Nanocarrier-based gene delivery for immune cell engineering.

Clinical advances in genetically modified immune cell therapies, such as chimeric antigen receptor T cell therapies, have raised hope for cancer treatment. The majority of these biotechnologies are based on viral methods for ex vivo genetic modification of the immune cells, while the non-viral methods are still in the developmental phase. Nanocarriers have been emerging as materials of choice for gene delivery to immune cells. This is due to their versatile physicochemical properties such as large surface area and size that can be optimized to overcome several practical barriers to successful gene delivery. The in vivo nanocarrier-based gene delivery can revolutionize cell-based cancer immunotherapies by replacing the current expensive autologous cell manufacturing with an off-the-shelf biomaterial-based platform. The aim of this research is to review current advances and strategies to overcome the challenges in nanoparticle-based gene delivery and their impact on the efficiency, safety, and specificity of the process. The main focus is on polymeric and lipid-based nanocarriers, and their recent preclinical applications for cancer immunotherapy.

Magnetically-assisted viral transduction (magnetofection) medical applications: An update.

Gene therapy involves replacing a faulty gene or adding a new gene inside the body's cells to cure disease or improve the body's ability to fight disease. Its popularity is evident from emerging concepts such as CRISPR-based genome editing and epigenetic studies and has been moved to a clinical setting. The strategy for therapeutic gene design includes; suppressing the expression of pathogenic genes, enhancing necessary protein production, and stimulating the immune system, which can be incorporated into both viral and non-viral gene vectors. Although non-viral gene delivery provides a safer platform, it suffers from an inefficient rate of gene transfection, which means a few genes could be successfully transfected and expressed within the cells. Incorporating nucleic acids into the viruses and using these viral vectors to infect cells increases gene transfection efficiency. Consequently, more cells will respond, more genes will be expressed, and sustained and successful gene therapy can be achieved. Combining nanoparticles (NPs) and nucleic acids protects genetic materials from enzymatic degradation. Furthermore, the vectors can be transferred faster, facilitating cell attachment and cellular uptake. Magnetically assisted viral transduction (magnetofection) enhances gene therapy efficiency by mixing magnetic nanoparticles (MNPs) with gene vectors and exerting a magnetic field to guide a significant number of vectors directly onto the cells. This research critically reviews the MNPs and the physiochemical properties needed to assemble an appropriate magnetic viral vector, discussing cellular hurdles and attitudes toward overcoming these barriers to reach clinical gene therapy perspectives. We focus on the studies conducted on the various applications of magnetic viral vectors in cancer therapies, regenerative medicine, tissue engineering, cell sorting, and virus isolation.

An update on dual targeting strategy for cancer treatment.

The key issue in the treatment of solid tumors is the lack of efficient strategies for the targeted delivery and accumulation of therapeutic cargoes in the tumor microenvironment (TME). Targeting approaches are designed for more efficient delivery of therapeutic agents to cancer cells while minimizing drug toxicity to normal cells and off-targeting effects, while maximizing the eradication of cancer cells. The highly complicated interrelationship between the physicochemical properties of nanoparticles, and the physiological and pathological barriers that are required to cross, dictates the need for the success of targeting strategies. Dual targeting is an approach that uses both purely biological strategies and physicochemical responsive smart delivery strategies to increase the accumulation of nanoparticles within the TME and improve targeting efficiency towards cancer cells. In both approaches, either one single ligand is used for targeting a single receptor on different cells, or two different ligands for targeting two different receptors on the same or different cells. Smart delivery strategies are able to respond to triggers that are typical of specific disease sites, such as pH, certain specific enzymes, or redox conditions. These strategies are expected to lead to more precise targeting and better accumulation of nano-therapeutics. This review describes the classification and principles of dual targeting approaches and critically reviews the efficiency of dual targeting strategies, and the rationale behind the choice of ligands. We focus on new approaches for smart drug delivery in which synthetic and/or biological moieties are attached to nanoparticles by TME-specific responsive linkers and advanced camouflaged nanoparticles.

