Reassessing Long-Term Cryopreservation Strategies for Improved Quality, Safety, and Clinical Use of Allogeneic Dermal Progenitor Cells.

In regenerative medicine, ongoing advancements in cell culture techniques, including isolation, expansion, banking, and transport, are crucial for clinical success. Cryopreservation ensures off-the-freezer availability of living cells, enabling long-term storage and transport. Customizing cryopreservation techniques and cryoprotective agents (CPAs) for specific cell types is crucial for cell source quality, sustainability, safety, and therapeutic intervention efficiency. As regenerative medicine progresses, it becomes imperative that the scientific community and industry provide a comprehensive, cell-specific landscape of available and effective cryopreservation techniques, preventing trial-and-error approaches and unlocking the full potential of cell-based therapies. Open-sharing data could lead to safer, more efficient cell therapies and treatments. Two decades of dermal progenitor cell use for burn wound treatment and Good Manufacturing Practice-compliant technology transfers have highlighted the need for further cryopreservation optimization in manufacturing workflows. In this paper, we present experimental data assessing 5 different cryopreservation formulae for long-term storage of clinical-grade FE002 primary progenitor fibroblasts, emphasizing the crucial difference between DMSO-based and DMSO-free CPAs. Our findings suggest that CryoOx, a DMSO-free CPA, is a promising alternative yielding cell viability similar to that of established commercial CPAs. This research highlights the importance of secure, robust, and efficient cryopreservation techniques in cell banking for maximizing quality, ensuring patient safety, and advancing regenerative medicine.

What drives the relationship between digitalization and energy demand? Exploring heterogeneity in German manufacturing firms.

The growing use of information and communication technologies (ICT) has the potential to increase productivity and improve energy efficiency. However, digital technologies also consume energy, resulting in a complex relationship between digitalization and energy demand and an uncertain net effect. To steer digital transformation towards sustainability, it is crucial to understand the conditions under which digital technologies increase or decrease firm-level energy consumption. This study examines the drivers of this relationship, focusing on German manufacturing firms and leveraging comprehensive administrative panel data from 2009 to 2017, analyzed using the Generalized Random Forest algorithm. Our results reveal that the relationship between digitalization and energy use at the firm level is heterogeneous. However, we find that digitalization more frequently increases energy use, mainly driven by a rise in electricity consumption. This increase is lower in energy-intensive industries and higher in markets with low competition. Smaller firms in structurally weak regions show higher energy consumption growth than larger firms in economically stronger regions. Our study contributes to the literature by using a non-parametric method to identify specific firm-level and external characteristics that influence the impact of digital technologies on energy demand, highlighting the need for carefully designed digitalization policies to achieve climate goals.

Formulation Strategy and An Overview of Nano-Structured Lipid Carrier-Based Topical Gel as a Novel Drug Delivery System.

Nano-Structured Lipid Carriers (NLCs) are improved Solid Lipid Nanoparticles (SLNs) that recover the permanency and capacity of drug payload. There are 3 different types of NLCs which have been anticipated. The aforementioned Lipid Nano Particles (LNPs) possess possible tenders in drug delivery systems, cosmeceuticals, clinical research and many others. Here, we highlight the structure, ingredients, different manufacturing techniques and analysis of NLCs which are rudiments in formulating a unique drug delivery system. These types of formulations are therapeutically advantageous like skin hydration, occlusion and improved bioavailability as well as skin targeting. In this article, we have also discussed the features, and novelty of NLCs, different advantages as promising assistance in topical drug delivery systems, shortcomings and utilisations of LNPs by concentrating on NLCs.

High-Resolution Structuring of Silica-Based Nanocomposites for the Fabrication of Transparent Multicomponent Glasses with Adjustable Properties.

Silicate-based multicomponent glasses are of high interest for technical applications due to their tailored properties, such as an adaptable refractive index or coefficient of thermal expansion. However, the production of complex structured parts is associated with high effort, since glass components are usually shaped from high-temperature melts with subsequent mechanical or chemical postprocessing. Here for the first time the fabrication of binary and ternary multicomponent glasses using doped nanocomposites based on silica nanoparticles and photocurable metal oxide precursors as part of the binder matrix is presented. The doped nanocomposites are structured in high resolution using UV-casting and additive manufacturing techniques, such as stereolithography and two-photon lithography. Subsequently, the composites are thermally converted into transparent glass. By incorporating titanium oxide, germanium oxide, or zirconium dioxide into the silicate glass network, multicomponent glasses are fabricated with an adjustable refractive index nD between 1.4584-1.4832 and an Abbe number V of 53.85-61.13. It is further demonstrated that by incorporating 7 wt% titanium oxide, glasses with ultralow thermal expansion can be fabricated with so far unseen complexity. These novel materials enable for the first time high-precision lithographic structuring of multicomponent silica glasses with applications from optics and photonics, semiconductors as well as sensors.

