Insights into Intra Periodontal Pocket Pathogenesis, Treatment, In Vitro-In Vivo Models, Products and Patents, Challenges and Opportunity.

Periodontal disease is a multifactorial pathogenic condition involving microbial infection, inflammation, and various systemic complications. Here, a systematic and comprehensive review discussing key-points such as the pros and cons of conventional methods, new advancements, challenges, patents and products, and future prospects is presented. A systematic review process was adopted here by using the following keywords: periodontal diseases, pathogenesis, models, patents, challenges, recent developments, and 3-D printing scaffolds. Search engines used were "google scholar", "web of science", "scopus", and "pubmed", along with textbooks published over the last few decades. A thorough study of the published data rendered an accurate and deep understanding of periodontal diseases, the gap of research so far, and future opportunities. Formulation scientists and doctors need to be interconnected for a better understanding of the disease to prescribe a quality product. Moreover, prime challenges (such as a lack of a vital testing model, scarcity of clinical and preclinical data, products allowing for high drug access to deeper tissue regions for prolonged residence, lack of an international monitoring body, lack of 4D or time controlled scaffolds, and lack of successful AI based tools) exist that must be addressed for designing new quality products. Generally, several products have been commercialized to treat periodontal diseases with certain limitations. Various strategic approaches have been attempted to target certain delivery regions, maximize residence time, improve efficacy, and reduce toxicity. Conclusively, the current review summarizes valuable information for researchers and healthcare professional to treat a wide range of periodontal diseases.

Proteomics strategies for urothelial bladder cancer diagnosis, prognosis and treatment: Trends for tumor biomarker sources.

Urothelial bladder cancer (UBC) is a heterogeneous multifactorial malignancy with a high recurrence rate. Current procedures for UBC diagnosis suffering from the lack of clinical sensitivity and specificity screening tests. Therefore, biomarkers have promising values to predict pathological conditions and can be considered as effective targets for early diagnosis, prognosis and antitumor immunotherapy. Recently, researchers have been interested for tumor proteins as biomarkers for different diseases. At present, proteomics methods have rapidly progressive that has potential identified biomarkers of UBC. Specifically, there has been several studies on the potential application of proteomics for the identification, quantification, and profiling of proteins for UBC in different sources. Based on these studies, using the panel of biomarkers as proteomic patterns may achieve higher sensitivity and specificity than single proteins in the diagnosis of UBC. In the present review, we evaluate recent literature related to the UBC proteome focusing especially on new proteomics techniques. Moreover, we classify UBC tumor biomarkers as diagnostic, prognostic, and therapeutic targets based on their sources (urine, serum/plasm, cell line, and tumor tissue) and we also discuss the advantages and limitations of each source. In this manner, this review article provides a critical assessment presentation of the advances in proteomics for all aspects of UBC diagnosis, prognosis, and treatment based on sources.

The food and biomedical applications of curcumin-loaded electrospun nanofibers: A comprehensive review.

Encapsulating curcumin (CUR) in nanocarriers such as liposomes, polymeric micelles, silica nanoparticles, protein-based nanocarriers, solid lipid nanoparticles, and nanocrystals could be efficient for a variety of industrial and biomedical applications. Nanofibers containing CUR represent a stable polymer-drug carrier with excellent surface-to-volume ratios for loading and cell interactions, tailored porosity for controlled CUR release, and diverse properties that fit the requirements for numerous applications. Despite the mentioned benefits, electrospinning is not capable of producing fibers from multiple polymers and biopolymers, and the product's effectiveness might be affected by various machine- and material-dependent parameters like the voltage and the flow rate of the electrospinning process. This review delves into the current and innovative recent research on nanofibers containing CUR and their various applications.

Quantification of Phytochemicals and Metal Ions as well as the Determination of Volatile Compounds, Antioxidant, Antimicrobial and Antacid Activities of the Mimosa pudica L. Leaf: Exploration of Neglected and Under-Utilized Part.

