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Biotechnology Advances Dec 20233D bioprinting is a new 3D manufacturing technology, that can be used to accurately distribute and load microorganisms to form microbial active materials with multiple... (Review)
Review
3D bioprinting is a new 3D manufacturing technology, that can be used to accurately distribute and load microorganisms to form microbial active materials with multiple complex functions. Based on the 3D printing of human cells in tissue engineering, 3D bioprinting technology has been developed. Although 3D bioprinting technology is still immature, it shows great potential in the environmental field. Due to the precise programming control and multi-printing pathway, 3D bioprinting technology provides a high-throughput method based on micron-level patterning for a wide range of environmental microbiological engineering applications, which makes it an on-demand, multi-functional manufacturing technology. To date, 3D bioprinting technology has been employed in microbial fuel cells, biofilm material preparation, microbial catalysts and 4D bioprinting with time dimension functions. Nevertheless, current 3D bioprinting technology faces technical challenges in improving the mechanical properties of materials, developing specific bioinks to adapt to different strains, and exploring 4D bioprinting for intelligent applications. Hence, this review systematically analyzes the basic technical principles of 3D bioprinting, bioinks materials and their applications in the environmental field, and proposes the challenges and future prospects of 3D bioprinting in the environmental field. Combined with the current development of microbial enhancement technology in the environmental field, 3D bioprinting will be developed into an enabling platform for multifunctional microorganisms and facilitate greater control of in situ directional reactions.
Topics: Humans; Bioprinting; Tissue Engineering; Printing, Three-Dimensional; Biofilms; Catalysis; Biocompatible Materials; Tissue Scaffolds
PubMed: 37647974
DOI: 10.1016/j.biotechadv.2023.108243 -
Tissue Engineering. Part C, Methods Sep 2023Allogeneic chondrocyte therapies need to be developed to allow more individuals to be treated with a cell therapy for cartilage repair and to reduce the burden and cost...
Allogeneic chondrocyte therapies need to be developed to allow more individuals to be treated with a cell therapy for cartilage repair and to reduce the burden and cost of the current two-stage autologous procedures. Upscale manufacture of chondrocytes using a bioreactor could help provide an off-the-shelf allogeneic chondrocyte therapy with many doses being produced in a single manufacturing run. In this study, we assess a good manufacturing practice-compliant hollow-fiber bioreactor (Quantum) for adult chondrocyte manufacture. Chondrocytes were isolated from knee arthroplasty-derived cartilage ( = 5) and expanded in media supplemented with 10% fetal bovine serum (FBS) or 5% human platelet lysate (hPL) on tissue culture plastic (TCP) for a single passage. hPL-supplemented cultures were then expanded in the Quantum bioreactor for a further passage. Matched, parallel cultures in hPL or FBS were maintained on TCP. Chondrocytes from all culture conditions were characterized in terms of growth kinetics, morphology, immunoprofile, chondrogenic potential (chondrocyte pellet assays), and single telomere length analysis. Quantum expansion of chondrocytes resulted in 86.4 ± 38.5 × 10 cells in 8.4 ± 1.5 days, following seeding of 10.2 ± 3.6 × 10 cells. This related to 3.0 ± 1.0 population doublings in the Quantum bioreactor, compared with 2.1 ± 0.6 and 1.3 ± 1.0 on TCP in hPL- and FBS-supplemented media, respectively. Quantum- and TCP-expanded cultures retained equivalent chondropotency and mesenchymal stromal cell marker immunoprofiles, with only the integrin marker, CD49a, decreasing following Quantum expansion. Quantum-expanded chondrocytes demonstrated equivalent chondrogenic potential (as assessed by ability to form and maintain chondrogenic pellets) with matched hPL TCP populations. hPL manufacture, however, led to reduced chondrogenic potential and increased cell surface positivity of integrins CD49b, CD49c, and CD51/61 compared with FBS cultures. Quantum expansion of chondrocytes did not result in shortened 17p telomere length when compared with matched TCP cultures. This study demonstrates that large numbers of adult chondrocytes can be manufactured in the Quantum hollow-fiber bioreactor. This rapid, upscale expansion does not alter chondrocyte phenotype when compared with matched TCP expansion. Therefore, the Quantum provides an attractive method of manufacturing chondrocytes for clinical use. Media supplementation with hPL for chondrocyte expansion may, however, be unfavorable in terms of retaining chondrogenic capacity.
