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Active research in tissue engineering is conducted in concern with different systems of body to regenerate the diseased or injured tissues. Scaffold is the cornerstone in tissue engineering which acts as a template for growing cells. The selection of biomaterials for the preparation of scaffolds is thus an important aspect to take into consideration. Various studies involving the use of different biomaterials (ceramics, natural and synthetic polymers) in scaffolds fabrication are discussed. This review mainly enlists various scaffold manufacturing techniques which are classified as conventional and rapid prototyping methods. Among the different conventional methods discussed in this review, electrospinning was found to be a versatile technique and is powerful in production of 3D nanofibrous structures. The recent advances in rapid prototyping methods lead to the development of 3D printing and bioprinting which are found to be potent scaffold fabricating techniques. The rapid prototyping methods have the potential to overcome the limitations of conventional methods. Few studies have implemented additive manufacturing techniques by combining different methods in preparation of scaffolds and have shown superior results. Even though there are well developed fabrication techniques, the limitations associated with each technique as described in this review should be carefully assessed and more studies to be conducted on modification/improvement of these techniques to exclude the limitations. In future days, the 3D printing and bioprinting have a potential to be the superior scaffold fabrication technique and there will be an enormous increase in usage of 3D printed organs in patients suffering with different pathological conditions. Scaffolds are found to be the backbone of tissue engineering. The fabrication of scaffolds thus gained a huge interest in the recent years as there are many techniques available. We, herein, have described various scaffold fabrications techniques with associated challenges and their current applications, hoping that the challenges will be addressed by the researchers in future studies. We also discussed about various biomaterials involved in fabrication of scaffolds and their applications. Recent advances in fabrication of scaffolds are enlisted; 3D printing and bioprinting were found to be the outstanding and newer ones. The pros and cons of different techniques and importance in tissue engineering/regenerative medicine were briefed.

Islet cells transplantation has limitations like low survivability, which can be overcome by using extracellular matrix mimicking three-dimensional (3D) scaffolds, which supports the growth and proliferation of seeded cells. This study was aimed to investigate the role of novel 3D carboxymethyl guargum (CMGG) nanocomposite with reduced graphene oxide (rGO) for proliferation of pancreatic islet cells (RIN-5F) and rate of insulin secretion of RIN-5F cells. Scanning electron microscope and Fourier transform infrared results have demonstrated good porosity and the chemical interactions between CMGG and rGO. Mechanical testing and thermogravimetric analysis of nanofibers have shown good tensile strength and thermal stability with rGO in the nanocomposite. These scaffolds demonstratedin vitrobiocompatibility with acceptable ranges of biodegradability and hemocompatibility. Thein vitrocell proliferation and viability of RIN-5F cells on 3D CMGG nanofibers have significantly increased compared to two-dimensional (2D) cell control. Moreover, the glucose dependent insulin secretion of RIN-5F cells on CMGG nanocomposite has significantly increased upto 4-5 folds than cells on 2D cell control. The biomaterials used in this 3D nanofiber scaffold have shown to be biodegradable and hemocompatible and can be a promising platform for the proliferation and secretion of insulin from beta cells and can be effectively used in transplantation type-1 diabetes.

Nanofiber scaffolds mimic the extracellular matrix (ECM) and help in fibroblasts proliferation which is the main constituent for wound healing. This study aims to evaluate the wound healing potential of electrospun nanofibers fabricated by carboxymethyl guargum (CMGG), reduced graphene oxide (rGO) and polyvinyl alcohol. The nanofibers have shown desired properties like excellent porosity and good water holding capacities. The porosity of nanofibers helps in the movement of oxygen to cells and the removal of waste materials and the swelling capacity helps to maintain the moisture content at the wound site. In addition, the in vitro hemocompatibility and wound healing assay have shown excellent results rendering the nanofibers biocompatible. The in vitro fibroblasts (3T3-L1) proliferation was significantly more in rGO/CMGG/PVA nanofibers than CMGG/PVA and cell control. Further, the in vivo wound healing evaluation of these nanofiber dressings in rabbits has shown significant wound closure compared to control and standard. Histology studies revealed the fast collagen formation and re-epithelialization necessary for wound healing among rGO/CMGG/PVA treated rabbits. Therefore, the rGO/CMGG/PVA nanofiber scaffolds can be potential wound dressing candidates and be further evaluated for clinical use.