Mimosa pudica L. (MP) is well-known plant in traditional medicinal system, especially in India. Unfortunately, leaves of MP are less explored. To determine the food and nutritional value of the neglected part of Mimosa pudica L. (MP), that is MP leaves, phytochemicals and metal ions of MP were quantified by newly developed HPLC and ICPOES-based methods. The content of phytochemicals observed using HPLC analysis for chlorogenic acid, catechin, and epicatechin was 141.823 (±8.171), 666.621 (±11.432), and 293.175 (±12.743) µg/g, respectively. Using GC/MS/MS analysis, fatty acid like oleic acid were identified. In ICP-OES analysis, a significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The observed TPC and TFC for MP leaf extracts was 44.327 (±1.041) mg GAE/ g of wt. and 214.217 (±4.372) mg QCE/ g of wt., respectively. The DPPH assay depicted a strong antioxidant activity of MP leaf extracts with IC50 values of 0.796 (±0.081) mg/mL and a TEAC value of 0.0356 (±0.0003). A significant antacid activity (666 mg MP+400 mg CaCO3 >400 mg CaCO3 ≫666 mg Gelusil) of MP leaves was noticed. The methanolic extract of MP leaves demonstrated anti-microbial activity against Staphylococcus aureus (15±2mm), Pseudomonas aeruginosa (12±2mm) and Escherichia coli (10±2mm). In silico studies confirmed the in vitro results obtained for antioxidant, antiacid, and anti-microbial activities. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the MP leaves. In summary, this study demonstrated the medicinal significance of MP leaves and the conversion of agro-waste or the under-utilized part of MP into pharmaceutical potent materials. Consequently, the present study highlighted that MP leaves alone have medicinal importance with good nutritional utility and possess large promise in the pharma industry along with improving bio-valorization and the environment.

The colorful world of carotenoids: a profound insight on therapeutics and recent trends in nano delivery systems.

The therapeutic effects of carotenoids as dietary supplements to control or even treat some specific diseases including diabetic retinopathy, cardiovascular diseases, bacterial infections, as well as breast, prostate, and skin cancer are discussed in this review and also thoughts on future research for their widespread use are emphasized. From the stability standpoint, carotenoids have low bioavailability and bioaccessibility owing to their poor water solubility, deterioration in the presence of environmental stresses such as oxygen, light, and high heat as well as rapid degradation during digestion. Nanoencapsulation technologies as wall or encapsulation materials have been increasingly used for improving food product functionality. Nanoencapsulation is a versatile process employed for the protection, entrapment, and the delivery of food bioactive products including carotenoids from diverse environmental conditions for extended shelf lives and for providing controlled release. Therefore, we present here, recent (mostly during the last five years) nanoencapsulation methods of carotenoids with various nanocarriers. To us, this review can be considered as the first highlighting not only the potential therapeutic effects of carotenoids on various diseases but also their most effective nanodelivery systems.HighlightsBioactive compounds are of deep interest to improve food properties.Carotenoids (such as ß-carotene and xanthophylls) play indispensable roles in maintaining human health and well-being.A substantial research effort has been carried out on developing beneficial nanodelivery systems for various carotenoids.Nanoencapsulation of carotenoids can enhance their functional properties.Stable nanoencapsulated carotenoids could be utilized in food products.

Stem cell-mediated angiogenesis in skin tissue engineering and wound healing.

The timely management of skin wounds has been an unmet clinical need for centuries. While there have been several attempts to accelerate wound healing and reduce the cost of hospitalisation and the healthcare burden, there remains a lack of efficient and effective wound healing approaches. In this regard, stem cell-based therapies have garnered an outstanding position for the treatment of both acute and chronic skin wounds. Stem cells of different origins (e.g., embryo-derived stem cells) have been utilised for managing cutaneous lesions; specifically, mesenchymal stem cells (MSCs) isolated from foetal (umbilical cord) and adult (bone marrow) tissues paved the way to more satisfactory outcomes. Since angiogenesis plays a critical role in all four stages of normal wound healing, recent therapeutic approaches have focused on utilising stem cells for inducing neovascularisation. In fact, stem cells can promote angiogenesis via either differentiation into endothelial lineages or secreting pro-angiogenic exosomes. Furthermore, particular conditions (e.g., hypoxic environments) can be applied in order to boost the pro-angiogenic capability of stem cells before transplantation. For tissue engineering and regenerative medicine applications, stem cells can be combined with specific types of pro-angiogenic biocompatible materials (e.g., bioactive glasses) to enhance the neovascularisation process and subsequently accelerate wound healing. As such, this review article summarises such efforts emphasising the bright future that is conceivable when using pro-angiogenic stem cells for treating acute and chronic skin wounds.