Applications of 3D-printed teeth in dental education: A narrative review.

Background: The contemporary era of education prompts the need for innovation that facilitates the comprehensible and immersive learning of students. Three-dimensional (3D) printing or additive manufacturing in the form of 3D-printed teeth provides an attractive alternative to extracted teeth and standard dental models, as they provide educational equality and realistic simulation of natural teeth. Aim: This review article summarises the literature that has proven the role and effectiveness of 3D-printed teeth in dental education. Method: This review article follows the Scale for the Assessment of Narrative Review Articles (SANRA) guidelines. Two electronic research databases, PubMed and Google Scholar, were used to search for relevant studies. Studies discussing the applications of 3D-printed teeth in dental education were included. Results: The positive and highly valuable role of 3D-printed teeth in dental education has been validated because of their feasible nature. Improvements in dental students' confidence, clinical skills, and learning experiences have also been proven. Conclusion: 3D-printed teeth can serve as a convenient and accessible alternative to extracted and standard dental models for dental education.

Fabrication, sustainability, and key performance indicators of bioelectronics via fiber building blocks.

Bioelectronics provide efficient information exchange between living systems and man-made devices, acting as a vital bridge in merging the domains of biology and technology. Using functional fibers as building blocks, bioelectronics could be hierarchically assembled with vast design possibilities across different scales, enhancing their application-specific biointegration, ergonomics, and sustainability. In this work, the authors review recent developments in bioelectronic fiber elements by reflecting on their fabrication approaches and key performance indicators, including the life cycle sustainability, environmental electromechanical performance, and functional adaptabilities. By delving into the challenges associated with physical deployment and exploring innovative design strategies for adaptability, we propose avenues for future development of bioelectronics via fiber building blocks, boosting the potential of "Fiber of Things" for market-ready bioelectronic products with minimized environmental impact.

Evaluating the impact of technological development policy on the high-quality development of the manufacturing industry: Mechanisms and threshold effects.

As the world's largest manufacturing country, the rapid growth of China's manufacturing industry has historically relied on factor input. To achieve high-quality development of the manufacturing industry, China must accelerate the transformation from extensive factor input to innovation. The purpose of this study is to further explore the impact mechanisms of technological development policy on the high-quality development of the manufacturing industry. It selected data from 30 provinces and cities in China spanning from 2011 to 2021 for the study. Initially, it established a benchmark regression model to verify the positive impact of technological development policies on the high-quality development of the manufacturing industry. Subsequently, a mediation effect model was used to analyze the role of high-tech industry development in mediating this impact, and a moderation effect model was applied to study the moderating effect of the level of infrastructure informatization. Additionally, taking the industrial structure as a threshold variable, a panel threshold effect model was employed to explore the impact of technological development policy on the high-quality development of the manufacturing industry. It was found that enhancing the level of high-tech industries further facilitates the high-quality development of the manufacturing industry through technological development policy. The level of infrastructure informatization positively moderates the impact of technological development policy on the high-quality development of the manufacturing industry. Moreover, the industrial structure exhibits a threshold effect in this impact.

Rapid Tissue Perfusion Using Sacrificial Percolation of Anisotropic Networks.

Tissue engineering has long sought to rapidly generate perfusable vascularized tissues with vessel sizes spanning those seen in humans. Current techniques such as biological 3D printing (top-down) and cellular self-assembly (bottom-up) are resource intensive and have not overcome the inherent tradeoff between vessel resolution and assembly time, limiting their utility and scalability for engineering tissues. We present a flexible and scalable technique termed SPAN - Sacrificial Percolation of Anisotropic Networks, where a network of perfusable channels is created throughout a tissue in minutes, irrespective of its size. Conduits with length scales spanning arterioles to capillaries are generated using pipettable alginate fibers that interconnect above a percolation density threshold and are then degraded within constructs of arbitrary size and shape. SPAN is readily used within common tissue engineering processes, can be used to generate endothelial cell-lined vasculature in a multi-cell type construct, and paves the way for rapid assembly of perfusable tissues.

Laser ultrasonic detection for defects of LAM components based on variable time window intensity mapping with adaptive 2σ thresholds.