Biomimetic scaffolds engineering for improved collagen, epithelial cutaneous and fibrous tissue regeneration remains challenging for wound healing. To address these issues, this study aimed to report on the fabrication and characterization of electrospun of carboxymethyl guargum (CMGG), reduced graphene oxide (rGO) nanocomposite dressings loaded with curcumin for chronic wound healing applications. SEM and XRD examined the morphology of nanofibers and resulted in excellent porosity. TGA and FT-IR were done, which revealed the nanofibers' thermal and chemical interactions. CMGG, rGO nanocomposite with curcumin was investigated for in-vitro wound healing assay by scratch wound healing model using 3T3 L1 fibroblast cell lines and conducted in vitro drug-releasing studies. These nanocomposites showed 100% wound closure by the proliferation of fibroblast cell lines 3T3-L1 within 48 h and showed controlled drug release. Further, in vivo results also showed that the CMGG, rGO nanocomposite with curcumin has the potential wound healing effects. Histological studies showed that the CMGG, rGO nanocomposite with curcumin has the potential for wound healing, which indicates that the biomimetic CMGG nanofibers have an excellent healing effect on chronic wounds.

Objective The women in menstruating age with thyroid disorders are at risk of getting menstrual disturbances due to the influence of thyroid hormones on ovulation through FSH mediated differentiation of granulosa cells. This may also lead to infertility due to anovulatory cycles and hyperprolactinemia caused by thyroid disorders. The objective of this study was to find the prevalence of menstrual disorders in women with hypothyroidism and hyperthyroidism. Methods This was a cross sectional study conducted in 249 menstruating age women with thyroid disorders (hypo, hyper). The patients were diagnosed and classified into hypothyroidism and hyperthyroidism based on their thyroid profile. Menstrual history was enquired from the patients. The thyroid profile of patients was subjected to statistical analysis. Results The prevalence of hypothyroidism was higher than hyperthyroidism with 83.93% and 16.06% respectively. The prevalence of menstrual irregularities in hypothyroid and hyperthyroid patients was found to be 30.62% and 7.5% respectively. The most presented menstrual disturbance in hypothyroid patients was irregular periods and in hyperthyroid patients was menorrhagia. The mean values of thyroid profile among hypothyroid females without and with menstrual irregularities were T3 (1.263 + 0.15, 1.236+ 0.12 ng/dl), T4 (6.769 + 0.81, 6.719 + 0.75 mcg/dl) and TSH (24.34 + 1.55, 28.77 + 1.15 mIU/ml) respectively. Hyperthyroid females without and with irregularities were T3 (1.83 + 0.66, 3.27 + 0.75 ng/dl), T4 (9.57 + 0.88, 13.88 + 0.91 mcg/dl) and TSH (0.636 + 0.44, 0.05 + 0.01 mIU/ml) with a significant difference between the groups. Conclusion Hypothyroidism women were at more risk of developing menstrual problems than hyperthyroid patients. The patients diagnosed with thyroid disorders should be cautious about the menstrual cycles and must report to physician if abnormalities are found. This will enable the medical practitioners to treat them with proper dosage of drugs for thyroid disorders to manage the complications.

