reaction operating conditions are temperature 70 - 90 °C and a pressure less than 10 bar with a residence time 45 min per reactor. Please click Additional Files below to see the full abstrac

Injectable hyaluronic acid based hydrogels for the repair of cartilage lesions

Hyaluronic acid (HA) is a natural polysaccharide which is found natively in cartilage tissue. HA hydrogels are formed by the modification of HA through its carboxyl and hydroxyl groups and subsequent crosslinking. For applications in cartilage repair, it has been found that HA hydrogels not only support and maintain chondrocyte viability and phenotype when cultured in vitro and in vivo, but also that HA hydrogel chemistry supports and promotes the chondrogenic differentiation of mesenchymal stem cells (MSCs). A promising, non-invasive method for the repair of cartilage lesions is based on the use of injectable hydrogels with desirable properties in combination with biomolecules and cells. Please click Additional Files below to see the full abstract

A Computational Model for the Analysis of Spreading of Viscoelastic Droplets over Flat Surfaces

The spreading of viscous and viscoelastic fluids on flat and curved surfaces is an important problem in many industrial and biomedical processes. In this work the spreading of a linear viscoelastic fluid with changing rheological properties over flat surfaces is investigated via a macroscopic model. The computational model is based on a macroscopic mathematical description of the gravitational, capillary, viscous, and elastic forces. The dynamics of droplet spreading are determined in sessile and pendant configurations for different droplet extrusion or formation times for a hyaluronic acid solution undergoing gelation. The computational model is employed to describe the spreading of hydrogel droplets for different extrusion times, droplet volumes, and surface/droplet configurations. The effect of extrusion time is shown to be significant in the rate and extent of spreading

Free Radical Polymerization: Heterogeneous Systems

Bulk free-radical polymerizations are carried out in the absence of a dispersion medium, and without (or with a very little) solvent. Many technical polymers such as LDPE, LLDPE, PVC, PS, HIPS, PMMA, nylon, and polyester are manufactured in bulk processes. Compared with suspension, emulsion, or solution processes, bulk polymerizations exhibit a higher reactor performance, higher product purity, and reduced transfer reactions to solvents or additives. The disadvantages are related with the high process viscosity, which in turn generates problems of heat removal, mixing, pumping, and reactor wall fouling, by film formation. Some bulk polymerizations (e.g., the production of crystal or general purpose PS) are homogeneous because the produced polymer is amorphous and completely soluble in the monomer. In contrast, PVC soon precipitates from its monomer. In the HIPS process, the heterogeneity results from the incompatibility between the initial PB prepolymer and the generated PS chains. Many thermoplastics are heterogeneous (or heterophase), because they contain liquid or rubber dispersions that improve their physical properties with respect to those of the continuous brittle phase. Examples of this are the softening of PVC by the presence of phthalate droplets, and the improved toughness of HIPS or ABS by addition of PB-based rubber particles. This chapter will focus on the (heterogeneous, bulk, and free-radical) polymerizations leading to the production of HIPS and PVC.Fil: Meira, Gregorio Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Kiparissides, Costas. Aristotle University of Thessaloniki; Greci

Synthesis and Characterization of Crosslinked Microparticles for Drug Delivery

Crosslinked chitosan and poly(hydroxypropyl methacrylate) microparticles containing a hydrophilic bioactive material, hydroquinone, were synthesized by suspension crosslinking and suspension polymerization, respectively and were extensively characterized. The produced microparticles had a spherical geometry and a smooth surface. The release rate of hydroquinone from the microparticles could be adjusted by varying the degree of polymer crosslinking as well as the initial polymer concentration. The degree of polymer swelling of the PHPMA microparticles could be properly modified by suitable adjustment of the degree of polymer crosslinking and of the composition of the solvent

Dynamic Monte Carlo Simulation of the l,l -Lactide Ring-Opening Polymerization

International audienc

Recent Developments in 3D-(Bio)printed Hydrogels as Wound Dressings

Wound healing is a physiological process occurring after the onset of a skin lesion aiming to reconstruct the dermal barrier between the external environment and the body. Depending on the nature and duration of the healing process, wounds are classified as acute (e.g., trauma, surgical wounds) and chronic (e.g., diabetic ulcers) wounds. The latter take several months to heal or do not heal (non-healing chronic wounds), are usually prone to microbial infection and represent an important source of morbidity since they affect millions of people worldwide. Typical wound treatments comprise surgical (e.g., debridement, skin grafts/flaps) and non-surgical (e.g., topical formulations, wound dressings) methods. Modern experimental approaches include among others three dimensional (3D)-(bio)printed wound dressings. The present paper reviews recently developed 3D (bio)printed hydrogels for wound healing applications, especially focusing on the results of their in vitro and in vivo assessment. The advanced hydrogel constructs were printed using different types of bioinks (e.g., natural and/or synthetic polymers and their mixtures with biological materials) and printing methods (e.g., extrusion, digital light processing, coaxial microfluidic bioprinting, etc.) and incorporated various bioactive agents (e.g., growth factors, antibiotics, antibacterial agents, nanoparticles, etc.) and/or cells (e.g., dermal fibroblasts, keratinocytes, mesenchymal stem cells, endothelial cells, etc.)

A Poly(Lactic-co-Glycolic) Acid Nanovaccine Based on Chimeric Peptides from Different Leishmania infantum Proteins Induces Dendritic Cells Maturation and Promotes Peptide-Specific IFNγ-Producing CD8+ T Cells Essential for the Protection against Experimental Visceral Leishmaniasis

Visceral leishmaniasis, caused by Leishmania (L.) donovani and L. infantum protozoan parasites, can provoke overwhelming and protracted epidemics, with high case-fatality rates. An effective vaccine against the disease must rely on the generation of a strong and long-lasting T cell immunity, mediated by CD4+ TH1 and CD8+ T cells. Multi-epitope peptide-based vaccine development is manifesting as the new era of vaccination strategies against Leishmania infection. In this study, we designed chimeric peptides containing HLA-restricted epitopes from three immunogenic L. infantum proteins (cysteine peptidase A, histone H1, and kinetoplastid membrane protein 11), in order to be encapsulated in poly(lactic-co-glycolic) acid nanoparticles with or without the adjuvant monophosphoryl lipid A (MPLA) or surface modification with an octapeptide targeting the tumor necrosis factor receptor II. We aimed to construct differentially functionalized peptide-based nanovaccine candidates and investigate their capacity to stimulate the immunomodulatory properties of dendritic cells (DCs), which are critical regulators of adaptive immunity generated upon vaccination. According to our results, DCs stimulation with the peptide-based nanovaccine candidates with MPLA incorporation or surface modification induced an enhanced maturation profile with prominent IL-12 production, promoting allogeneic T cell proliferation and intracellular production of IFNγ by CD4+ and CD8+ T cell subsets. In addition, DCs stimulated with the peptide-based nanovaccine candidate with MPLA incorporation exhibited a robust transcriptional activation, characterized by upregulated genes indicative of vaccine-driven DCs differentiation toward type 1 phenotype. Immunization of HLA A2.1 transgenic mice with this peptide-based nanovaccine candidate induced peptide-specific IFNγ-producing CD8+ T cells and conferred significant protection against L. infantum infection. Concluding, our findings supported that encapsulation of more than one chimeric multi-epitope peptides from different immunogenic L. infantum proteins in a proper biocompatible delivery system with the right adjuvant is considered as an improved promising approach for the development of a vaccine against VL