The preclinical and clinical progress of cell sheet engineering in regenerative medicine.

Cell therapy is an accessible method for curing damaged organs or tissues. Yet, this approach is limited by the delivery efficiency of cell suspension injection. Over recent years, biological scaffolds have emerged as carriers of delivering therapeutic cells to the target sites. Although they can be regarded as revolutionary research output and promote the development of tissue engineering, the defect of biological scaffolds in repairing cell-dense tissues is apparent. Cell sheet engineering (CSE) is a novel technique that supports enzyme-free cell detachment in the shape of a sheet-like structure. Compared with the traditional method of enzymatic digestion, products harvested by this technique retain extracellular matrix (ECM) secreted by cells as well as cell-matrix and intercellular junctions established during in vitro culture. Herein, we discussed the current status and recent progress of CSE in basic research and clinical application by reviewing relevant articles that have been published, hoping to provide a reference for the development of CSE in the field of stem cells and regenerative medicine.

The Role of Advanced Technologies against COVID-19: Prevention, Detection, and Treatments.

Concurrent with the global outbreak of COVID-19, the race began among scientists to generate effective therapeutics for the treatment of COVID-19. In this regard, advanced technology such as nanotechnology, cell-based therapies, tissue engineering and regenerative medicine, nerve stimulation and artificial intelligence (AI) are attractive because they can offer new solutions for the prevention, diagnosis and treatment of COVID-19. Nanotechnology can design rapid and specific tests with high sensitivity for detecting infection and synthases new drugs and vaccines based on nanomaterials to directly deliver the intended antiviral agent to the desired site in the body and also provide new surfaces that do not allow virus adhesion. Mesenchymal stem cells and exosomes secreted from them apply in regenerative medicine and regulate inflammatory responses. Cell therapy and tissue engineering are combined to repair or substitute damaged tissues or cells. Tissue engineering using biomaterials, cells, and signaling molecules can develop new therapeutic and diagnostic platforms and help scientists fight viral diseases. Nerve stimulation technology can augment body's natural ability to modulate the inflammatory response and inhibit pro-inflammatory cytokines and consequently suppress cytokine storm. People can access free online health counseling services through AI and it helps very fast for screening and diagnosis of COVID-19 patients. This study is aimed first to give brief information about COVID-19 and the epidemiology of the disease. After that, we highlight important developments in the field of advanced technologies relevant to the prevention, detection, and treatment of the current pandemic.

Life threatening non-accidental burns, pandemic dependent telemedicine, and successful use of cultured Zurich Skin in a neonate - A case report

Life threatening burns of non-accidental origin in neonates are extremely rare. Their management represents a great challenge, particularly since necrosectomy of deep burns and grafting at this young age are technically very demanding. Thus, a strategic surgical master plan is mandatory to achieve rapid and definitive autologous coverage and avoidance of undue risks and iatrogenic burden for the fragile neonatal patient. We present the case of a four day-old neonate who sustained non-accidental deep burns involving 40 % of its total body surface area (TBSA) and the successful application of a laboratory grown, autologous dermo-epidermal skin analogue, termed Zurich Skin (also named denovoSkin), within a clinical trial sub-study. Due to COVID-19 pandemic restrictions, a telemedicine-based approach was installed and a total of 260 cm2 Zurich Skin were transplanted, video assisted, on a wound bed previously prepared with a dermal substitute, thereby covering 20 % TBSA. Take of Zurich Skin was excellent on the chest, good to moderate on the abdomen, and poor on other small areas, where we observed a prolonged healing. After maturation, Zurich Skin showed a close to natural skin coverage without need for further reconstructive surgery. This unique case delivers the proof of concept that Zurich Skin can be successfully applied in early life and even under most adverse medical and paramedical circumstances, provided a carefully crafted masterplan properly addressing the key issues can be executed by joint forces of committed partner institutions.Copyright © 2023 The Authors

Three-Dimensional Bioprinting of an In Vitro Lung Model.