Evaluation of antimicrobial and cytotoxic effects of Echinacea and Arctium extracts and Zataria essential oil.

Dental caries and oral infections have become a widespread issue in the modern world. This study aimed to investigate the antibacterial, antifungal, and cytotoxicity characteristics of the extracts of Echinacea purpura, Arctium lappa, and the essential oil of Zataria multiflora as a potential herbal mouthwash. The essential oil of Z. multiflora leaves and the extracts of E. purpurea and A. lappa roots were prepared. The characterization was carried out by GC-MS and also, total phenol and flavonoid were assed for all three samples. The antimicrobial and anti-biofilm effects were evaluated against Streptococcus mutans, Streptococcus mitis, Streptococcus salivarius, Lactobacillus acidophilus, Escherichia coli, Staphylococcus aureus, and Candida albicans. The cytotoxic effect of the samples was evaluated on HEK 293 and HDFa cells by MTT test. Thymol and carvacrol contents in EO of Z. multiflora were measured at 31% and 42.2%, respectively. A. lappa had the lowest total phenolic and flavonoid value among the samples. On the other hand, the total phenolic content of Z. multiflora and the total flavonoid content of E. purpurea were the highest. The MIC values of Zataria, Arctium, and Echinacea against S. mutans were 0.011% v/v, 187.5 mg/ml, and 93.75 mg/ml, while MBC were 0.011% v/v, 375 mg/ml, and 187.5 mg/ml, respectively. The formulation showed bactericidal activity against S. mutans in the concentration of 5.86 mg/ml for Echinacea and Burdock extracts and 0.08 µl/ml for EO of Zataria. The formulation significantly affected microbial biofilm formation and induced biofilm degradation. The cell viability percentages were higher than 50% during 24 and 48 h. The formulation had a significant antimicrobial effect on cariogenic bacteria and C. albicans, with the lowest cytotoxic effects. Therefore, this formulation can be an appropriate candidate for mouthwash.

Chemotherapeutic effects of Apigenin in breast cancer: Preclinical evidence and molecular mechanisms; enhanced bioavailability by nanoparticles.

This review highlights using nanotechnology in increasing the bioavailability of AP (Apigenin) to enhance its therapeutic efficacy in breast cancer treatment. Breast cancer is one of the most leading causes of cancer death in women both in developed and developing countries. According to several epidemiological and clinical trial studies that indicate progestin-stimulated breast cancer in post-menopausal women; it is necessary to determine compounds to suppress or attenuate the tumor-promoting effects of progestins in breast cells. For this purpose, using the natural anti-progestins, including AP compared with the chemical ones could be significantly effective due to the lack of toxicities and contradiction effects. However, AP is categorized as a Class II drug of Biopharmaceutical Classification System with low solubility in water which limited its therapeutic effects. Therefore, nanotechnology due to the presentation of remarkable properties has overcome this limitation through enhanced the solubility and bioavailability of AP. In this regard, various nanocarriers such as nanocrystals, micelles, liposomes, PLGA, etc., have highlighted the significantly increased bioavailability and therapeutic efficacy of AP. Therefore, we will focus on the anticancer effects of AP in breast cancers, including involved mechanisms, the chemistry of AP and its bioavailability, finally different nanostructure systems to enhance the bioavailability of AP.

Stem Cell Differentiation into Cardiomyocytes: Current Methods and Emerging Approaches.

