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For several tissue engineering applications, in particular food products, scaling up culture of mammalian cells is a necessary task. The prevailing method for large scale cell culture is the stirred tank bioreactor where anchor dependent cells are grown on microcarriers suspended in medium. We use a spinner flask system with cells grown on microcarriers to optimize the growth of bovine myoblasts. Freshly isolated primary cells were seeded on microcarriers (Synthemax ® , CellBIND ® and Cytodex ® 1 MCs). In this study, we provide proof of principle that bovine myoblasts can be cultured on microcarriers. No major differences were observed between the three tested microcarriers, except that sparsely populated beads were more common with CellBIND ® and Synthemax ® II beads suggesting a slower initiation of exponential growth than on Cytodex ® . We also provide direct evidence that bovine myoblasts display bead-to-bead transfer. A remarkable pick up of growth was observed by adding new MCs. Bovine myoblasts seem to behave like human mesenchymal stem cells. Thus, our results provide valuable data to further develop and scale-up the production of bovine myoblasts as a prerequisite for efficient and cost-effective development of cultured meat. Applicability to other anchorage dependent cells can extend the importance of these results to cell culture for medical tissue engineering or cell therapy.

Microcarriers are 100- to 300-micron support matrices that permit the growth of adherent cells in bioreactor systems. They have a larger surface area to volume ratio in comparison to single cell monolayers, enabling cost-effective cell production and expansion. Microcarriers are composed of a solid matrix that must be separated from expanded cells during downstream processing stages. The detachment method is chosen on the basis of several factors like cell type, microcarrier surface chemistry, cell confluency and degree of aggregation. The development of microcarriers with a range of physiochemical properties permit controlled cell and protein associations that hold utility for novel therapeutics. In this review, we provide an overview of the recent advances in microcarrier cell culture technology. We also discuss its significance as an ex vivo research tool and the therapeutic potential of newly designed microcarrier systems in vivo.

For several decades microparticles have been exclusively and extensively explored as spherical drug delivery vehicles and large-scale cell expansion carriers. More recently, microparticulate structures gained interest in broader bioengineering fields, integrating myriad strategies that include bottom-up tissue engineering, 3D bioprinting, and the development of tissue/disease models. The concept of bulk spherical micrometric particles as adequate supports for cell cultivation has been challenged, and systems with finely tuned geometric designs and (bio)chemical/physical features are current key players in impacting technologies. Herein, we critically review the state of the art and future trends of biomaterial microparticles in contact with cells and tissues, excluding internalization studies, and with emphasis on innovative particle design and applications. Promising outputs have been delivered by microparticles as microcarriers with enhanced surface area in response to high cellular demands. However, their ability to adapt to clinically translatable setups, including xeno-free conditions and the use of biodegradable materials, is still a leading-edge trend. Advances in particle design and control over their architecture and morphology, along with understanding of the role of tailorable (bio)chemical/physical aspects, enable the modulation of cellular response. Finely tailored systems may be attained through several enabling technologies and fabrication methods. Recent applications of microparticles include their exploitation as building blocks for bottom-up tissue engineering strategies, have integrated in vitro 3D cellular tissue/disease models as cue providers, and have been used as reinforcement units in bioinks for 3D bioprinting.

Usnic acid is one of the most investigated lichen secondary metabolites, with several proven biological properties with potential medical relevance. However, its unfavorable physico-chemical properties, as well as observed hepatotoxicity, have discouraged wide-range utilization of usnic acid as a promising therapeutic agent. In accordance with the growing research interest in the development of nanotechnology, especially in the arena of preparations based on natural sources of medicinal compounds, usnic acid incorporated into nano- and microsized colloidal carriers has been a subject of a large number of publications. Therefore, this review discusses the overall results of the studies dealing with usnic acid encapsulated into lipid-based, polymeric and nonorganic micro- and/or nanocarriers, as potential drug delivery systems for this natural compound, in an attempt to introduce its usage as a potential antitumor, antimicrobial, wound-healing, antioxidative and anti-inflammatory drug.

To fully utilize the potential of human induced pluripotent stem cells (hiPSCs) for allogeneic stem cell–based therapies, efficient and scalable expansion procedures must be developed. For other adherent human cell types, the combination of microcarriers (MCs) and stirred tank bioreactors has been shown to meet these demands. In this study, a hiPSC quasi-perfusion expansion procedure based on MCs was developed at 100-mL scale in spinner flasks. Process development began by assessing various medium exchange strategies and MC coatings, indicating that the hiPSCs tolerated the gradual exchange of medium well when cultivated on Synthemax II–coated MCs. This procedure was therefore scaled-up to the 1.3-L Eppendorf BioBLU 1c stirred tank bioreactor by applying the lower limit of Zwietering’s suspension criterion ( N s 1 u ), thereby demonstrating proof-of-concept when used in combination with hiPSCs for the first time. To better understand the bioreactor and its bioengineering characteristics, computational fluid dynamics and bioengineering investigations were performed prior to hiPSC cultivation. In this manner, improved process understanding allowed an expansion factor of ≈ 26 to be achieved, yielding more than 3 × 10 9 cells within 5 days. Further quality analyses confirmed that the hiPSCs maintained their viability, identity, and differentiation potential throughout cultivation. Key points • N s 1 u  can be used as a scale-up criterion for hiPSC cultivations in MC-operated stirred bioreactors • Uniform distribution and attachment of cells to the MCs are crucial for efficient expansion • Perfusion is advantageous and supports the cultivation of hiPSCs