In December 2019, COVID-19 emerged in China, and in January 2020, the World Health Organization declared a state of international emergency. Within this context, there is a significant search for new drugs to fight the disease and a need for in vitro models for preclinical drug tests. This study aims to develop a 3D lung model. For the execution, Wharton's jelly mesenchymal stem cells (WJ-MSC) were isolated and characterized through flow cytometry and trilineage differentiation. For pulmonary differentiation, the cells were seeded in plates coated with natural functional biopolymer matrix as membrane until spheroid formation, and then the spheroids were cultured with differentiation inductors. The differentiated cells were characterized using immunocytochemistry and RT-PCR, confirming the presence of alveolar type I and II, ciliated, and goblet cells. Then, 3D bioprinting was performed with a sodium alginate and gelatin bioink in an extrusion-based 3D printer. The 3D structure was analyzed, confirming cell viability with a live/dead assay and the expression of lung markers with immunocytochemistry. The results showed that the differentiation of WJ-MSC into lung cells was successful, as well as the bioprinting of these cells in a 3D structure, a promising alternative for in vitro drug testing.

Membranes for the life sciences and their future roles in medicine.

Since the global outbreak of COVID-19, membrane technology for clinical treatments, including extracorporeal membrane oxygenation (ECMO) and protective masks and clothing, has attracted intense research attention for its irreplaceable abilities. Membrane research and applications are now playing an increasingly important role in various fields of life science. In addition to intrinsic properties such as size sieving, dissolution and diffusion, membranes are often endowed with additional functions as cell scaffolds, catalysts or sensors to satisfy the specific requirements of different clinical applications. In this review, we will introduce and discuss state-of-the-art membranes and their respective functions in four typical areas of life science: artificial organs, tissue engineering, in vitro blood diagnosis and medical support. Emphasis will be given to the description of certain specific functions required of membranes in each field to provide guidance for the selection and fabrication of the membrane material. The advantages and disadvantages of these membranes have been compared to indicate further development directions for different clinical applications. Finally, we propose challenges and outlooks for future development.

Recombinant human plasma gelsolin reverses increased permeability of the blood-brain barrier induced by the spike protein of the SARS-CoV-2 virus.

BACKGROUND: Plasma gelsolin (pGSN) is an important part of the blood actin buffer that prevents negative consequences of possible F-actin deposition in the microcirculation and has various functions during host immune response. Recent reports reveal that severe COVID-19 correlates with reduced levels of pGSN. Therefore, using an in vitro system, we investigated whether pGSN could attenuate increased permeability of the blood-brain barrier (BBB) during its exposure to the portion of the SARS-CoV-2 spike protein containing the receptor binding domain (S1 subunit). MATERIALS AND METHODS: Two- and three-dimensional models of the human BBB were constructed using the human cerebral microvascular endothelial cell line hCMEC/D3 and exposed to physiologically relevant shear stress to mimic perfusion in the central nervous system (CNS). Trans-endothelial electrical resistance (TEER) as well as immunostaining and Western blotting of tight junction (TJ) proteins assessed barrier integrity in the presence of the SARS-CoV-2 spike protein and pGSN. The IncuCyte Live Imaging system evaluated the motility of the endothelial cells. Magnetic bead-based ELISA was used to determine cytokine secretion. Additionally, quantitative real-time PCR (qRT-PCR) revealed gene expression of proteins from signaling pathways that are associated with the immune response. RESULTS: pGSN reversed S1-induced BBB permeability in both 2D and 3D BBB models in the presence of shear stress. BBB models exposed to pGSN also exhibited attenuated pro-inflammatory signaling pathways (PI3K, AKT, MAPK, NF-κB), reduced cytokine secretion (IL-6, IL-8, TNF-α), and increased expression of proteins that form intercellular TJ (ZO-1, occludin, claudin-5). CONCLUSION: Due to its anti-inflammatory and protective effects on the brain endothelium, pGSN has the potential to be an alternative therapeutic target for patients with severe SARS-CoV-2 infection, especially those suffering neurological complications of COVID-19.

