The use of animal models in preclinical investigations for the development of a surgical mesh for pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: Polypropylene (PP) mesh for the treatment of pelvic organ prolapse (POP) has raised substantial concerns over long-term complications, leading to its ban in multiple countries. In response, emerging materials are being explored as alternatives for prolapse surgery. Preclinical animal models have historically played a pivotal role in validating medical devices, prior to clinical trials. Successful translation of these materials necessitates the identification of suitable animal models that replicate the female human pelvis and its biomechanical properties. Preclinical in vivo testing assesses the safety of surgical mesh and treatment efficacy in preventing POP recurrence. METHODS: The research critically reviews animal models used for preclinical pelvic mesh testing over the last decade and proposes a promising model for future preclinical studies. RESULTS: Rats were the most common mammal used for toxicity and biocompatibility investigations through abdominal implantation. Although non-human primates serve as a gold standard for efficacy testing, ethical considerations limit their use owing to their close biological and cognitive resemblance to humans. Consequently, sheep were the most preferred large animal model owing to their reproductive system similarities and propensity for spontaneous POP following parity. CONCLUSION: The study contributes valuable insights into the selection of appropriate animal models for preclinical pelvic mesh testing, offering guidance that is crucial for enhancing the safety and efficacy of novel surgical interventions in the treatment of POP.

Dysmenorrhoea: Can Medicinal Cannabis Bring New Hope for a Collective Group of Women Suffering in Pain, Globally?

Dysmenorrhoea effects up to 90% of women of reproductive age, with medical management options including over-the-counter analgesia or hormonal contraception. There has been a recent surge in medicinal cannabis research and its analgesic properties. This paper aims to critically investigate the current research of medicinal cannabis for pain relief and to discuss its potential application to treat dysmenorrhoea. Relevant keywords, including medicinal cannabis, pain, cannabinoids, tetrahydrocannabinol, dysmenorrhoea, and clinical trial, have been searched in the PubMed, EMBASE, MEDLINE, Google Scholar, Cochrane Library (Wiley) databases and a clinical trial website (clinicaltrials.gov). To identify the relevant studies for this paper, 84 papers were reviewed and 20 were discarded as irrelevant. This review critically evaluated cannabis-based medicines and their mechanism and properties in relation to pain relief. It also tabulated all clinical trials carried out investigating medicinal cannabis for pain relief and highlighted the side effects. In addition, the safety and toxicology of medicinal cannabis and barriers to use are highlighted. Two-thirds of the clinical trials summarised confirmed positive analgesic outcomes, with major side effects reported as nausea, drowsiness, and dry mouth. In conclusion, medicinal cannabis has promising applications in the management of dysmenorrhoea. The global medical cannabis market size was valued at USD 11.0 billion in 2021 and is expected to expand at a compound annual growth rate (CAGR) of 21.06% from 2022 to 2030. This will encourage academic as well as the pharmaceutical and medical device industries to study the application of medical cannabis in unmet clinical disorders.

Conductive Polymers: Opportunities and Challenges in Biomedical Applications.

Research pertaining to conductive polymers has gained significant traction in recent years, and their applications range from optoelectronics to material science. For all intents and purposes, conductive polymers can be described as Nobel Prize-winning materials, given that their discoverers were awarded the Nobel Prize in Chemistry in 2000. In this review, we seek to describe the chemical forms and functionalities of the main types of conductive polymers, as well as their synthesis methods. We also present an in-depth analysis of composite conductive polymers that contain various nanomaterials such as graphene, fullerene, carbon nanotubes, and paramagnetic metal ions. Natural polymers such as collagen, chitosan, fibroin, and hydrogel that are structurally modified for them to be conductive are also briefly touched upon. Finally, we expound on the plethora of biomedical applications that harbor the potential to be revolutionized by conductive polymers, with a particular focus on tissue engineering, regenerative medicine, and biosensors.

Translational Regenerative Therapies for Chronic Spinal Cord Injury.

Spinal cord injury is a chronic and debilitating neurological condition that is currently being managed symptomatically with no real therapeutic strategies available. Even though there is no consensus on the best time to start interventions, the chronic phase is definitely the most stable target in order to determine whether a therapy can effectively restore neurological function. The advancements of nanoscience and stem cell technology, combined with the powerful, novel neuroimaging modalities that have arisen can now accelerate the path of promising novel therapeutic strategies from bench to bedside. Several types of stem cells have reached up to clinical trials phase II, including adult neural stem cells, human spinal cord stem cells, olfactory ensheathing cells, autologous Schwann cells, umbilical cord blood-derived mononuclear cells, adult mesenchymal cells, and autologous bone-marrow-derived stem cells. There also have been combinations of different molecular therapies; these have been either alone or combined with supportive scaffolds with nanostructures to facilitate favorable cell⁻material interactions. The results already show promise but it will take some coordinated actions in order to develop a proper step-by-step approach to solve impactful problems with neural repair.