Metallurgical defects in metal laser additive manufacturing (LAM) are inevitable due to complex non-equilibrium thermodynamics. A laser ultrasonic system was designed for detecting surface/near-surface defects in the layer-by-layer LAM process. An approach was proposed for ultrasonic imaging of defects based on variable time window intensity mapping with adaptive 2σ threshold denoising. The Gaussian mixture model hypothesis and expectation-maximization algorithm can automatically differentiate between components dominated by defects and background noises, thereby providing an adaptive threshold that accommodates detection environments and surface roughness levels. Results show that the ultrasonic wave reflection at defect boundaries diminishes far-field ultrasonic intensity upon pulsed laser irradiation on surface defects, enabling defect size and location characterization. This method is applicable to LAM samples with a significant surface roughness of up to 37.5 µm. It can detect superficial and near-surface defects down to 0.5 mm in diameter and depth, making it significant for online defect detection in additive manufacturing.

Characterisation of 3D-printed acetabular hip implants.

Three-dimensional printing is a rapidly growing manufacturing method for orthopaedic implants and it is currently thriving in several other engineering industries. It enables the variation of implant design and the construction of complex structures which can be exploited in orthopaedics and other medical sectors. In this review, we develop the vocabulary to characterise 3D printing in orthopaedics from terms defined by industries employing 3D printing, and by fully examining a 3D-printed off-the-shelf acetabular cup (Fig. 1). This is a commonly used 3D-printed implant in orthopaedics, and it exhibits a range of prominent features brought about by 3D printing. The key features and defects of the porous and dense regions of the implant are clarified and discussed in depth to determine reliable definitions and a common understanding of characteristics of 3D printing between engineers and medical experts in orthopaedics. Despite the extensive list of terminology derived here, it is clear significant gaps exist in the knowledge of this field. Therefore, it is necessary for continued investigations of unused implants, but perhaps more significantly, examining those in vivo and retrieved to understand their long-term impact on patients and the effects of certain features (e.g. surface-adhered particles). Analyses of this kind will establish an understanding of 3D printing in orthopaedics and additionally it will help to update the regulatory approach to this new technology.

Peanut hulls, an underutilized nutritious culinary ingredient: valorizing food waste for global food, health, and farm economies-a narrative review.

Peanut hulls (PHs) are an edible food waste that is an underutilized food source for human consumption. While edible and palatable, currently they are mainly diverted to livestock feed or building materials. Here, we describe existing literature supporting human food valorization of PHs, and propose methods to optimize recapturing nutrients (protein, fiber, phenols and other phytonutrients) lost by treating PHs as waste. Incorporated into common foods, PHs could be processed into functional ingredients to improve nutrient-density with anticipated corresponding positive health outcomes associated with increases in plant foods. Valorization of PHs addresses multiple priorities of the UN Sustainable Development Goals using a Food Systems Approach (FSA) including reducing food waste, increasing economic opportunities for farmers, and increasing the availability of healthy shelf-stable foodstuffs to address food security. Recent advances in sustainable food processing technologies can be utilized to safely incorporate PHs into human food streams. We propose future applications that could make meaningful impacts for food availability and the nutritional composition of common foods like bread and plant-based meat alternatives. While the limited literature on this topic spans several decades, no commercial operations currently exist to process PHs for human consumption, and most literature on the topic precedes the technological "green revolution." The approaches outlined in this review may help bolster commercialization of this underutilized and nutritious food potentially improving opportunities for multiple global stakeholders.

Influence of impression method and shoulder design on the marginal adaptation of CAD/CAM nanoceramic resin onlay restorations.

Objective: This in-vitro study investigates the influence of two different impression techniques and two shoulder designs on the marginal adaptation of computer-aided design/computer-aided manufacturing restorations. Methods: Forty mandibular first premolars were cast into dental arch models for this in vitro study. Fragile cusps and concavities on the mesial-buccal-occlusal surfaces were treated, with 2 mm of the occlusal surface removed. Teeth were categorised into two groups based on shoulder preparation. Digital scanning using a 3Shape 3D scanner identified them further for allocation into conventional and digital impression subgroups. The restorations were created from nanoceramic resin blocks using prescribed guidelines. Microscopic evaluation assessed the restoration's marginal adaptation, with data analysed using SPSS 27.0. The level of significance was set at p ≤ 0.05. Results: Digital intraoral scanning consistently demonstrated smaller marginal gaps than the traditional impression method, regardless of shoulder preparation, with the differences being statistically significant (p < 0.05). Furthermore, shoulder preparation significantly reduced the marginal gaps in both the digital and traditional impression groups (p < 0.05). Conclusions: The onlay preparation design with a shoulder led to restorations with improved marginal adaptation compared with the design with no shoulder. Direct digital impression techniques produced restorations within a better marginal discrepancy than traditional impressions.