Valorization of Aloe barbadensis Miller. (Aloe vera) Processing Waste

Aloe vera plant is known worldwide for its medicinal properties and application in gel-based products such as shampoo, soap, and sunscreen. However, the demand for these gel-based products has led to a surplus production of Aloe vera processing waste. An Aloe vera gel processing facility could generate up to 4000 kg of Aloe vera waste per month. Currently the Aloe vera waste is being disposed to the landfill or used as fertilizer. A sustainable management system for the Aloe vera processing waste should be considered, due to the negative societal and environmental impacts of the currents waste disposal methods. Therefore, this review focuses on various approaches that can be used to valorize Aloe vera waste into value-added products, such as animal and aquaculture feeds, biosorbents, biofuel and natural polymers. Researchers have reported Aloe vera waste for environmental applications biosorbents used for wastewater treatment of various pollutants. Several studies have also reported on the valorization of Aloe vera waste for production of biofuels such as bioethanol, mixed alcohol fuels, biogas and syn-gas. Aloe vera waste could also be valorized through isolation and synthesis of natural polymers for application in wound dressing, tissue engineering and drug delivery systems. Aloe vera waste valorization was also reviewed through extraction of value-added bioactive compounds such as aloe-emodin, aloin and aloeresin. These value-added bioactive compounds have various applications in the cosmetics (non-steroidal anti-inflammatory, tyrosinase inhibitors) and pharmaceutical (anticancer agent and COVID 19 inhibitors) industry. © 2023, Tech Science Press. All rights reserved.

Matrices Activated with Messenger RNA.

Over two decades of preclinical and clinical experience have confirmed that gene therapy-activated matrices are potent tools for sustained gene modulation at the implantation area. Matrices activated with messenger RNA (mRNA) are the latest development in the area, and they promise an ideal combination of efficiency and safety. Indeed, implanted mRNA-activated matrices allow a sustained delivery of mRNA and the continuous production of therapeutic proteins in situ. In addition, they are particularly interesting to generate proteins acting on intracellular targets, as the translated protein can directly exert its therapeutic function. Still, mRNA-activated matrices are incipient technologies with a limited number of published records, and much is still to be understood before their successful implementation. Indeed, the design parameters of mRNA-activated matrices are crucial for their performance, as they affect mRNA stability, device immunogenicity, translation efficiency, and the duration of the therapy. Critical design factors include matrix composition and its mesh size, mRNA chemical modification and sequence, and the characteristics of the nanocarriers used for mRNA delivery. This review aims to provide some background relevant to these technologies and to summarize both the design space for mRNA-activated matrices and the current knowledge regarding their pharmaceutical performance. Furthermore, we will discuss potential applications of mRNA-activated matrices, mainly focusing on tissue engineering and immunomodulation.

Nanotechnology and COVID-19: Prevention, diagnosis, vaccine, and treatment strategies

In December 2019, Coronavirus pandemic (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viruses, which affected the whole world, is emerged. The details on the epidemiology, infection source, transmission mode, and prognosis of SARS-CoV-2 gave in this review. Universal infection control standards such as hand hygiene, environmental cleanliness, use of personal protective equipment, and quarantine used to prevent the spread of COVID-19 without vaccine. However, many vaccine candidate studies carried out globally with using traditional and technological approaches. Innovations in technology allow the development of nanotechnological tools and the formation of systems that will inactivate SARS-CoV-2 in patients. It expected to include technologies that combine different disciplines, especially robotic applications, antimicrobial nanotechnology, and tissue engineering for the future treatment of COVID-19. This review-based work discusses the relationship of COVID-19 and nanotechnology based working principles. Copyright © 2023 Ayan, Aranci-Ciftci, Ciftci and Ustundag.