The long-term use of proton pump inhibitors (PPIs) can lead to increased gastric pH, hypochlorhydria and in some cases to achlorhydria when compared to other acid-suppressing agents like histamine-2 (H2) receptor blockers and antacids. These consequences by the use of long-term PPIs may lead to significant vitamin (B12 and C) and mineral (iron, calcium and magnesium) deficiencies which needs gastric acid for their absorption and bioavailability. Long-term use of PPIs by the pregnant patients may impose a potential risk of congenital malformations. Various studies have recommended the life style modifications and antacid use as first choice among pregnant womens by preserving PPIs (omeprazole as a safe choice of PPI) for severe conditions of gastroesophageal reflux disease. The long-term acid suppression by PPIs can also lead to enteric, respiratory and urinary tract infections. The hypochlorhydria by chronic PPIs use may induce hypergastrinemia, which ultimately mediates the gastric polyps, gastric carcinoids and gastric cancer. The concomitant use of PPIs with antiplatelet drugs like clopidogrel can impose the patients to major adverse cardiac events. This review has enlisted the comprehensive information regarding the adverse effects induced by long-term use of PPIs and their possible relations. Considerable studies like case-control, randomized trials, cohort studies and meta-analysis were reported in supporting these adverse effects. The clinicians and patients should be cautious about these effects so that they can avoid the serious outcomes. PPIs should be avoided for long-term use mainly in older adults unless there is a proper indication.

Although graphene has proven to be a potential 2D nanomaterial in various applications especially in the field of biomedicine, it is not without any toxicity. The graphene family nanomaterials (GFNs) comprises diverse materials of which pristine graphene, graphene oxide, reduced graphene oxide, quantum graphene dots are mostly used. The use of these materials in applications of various fields has increased the risk of human exposure which raised the safety and toxicity concerns. The GFNs toxicity is dependent on its physiochemical properties like size, shape, surface charge. The toxicity exerted by GFNs is mediated by several mechanisms which are discussed in this chapter. The important mechanisms involved are by direct physical damage to cell membranes, oxidative stress induced by reactive oxygen species generation and damage to nucleic acids. The entry of GFNs into body through occupational exposure is mediated by various routes like inhalation, ocular, cutaneous and unintentional ingestion. Various in vitro cytotoxicity studies are enlisted which demonstrated the dose dependent toxicity to several cell lines. GFNs have also showed significant cytotoxicity against various strains of bacteria and fungi. GFNs have shown to be get accumulated in various organs like liver, kidney, lungs, spleen and few other which are discussed in this review. The accumulated GFNs show dose and time dependent tissue damage. The functionalization of GFNs with polymers like polyethylene glycol, chitosan, polyvinyl alcohol, etc., tend to improve their biocompatibility, decrease toxicity and enhances their clearance from organs. The studies on functionalized GFNs and potential polymers that can be used in functionalization should be taken as hot area of interest among researchers so that in near future these composites can be used in various applications to eliminate the toxicity imposed by GFNs.

Thyroid disorders are the most common endocrine problems in women. In most of the cases, thyroid can lead to infertility or miscarriages. The etiology of infertility is multifactorial with thyroid disorders as the most common presenting factor, hypothyroidism in particular. Infertility in women can lead to emotional and psychological stress. The prevalence of hypothyroidism during pregnancy is estimated to be 0.3%-0.5%. Hypothyroidism and hyperthyroidism can result in menstrual irregularities and anovulatory cycles, thus affecting the fertility. There is a significant high prolactin (PRL) level in infertile women with hypothyroidism when compared to euthyroid patients, indicating the relation between hypothyroidism and hyperprolactinemia. The amount of thyrotropin releasing hormone (TRH) from the hypothalamus is markedly increased by inhibition of pyroglutamyl peptidase II, the enzyme catalyzing TRH. The increased TRH in hypothyroidism causes increased thyroid-stimulating hormone and PRL secretion by pituitary, leading to infertility and galactorrhea. In recent years, a neuropeptide called kisspeptin, encoded by Kiss1 gene, a potent stimulus for GnRH secretion, has been recognized, which suggests a future direction of treatment with kisspeptin and benefits the fertility induction among hyperprolactinemic infertile patients. Untreated hypothyroidism during pregnancy can lead to subfertility, fetal deaths, premature deliveries, and abortions. Therefore, women planning for pregnancy and infertile women should be assessed for thyroid hormones and serum PRL.