Recent Advances in Therapeutics and Manufacturing Processes of Recombinant Adeno-Associated Virus for the Treatment of Lung Diseases.

Developing delivery vectors capable of transducing genetic material across the lung epithelia and mucus barrier is a major challenge and of great interest to enable gene therapies to treat pulmonary diseases. Recombinant Adeno-associated Viruses (rAAVs) have emerged as attractive candidates among viral and non-viral vectors due to their broad tissue tropism, ability to transduce dividing and quiescent cells, and their safety profile in current human applications. While rAAVs have demonstrated safety in earlier clinical trials for lung disease applications, there are still some limitations regarding rAAV-transgene delivery in pulmonary cells. Thus, further improvements in rAAV engineering are needed to enhance the effectiveness of rAAV-based therapies for lung diseases. Such therapies could benefit patients with chronic lung diseases, such as asthma, chronic obstructive pulmonary disease, pulmonary hypertension, and cystic fibrosis, among others, by regulating hereditary gene mutations or acquired gene deregulations causing these conditions. Alongside therapeutic development, advances in the rAAV production process are essential to meet increasing production demands, while reducing manufacturing costs. This review discusses current challenges and recent advances in the field of rAAV engineering and manufacturing to encourage the clinical development of new pulmonary gene therapy treatments.

Systematic investigation of the impact of screw elements in continuous wet granulation.

Twin-screw wet granulation (TSG) is a continuous manufacturing technique either for granules as final dosage form or as an intermediate before tableting or capsule filling. A comprehensive process understanding is required to implement TSG, considering various parameters influencing granule and tablet quality. This study investigates the impact of screw configuration on granule properties followed by tableting, using a systematic approach for lactose-microcrystalline cellulose (lactose-MCC) and ibuprofen-mannitol (IBU) formulations. The most affecting factor, as observed by other researchers, was the L/S ratio impacting the granule size, strength and tabletability. Introducing tooth-mixing-elements at the end of the screw, as for the IBU formulation, resulted in a high proportion of oversized granules, with values between 36% and 78%. Increasing the thickness of kneading elements (KEs) produced denser, less friable granules with reduced tablet tensile strength. Granulation with more KEs, larger thickness or stagger angle increased torque values and residence time from 30 to 65 s. Generally, IBU granules exhibited high tabletability, requiring low compression pressure for sufficient tensile strength. At a compression pressure of 50 MPa, IBU tablets where at least one kneading zone was included resulted in approximately 2.5 MPa compared to lactose-MCC with 0.5 MPa. In conclusion, the TSG process demonstrated robustness by varying the screw design with minimal impact on subsequent tableting processes.

Exploring Musculoskeletal Complaints in a Needle Manufacturing Industry: A Cross-Sectional Study.

Musculoskeletal disorders (MSD) encompass a variety of conditions affecting muscles, joints, and nerves. In Portugal, MSDs are the most prevalent occupational health problem in companies. Based on the relevance of work-related MSD (WMSD), this study aims to assess the prevalence of MSD complaints in a needle manufacturing industry in Northern Portugal, following a cross-sectional approach. Thus, 526 workers from five departments (i.e., operator, tuning, maintenance, administration, and logistics) answered a sociodemographic questionnaire and the Nordic Musculoskeletal Questionnaire (NMQ). Within the last 12 months, females exhibited a higher frequency of complaints than males across all body parts except for ankles/feet. The body parts eliciting the most percentage of complaints for both genders include the lower back (54.2%), neck (42.2%), shoulders (39.0%), ankles/feet (38.2%), and wrists/hands (35.7%). No significant association was found between Body Mass Index (BMI) and body part complaints. Tuners reported the highest complaint rate, with occupations as substantial predictors of complaints in certain body parts. Likewise, complaints tend to increase with age. The findings advocate for ergonomic interventions that are gender-, age-, and job-sensitive.

Scalability of API-Loaded Multifilament Yarn Production by Hot-Melt Extrusion and Evaluation of Fiber-Based Dosage Forms.

Fiber-based technologies are widely used in various industries, but their use in pharmaceuticals remains limited. While melt extrusion is a standard method for producing medical fibers such as sutures, it is rarely used for pharmaceutical fiber-based dosage forms. The EsoCap system is a notable exception, using a melt-extruded water-soluble filament as the drug release trigger mechanism. The challenge of producing drug-loaded fibers, particularly due to the use of spinning oils, and the processing of the fibers are addressed in this work using other approaches. The aim of this study was to develop processes for the production and processing of pharmaceutical fibers for targeted drug delivery. Fibers loaded with polyvinyl alcohol and fluorescein sodium as a model drug were successfully prepared by a continuous melt extrusion process and directly spun. These fibers exhibited uniform surface smoothness and consistent tensile strength. In addition, the fibers were further processed into tubular dosage forms using a modified knitting machine and demonstrated rapid drug release in a flow cell.

