Spray freeze-drying for inhalation application: process and formulation variables.

High porous particles with specific aerodynamic properties were processed by the spray freeze-drying (SFD) method. Comprehensive knowledge about all aspects of the SFD method is required for particle engineering of various pharmaceutical products with good flow properties. In this review, different types of the SFD method, the most frequently employed excipients, properties of particles prepared by this method, and most recent approaches concerning SFD are summarized. Generally, this technique can prepare spherical-shaped particles with a highly porous interior structure, responsible for the very low density of powders. Increasing the solubility of spray freeze-dried formulations achieves the desired efficacy. Also, due to the high efficiency of SFD, by determining the different features of this method and optimizing the process by model-based studies, desirable results for various inhaled products can be achieved and significant progress can be made in the field of pulmonary drug delivery.

Multiple functions of microfluidic platforms: Characterization and applications in tissue engineering and diagnosis of cancer.

Microfluidic system, or lab-on-a-chip, has grown explosively. This system has been used in research for the first time and then entered in the clinical section. Due to economic reasons, this technique has been used for screening of laboratory and clinical indices. The microfluidic system solves some difficulties accompanied by clinical and biological applications. In this review, the interpretation and analysis of some recent developments in microfluidic systems in biomedical applications with more emphasis on tissue engineering and cancer will be discussed. Moreover, we try to discuss the features and functions of microfluidic systems.

Towards the development of sensation-enabled skin substitutes.

Recent advances in cell and biofabrication technologies have contributed to the development of complex human organs. In particular, several skin substitutes are being generated using tissue engineering and regenerative medicine (TERM) technologies. However, recent studies mainly focus on the restoration of the dermis and epidermis layers rather than the regeneration of a fully functional innervated skin organ. Innervation is a critical step in functional tissue repair which has been overlooked in the current TERM studies. In the current study, we highlight the importance of sensation in the skin as the largest sensory organ in the human body. In large non-healing skin wounds, the skin sensation is severely diminished or completely lost and ultimately lead to chronic pain and wound healing process interruption. Current therapeutics for restoring skin sensation after trauma are limited. Recent regenerative medicine-based studies could successfully induce neural networks in skin substitutes, but the effectiveness of these technologies in enhancing sensory capability needs further investigation.

Fabrication of a tailor-made conductive polyaniline/ascorbic acid-coated nanofibrous mat as a conductive and antioxidant cell-free cardiac patch.

Polyaniline (PANI) wasin-situpolymerized on nanofibrous polycaprolactone mats as cell-free antioxidant cardiac patches (CPs), providing electrical conductivity and antioxidant properties. The fabricated CPs took advantage of intrinsic and additive antioxidant properties in the presence of PANI backbone and ascorbic acid as a biocompatible dopant of PANI. The antioxidant nature of CPs may reduce the serious repercussions of oxidative stress, produced during the ischemia-reperfusion (I/R) process following myocardial infarction. The polymerization parameters were considered as aniline (60 mM, 90 mM, and 120 mM), ascorbic acid concentrations ([aniline]:[ascorbic acid] = 3:0, 3:0.5, 3:1, 3:3), and polymerization time (1 h and 3 h). Mainly, the more aniline concentrations and polymerization time, the less sheet resistance was obtained. 1,1 diphenyl-2-picrylhydrazyl (DPPH) assay confirmed the dual antioxidant properties of prepared samples. The advantage of the employedin-situpolymerization was confirmed by the de-doping/re-doping process. Non-desirable groups were excluded based on their electrical conductivity, antioxidant properties, and biocompatibility. The remained groups protected H9c2 cells against oxidative stress and hypoxia conditions. Selected CPs reduced the intracellular reactive oxygen species content and mRNA level of caspase-3 while the Bcl-2 mRNA level was improved. Also, the selected cardiac patch could attenuate the hypertrophic impact of hydrogen peroxide on H9c2 cells. Thein vivoresults of the skin flap model confirmed the CP potency to attenuate the harmful impact of I/R.

Microfluidic fabrication of alendronate-loaded chitosan nanoparticles for enhanced osteogenic differentiation of stem cells.

AIMS: In this study, we used a cross-junction microfluidic device for preparation of alendronate-loaded chitosan nanoparticles with desired characteristics to introduce a suitable element for bone tissue engineering scaffolds. MAIN METHODS: By controlling the reaction condition in microfluidic device, six types of alendronate-loaded chitosan nanoparticles were fabricated which had different physical properties. Hydrodynamic diameter of synthetized particles was evaluated by dynamic light scattering (102 to 215 nm). Nanoparticle morphology was determined by SEM and AFM images. The osteogenic effects of prepared selected nanoparticles on human adipose stem cells (hA-MSCs) were evaluated by assessment of alkaline phosphatase (ALP) activity, calcium deposition, ALP and osteopontin gene expression. KEY FINDINGS: The highest loading efficiency percentage (%LE) was %32.42 ± 2.02. Based on MTT assessment, two samples which had no significant cytotoxicity were chosen for further studies (particle sizes and %LE were 142 ± 6.1 nm, 198 ± 16.56 nm, %16.76 ± 3.91 and %32.42 ± 2.02, respectively). In vitro release behavior of nanoparticles displayed pH responsive characteristics. Significant faster release was seen in acidic pH = 5.8 than neutral pH = 7.4. The selected nanoparticles demonstrated higher ALP activity at 14 days in comparison to selected blank sample and osteogenic differentiation media (ODM) and a downregulation at 21 days in comparison to 14 days. Calcium content assay at 21 days displayed significant differences between alendronate-loaded nanoparticles and ODM. ALP and osteopontin mRNA expression was significantly higher than the cells cultured in ODM at 14 and 21 days. SIGNIFICANCE: We concluded that our prepared nanoparticles significantly enhanced osteogenic differentiation of hA-MSCs and can be a suitable compartment of bone tissue engineering scaffolds.

Nanofibrous Scaffolds Containing Hydroxyapatite and Microfluidic-Prepared Polyamidoamin/BMP-2 Plasmid Dendriplexes for Bone Tissue Engineering Applications.

OBJECTIVE: The aim of this study is to fabricate functional scaffolds to gene delivery bone morphogenetic protein-2 (BMP-2) plasmid for bone formation in bone tissue engineering. METHODS: Dendriplexes (DPs) of generation 4 polyamidoamin (G4-PAMAM)/BMP-2 plasmid were prepared through microfluidic (MF) platform. The physiochemical properties and toxicity of DPs were evaluated by DLS, AFM, FESEM and MTT assay. In order to create a suitable environment for stem cell growth and differentiation, poly-l-lactic acid (PLLA) and poly-l-lactic acid/poly (ethylene oxide) (PLLA/PEO) scaffolds containing hydroxyapatite nanoparticles (HA) and DPs were fabricated by the electrospinning method. The osteogenic potency of the scaffolds on human adipose tissue-derived mesenchymal stem cells (hASCs) was investigated. RESULTS: The results revealed that tuning the physical properties of DPs by adjusting flow parameters in microfluidic platform can easily improve the cell viability compared to conventional bulk mixing method. Also, the result showed that the presence of HA and DPs in PLLA/PEO scaffold enhanced alkaline phosphatase (ALP) activity and increased the amount of deposited Ca, as well as, related to osteogenesis gen markers. CONCLUSION: This study indicated that on using the MF platform in preparation of DPs and loading them along with HA in PLLA/PEO scaffold, the osteogenic differentiation of hASCs could be tuned.