Emerging polymeric biomaterials and manufacturing-based tissue engineering approaches for neuro regeneration-A critical review on recent effective approaches

The nervous system is a crucial part of the human body that is damaged by traumatic injury, stroke, and neurodegenerative diseases. Recent studies also have shown that neurodegenerative diseases are associated with a subsequently increased risk of COVID-19-related death. Presently used pharmacological and therapeutic strategies are only the symptomatic treatments that involve the disruption of axonal tracts and are unable to repair and regenerate damaged CNS tissue thereby leading to significant unmet clinical needs involved in neural degeneration. The use of stem cell based regenerative medicine approaches is also limited due to heavy cost, ethical concerns and graft rejection. To address all these limitations, the neural tissue engineering philosophy has been developed that focuses on exploring and developing smart biomaterials for neural tissue repair and regeneration. A scaffold based upon natural and synthetic polymers has meant a very potential role to mimic the extracellular matrix of cells and permit the growth of different types of cells thereby improving the biological behavior in vitro and in vivo effects. They treat neurological disorders without the classic drug delivery limitations. Among these biopolymers, the collagen-based hydrogel is successfully applied conduits for clinical trials that ultimately replicate the native physiological environment of the neural tissues and control cell behavior and favor the regeneration of the damaged nerve tissue. The main objective of this review is to investigate the recent approaches and applications of next-generation polymeric biomaterials useful in the management of neurodegenerative diseases. We also discuss the outlook of the polymeric scaffolds that could pave the way for successful clinical practices. © 2022 The Authors

Additive manufacturing for biomedical applications: a review on classification, energy consumption, and its appreciable role since COVID-19 pandemic

The exponential rise of healthcare problems like human aging and road traffic accidents have developed an intrinsic challenge to biomedical sectors concerning the arrangement of patient-specific biomedical products. The additively manufactured implants and scaffolds have captured global attention over the last two decades concerning their printing quality and ease of manufacturing. However, the inherent challenges associated with additive manufacturing (AM) technologies, namely process selection, level of complexity, printing speed, resolution, biomaterial choice, and consumed energy, still pose several limitations on their use. Recently, the whole world has faced severe supply chain disruptions of personal protective equipment and basic medical facilities due to a respiratory disease known as the coronavirus (COVID-19). In this regard, local and global AM manufacturers have printed biomedical products to level the supply-demand equation. The potential of AM technologies for biomedical applications before, during, and post-COVID-19 pandemic alongwith its relation to the industry 4.0 (I4.0) concept is discussed herein. Moreover, additive manufacturing technologies are studied in this work concerning their working principle, classification, materials, processing variables, output responses, merits, challenges, and biomedical applications. Different factors affecting the sustainable performance in AM for biomedical applications are discussed with more focus on the comparative examination of consumed energy to determine which process is more sustainable. The recent advancements in the field like 4D printing and 5D printing are useful for the successful implementation of I4.0 to combat any future pandemic scenario. The potential of hybrid printing, multi-materials printing, and printing with smart materials, has been identified as hot research areas to produce scaffolds and implants in regenerative medicine, tissue engineering, and orthopedic implants.

MXene-Based Nanomaterials for Biomedical Applications: Healthier Substitute Materials for the Future

MXene-based nanomaterial is a revolution 2D material achieving outstanding scientific attention owing to its universal characteristics for different applications (such as electronic appliances, power production, sensors, drug transfer, and biomedical). Although, the cytotoxic consequences of MXene have a considerable circumstance. Thus, rigorous investigation of the biocompatibility of MXene is a crucial prerequisite, formerly the preface to the human biological approach. Literature reveals functional outcomes wherever MXenes are used in vitro and in vivo cancer representatives. It affects drug transfer methods, sensoring electrodes, and assisting mechanisms for photothermal treatment and hyperthermy techniques. In this review, the synthesis process (such as top-down and bottom-up approaches) and properties (such as mechanical, electrical, optical, oxidative/thermal stability, and magnetic) of MXene-based nanomaterials (NMs) are discussed. In addition, the different applications (such as tissue engineering, cancer theranostic, and other biomedical [such as drug delivery biosensors and surface-enhanced Raman spectroscopy substrates for biomedical applications], antiviral, and immunomodulatory properties against SARS-CoV-2) of MXene-based NMs are discussed in detail. Finally, the conclusion, existing challenges, and future outlooks are highlighted for more scope in this field.