Cardiovascular diseases (CVDs) are globally known to be important causes of mortality and disabilities. Common treatment strategies for CVDs, such as pharmacological therapeutics impose serious challenges due to the failure of treatments for myocardial necrosis. By contrast, stem cells (SCs) based therapies are seen to be promising approaches to CVDs treatment. In such approaches, cardiomyocytes are differentiated from SCs. To fulfill SCs complete potential, the method should be appointed to generate cardiomyocytes with more mature structure and well-functioning operations. For heart repairing applications, a greatly scalable and medical-grade cardiomyocyte generation must be used. Nonetheless, there are some challenges such as immune rejection, arrhythmogenesis, tumorigenesis, and graft cell death potential. Herein, we discuss the types of potential SCs, and commonly used methods including embryoid bodies related techniques, co-culture, mechanical stimulation, and electrical stimulation and their applications, advantages and limitations in this field. An estimated 17.9 million people died from CVDs in 2019, representing 32 % of all global deaths. Of these deaths, 85 % were due to heart attack and stroke.

Can we Succeed in the Fight Against SARS-CoV-2 with its Emerging New Variants?

In 2019, the whole world came together to confront a life-threatening virus named SARS-CoV-2, causing COVID-19 illness. The virus infected the human host by attaching to the ACE2 and CD147 receptors in some human cells, resulting in cytokine storm and death. The new variants of the virus that caused concern are Alpha, Beta, Gamma, Delta, and Epsilon, according to the WHO label. However, Pango lineages designated them as B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.429. Variants may be progressively formed in one chronic COVID-19 patient and transmitted to others. They show some differences in cellular and molecular mechanisms. Mutations in the receptor-binding domain (RBD) and N-terminal domain (NTD) lead to alterations in the host's physiological responses. They show significantly higher transmissibility rates and viral load while evading neutralizing antibodies at different rates. These effects are through mutations, deletion, and conformational alterations in the virus, resulting in the enhanced affinity of RBD to PD of ACE2 protein, virus entry, and spike conformational change. In the clinical laboratory, new variants may diagnose from other variants using specific primers for RBD or NTD. There are some controversial findings regarding the efficacy of the developed vaccines against the new variants. This research aimed to discuss the cellular and molecular mechanisms beyond COVID-19 pathogenesis, focusing on the new variants. We glanced at why the mutations and the ability to transmit the virus increase and how likely the available vaccines will be effective against these variants.

The Potential Application of Green-Synthesized Metal Nanoparticles in Dentistry: A Comprehensive Review.

Orodental problems have long been managed using herbal medicine. The development of nanoparticle formulations with herbal medicine has now become a breakthrough in dentistry because the synthesis of biogenic metal nanoparticles (MNPs) using plant extracts can address the drawbacks of herbal treatments. Green production of MNPs such as Ag, Au, and Fe nanoparticles enhanced by plant extracts has been proven to be beneficial in managing numerous orodental disorders, even outperforming traditional materials. Nanostructures are utilized in dental advances and diagnostics. Oral disease prevention medicines, prostheses, and tooth implantation all employ nanoparticles. Nanomaterials can also deliver oral fluid or pharmaceuticals, treating oral cancers and providing a high level of oral healthcare. These are also found in toothpaste, mouthwash, and other dental care products. However, there is a lack of understanding about the safety of nanomaterials, necessitating additional study. Many problems, including medication resistance, might be addressed using nanoparticles produced by green synthesis. This study reviews the green synthesis of MNPs applied in dentistry in recent studies (2010-2021).

Emerging treatment strategies in wound care.

Wound healing is a complex process in tissue regeneration through which the body responds to the dissipated cells as a result of any kind of severe injury. Diabetic and non-healing wounds are considered an unmet clinical need. Currently, different strategic approaches are widely used in the treatment of acute and chronic wounds which include, but are not limited to, tissue transplantation, cell therapy and wound dressings, and the use of an instrument. A large number of literatures have been published on this topic; however, the most effective clinical treatment remains a challenge. The wound dressing involves the use of a scaffold, usually using biomaterials for the delivery of medication, autologous stem cells, or growth factors from the blood. Antibacterial and anti-inflammatory drugs are also used to stop the infection as well as accelerate wound healing. With an increase in the ageing population leading to diabetes and associated cutaneous wounds, there is a great need to improve the current treatment strategies. This research critically reviews the current advancement in the therapeutic and clinical approaches for wound healing and tissue regeneration. The results of recent clinical trials suggest that the use of modern dressings and skin substitutes is the easiest, most accessible, and most cost-effective way to treat chronic wounds with advances in materials science such as graphene as 3D scaffold and biomolecules hold significant promise. The annual market value for successful wound treatment exceeds over $50 billion US dollars, and this will encourage industries as well as academics to investigate the application of emerging smart materials for modern dressings and skin substitutes for wound therapy.