Accelerated neutral atom beam (ANAB) modified polyethylene for decreased wear and reduced bacteria colonization: An in vitro study.

Ultra-high molecular weight polyethylene (UHMWPE) model implants were modified using accelerated neutral atom beam (ANAB) technology and tested for in vitro wear properties and bacteria colonization. Material characterization studies using atomic force microscopy (AFM), surface energy, and in vitro protein adsorption events were also conducted to better understand the mechanism behind such wear properties and bacteria colonization. ANAB modified UHMWPE showed significantly reduced wear properties compared to controls due to nanostructured features, greater surface energy, and improved adsorption of lubricin, a synovial fluid lubricating protein. There was significantly greater adsorption of proteins known to reduce bacteria colonization (specifically, mucin, casein, and lubricin) after 4 h on UHMWPE after ANAB treatment. Such changes in initial protein events led to significantly decreased bacteria (including methicillin resistant Staph. aureus (or MRSA), Staph. aureus, E. coli, multi-drug resistant E. coli, Pseudomonas aeruginosa and Staph. epidermidis) colonization after 24 h without resorting to antibiotic use.

Recent progress and challenges for polymeric microsphere compared to nanosphere drug release systems: Is there a real difference?

Polymeric microspheres (MSs) and nanospheres (NSs) composed of synthetic and natural polymers can encapsulate anticancer drugs, among other therapeutics, acting as drug carriers to release them at controlled rates over long periods of time. These carriers present several potential advantages including simple preparation methods, suitable control over the sustained release of medications or stem cells, triggered release resulting from stimulus-responsive delivery, improved physical properties such as porosity and stable scaffolds for tissue engineering, and possible applications as microreactors and nanoreactors compared to conventional drug delivery systems. Moreover, many of these factors can impact drug release rates by polymeric MSs and NSs. Herein, drug delivery systems based on polymeric MSs and NSs are described and compared according to recent advances and challenges, and poignant thoughts on what the field needs to progress are presented.

The promising use of nano-molecular imprinted templates for improved SARS-CoV-2 detection, drug delivery and research.

Molecular imprinting (MI) is a technique that creates a template of a molecule for improving complementary binding sites in terms of size and shape to a peptide, protein, bacteria, mammalian cell, or virus on soft materials (such as polymers, hydrogels, or self-assembled materials). MI has been widely investigated for over 90 years in various industries but is now focused on improved tissue engineering, regenerative medicine, drug delivery, sensors, diagnostics, therapeutics and other medical applications. Molecular targets that have been studied so far in MI include those for the major antigenic determinants of microorganisms (like bacteria or viruses) leading to innovations in disease diagnosis via solid-phase extraction separation and biomimetic sensors. As such, although not widely investigated yet, MI demonstrates much promise for improving the detection of and treatment for the current Coronavirus Disease of 2019 (COVID-2019) pandemic as well as future pandemics. In this manner, this review will introduce the numerous applications of MI polymers, particularly using proteins and peptides, and how these MI polymers can be used as improved diagnostic and therapeutic tools for COVID-19.

A novel technique to produce tubular scaffolds based on collagen and elastin.

Tubular polymer scaffolds based on tissue engineering techniques have been studied as potential alternatives for vascular regeneration implants. The blood vessels of the cardiovascular system are mainly fibrous, composed of collagen (Col) and elastin (El), and its inner layer consists of endothelial cells. In this work, Col and El were combined with polyurethane (PU), a biocompatible synthetic polymer, and rotary jet spinning, a new and highly productive technique, to produce fibrous scaffolds. The scaffolds produced at 18 000 rpm presented homogeneous, bead-free, and solvent-free fibers. The blend formation between PU-Col-El was identified by chemical composition analysis and enhanced the thermal stability up to 324°C. The hydrophilic nature of the scaffold was revealed by its low contact angle. Cell viability of human umbilical vein endothelial cells with the scaffold was proven for 72 hours. The combined strategy of rotary jet spinning with a polymer blend containing Col and El was verified as an effective and promising alternative to obtain tubular scaffolds for tissue engineering on a large-scale production.

Improved green biosynthesis of chitosan decorated Ag- and Co3O4-nanoparticles: A relationship between surface morphology, photocatalytic and biomedical applications.