Polypropylene Pelvic Mesh: What Went Wrong and What Will Be of the Future?

BACKGROUND: Polypropylene (PP) pelvic mesh is a synthetic mesh made of PP polymer used to treat pelvic organ prolapse (POP). Its use has become highly controversial due to reports of serious complications. This research critically reviews the current management options for POP and PP mesh as a viable clinical application for the treatment of POP. The safety and suitability of PP material were rigorously studied and critically evaluated, with consideration to the mechanical and chemical properties of PP. We proposed the ideal properties of the 'perfect' synthetic pelvic mesh with emerging advanced materials. METHODS: We performed a literature review using PubMed/Medline, Embase, Cochrane Library (Wiley) databases, and ClinicalTrials.gov databases, including the relevant keywords: pelvic organ prolapse (POP), polypropylene mesh, synthetic mesh, and mesh complications. RESULTS: The results of this review found that although PP is nontoxic, its physical properties demonstrate a significant mismatch between its viscoelastic properties compared to the surrounding tissue, which is a likely cause of complications. In addition, a lack of integration of PP mesh into surrounding tissue over longer periods of follow up is another risk factor for irreversible complications. CONCLUSIONS: PP mesh has caused a rise in reports of complications involving chronic pain and mesh exposure. This is due to the mechanical and physicochemical properties of PP mesh. As a result, PP mesh for the treatment of POP has been banned in multiple countries, currently with no alternative available. We propose the development of a pelvic mesh using advanced materials including emerging graphene-based nanocomposite materials.

Graphene-Based Materials for Inhibition of Wound Infection and Accelerating Wound Healing.

Bacterial infection of the wound could potentially cause serious complications and an enormous medical and financial cost to the rapid emergence of drug-resistant bacteria. Nanomaterials are an emerging technology, that has been researched as possible antimicrobial nanomaterials for the inhibition of wound infection and enhancement of wound healing. Graphene is 2-dimensional (2D) sheet of sp2 carbon atoms in a honeycomb structure. It has superior properties, strength, conductivity, antimicrobial, and molecular carrier abilities. Graphene and its derivatives, Graphene oxide (GO) and reduced GO (rGO), have antibacterial activity and could damage bacterial morphology and lead to the leakage of intracellular substances. Besides, for wound infection management, Graphene-platforms could be functionalized by different antibacterial agents such as metal-nanoparticles, natural compounds, and antibiotics. The Graphene structure can absorb near-infrared wavelengths, allowing it to be used as antimicrobial photodynamic therapy. Therefore, Graphene-based material could be used to inhibit pathogens that cause serious skin infections and destroy their biofilm community, which is one of the biggest challenges in treating wound infection. Due to its agglomerated structure, GO hydrogel could entrap and stack the bacteria; thus, it prevents their initial attachment and biofilm formation. The sharp edges of GO could destroy the extracellular polymeric substance surrounding the biofilm and ruin the biofilm biomass structure. As well as, Chitosan and different natural and synthetic polymers such as collagen and polyvinyl alcohol (PVA) also have attracted a great deal of attention for use with GO as wound dressing material. To this end, multi-functional polymers based on Graphene and blends of synthetic and natural polymers can be considered valid non-antibiotic compounds useful against wound infection and improvement of wound healing. Finally, the global wound care market size was valued at USD 20.8 billion in 2022 and is expected to expand at a compound annual growth rate (CAGR) of 5.4% from 2022 to 2027 (USD 27.2 billion). This will encourage academic as well as pharmaceutical and medical device industries to investigate any new materials such as graphene and its derivatives for the treatment of wound healing.

Using Ginger Oil to Treat Nausea and Vomiting Following Breast Augmentation Surgery.