A Novel Out-of-Control Action Plan (OCAP) for Optimizing Efficiency and Quality in the Wafer Probing Process for Semiconductor Manufacturing.

The out-of-control action plan (OCAP) is crucial in the wafer probing process of semiconductor manufacturing as it systematically addresses and corrects deviations, ensuring the high quality and reliability of semiconductor devices. However, the traditional OCAP involves many redundant and complicated processes after failures occur on production lines, which can delay production and escalate costs. To overcome the traditional OCAP's limitations, this paper proposes a novel OCAP aimed at enhancing the wafer probing process in semiconductor manufacturing. The proposed OCAP integrates proactive measures such as preventive maintenance and advanced monitoring technologies, which are tested and verified through a comprehensive experimental setup. Implementing the novel OCAP in a case company's production line reduced machine downtime by over 24 h per week and increased wafer production by about 23 wafers per week. Additionally, probe test yield improved by an average of 1.1%, demonstrating the effectiveness of the proposed method. This paper not only explores the implementation of the novel OCAP but also compares it with the traditional OCAP, highlighting significant improvements in efficiency and production output. The results underscore the potential of advanced OCAP to enhance manufacturing processes by reducing dependency on human judgment, thus lowering the likelihood of errors and improving overall equipment effectiveness (OEE).

Eddy Current Sensor Probe Design for Subsurface Defect Detection in Additive Manufacturing.

Pore and crack formation in parts produced by additive manufacturing (AM) processes, such as laser powder bed fusion, is one of the issues associated with AM technology. Surface and subsurface cracks and pores are induced during the printing process, undermining the printed part durability. In-situ detection of defects will enable the real-time or intermittent control of the process, resulting in higher product quality. In this paper, a new eddy current-based probe design is proposed to detect these defects in parts with various defects that mimic pores and cracks in additively manufactured parts. Electromagnetic finite element analyses were carried out to optimize the probe geometry, followed by fabricating a prototype. Artificial defects were seeded in stainless steel plates to assess the feasibility of detecting various flaws with different widths and lengths. The smallest defect detected had a 0.17 mm radius for blind holes and a 0.43 mm notch with a 5 mm length. All the defects were 0.5 mm from the surface, and the probe was placed on the back surface of the defects. The surface roughness of the tested samples was less than 2 µm. The results show promise for detecting defects, indicating a potential application in AM.

Smart Spare Parts (SSP) in the Context of Industry 4.0: A Systematic Review.

The implementation of Industry 4.0 has integrated manufacturing, electronics, and engineering materials, leading to the creation of smart parts (SPs) that provide information on production system conditions. However, SP development faces challenges due to limitations in manufacturing processes and integrating electronic components. This systematic review synthesizes scientific articles on SP fabrication using additive manufacturing (AM), identifying the advantages and disadvantages of AM techniques in SP production and distinguishing between SPs and smart spare parts (SSPs). The methodology involves establishing a reference framework, formulating SP-related questions, and applying inclusion criteria and keywords, initially resulting in 1603 articles. After applying exclusion criteria, 70 articles remained. The results show that while SP development is advancing, widespread application of AM-manufactured SP is recent. SPs can anticipate production system failures, minimize design artifacts, and reduce manufacturing costs. Furthermore, the review highlights that SSPs, a subcategory of SPs, primarily differs by replacing conventional critical parts in the industry, offering enhanced functionality and reliability in industrial applications. The study concludes that continued research and development in this field is essential for further advancements and broader adoption of these technologies.

Abolishing Retro-Transduction of Producer Cells in Lentiviral Vector Manufacturing.

Transduction of producer cells during lentiviral vector (LVV) production causes the loss of 70-90% of viable particles. This process is called retro-transduction and it is a consequence of the interaction between the LVV envelope protein, VSV-G, and the LDL receptor located on the producer cell membrane, allowing lentiviral vector transduction. Avoiding retro-transduction in LVV manufacturing is crucial to improve net production and, therefore, the efficiency of the production process. Here, we describe a method for quantifying the transduction of producer cells and three different strategies that, focused on the interaction between VSV-G and the LDLR, aim to reduce retro-transduction.