Topics: Adult; Humans; Chondrocytes; Cartilage; Cells, Cultured; Extracellular Matrix; Hematopoietic Stem Cell Transplantation; Cell Differentiation; Cell Proliferation
PubMed: 37395490
DOI: 10.1089/ten.TEC.2023.0037 -
Gels (Basel, Switzerland) Dec 2023Rheological characterisation plays a crucial role in developing and optimising advanced materials in the form of hydrogels and aerogels, especially if 3D printing... (Review)
Review
Rheological characterisation plays a crucial role in developing and optimising advanced materials in the form of hydrogels and aerogels, especially if 3D printing technologies are involved. Applications ranging from tissue engineering to environmental remediation require the fine-tuning of such properties. Nonetheless, their complex rheological behaviour presents unique challenges in additive manufacturing. This review outlines the vital rheological parameters that influence the printability of hydrogel and aerogel inks, emphasising the importance of viscosity, yield stress, and viscoelasticity. Furthermore, the article discusses the latest developments in rheological modifiers and printing techniques that enable precise control over material deposition and resolution in 3D printing. By understanding and manipulating the rheological properties of these materials, researchers can explore new possibilities for applications such as biomedicine or nanotechnology. An optimal 3D printing ink requires strong shear-thinning behaviour for smooth extrusion, forming continuous filaments. Favourable thixotropic properties aid viscosity recovery post-printing, and adequate yield stress and ' are crucial for structural integrity, preventing deformation or collapse in printed objects, and ensuring high-fidelity preservation of shapes. This insight into rheology provides tools for the future of material design and manufacturing in the rapidly evolving field of 3D printing of hydrogels and aerogels.
PubMed: 38131974
DOI: 10.3390/gels9120986 -
Comprehensive Analysis of Geopolymer Materials: Properties, Environmental Impacts, and Applications.Materials (Basel, Switzerland) Nov 2023The advancement of eco-friendly technology in the construction sector has been improving rapidly in the last few years. As a result, multiple building materials were... (Review)
Review
The advancement of eco-friendly technology in the construction sector has been improving rapidly in the last few years. As a result, multiple building materials were developed, enhanced, and proposed as replacements for some traditional materials. One notable example presents geopolymer as a substitute for ordinary Portland concrete (OPC). The manufacturing process of (OPC) generates CO emissions and a high energy demand, both of which contribute to ozone depletion and global warming. The implementation of geopolymer concrete (GPC) technology in the construction sector provides a path to more sustainable growth and a cleaner environment. This is due to geopolymer concrete's ability to reduce environmental pollutants and reduce the construction industry's carbon footprint. This is achieved through its unique composition, which typically involves industrial byproducts like fly ash or slag. These materials, rich in silicon and aluminum, react with alkaline solutions to form a binding gel, bypassing the need for the high-energy clinker production required in OPC. The use of such byproducts not only reduces CO emissions but also contributes to waste minimization. Additionally, geopolymer offers extra advantages compared to OPC, including improved mechanical strength, enhanced durability, and good stability in acidic and alkaline settings. Such properties make GPC particularly suitable for a range of construction environments, from industrial applications to infrastructure projects exposed to harsh conditions. This paper comprehensively reviews the different characteristics of geopolymers, which include their composition, compressive strength, durability, and curing methods. Furthermore, the environmental impacts related to the manufacturing of geopolymer materials were evaluated through the life-cycle assessment method. The result demonstrated that geopolymer concrete maintains positive environmental impacts due to the fact that it produces fewer carbon dioxide CO emissions compared to OPC concrete during its manufacturing; however, geopolymer concrete had some minor negative environmental impacts, including abiotic depletion, human toxicity, freshwater ecotoxicity, terrestrial ecotoxicity, and acidification. These are important considerations for ongoing research aimed at further improving the sustainability of geopolymer concrete. Moreover, it was determined that silicate content, curing temperature, and the proportion of alkaline solution to binder are the major factors significantly influencing the compressive strength of geopolymer concrete. The advancement of geopolymer technology represents not just a stride toward more sustainable construction practices but also paves the way for innovative approaches in the field of building materials.
PubMed: 38068107
DOI: 10.3390/ma16237363 -
Clinical Infectious Diseases : An... Nov 2023Manufacturing and formulation of stable, high purity, and high dose bacteriophage drug products (DPs) suitable for clinical usage would benefit from improved process...