Neuronal proliferation can play a crucial role as a therapeutic modality for many disorders associated with neuronal damage. The biopolymer, carboxymethyl tamarind gum (CMTG) potentiated with reduced graphene oxide (rGO) and poly vinyl alcohol (PVA) was fabricated as nanofiber films using electrospinning for possible proliferation of neuronal cells. The thin CMTG/rGO/PVA films were examined under scanning electron microscope (SEM) and found to be highly porous which facilitate the neuronal cell seeding and infiltration. Thermal analysis revealed that the addition of rGO makes the CMTG/rGO/PVA nanofibers thermally stable compared to CMTG/PVA. The PC12 cells have shown significant proliferation and viability on the CMTG/rGO/PVA nanofibers with no observed toxicity compared to CMTG/PVA and control. This infers that blending of rGO in CMTG nanofibers could effectively help in excellent neuronal proliferation by additive effect and plays a crucial role as mimicking extracellular matrix (ECM) and can be clinically evaluated for various neurodegenerative disorders.

The usage of plant origin natural gum polysaccharides in various biomedical applications is steadily rising in recent years because of their peculiar properties like biocompatibility, biodegradability, cytocompatibility and with no eliciting of immune response. The natural gums were used in various dosage forms as thickening agents, suspending agents, binders, emulsifying agents and have showed excellent controlled drug release profiles because of their good drug holding capacity. These polysaccharides were found to be efficient biopolymers than the other biomaterials (ceramics and synthetic polymers) used in tissue engineering applications because of their exceptional properties. In this review various natural gums (tragacanth, guar gum, gum acacia, locust bean gum and cashew gum) and their specific properties which facilitated their use in biomedical applications were discussed. The natural gum exudates have been found to be promising candidates in fabrication of scaffolds for tissue engineering applications due to their high solubility, porosity and large surface area. Applications of natural gums in drug delivery, stem cell culture and tissue engineering were enlisted with relevant studies. The ongoing research in nanotechnology and polysaccharides has opened the gates to integrate topographical, morphological and biological properties into these compounds. Nano composites have the ability to provide better drug delivery and also help in improved cell proliferations when used in scaffold fabrication. The gum polysaccharides have the potential to improve the physical, mechanical and biological properties of the fabricated scaffold when used as composites with other biomaterials. The cytotoxicity of the various biomaterials can be overcome by blending them with the natural gum polysaccharides.

The peculiar features of graphene like excellent physicochemical, electrical, large surface area and biocompatibility are revealing through the past decade, leading to continuous research on the use of graphene nanomaterial in various clinical applications and regenerative medicine. In this review, we highlighted the recent applications and challenges of graphene and its derivatives in stem cell proliferation, bone tissue engineering, neuronal proliferation and in biosensors. Graphene or graphene oxide has shown interesting results in angiogenesis, neuronal regeneration and immunomodulation in various in vitro and in vivo studies. Graphene based materials have a potential to be emerging as next generation nanomaterials. We discussed about the conventional procedures and related challenges in synthesis of graphene oxide. This review aims in summarizing the recent progresses of various graphene based nanomaterials and their hybrids in biomedical applications. Graphene as two dimensional, three dimensional and hybrids are attracting interest in biosensing and bioimaging. However, besides the fascinating properties of graphene, its biocompatibility and biodegradability related toxicities are still a question to researchers. Graphene nanomaterials use in various tissue scaffolds should be taken as an active area of interest by the researchers in near future. This review also enlisted the recent advancements of graphene as anticancer therapy and targeted drug delivery system. We hope the summary of this review inspires the researchers to conduct more studies on graphene based applications and its possible toxicities in humans, so that it can be implemented as cost effective and safe treatment to many pathological conditions.