Preparation of poly(glycerol sebacate) fibers for tissue engineering applications

Poly(glycerol sebacate) (PGS) was discovered in the previous decade and is a promising bioelastomer with tuneable mechanical, biodegradable and biocompatible properties. Despite of these superiorities, PGS possesses solubility and processability disadvantages. To overcome these drawbacks of PGS, blends could be formed with a polymer which is soluble in a common solvent with PGS prepolymer, having a melting temperature above the crosslinking temperature and which can be removed from the structure after crosslinking. In this study, PGS fibers were fabricated for the first time using pressurized gyration as scaffolds. Fibers were obtained through blending the synthesized PGS prepolymer with poly(vinyl alcohol) (PVA) to overcome solubility/melting drawbacks of crosslinked PGS polymer. Obtained fiber diameters have a narrow size distribution which did not change after thermal crosslinking. After the washing procedure, ∼25% decrease in the average fiber diameter was observed due to the PVA removal. Resulting PGS fibers were characterized in terms of chemical structure, morphology, and cell viability. Fibroblast cell adhesion and spreading on three-dimensional fiber networks were determined by microscopy. PGS fibers supported cell adhesion and proliferation. After 7 days of cell-PGS fiber interactions, cell proliferation and spreading increased without any toxicity

Biofabrication of Gelatin Tissue Scaffolds with Uniform Pore Size via Microbubble Assembly

The control of pore size and uniform porosity remains as an important challenge in gelatin scaffolds. The precise control in building blocks of tissue scaffolds without any additional porogen is possible with costly equipment and techniques, though some pre‐requirements for polymeric material, such as photo‐polymerizability or sintering ability, may be needed prior to construction. Herein, a method for the fabrication of gelatin scaffolds with homogenous porosity using simple T‐junction microfluidics is described. The size of the microbubbles is precisely controlled with 5% deviation from the average. Porous gelatin scaffolds are obtained by building‐up the monodispersed microbubbles in dilute cross‐linker solutions. The effect of cross‐linker density on pore diameter is also investigated. After cross‐linking, pore size of the resultant five scaffold groups are precisely controlled as 135 ± 11, 193 ± 11, 216 ± 9, 231 ± 5, and 250 ± 12 µm. Porosity ratios above 65% are achieved in every sample group. According to the cell culture experiments, structures support high cell adhesion, viability, and migration through the porous network via interconnectivity. This study offers a practical and economical approach for the preparation of porous gelatin scaffolds with homogenous porosity which can be utilized in diverse tissue engineering applications

Self-assembled micro-stripe patterning of sessile polymeric nanofluid droplets

When sessile nanofluid droplets evaporate, solid nanoparticles can be organized in a wide variety of patterns on the substrate. The composition of the nanofluid, internal flow type of droplet and the rate of drying affect drop geometry, and the final pattern. Using poly(lactic-co-glycolic acid)-block-poly(ethylene glycol)(PLGA-b-PEG) as the example, we produced micro-stripe patterning from nanoparticles by drying of sessile fluid droplets. We investigated the nanoparticle properties and flow dynamics to clarify their effects on the patterning. Nanoparticles were prepared by hydrodynamic flow focusing using a T-junction microfluidic device with high production efficiency and the ability to generate an extremely narrow size distribution. PLGA-b-PEG was prepared as oil phase in acetonitrile and water/oil flow rate was changed from 1 to 3 at constant oil phase flow rate (50 μL/min). Then, nanofluid was collected on the surface as sessile droplets within acetonitrile/water binary dispersed phase. Depending on size, charge and size-distribution, the nanoparticles deposited on the surface exhibited various patterns. Dynamic Light and X-ray Scattering measurements showed that, approximately 100 nm particles with relatively low PDI (0.04) were produced for the first time in surfactant free conditions in a microfluidic device and they generated self-assembled ordered patterns, which are regulated by the type of internal flow in the sessile nanofluid droplet during sequential evaporation of acetonitrile and water

Co-Axial Gyro-Spinning of PCL/PVA/HA Core-Sheath Fibrous Scaffolds for Bone Tissue Engineering

The present study aspires towards fabricating core-sheath fibrous scaffolds by state-of-the-art pressurized gyration for bone tissue engineering applications. The core-sheath fibers comprising dual-phase poly-ε-caprolactone (PCL) core and polyvinyl alcohol (PVA) sheath are fabricated using a novel "co-axial" pressurized gyration method. Hydroxyapatite (HA) nanocrystals are embedded in the sheath of the fabricated scaffolds to improve the performance for application as a bone tissue regeneration material. The diameter of the fabricated fiber is 3.97 ± 1.31 µm for PCL-PVA/3%HA while pure PCL-PVA with no HA loading gives 3.03 ± 0.45 µm. Bead-free fiber morphology is ascertained for all sample groups. The chemistry, water contact angle and swelling behavior measurements of the fabricated core-sheath fibrous scaffolds indicate the suitability of the structures in cellular activities. Saos-2 bone osteosarcoma cells are employed to determine the biocompatibility of the scaffolds, wherein none of the scaffolds possess any cytotoxicity effect, while cell proliferation of 94% is obtained for PCL-PVA/5%HA fibers. The alkaline phosphatase activity results suggest the osteogenic activities on the scaffolds begin earlier than day 7. Overall, adaptations of co-axial pressurized gyration provides the flexibility to embed or encapsulate bioactive substances in core-sheath fiber assemblies and is a promising strategy for bone healing