Manufacturing and formulation of stable, high purity, and high dose bacteriophage drug products (DPs) suitable for clinical usage would benefit from improved process monitoring and control of critical process parameters that affect product quality attributes. Chemistry, Manufacturing, and Controls (CMC) for both upstream (USP) and downstream processes (DSP) need mapping of critical process parameters (CPP) and linking these to critical quality attributes (CQA) to ensure quality and consistency of phage drug substance (DS) and DPs development. Single-use technologies are increasingly becoming the go-to manufacturing option with benefits both for phage bioprocess development at the engineering run research stage and for final manufacture of the phage DS. Future phage DPs under clinical development will benefit from implementation of process analytical technologies (PAT) for better process monitoring and control. These are increasingly being used to improve process robustness (to reduce batch-to-batch variability) and productivity (yielding high phage titers). Precise delivery of stable phage DPs that are suitably formulated as liquids, gels, solid-oral dosage forms, and so forth, could significantly enhance efficacy of phage therapy outcomes. Pre-clinical development of phage DPs must include at an early stage of development, considerations for their formulation including their characterization of physiochemical properties (size, charge, etc.), buffer pH and osmolality, compatibility with regulatory approved excipients, storage stability (packaging, temperature, humidity, etc.), ease of application, patient compliance, ease of manufacturability using scalable manufacturing unit operations, cost, and regulatory requirements.
Topics: Humans; Bacteriophages; Pharmaceutical Preparations; Excipients
PubMed: 37932112
DOI: 10.1093/cid/ciad555 -
Advanced Healthcare Materials Jan 2024Soft gelatin capsules (SGCs) are the most widely used pharmaceutical form after tablets. The active components, active pharmaceutical ingredients (APIs), or nutrients... (Review)
Review
Soft gelatin capsules (SGCs) are the most widely used pharmaceutical form after tablets. The active components, active pharmaceutical ingredients (APIs), or nutrients are dissolved, dispersed, or suspended in a liquid or semisolid fill, which is covered with a gelatin shell. Several factors can modify the properties of the gelatin shell and subsequently affect their operative handling during manufacturing process and the stability of the soft gelatin capsules. Three elements appear to be crucial: the shell formulation (type and content of the different components such as gelatins-source, extraction method-plasticizers, or additives); the manufacture and storage conditions (temperature, humidity, light) as well as the interactions between fill-shell formulas. Mechanical and thermal analysis arise as straightforward but highly useful tools to monitor the properties of the gelatin shell. This review provides an updated overview on the shell formulation and design. Additionally, it presents the uses of mechanical and thermal techniques to characterize and evaluate the impact of different parameters on the gelatin behavior over the production and stability of these pharmaceutical forms. This will help to detect changes that are yet not visible by visual inspection ensuring a suitable finished product over its shelf-life.
Topics: Gelatin; Capsules; Temperature; Food
PubMed: 37775861
DOI: 10.1002/adhm.202302250 -
Drug Delivery and Translational Research Feb 2024Oral administration is the most commonly used form of treatment due to its advantages, including high patient compliance, convenient administration, and minimal... (Review)
Review
Oral administration is the most commonly used form of treatment due to its advantages, including high patient compliance, convenient administration, and minimal preparation required. However, the traditional preparation process of oral solid preparation has many defects. Although continuous manufacturing line that combined all the unit operations has been developed and preliminarily applied in the pharmaceutical industry, most of the currently used manufacturing processes are still complicated and discontinuous. As a result, these complex production steps will lead to low production efficiency and high quality control risk of the final product. Additionally, the large-scale production mode is inappropriate for the personalized medicines, which commonly is customized with small amount. Several attractive techniques, such as hot-melt extrusion, fluidized bed pelletizing and spray drying, could effectively shorten the process flow, but still, they have inherent limitations that are challenging to address. As a novel manufacturing technique, 3D printing could greatly reduce or eliminate these disadvantages mentioned above, and could realize a desirable continuous production for small-scale personalized manufacturing. In recent years, due to the participation of 3D printing, the development of printed drugs has progressed by leaps and bounds, especially in the design of oral drug dosage forms. This review attempts to summarize the new development of 3D printing technology in oral preparation and also discusses their advantages and disadvantages as well as potential applications.
Topics: Humans; Technology, Pharmaceutical; Drug Industry; Pharmaceutical Preparations; Administration, Oral; Printing, Three-Dimensional
PubMed: 37620647
DOI: 10.1007/s13346-023-01414-8 -
Light, Science & Applications Oct 2023Three-dimensional (3D) surface geometry provides elemental information in various sciences and precision engineering. Fringe Projection Profilometry (FPP) is one of the...