Characterization of COVID-19 Diseased Lung Tissue Based on Texture Features

Although real time polymerase chain reaction test (RT-PCR) is the gold standard method for the diagnosis of COVID-19 patients, the use of Computed Tomography (CT) images for diagnosis, assessment of the severity of this disease and its evolution is widely accepted due to the possibility to observe the lungs damage. This evaluation is mainly made qualitatively, therefore, techniques have been proposed to obtain relevant additional clinical information, such as texture features. In this work, CT scans from 46 patients with COVID-19 were used to characterize the lungs by means of textural features. In the proposed approach, pulmonary parenchyma was delimited using a U-NET previously trained with images from different pulmonary diseases. Texture metrics were calculated using co-occurrence and run-length matrices considering both lungs, right and left lung, as well as apex, middle zone and base lung regions. A boxplot descriptive analysis was performed looking for significant differences between regions of each estimated texture metric. Results show that Gray Level Non-Uniformity (GLNU) and Run-Length Non-Uniformity (RLNU) features have more significant differences between regions, suggesting that these metrics may provide a proper characterization of the pulmonary damage caused by COVID-19. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Physics of droplet impact on flexible materials: A review

Droplet impact on a flexible substrate is a prevalent phenomenon in nature and various advanced technologies such as soft bio-printing, tissue engineering, smart biomaterials and flexible electronics. Recent rapid advancement in new functional surfaces, ultra-high-speed imaging, nanotechnology, deep learning, advanced computational strength and the relation between fluid dynamics and interfacial science have intensified the physical understanding of droplet impact on soft materials. Once a droplets impacts on a solid surface, it deposits, spreads, rebounds or splashes. Given the importance of the droplet impact onto soft substrates in biotechnology, medicine and advanced flexible electronics, a deep physical understanding of such complex phenomenon is vital. This review initially presents the liquid-solid interaction physics and relevant interfacial science. Next, this review discusses the physics of droplet impact on soft materials with different physical and interfacial characteristics. Moreover, this review presents advancements in droplet impact on elastic materials relevant to new technologies such as soft electronics, elastic smart biomaterials, tissue engineering and the fight against COVID-19 pandemic. Finally, this review lays out future research directions related to current problems in such complex physical phenomenon.

Mesenchymal Stem Cells and MSCs-Derived Extracellular Vesicles in Infectious Diseases: From Basic Research to Clinical Practice.

Mesenchymal stem cells (MSCs) are attractive in various fields of regenerative medicine due to their therapeutic potential and complex unique properties. Basic stem cell research and the global COVID-19 pandemic have given impetus to the development of cell therapy for infectious diseases. The aim of this review was to systematize scientific data on the applications of mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) in the combined treatment of infectious diseases. Application of MSCs and MSC-EVs in the treatment of infectious diseases has immunomodulatory, anti-inflammatory, and antibacterial effects, and also promotes the restoration of the epithelium and stimulates tissue regeneration. The use of MSC-EVs is a promising cell-free treatment strategy that allows solving the problems associated with the safety of cell therapy and increasing its effectiveness. In this review, experimental data and clinical trials based on MSCs and MSC-EVs for the treatment of infectious diseases are presented. MSCs and MSC-EVs can be a promising tool for the treatment of various infectious diseases, particularly in combination with antiviral drugs. Employment of MSC-derived EVs represents a more promising strategy for cell-free treatment, demonstrating a high therapeutic potential in preclinical studies.