Therapeutic proteins, including monoclonal antibodies, single chain variable fragment (ScFv), crystallizable fragment (Fc), and fragment antigen binding (Fab), have accounted for one-third of all drugs on the world market. In particular, these medicines have been widely used in ocular therapies in the treatment of various diseases, such as age-related macular degeneration, corneal neovascularization, diabetic retinopathy, and retinal vein occlusion. However, the formulation of these biomacromolecules is challenging due to their high molecular weight, complex structure, instability, short half-life, enzymatic degradation, and immunogenicity, which leads to the failure of therapies. Various efforts have been made to overcome the ocular barriers, providing effective delivery of therapeutic proteins, such as altering the protein structure or including it in new delivery systems. These strategies are not only cost-effective and beneficial to patients but have also been shown to allow for fewer drug side effects. In this review, we discuss several factors that affect the design of formulations and the delivery of therapeutic proteins to ocular tissues, such as the use of injectable micro/nanocarriers, hydrogels, implants, iontophoresis, cell-based therapy, and combination techniques. In addition, other approaches are briefly discussed, related to the structural modification of these proteins, improving their bioavailability in the posterior segments of the eye without affecting their stability. Future research should be conducted toward the development of more effective, stable, noninvasive, and cost-effective formulations for the ocular delivery of therapeutic proteins. In addition, more insights into preclinical to clinical translation are needed.

Cell therapeutics — using cells as living drugs — have made advances in many areas of medicine. One of the most clinically studied cell-based therapy products is mesenchymal stromal cells (MSCs), which have shown promising results in promoting tissue regeneration and modulating inflammation. However, MSC therapy requires large numbers of cells, the generation of which is not feasible via conventional planar tissue culture methods. Scale-up manufacturing methods (e.g., propagation on microcarriers in stirred-tank bioreactors), however, are not specifically tailored for MSC expansion. These processes may, in principle, alter the cell secretome, a vital component underlying the immunosuppressive properties and clinical effectiveness of MSCs. This review outlines our current understanding of MSC properties and immunomodulatory function, expansion in commercial manufacturing systems, and gaps in our knowledge that need to be addressed for effective up-scaling commercialization of MSC therapy.

Rapidly expanding skeletal muscle satellite cells with cost-effective methods have been presented as a solution for meeting the growing global demand for meat. A common strategy for scaling cell proliferation employs microcarriers, small beads designed to support anchorage-dependent cells in suspension-style bioreactors. No carrier has yet been marketed for the cultivation of lab-grown meat. The objective of this study was to demonstrate a rapid, food safe, decellularization procedure to yield cell-free extracellular matrix scaffolds and evaluate them as cell carriers for lab grown meat. Broccoli florets were soaked in SDS, Tween-20, and bleach for 48 h. The decellularization process was confirmed via histology, which showed an absence of cell nuclei, and DNA quantification (0.0037 ± 0.00961 μg DNA/mg tissue). Decellularized carriers were sorted by cross sectional area (7.07 ± 1.74 mm2, 3.03 ± 1.15 mm2, and 0.49 ± 0.3 mm2) measured for eccentricity (0.73 ± 0.16). Density measurements of decellularized carriers (1.01 ± 0.01 g/cm) were comparable to traditional microcarriers. Primary bovine satellite cells were inoculated into and cultured within a reactor containing decellularized carriers. Cell adhesion was observed and cell death was limited to 2.55 ± 1.09%. These studies suggested that broccoli florets may serve as adequate edible carrier scaffolds for satellite cells.

Encapsulation of bioactive compound has some encountered issues associated particularly to their mode of fabrication, design, and biodegradability. For these reasons, selecting appropriate coating materials like hydroxyl cellulose has several advantages such as modification of moisture, crystal growth, and viscosity. In addition, starches, maltodextrins, whey proteins, chitosan, zein/pectin, and alginates are considered an important coating materials used during microencapsulation processing steps. Thus, the variability in the hydrophilicity, lipophilicity and chargeability levels of those coating materials along with the encapsulation is considered among the molecular aspects in forming genius emulsion vesicles, microgels, solid lipid nanoparticles, liposomes, or core shell nanoparticles. These encapsulation designs are capable in promoting variable physicochemical and therapeutic features such as intra-atomic dimensions, dispersed volumes, release kinetics, and stability levels. Under these desired structural and molecular parameters, in addition to proper optimization of processing conditions, perfect microcarriers and microcapsules could be achieved. Moreover, appropriate control of copolymerization and crystallization of the coating materials with some antagonistic pharmaceutical drugs needs special emphasize. In general, this manuscript reviews various important aspects of structured materials used along with their production and potential uses for enhancing targeted delivery and release of therapeutic foods.

Nitric oxide (NO) has shown great potential in tumor therapy, and the development of a platform for precise and controllable NO release still needs to be explored. Herein, a microfluidic electrospray strategy is proposed for the fabrication of hydrogel microspheres encapsulating NO donors (S‐nitrosoglutathione, GSNO) together with black phosphorus (BP) and chemotherapeutic doxorubicin (DOX) as microcarriers for tumor therapy. Based on the excellent photothermal property of BP and thermal sensitivity of GSNO, the microcarriers exhibit a near‐infrared light (NIR)‐responsive NO release behavior. Besides, the photothermal performance of the microcarriers accelerates the release of DOX. All these contribute to the excellent tumor‐killing effect of the microcarriers by combining multiple therapeutic strategies including NO therapy, photothermal therapy, and chemotherapy. Moreover, it was demonstrated that the NIR‐responsive NO delivery microcarriers could significantly inhibit tumor growth without apparent side effects in vivo. Therefore, it is believed that the novel NIR‐responsive NO microcarriers are promising candidates in clinical tumor therapy applications. Schematic illustration of the preparation of the NIR‐responsive NO microcarriers loaded with black phosphorus (BP), NO donors (GSNO) and DOX and the localized delivery of the microcarriers for multimodal tumor therapy.