Effectiveness of Oil-Layered Albumin Microbubbles Produced Using Microfluidic T-Junctions in Series for In Vitro Inhibition of Tumor Cells

This work focuses on the synthesis of oil-layered microbubbles using two microfluidic T-junctions in series and evaluation of the effectiveness of these microbubbles loaded with doxorubicin and curcumin for cell invasion arrest from 3D spheroid models of triple negative breast cancer (TNBC), MDA-MB-231 cell line. Albumin microbubbles coated in the drug-laden oil layer were synthesized using a new method of connecting two microfluidic T-mixers in series. Double-layered microbubbles thus produced consist of an innermost core of nitrogen gas encapsulated in an aqueous layer of bovine serum albumin (BSA) which in turn, is coated with an outer layer of silicone oil. In order to identify the process conditions leading to the formation of double-layered microbubbles, a regime map was constructed based on capillary numbers for aqueous and oil phases. The microbubble formation regime transitions from double-layered to single layer microbubbles and then to formation of single oil droplets upon gradual change in flow rates of aqueous and oil phases. In vitro dissolution studies of double-layered microbubbles in an air-saturated environment indicated that a complete dissolution of such bubbles produces an oil droplet devoid of a gas bubble. Incorporation of doxorubicin and curcumin was found to produce a synergistic effect, which resulted in higher cell deaths in 2D monolayers of TNBC cells and inhibition of cell proliferation from 3D spheroid models of TNBC cells compared to the control

Wound dressings for a proteolytic-rich environment

Wound dressings have experienced continuous and significant changes over the years based on the knowledge of the biochemical events associated with chronic wounds. The development goes from natural materials used to just cover and conceal the wound to interactive materials that can facilitate the healing process, addressing specific issues in non-healing wounds. These new types of dressings often relate with the proteolytic wound environment and the bacteria load to enhance the healing. Recently, the wound dressing research is focusing on the replacement of synthetic polymers by natural protein materials to delivery bioactive agents to the wounds. This article provides an overview on the novel protein-based wound dressings such as silk fibroin keratin and elastin. The improved properties of these dressings, like the release of antibiotics and growth factors, are discussed. The different types of wounds and the effective parameters of healing process will be reviewed

POLYURETHANES - EFFECT OF CHEMICAL-COMPOSITION ON MECHANICAL-PROPERTIES AND OXYGEN PERMEABILITY

A series of polyether urethane films with varying hard/soft segment ratio were synthesized using toluene-2,4-diisocyanate (TDI) and polypropylene glycol (PPG) in order to evaluate them as biomaterials. In order to obtain medical purity the polymerization reactions were carried out in bulk without using any other ingredients such as solvent, catalyst, u.v. absorber, etc. The effects of chemical composition and the presence of the chain extender on some properties were examined. For the samples with higher TDI to PPG ratio, a decrease in ultimate elongation and an increase in tensile strength were observed. Addition of chain extender caused an increase in both. On the other hand, the ultimate elongation increased and tensile strength decreased with an increase in molecular weight of the PPG used. As the chemical compositions are changed by increasing the polyol content, an increase in oxygen permeability is also observed

Polymeric materials in wound healing

There is a high need for rapid healing in the treatment of severe burns, trauma, diabetic, decubitus ulcers and other conditions where a great damage of the tissue is exist. In those cases, wound should be covered with a dressing which replaces the functions of the natural skin by protecting the loss of body fluid and proteins, preventing bacterial invasion, improving and stimulating the healing process by providing a support for the proliferating cell

Gelatin microspheres and sponges for delivery of macromolecules

Gelatin microspheres and gelatin sponges were prepared by coacervation and freeze drying techniques, respectively. Both systems were crosslinked with glutaraldehyde. The mean diameter of the microspheres were in the range of 40-80 mum and the mean pore size of the sponges was 130-220 mum depending on the preparation conditions. Bovine serum albumin (BSA) was added into the preparation solutions and entrapped in the microspheres and sponges. BSA addition to sponges was also achieved by addition of BSA-containing microspheres into the sponges. The release kinetics of BSA from the prepared systems were examined. Studies demonstrated that release is dependent on the amount of BSA present in the system and crosslinking densities of microspheres. It was concluded that gelatin microspheres and gelatin sponges are promising carrier matrices for macromolecules