Multi-walled carbon nanotube/hydroxyapatite nanocomposite with leukocyte- and platelet-rich fibrin for bone regeneration in sheep model.

BACKGROUND: The aim of this study was to evaluate the effects of multi-walled carbon nanotubes/hydroxyapatite (MWCNT/HA) granules with or without leukocyte- and platelet-rich fibrin (L-PRF) on bone regeneration in cancellous bone of sheep model. METHODS: Totally, 32 cylindrical holes were drilled in female sheep (n = 4) in the distal epiphysis and proximal metaphysis of right and left humerus and femur. The defects were randomly filled with (1) MWCNT/HA, (2) MWCNT/HA mixed with L-PRF, (3) L-PRF, and (4) left empty as control. After 8 weeks, defects were evaluated and compared radiographically using multi-slice computed tomographic (CT) scan and cone beam CT scans, histologically and histomorphometrically. RESULTS: The results showed that there was no significant inflammation (> 10%) or foreign body reaction around the granules. The new lamellar bone was regenerated around the MWCNT/HA nanocomposite granules. Addition of L-PRF to MWCNT/HA demonstrated significantly improvement of new bone formation, about 27.40 ± 1.08%, in comparison with the L-PRF alone, about (12.16 ± 1.46%) (P < 0.01). Also, the rate of new bone formation was significantly greater with the use of MWCNT/HA granules (24.59 ± 1.54%) compared to the control (10.36 ± 1.17%) (P < 0.01). CONCLUSION: Consequently, both biocompatibility and osteoconductivity of MWCNT/HA nanocomposite were demonstrated in the preclinical sheep model, and the use of L-PRF in combination with MWCNT/HA nanocomposite can improve bone regeneration.

Emerging Application of Magnetic Nanoparticles for Diagnosis and Treatment of Cancer.

Cancer is a disease that has resulted in millions of deaths worldwide. The current conventional therapies utilized for the treatment of cancer have detrimental side effects. This led scientific researchers to explore new therapeutic avenues with an improved benefit to risk profile. Researchers have found nanoparticles, particles between the 1 and 100 nm range, to be encouraging tools in the area of cancer. Magnetic nanoparticles are one of many available nanoparticles at present. Magnetic nanoparticles have increasingly been receiving a considerable amount of attention in recent years owing to their unique magnetic properties, among many others. Magnetic nanoparticles can be controlled by an external magnetic field, signifying their ability to be site specific. The most popular approaches for the synthesis of magnetic nanoparticles are co-precipitation, thermal decomposition, hydrothermal, and polyol synthesis. The functionalization of magnetic nanoparticles is essential as it significantly increases their biocompatibility. The most utilized functionalization agents are comprised of polymers. The synthesis and functionalization of magnetic nanoparticles will be further explored in this review. The biomedical applications of magnetic nanoparticles investigated in this review are drug delivery, magnetic hyperthermia, and diagnosis. The diagnosis aspect focuses on the utilization of magnetic nanoparticles as contrast agents in magnetic resonance imaging. Clinical trials and toxicology studies relating to the application of magnetic nanoparticles for the diagnosis and treatment of cancer will also be discussed in this review.

Biocompatible and Biomaterials Application in Drug Delivery System in Oral Cavity.