Recent Advances in Silver Nanoparticles Containing Nanofibers for Chronic Wound Management.

Infections are the primary cause of death from burns and diabetic wounds. The clinical difficulty of treating wound infections with conventional antibiotics has progressively increased and reached a critical level, necessitating a paradigm change for enhanced chronic wound care. The most prevalent bacterium linked with these infections is Staphylococcus aureus, and the advent of community-associated methicillin-resistant Staphylococcus aureus has posed a substantial therapeutic challenge. Most existing wound dressings are ineffective and suffer from constraints such as insufficient antibacterial activity, toxicity, failure to supply enough moisture to the wound, and poor mechanical performance. Using ineffective wound dressings might prolong the healing process of a wound. To meet this requirement, nanoscale scaffolds with their desirable qualities, which include the potential to distribute bioactive agents, a large surface area, enhanced mechanical capabilities, the ability to imitate the extracellular matrix (ECM), and high porosity, have attracted considerable interest. The incorporation of nanoparticles into nanofiber scaffolds constitutes a novel approach to "nanoparticle dressing" that has acquired significant popularity for wound healing. Due to their remarkable antibacterial capabilities, silver nanoparticles are attractive materials for wound healing. This review focuses on the therapeutic applications of nanofiber wound dressings containing Ag-NPs and their potential to revolutionize wound healing.

Health Education In The Self Care Process Of The Chronic Wounds Healing Of The Diabetic Foot

Purpose/Objectives: The increase in life expectancy in recent years is closely related to scientific advances in health area. Thus, longevity led to a greater emergence of chronic diseases, such as diabetes mellitus (DM). In this scenario, chronic wounds represent a serious public health problem. It is estimated that 85% of lower extremity amputations in individuals with DM are related to the presence of foot ulcers. The perception of changes in the skin, such as deformities, superficial traumas and cracks, is impaired in diabetics due to loss of sensitivity, predisposing the appearance of wounds. Ulcers and other injuries can be prevented through simple measures, such as regular skin inspection, specialized care and the use of adequate footwear;as the greater understanding of self-care, the greater the benefits of treatment. In this sense, Primary Care is an effective mean of assisting such individuals, as health education actions can be carried out for this population, their families and caregivers, with a view of promoting health. In addition, the health education process must take place in parallel with medication and dressings, which are essential, especially the latter, given the specificity of the product and the level of tissue regeneration. The primary objective of this study is to present the educational activities developed by the Extension Project Physiotherapy in the Community of the State University of Paraíba in partnership with the research project Tissue Engineering in Epithelial Repair: Biodegradable Scaffold for Tissue Regeneration, which is developing chitosan/Jatropha mollissima scaffolds, in the Laboratory of Evaluation and Development of Biomaterials from the Northeast of the Federal University of Campina Grande. Methodology: The participants consisted of users of Basic Health Units (BHU) in the city of Campina Grande/Paraiba/Brazil. The educational material on Diabetes and Diabetic Foot Wound Care was produced from documents such as articles, guidelines and booklets. The CANVA application was used to create the images and infographics, to facilitate the understanding of the participants, and it was sent along with an explanatory audio. The disclosure took place on the public profile on Instagram @fisionacomunidadeuepb and also through the WhatsApp application for the diabetic elderly who participate in the project, in addition to face-to-face meetings at BHU, to clarify doubts at previously scheduled times and with a limited number of people due to the covid 19 pandemic. Results: The results included a greater understanding of the process of illness and wound development, as well as awareness of the importance of adherence to treatment and care in the use of dressings, especially. According to the records, the participation in the means used was intense, which suggests that these people will also be multipliers in the health education process. Conclusion/Significance: It is concluded that health education strategies, even at the time of a pandemic, are useful in the process of correct information dissemination, helping the most vulnerable population to understand their disease and, at the same time, help them in self care and responsibility, thus facilitating the intervention used by the health and engineering team.