We conducted a double-blind, randomized, placebo-controlled, single-center study involving 30 women undergoing breast augmentation surgery with silicone breast implants. All patients had an A cup breast size and a similar body mass index. We placed the same type of implant in a subpectoral dual plane in each patient. We randomly allocated the study participants to receive either three drops of ginger oil (110 mg Zingiber officinale) or three drops of a placebo control oil placed on their laryngeal mask before insertion. We used a postoperative nausea and vomiting (PONV) and a visual analog scale (VAS) scores as outcome measures and compared the scale results with the dose of morphine used by the patient. The results of the multivariate analysis of variance showed that the ginger oil had a significant effect on PONV/VAS scores, V = 0.87, F(3, 16) = 34.78, p < .001. The results of the univariate analysis of variance showed that using the ginger oil provided significant treatment effects on PONV, F(1, 18) = 73.05, p < .001. These results are also reflected in the descriptive statistics. The mean PONV score for the experimental group and the control group was 1.70 ± 0.48 and 4.20 ± 0.79, respectively. The mean VAS score for the experimental group and the control group was 5.0 ± 1.63 and 5.9 ± 2.33, respectively. The results of our study showed that ginger oil has an important role in preventing PONV and reducing the use of postoperative opioids in women who have undergone breast augmentation surgery.

An Overview on the Recent Advances in the Treatment of Infected Wounds: Antibacterial Wound Dressings.

A wound can be surgical cuts from an operation or due to accident and trauma. The infected wound, as a result of bacteria growth within the damaged skin, interrupts the natural wound healing process and significantly impacts the quality of life. Wound dressing is an important segment of the skincare industry with its economic burden estimated at $ 20.4 billion (in 2021) in the global market. The results of recent clinical trials suggest that the use of modern dressings can be the easiest, most accessible, and most cost-effective way to treat chronic wounds and, hence, holds significant promise. With the sheer number of dressings in the market, the selection of correct dressing is confusing for clinicians and healthcare workers. The aim of this research is to review widely used types of antibacterial wound dressings, as well as emerging products, for their efficiency and mode of action. In this review, introducing antibiotics and antibacterial nanoparticles as two important and clinically widely used categories of antibacterial agents is focused. The perspectives and challenges for paving the way for future research in this field are also discussed.

Plasma-Rich in Growth Factor and its Clinical Application.

The potential use of growth factors in stem cell-based therapies for the repair and regeneration of tissues and organs offers a paradigm shift in regenerative medicine. Growth factors are critical signalling molecules that play an important role in tissue development and remodelling. Plasma rich in growth factor (PRGF) is a biotechnological strategy for the harvesting of the active substances of platelets, including growth factors, from the patient's blood. Because of their tremendous essential growth factor and bioactive agents, as well as their paracrine mechanisms, PRGF has been used as an efficacious option and adjuvant biological therapy in the repair and replacement of damaged organs. This article provides an overview of PRGF extraction and its properties and critically reviewed its clinical benefit and clinical trials in the treatment and regeneration of human organs. Regenerative medicine is a multi-billion-dollar industry with huge interest to clinicians, academics and industries, being considered as an emerging technology.

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.

Genetic Investigation of 261 Cases of Turner Syndrome Patients Referred to the Genetic Clinic.

BACKGROUND: Turner syndrome (TS), also known as 45,X, is a genetic disorder caused by the partial or complete lack of an X chromosome. TS can cause a variety of medical and developmental conditions. We aimed to investigate TS mosaicism and variants pattern and research the presence of a correlation between the different variant's factors and TS occurrence. METHODS: From 1984-2018, 100,234 patients referred to the Farhud Genetic Clinic, Tehran, Iran, for karyotyping were studied. TS was determined by the chromosomal assay, and the patients' karyotype was obtained from amniotic fluid and blood samples. Different variants of the TS diagnosed patients were investigated, including maternal and paternal age at pregnancy, parental consanguinity, and the presence/absence of a family history of the disease. RESULTS: Overall, 261/100,234 (0.26%) were diagnosed with TS. These, 150 cases were identified to have the classical 45,X karyotype and 111 cases were identified to have either TS mosaicism or other less common variations of TS karyotyping. Higher parental age at pregnancy and TS data suggested that the occurrence of TS is significantly higher. CONCLUSION: Data suggest parental age at pregnancy is an important factor for TS occurrence. Hence, prenatal screening in these groups of parents recommended. This study also implicates early medical diagnostic testing before the onset of puberty or as soon as symptoms arise is essential for early treatment.

Graphene Oxide: Opportunities and Challenges in Biomedicine.

