Preparation of microfluidic-based pectin microparticles loaded carbon dots conjugated with BMP-2 embedded in gelatin-elastin-hyaluronic acid hydrogel scaffold for bone tissue engineering application.

The controlled delivery of the bone morphogenetic protein-2 (BMP-2) with tracking ability would overcome most of the side effects linked to the burst release and uncontrolled delivery of this growth factor for bone regeneration. Herein, BMP-2-conjugated carbon dots (CDs) was used as noninvasive detection platforms to deliver BMP-2 for therapeutic applications where osteogenesis and bioimaging are both required. With this in mind, the present work aimed to develop a controlled BMP-2-CDs release system using composite scaffolds containing BMP-2-CDs loaded pectin microparticles, which had been optimized for bone regeneration. By using microfluidic approach, we encapsulated BMP-2-CDs in pectin microparticles with narrow size distribution and then incorporated into composite scaffolds composed of gelatin, elastin, and hyaluronic acid. The BMP-2-CDs was released from the composite scaffolds in a sustained fashion for up to 21 days exhibited a high controlled delivery capacity. When tested in vitro with MG-63 cells, these extraction mediums showed the intercellular uptake of BMP-2-CDs and enhanced biological properties and pro-osteogenic effect. By utilizing the pectin microparticles carrying BMP-2-CDs as promising bioimaging agents for growth factor delivery and by tuning the composition of the scaffolds, this platform has immense potential in the field of bone tissue regeneration.

Investigation of porous cells interface on elastic property of orthopedic implants: Numerical and experimental studies.

Application of porous cells in orthopedic implants makes it possible to better approximation of elastic property of human bones. Although the mechanical and biological properties of orthopedic porous implants are studied in many researches, the interaction between different porous unit cells from geometrical compatibility and also, considering manufacturing conditions for the ultimate goal of bone ingrowth is not thoroughly investigated. In this study, a kelvin cell is designed with 530 to 810 µm pore sizes, which is the appropriate range for bone ingrowth. Due to anatomical position of implants in the human body and the limited range of the elastic modulus of kelvin cell with different geometrical parameters, this unit cell is combined with other cells to extend the range of its elastic modulus. After selecting the appropriate combination of cells to achieve desired properties, they are fabricated with Stainless Steel 316 L using radially gradient porosity in the range of 64% to 80%, and then finite element method (FEM) is performed to evaluate the elastic modulus, stress distribution, and strain energy of the proposed structures. Gradient and uniform structures are fabricated using selective laser melting (SLM) to validate FEM results. The simulation and experimental results are close to each other with an average error of about 4.5%. The elastic modulus derived from FEM for the designed gradient structures are in the range of 7.48 to 10.49 GPa, which can be modified, and present mechanical properties close to trabecular or compact bone based on the position and conditions of the bone defect.

Polyvinylidene fluoride-Hyaluronic acid wound dressing comprised of ionic liquids for controlled drug delivery and dual therapeutic behavior.