Biomaterials applications have rapidly expanded into different fields of sciences. One of the important fields of using biomaterials is dentistry, which can facilitate implantation, surgery, and treatment of oral diseases such as peri-implantitis, periodontitis, and other dental problems. Drug delivery systems based on biocompatible materials play a vital role in the release of drugs into aim tissues of the oral cavity with minimum side effects. Therefore, scientists have studied various delivery systems to improve the efficacy and acceptability of therapeutic approaches in dental problems and oral diseases. Also, biomaterials could be utilized as carriers in biocompatible drug delivery systems. For instance, natural polymeric substances, such as gelatin, chitosan, calcium phosphate, alginate, and xanthan gum are used to prepare different forms of delivery systems. In addition, some alloys are conducted in drug complexes for the better in transportation. Delivery systems based on biomaterials are provided with different strategies, although individual biomaterial has advantages and disadvantages which have a significant influence on transportation of complex such as solubility in physiological environments or distribution in tissues. Biomaterials have antibacterial and anti-inflammatory effects and prolonged time contact and even enhance antibiotic activities in oral infections. Moreover, these biomaterials are commonly prepared in some forms such as particulate complex, fibers, microspheres, gels, hydrogels, and injectable systems. In this review, we examined the application of biocompatible materials in drug delivery systems of oral and dental diseases or problems.

Investigating the Application of Liposomes as Drug Delivery Systems for the Diagnosis and Treatment of Cancer.

Chemotherapy is the routine treatment for cancer despite the poor efficacy and associated off-target toxicity. Furthermore, therapeutic doses of chemotherapeutic agents are limited due to their lack of tissue specificity. Various developments in nanotechnology have been applied to medicine with the aim of enhancing the drug delivery of chemotherapeutic agents. One of the successful developments includes nanoparticles which are particles that range between 1 and 100 nm that may be utilized as drug delivery systems for the treatment and diagnosis of cancer as they overcome the issues associated with chemotherapy; they are highly efficacious and cause fewer side effects on healthy tissues. Other nanotechnological developments include organic nanocarriers such as liposomes which are a type of nanoparticle, although they can deviate from the standard size range of nanoparticles as they may be several hundred nanometres in size. Liposomes are small artificial spherical vesicles ranging between 30 nm and several micrometres and contain one or more concentric lipid bilayers encapsulating an aqueous core that can entrap both hydrophilic and hydrophobic drugs. Liposomes are biocompatible and low in toxicity and can be utilized to encapsulate and facilitate the intracellular delivery of chemotherapeutic agents as they are biodegradable and have reduced systemic toxicity compared with free drugs. Liposomes may be modified with PEG chains to prolong blood circulation and enable passive targeting. Grafting of targeting ligands on liposomes enables active targeting of anticancer drugs to tumour sites. In this review, we shall explore the properties of liposomes as drug delivery systems for the treatment and diagnosis of cancer. Moreover, we shall discuss the various synthesis and functionalization techniques associated with liposomes including their drug delivery, current clinical applications, and toxicology.

Comparison of two routes of administration of a cationic liposome formulation for a prophylactic DC vaccination in a murine melanoma model.

Dendritic cell (DC) vaccination can be achieved via straight loading of vaccine into DCs ex vivo or administration to DCs in vivo. However, there is no certain consensus on which approach is preferable, and each strategy has its advantages and disadvantages, which affect the efficacy and safety of vaccines. It will also be more complicated when a vaccine delivery system is included. In this study, the efficacy of ex vivo pulsed DC-based vaccine compared with in vivo subcutaneous administration of a cationic liposomes (CLs) formulation containing gp100 antigen (gp100-CLs) was evaluated in a murine melanoma model. In combination with an anti-PD-1 antibody, the ex vivo approach of gp100-CLs yielded a significant (P < 0.01) increase in the number of antigen-specific tumors infiltrated lymphocytes (TILs) with a significant upregulation of IFN-γ (P < 0.0001) and PD-1 (P < 0.0001) expression level. They also dampened the function of immunosuppressive regulatory T cells (Tregs) via significant downregulation of IL-10 and TGF-ß (P < 0.0001) expression level compared to in vivo approach in the tumor microenvironment (TME). Furthermore, prophylactic immunization with gp100-CLs pulsed DCs ex vivo delayed tumor growth and induced the survival benefit over in vivo immunization. Collectively, the ex vivo DC-based vaccination pulsed with gp100 encapsulated in liposomes synergizes with anti-PD-1 antibody and represents a preferable approach against melanoma.