Desirable carbon allotropes such as graphene oxide (GO) have entered the field with several biomedical applications, owing to their exceptional physicochemical and biological features, including extreme strength, found to be 200 times stronger than steel; remarkable light weight; large surface-to-volume ratio; chemical stability; unparalleled thermal and electrical conductivity; and enhanced cell adhesion, proliferation, and differentiation properties. The presence of functional groups on graphene oxide (GO) enhances further interactions with other molecules. Therefore, recent studies have focused on GO-based materials (GOBMs) rather than graphene. The aim of this research was to highlight the physicochemical and biological properties of GOBMs, especially their significance to biomedical applications. The latest studies of GOBMs in biomedical applications are critically reviewed, and in vitro and preclinical studies are assessed. Furthermore, the challenges likely to be faced and prospective future potential are addressed. GOBMs, a high potential emerging material, will dominate the materials of choice in the repair and development of human organs and medical devices. There is already great interest among academics as well as in pharmaceutical and biomedical industries.

Multifunctional and Self-Healable Intelligent Hydrogels for Cancer Drug Delivery and Promoting Tissue Regeneration In Vivo.

Regenerative medicine seeks to assess how materials fundamentally affect cellular functions to improve retaining, restoring, and revitalizing damaged tissues and cancer therapy. As potential candidates in regenerative medicine, hydrogels have attracted much attention due to mimicking of native cell-extracellular matrix (ECM) in cell biology, tissue engineering, and drug screening over the past two decades. In addition, hydrogels with a high capacity for drug loading and sustained release profile are applicable in drug delivery systems. Recently, self-healing supramolecular hydrogels, as a novel class of biomaterials, are being used in preclinical trials with benefits such as biocompatibility, native tissue mimicry, and injectability via a reversible crosslink. Meanwhile, the localized therapeutics agent delivery is beneficial due to the ability to deliver more doses of therapeutic agents to the targeted site and the ability to overcome post-surgical complications, inflammation, and infections. These highly potential materials can help address the limitations of current drug delivery systems and the high clinical demand for customized drug release systems. To this aim, the current review presents the state-of-the-art progress of multifunctional and self-healable hydrogels for a broad range of applications in cancer therapy, tissue engineering, and regenerative medicine.

Mechanism of Anosmia Caused by Symptoms of COVID-19 and Emerging Treatments.

The occurrence of anosmia, the loss or change in sense of smell, is one of the most common symptoms of COVID-19 experienced by almost 53% of those affected. Several hypotheses explain the mechanism of anosmia in patients suffering from COVID-19. This study aims to review the related mechanisms and answer the questions regarding COVID-19-related anosmia as well as propose a new strategy for treatment of long-term anosmia as a result of COVID-19 infection. This paper covers all of the studies investigating olfactory disorders following COVID-19 infection and explains the possible reasons for the correlated anosmia, including olfactory cleft syndrome, local inflammation in the nasal epithelium, early apoptosis of olfactory cells, changes in olfactory cilia and odor transmission, damage to microglial cells, effect on olfactory bulbs, epithelial olfactory injury, and impairment of olfactory neurons and stem cells. The key questions that arise in this field have been discussed, such as why prevalent anosmia is varied among the age categories and among sexes and the correlation of anosmia with mild or severe COVID-19 infection. The angiotensin-converting enzyme 2 receptor is a significant player in the mechanism of anosmia in COVID-19 patients. Based on current studies, a novel approach to treat long-COVID-19 with ongoing anosmia has been proposed. The fields of smart drug delivery, tissue engineering, and cell therapy provide a hypothesized strategy that can minimize the side effects of current treatments and support efficient recovery of the olfactory system.

A New Nanocomposite Copolymer Based On Functionalised Graphene Oxide for Development of Heart Valves.

Polymeric heart valves seem to be an attractive alternative to mechanical and biological prostheses as they are more durable, due to the superior properties of novel polymers, and have the biocompatibility and hemodynamics comparable to tissue substitutes. This study reports a comprehensive assessment of a nanocomposite based on the functionalised graphene oxide and poly(carbonate-urea)urethane with the trade name "Hastalex" in comparison with GORE-TEX, a commercial polymer routinely used for cardiovascular medical devices. Experimental data have proved that GORE-TEX has a 2.5-fold (longitudinal direction) and 3.5-fold (transverse direction) lower ultimate tensile strength in comparison with Hastalex (p < 0.05). The contact angles of Hastalex surfaces (85.2 ± 1.1°) significantly (p < 0.05) are lower than those of GORE-TEX (127.1 ± 6.8°). The highest number of viable cells Ea.hy 926 is on the Hastalex surface exceeding 7.5-fold when compared with the GORE-TEX surface (p < 0.001). The platelet deformation index for GORE-TEX is 2-fold higher than that of Hastalex polymer (p < 0.05). Calcium content is greater for GORE-TEX (8.4 mg/g) in comparison with Hastalex (0.55 mg/g). The results of this study have proven that Hastalex meets the main standards required for manufacturing artificial heart valves and has superior mechanical, hemocompatibility and calcific resistance properties in comparison with GORE-TEX.