AgNPs@Chitosan and Co3O4-NPs@Chitosan were fabricated with Salvia hispanica. Results showed MZI values of 5 and 30 mm for Co3O4-NPs- and AgNPs@Chitosan against S. aureus, and 15 and 21 mm for Co3O4-NPs- and AgNPs@Chitosan against E. coli (24 h, 20 µg/mL), respectively. MTT assays showed up to 80% and 90%, 71% and 75%, and 91% and 94% mammalian cell viability for the green synthesized, chemically synthesized AgNPs and green synthesized AgNPs@Chitosan for HEK-293 and PC12 cells, respectively, and 70% and 71%, 59% and 62%, and 88% and 73% for the related Co3O4-NPs (24 h, 20 µg/mL). The photocatalytic activities showed dye degradation after 135 and 105 min for AgNPs@Chitosan and Co3O4-NPs@Chitosan, respectively. FESEM results showed differences in particle sizes (32 ±â€¯3.0 nm for the AgNPs and 41 ±â€¯3.0 nm for the Co3O4NPs) but AFM results showed lower roughness of the AgNPs@Chitosan (7.639 ±â€¯0.85 nm) compared to Co3O4NPs@Chitosan (9.218 ±â€¯0.93 nm), which resulted in potential biomedical applications.

The Use of Infrapatellar Fat Pad-Derived Mesenchymal Stem Cells in Articular Cartilage Regeneration: A Review.

Cartilage is frequently damaged with a limited capacity for repair. Current treatment strategies are insufficient as they form fibrocartilage as opposed to hyaline cartilage, and do not prevent the progression of degenerative changes. There is increasing interest in the use of autologous mesenchymal stem cells (MSC) for tissue regeneration. MSCs that are used to treat articular cartilage defects must not only present a robust cartilaginous production capacity, but they also must not cause morbidity at the harvest site. In addition, they should be easy to isolate from the tissue and expand in culture without terminal differentiation. The source of MSCs is one of the most important factors that may affect treatment. The infrapatellar fat pad (IPFP) acts as an important reservoir for MSC and is located in the anterior compartment of the knee joint in the extra-synovial area. The IPFP is a rich source of MSCs, and in this review, we discuss studies that demonstrate that these cells have shown many advantages over other tissues in terms of ease of isolation, expansion, and chondrogenic differentiation. Future studies in articular cartilage repair strategies and suitable extraction as well as cell culture methods will extend the therapeutical application of IPFP-derived MSCs into additional orthopedic fields, such as osteoarthritis. This review provides the latest research concerning the use of IPFP-derived MSCs in the treatment of articular cartilage damage, providing critical information for the field to grow.

Green synthesis of CuO- and Cu2O-NPs in assistance with high-gravity: The flowering of nanobiotechnology.

This study, for the first time, reports the synthesis of CuO- and Cu2O nanoparticles (NPs) using the Salvia hispanica extract by a high-gravity technique. The original green synthesis procedure led to the formation of nanoparticles with promising catalytic and biological properties. The synthesized nanoparticles were fully characterized and their catalytic activity was evaluated through a typical Azide-Alkyne Cycloaddition (AAC) reaction. The potential antibacterial activity against gram positive (S. aureus) and gram negative (E. coli) bacteria were investigated. It was shown that the antibacterial properties were independent of the NP morphology as well as of the texture of the synthesis media. As a result, the presently synthesized nanoparticles showed very good photocatalytic and catalytic activities in comparison with the literature. From a biological perspective, they showed lower cytotoxicity in comparison with the literature, and also showed higher antioxidant and antibacterial activities. Thus, these present green CuO and Cu2O nanoparticles deserve further attention to improve numerous medical applications.

High-gravity-assisted green synthesis of palladium nanoparticles: the flowering of nanomedicine.

This study investigated the synthesis of Pd nanoparticles (NPs) using a high-gravity technique mediated by Salvia hispanica leaf extracts. Biological assays confirmed their antibacterial activity against gram positive (S. aureus) and gram negative (E. coli) bacteria with significant antioxidant activity in comparison with the standards as well as low cellular toxicity on PC12 and HEK293 cell lines. To the best of our knowledge, this study can be considered as the first investigation of Pd-NPs synthesized by Salvia hispanica leaf extracts assisted by a high-gravity technique. In addition, the mentioned green synthesis procedure led to the formation of nanoparticles with considerable antibacterial properties independent of the morphology and texture of the green media of these nanoparticles. Considering the increasing rate of antimicrobial resistant bacteria deaths worldwide, this study introduces a novel green synthesis method and non-antibiotic nanoparticle which should be studied for a wide range of medical applications.