Strengthening the CAR-T cell therapeutic application using CRISPR/Cas9 technology.

Adoptive cell immunotherapy with chimeric antigen receptor T (CAR-T) cell has brought a revolutionary means of treatment for aggressive diseases such as hematologic malignancies and solid tumors. Over the last decade, the United States Food and Drug Administration (FDA) approved five types of CAR-T cell therapies for hematologic malignancies, including Idecabtagene vicleucel (Abecma), Lisocabtagene maraleucel (Breyanzi), Brexucabtagene autoleucel (Tecartus), Tisagenlecleucel (Kymriah), and Axicabtagene ciloleucel (Yescarta). Despite outstanding results gained from different clinical trials, CAR-T cell therapy is not free from side effects and toxicities, and needs careful investigations and improvements. Gene-editing technology, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, has emerged as a promising tool to address some of the CAR-T therapy hurdles. Using CRISPR/Cas9 technology, CAR expression as well as other cellular pathways can be modified in various ways to enhance CAR-T cells antitumor function and persistence in immunosuppressive tumor microenvironment. CRISPR/Cas9 technology can also be used to decrease CAR-T cell toxicities and side effects. Hereby, we discussed the practical challenges and hurdles related to the accuracy, efficiency, efficacy, safety, and delivery of CRISPR/Cas9 technology to the genetically engineered-T cells. Combining of these two state-of-the-art technologies, CRISPR/Cas9 and CAR-T cells, the field of oncology has an extraordinary opportunity to enter a new era of immunotherapy, which offers novel therapeutic options for different types of tumors.

The risk of pancreatic adenocarcinoma following SARS-CoV family infection.

COVID 19 disease has become a global catastrophe over the past year that has claimed the lives of over two million people around the world. Despite the introduction of vaccines against the disease, there is still a long way to completely eradicate it. There are concerns about the complications following infection with SARS-CoV-2. This research aimed to evaluate the possible correlation between infection with SARS-CoV viruses and cancer in an in-silico study model. To do this, the relevent dataset was selected from GEO database. Identification of differentially expressed genes among defined groups including SARS-CoV, SARS-dORF6, SARS-BatSRBD, and H1N1 were screened where the |Log FC| ≥ 1and p < 0.05 were considered statistically significant. Later, the pathway enrichment analysis and gene ontology (GO) were used by Enrichr and Shiny GO databases. Evaluation with STRING online was applied to predict the functional interactions of proteins, followed by Cytoscape analysis to identify the master genes. Finally, analysis with GEPIA2 server was carried out to reveal the possible correlation between candidate genes and cancer development. The results showed that the main molecular function of up- and down-regulated genes was "double-stranded RNA binding" and actin-binding, respectively. STRING and Cytoscape analysis presented four genes, PTEN, CREB1, CASP3, and SMAD3 as the key genes involved in cancer development. According to TCGA database results, these four genes were up-regulated notably in pancreatic adenocarcinoma. Our findings suggest that pancreatic adenocarcinoma is the most probably malignancy happening after infection with SARS-CoV family.

Induced Pluripotent Stem Cells (iPSCs) Provide a Potentially Unlimited T Cell Source for CAR-T Cell Development and Off-the-Shelf Products.