Circadian Rhythms: Will It Revolutionise the Management of Diseases?

The Nobel Prize for Medicine in 2017 was awarded to Michael Young, Michael Rosbash and Jeffrey Hall for their discoveries into the molecular mechanisms controlling circadian rhythms (CR). The aims of this paper were to present the mechanisms behind the CRs and discuss the impact this could have on human health. We argued that further research in this field has the potential to revolutionise healthcare through understanding the influence on the pathogenesis of disease, including in cardiovascular, mental and neurological health, as well as influence on cognitive function. The research has shown that intrinsic CRs have physiological and biochemical influences on the body, which may affect the efficiency of drug absorption due to the altered activity of enzymes. There is strong data to suggest CR disturbances, due to either shift work, sleep disorders or frequent travel between time zones, has negative impact on health. This article aims to summarise the extent of this impact and analyse CRs as a potential therapeutic target, as well as describing the pathophysiology and mechanisms driving the course of disease among people with CR disorders. These new discoveries may revolutionise the way in which treatment is provided in the future with more focus on lifestyle changes to provide treatment and more optimal precision medicine. Pharmaceutical companies and healthcare staff must consider the significant message provided from this data and use the information to optimise drug delivery and treatment provision. The facts of CRs role in healthcare can no longer be ignored.

Emerging In Vitro 3D Tumour Models in Nanoparticle-Based Gene and Drug Therapy.

3D models are emerging as valuable tools for personalised nanoparticle-based cancer treatments. 3D models represent in vivo cancers more realistically than 2D patterns that are grown in Petri dishes. However, creating a 3D cancer model that mimics the complexity and heterogeneity of cancers in vivo remains difficult.

Development of a Cost-Effective and Simple Protocol for Decellularization and Preservation of Human Amniotic Membrane as a Soft Tissue Replacement and Delivery System for Bone Marrow Stromal Cells.

The aim of this study is to develop a simple and cost-effective method for decellularization and preservation of human amniotic membrane (HAM) as a soft tissue replacement and a delivery system for stem cells. The HAM is decellularized (D) using new chemical and mechanical techniques. The decellularization scaffold is evaluated histologically and fully characterized. The cell adhesion and proliferation on the scaffold are also investigated and the biocompatibility of D tissues is evaluated in vivo. The histological studies reveal that the cells are successfully removed from the D tissue. The DNA extraction shows more than 95% cell removal (p = 0.001). The in vitro results indicate that the decellularisation process does not deteriorate the mechanical properties of the tissue, whereas it increases the in vitro biodegradation value (p < 0.05). In the D samples, there is no significant cytotoxicity, and no changes are found in the rate of cell proliferation (p > 0.05). Immunohistochemistry staining indicates that all the tested components remain unchanged within the D tissues. The count of inflammatory cells show that the decellularization process slightly increases the biocompatibility of the tissue after 7 days post-surgery. The results indicate that scaffold proves to be reproducible, rapid, and cost-effective, with a potential role for clinical application.

Stem cell tracking using iron oxide nanoparticles.

Superparamagnetic iron oxide nanoparticles (SPIONs) are an exciting advancement in the field of nanotechnology. They expand the possibilities of noninvasive analysis and have many useful properties, making them potential candidates for numerous novel applications. Notably, they have been shown that they can be tracked by magnetic resonance imaging (MRI) and are capable of conjugation with various cell types, including stem cells. In-depth research has been undertaken to establish these benefits, so that a deeper level of understanding of stem cell migratory pathways and differentiation, tumor migration, and improved drug delivery can be achieved. Stem cells have the ability to treat and cure many debilitating diseases with limited side effects, but a main problem that arises is in the noninvasive tracking and analysis of these stem cells. Recently, researchers have acknowledged the use of SPIONs for this purpose and have set out to establish suitable protocols for coating and attachment, so as to bring MRI tracking of SPION-labeled stem cells into common practice. This review paper explains the manner in which SPIONs are produced, conjugated, and tracked using MRI, as well as a discussion on their limitations. A concise summary of recently researched magnetic particle coatings is provided, and the effects of SPIONs on stem cells are evaluated, while animal and human studies investigating the role of SPIONs in stem cell tracking will be explored.