Three-dimensional (3D) surface geometry provides elemental information in various sciences and precision engineering. Fringe Projection Profilometry (FPP) is one of the most powerful non-contact (thus non-destructive) and non-interferometric (thus less restrictive) 3D measurement techniques, featuring at its high precision. However, the measurement precision of FPP is currently evaluated experimentally, lacking a complete theoretical model for guidance. We propose the first complete FPP precision model chain including four stage models (camera intensity, fringe intensity, phase and 3D geometry) and two transfer models (from fringe intensity to phase and from phase to 3D geometry). The most significant contributions include the adoption of a non-Gaussian camera noise model, which, for the first time, establishes the connection between camera's electronics parameters (known in advance from the camera manufacturer) and the phase precision, and the formulation of the phase to geometry transfer, which makes the precision of the measured geometry representable in an explicit and concise form. As a result, we not only establish the full precision model of the 3D geometry to characterize the performance of an FPP system that has already been set up, but also explore the expression of the highest possible precision limit to guide the error distribution of an FPP system that is yet to build. Our theoretical models make FPP a more designable technique to meet the challenges from various measurement demands concerning different object sizes from macro to micro and requiring different measurement precisions from a few millimeters to a few micrometers.
PubMed: 37899479
DOI: 10.1038/s41377-023-01294-0 -
ACS Synthetic Biology Oct 2023Fructose is an important monosaccharide product widely applied in the food, medicine, and chemical industries. Currently, fructose is mainly manufactured with plant...
Fructose is an important monosaccharide product widely applied in the food, medicine, and chemical industries. Currently, fructose is mainly manufactured with plant biomass-sourced polysaccharides through multiple steps of digestion, conversion, separation, and purification. The development of cyanobacterial metabolic engineering provides an attractive alternative route for the one-step direct production of fructose utilizing carbon dioxide and solar energy. In this work, we developed a paradigm for engineering cyanobacterial chassis cells into efficient cell factories for the photosynthetic production of fructose. In a representative cyanobacterial strain, PCC 7942, knockout of fructokinase effectively activated the synthesis and secretion of fructose in hypersaline conditions, independent of any heterologous transporters. The native sucrose synthesis pathway was identified as playing a primary role in fructose synthesis. Through combinatory optimizations on the levels of metabolism, physiology, and cultivation, the fructose yield of the cell factories was stepwise improved to 3.9 g/L. Such a paradigm was also adopted to engineer another strain, the marine species sp. PCC 7002, and facilitated an even higher fructose yield of over 6 g/L. Finally, the fructose synthesized and secreted by the cyanobacterial photosynthetic cell factories was successfully extracted and prepared from the culture broth in the form of products with 86% purity through multistep separation-purification operations. This work demonstrated a paradigm for systematically engineering cyanobacteria for photosynthetic production of desired metabolites, and it also confirmed the feasibility and potential of cyanobacterial photosynthetic biomanufacturing as a simple and efficient route for fructose production.
Topics: Fructose; Synechococcus; Photosynthesis; Metabolic Engineering; Carbohydrate Metabolism; Sucrose; Carbon Dioxide
PubMed: 37728873
DOI: 10.1021/acssynbio.3c00338 -
Molecular Therapy. Methods & Clinical... Dec 2023Base editing is a revolutionary gene-editing technique enabling the introduction of point mutations into the genome without generating detrimental DNA double-stranded...
Base editing is a revolutionary gene-editing technique enabling the introduction of point mutations into the genome without generating detrimental DNA double-stranded breaks. Base-editing enzymes are commonly delivered in the form of modified linear messenger RNA (mRNA) that is costly to produce. Here, we address this problem by developing a simple protocol for manufacturing base-edited cells using circular RNA (circRNA), which is less expensive to synthesize. Compared with linear mRNA, higher editing efficiencies were achieved with circRNA, enabling an 8-fold reduction in the amount of RNA required. We used this protocol to manufacture a clinical dose (1 × 10 cells) of base-edited chimeric antigen receptor (CAR) T cells lacking expression of the inhibitory receptor, PD-1. Editing efficiencies of up to 86% were obtained using 0.25 μg circRNA/1 × 10 cells. Increased editing efficiencies with circRNA were attributed to more efficient translation. These results suggest that circRNA, which is less expensive to produce than linear mRNA, is a viable option for reducing the cost of manufacturing base-edited cells at scale.
PubMed: 37886606
DOI: 10.1016/j.omtm.2023.101123