Chimeric antigen receptor T (CAR-T) cell therapy has been increasingly conducted for cancer patients in clinical settings. Progress in this therapeutic approach is hampered by the lack of a solid manufacturing process, T lymphocytes, and tumor-specific antigens. T cell source used in CAR-T cell therapy is derived predominantly from the patient's own T lymphocytes, which makes this approach impracticable to patients with progressive diseases and T leukemia. The generation of autologous CAR-T cells is time-consuming due to the lack of readily available T lymphocytes and is not applicable for third-party patients. Pluripotent stem cells, such as human induced pluripotent stem cells (hiPSCs), can provide an unlimited T cell source for CAR-T cell development with the potential of generating off-the-shelf T cell products. T-iPSCs (iPSC-derived T cells) are phenotypically defined, expandable, and as functional as physiological T cells. The combination of iPSC and CAR technologies provides an exciting opportunity to oncology and greatly facilitates cell-based therapy for cancer patients. However, T-iPSCs, in combination with CARs, are at the early stage of development and need further pre-clinical and clinical studies. This review will critically discuss the progress made in iPSC-derived T cells and provides a roadmap for the development of CAR iPSC-derived T cells and off-the-shelf T-iPSCs.

Recent advances in the modification of carbon-based quantum dots for biomedical applications.

Carbon-based quantum dots (CDs) are mainly divided into two sub-groups; carbon quantum dots (CQDs) and graphene quantum dots (GQDs), which exhibit outstanding photoluminescence (PL) properties, low toxicity, superior biocompatibility and facile functionalization. Regarding these features, they have been promising candidates for biomedical science and engineering applications. In this work, we reviewed the efforts made to modify these zero-dimensional nano-materials to obtain the best properties for bio-imaging, drug and gene delivery, cancer therapy, and bio-sensor applications. Five main surface modification techniques with outstanding results are investigated, including doping, surface functionalization, polymer capping, nano-composite and core-shell structures, and the drawbacks and challenges in each of these methods are discussed.

Will stem cells from fat and growth factors from blood bring new hope to female patients with reproductive disorders?

Female reproductive system disorders (FRSD) with or without infertility are prevalent women's health problems with a variety of treatment approaches including surgery and hormone therapy. It currently considering to sub-branch of regenerative medicine including stem cells or growth factors injection-based delivery treatment might be improved female reproductive health life. The most common products used for these patients treatment are autologous cell or platelet-based products from patients, including platelet-rich plasma, plasma rich in growth factor, platelet-rich fibrin, and stromal vascular fraction. In this review, we discuss each of the above products used in treatment of FRSD and critically evaluate the clinical outcome.

Graphene-Based Materials Prove to Be a Promising Candidate for Nerve Regeneration Following Peripheral Nerve Injury.

Peripheral nerve injury is a common medical condition that has a great impact on patient quality of life. Currently, surgical management is considered to be a gold standard first-line treatment; however, is often not successful and requires further surgical procedures. Commercially available FDA- and CE-approved decellularized nerve conduits offer considerable benefits to patients suffering from a completely transected nerve but they fail to support neural regeneration in gaps > 30 mm. To address this unmet clinical need, current research is focused on biomaterial-based therapies to regenerate dysfunctional neural tissues, specifically damaged peripheral nerve, and spinal cord. Recently, attention has been paid to the capability of graphene-based materials (GBMs) to develop bifunctional scaffolds for promoting nerve regeneration, often via supporting enhanced neural differentiation. The unique features of GBMs have been applied to fabricate an electroactive conductive surface in order to direct stem cells and improve neural proliferation and differentiation. The use of GBMs for nerve tissue engineering (NTE) is considered an emerging technology bringing hope to peripheral nerve injury repair, with some products already in preclinical stages. This review assesses the last six years of research in the field of GBMs application in NTE, focusing on the fabrication and effects of GBMs for neurogenesis in various scaffold forms, including electrospun fibres, films, hydrogels, foams, 3D printing, and bioprinting.