To improve the efficacy of transdermal drug delivery systems, the physical and chemical properties of drugs need to be optimized to better penetrate into the stratum corneum and to better diffuse into the epidermis and dermis layers. Accordingly, dual-biological function ionic liquids composed of active pharmaceutical ingredients were synthesized, comprising both analgesic and anti-inflammatory properties, by combining a cation derived from lidocaine and anions derived from hydrophobic nonsteroidal anti-inflammatory drugs. Active pharmaceutical ingredient ionic liquids (API-ILs) were characterized through nuclear magnetic resonance, cytotoxicity assay, and water solubility assay. All properties were compared with those of the original drugs. By converting the analgesic and anti-inflammatory drugs into dual-function API-ILs, their water solubility increased up to 470-fold, without affecting their cytotoxic profile. These API-ILs were incorporated into a bilayer wound dressing composed of a hydrophobic polyvinylidene fluoride (PVDF) membrane to act as a drug reservoir and a biocompatible hyaluronic acid (HA) layer. The prepared bilayer wound dressing was characterized in terms of mechanical properties, membrane drug uptake and drug release behavior, and application in transdermal delivery, demonstrating to have desirable mechanical properties and improved release of API-ILs. The assessment of anti-inflammatory activity through the inhibition of LPS-induced production of nitric oxide and prostaglandin E2 by macrophages revealed that the prepared membranes containing API-ILs are as effective as those with the original drugs. Cell adhesion of fibroblasts on membrane surfaces and cell viability assay confirmed improved the viability and adhesion of fibroblasts on PVDF/HA membranes. Finally, wound healing assay performed with fibroblasts showed that the bilayer membranes containing dual-function API-ILs are not detrimental to wound healing, while displaying increased and controlled drug delivery and dual therapeutic behavior. STATEMENT OF SIGNIFICANCE: This work shows the preparation and characterization of bilayer wound dressings comprising dual-biological function active pharmaceutical ingredients based on ionic liquids with improved and controlled drug release and dual therapeutic efficiency. By converting analgesic and anti-inflammatory drugs into ionic liquids, their water solubility increases up to 470-fold. The prepared bilayer wound dressing membranes have desirable mechanical properties and improved release of drugs. The prepared membranes comprising ionic liquids display anti-inflammatory activity as effective as those with the original drugs. Cell adhesion of fibroblasts on membrane surfaces and cell viability assays show improved viability and adhesion of fibroblasts on PVDF/HA membranes, being thus of high relevance as effective transdermal drug delivery systems.

Hyaluronic acid/ carboxylated Zeolitic Imidazolate Framework film with improved mechanical and antibacterial properties.

Hyaluronic acid (HA), a naturally sourced polysaccharide, has shown remarkable effectiveness on wound healing, but its low mechanical strength and instability limits its frequent application in this field. In order to minimize this shortcoming, hyaluronic acid based wound dressings were blended with functionalized ZIF-8, which not only provides high mechanical strength, but also introduces antibacterial properties and promotes fibroblast migration and proliferation. To analyze physiochemical and biological characteristics of prepared wound dressings, tests including DLS, XRD, FTIR as well as antibacterial and cell adhesion assays were carried out. Results indicated that HA film modification boosted the Young's modulus from 138 to 176 K Pa, and reduced the water contact angle from 37.4 to 27.7 proving enhancement in hydrophilicity. Ameliorated antibacterial properties and better cell adhesion were also observed. Suitable cell viability was observed in samples with FZIF-8, since released Zn ions maintained within a safe concentration range.

A hybrid micromixer with planar mixing units.

The application of microfluidic systems in chemical and biological assays has progressed dramatically in recent years. One of the fundamental operations that microfluidic devices must achieve is a high mixing index. Of particular importance is the role of planar mixing units with repetitive obstacles (MURO) in the formation of micromixers. To date, a myriad of planar passive micromixers has been proposed. However, a strategy for the combination of these units to find an efficient planar mixer has not been investigated. As such, five different MURO have been selected to form a "hybrid micromixer," and their combination was evaluated via numerical and experimental methods. These mixing units include ellipse-like, Tesla, nozzle and pillar, teardrop, and obstruction in a curved mixing unit. Since these units have distinctive dimensions, dynamic and geometric similarities were used to scale and connect them. Afterwards, six slots were designated to house each mixing unit. Since the evaluation of all possible unit configurations is not feasible, the design of experiment method is applied to reduce the total number of experiments from 15 625 to 25. Following this procedure, the "hybrid" micromixer proposed here, comprising Tesla, nozzle and pillar, and obstruction units, shows improved performance for a wide range of Re (i.e., mixing index of >90% for Re 0.001-0.1, 22-45) over existing designs. The use of velocity profiles, concentration diagrams, vorticity and circulation plots assist in the analysis of each unit. Comparison of the proposed "hybrid" micromixer with other obstacle-based planar micromixers demonstrates improved performance, indicating the combination of planar mixing units is a useful strategy for building high-performance micromixers.