A Soluplus/Poloxamer 407-based self-nanoemulsifying drug delivery system for the weakly basic drug carvedilol to improve its bioavailability.

Carvedilol (CAR), a ß-adrenoceptor and α1-receptor blocker, has pH-dependent solubility, which greatly limits its oral bioavailability. In this work, a precipitation inhibitor-based self-nanoemulsifying drug delivery system (PI-SNEDDS) was developed by employing Soluplus and Poloxamer 407 to improve drug dissolution and to inhibit drug precipitation in the gastrointestinal tract. In vitro phase distribution and in vivo dissolution studies indicated that PI-SNEDDS significantly increased drug content in the oil phase of the nanoemulsions in the stomach and greatly inhibited the subsequent precipitation of CAR in the intestine compared with the carvedilol self-nanoemulsifying drug delivery system (CAR SNEDDS) and the carvedilol tablets. Moreover, a 1.56-fold increase in the relative bioavailability of CAR was observed for the CAR PI-SNEDDS (397.41%) compared to a CAR SNEDDS (254.09%) with commercial capsules as a reference. Therefore, our developed PI-SNEDDS is a promising vehicle for improving the dissolution and bioavailability of poorly soluble drugs with pH-dependent solubility.

Iron oxide nanoparticle core-shell magnetic microspheres: Applications toward targeted drug delivery.

This study describes a sensitive reactive oxygen species (ROS)-responsive lecithin (LEC) incorporated iron oxide nanoparticle (Fe3O4 NP) system with potent anti-inflammatory properties and even more so when the antioxidant drug curcumin (CUR) is encapsulated in the PLGA hybrid magnetic microsphere system (Fe3O4@LEC-CUR-PLGA-MMS). The delivery system is responsive to ROS including an H2O2 environment to release the payload (CUR) drug. Greater cytotoxicity properties were observed in the presence of Fe3O4@LEC-CUR-PLGA-MMS against A549 and HeLa S3 cells with IC50 values after 24 h of 10 and 12 µg/mL and 10 and 20 µg/mL, respectively. The present Fe3O4@LEC-CUR-PLGA-MMS system demonstrated much better in vitro cytotoxicity, cellular morphological changes and moreover an ability to limit colony formation for A549 and HeLa S3 cancer cell lines than non-cancerous cells, and thus, should be further studied for a wide range of medical applications.

Co-delivery of Poria cocos extract and doxorubicin as an 'all-in-one' nanocarrier to combat breast cancer multidrug resistance during chemotherapy.

Recent studies have indicated that multidrug resistance (MDR) can significantly limit the effects of conventional chemotherapy. In this study, PT (Pachymic acid and dehydrotumulosic acid) are the two major triterpenoid components purified and identified in P. cocos. A liposomal co-delivery system encapsulating doxorubicin (DOX) and PT was prepared. Notably, the mechanism of PT reversed P-glycoprotein (P-gp) mediated MDR mainly relied on the inhibition of the P-gp function, which further decreased the levels of P-gp and caveolin-1 proteins. In drug-resistant MCF cells, co-administration with 5 µg/ml PT significantly enhanced sensitivity of DOX. Finally, liposome-mediated co-delivery with PT significantly improved the anti-tumor effect of DOX in tumor-bearing mice when compared to other single therapy groups. In conclusion, this study showed for the first time that DOX and PT act synergistically as an "all-in-one" treatment to reverse MDR during tumor treatment and, thus, should be studied further for a wide range of anti-cancer applications.

Advances in dual functional antimicrobial and osteoinductive biomaterials for orthopaedic applications.

A vast growing problem in orthopaedic medicine is the increase of clinical cases with antibiotic resistant pathogenic microbes, which is predicted to cause higher mortality than all cancers combined by 2050. Bone infectious diseases limit the healing ability of tissues and increase the risk of future injuries due to pathologic tissue remodelling. The traditional treatment for bone infections has several drawbacks and limitations, such as lengthy antibiotic treatment, extensive surgical interventions, and removal of orthopaedic implants and/or prosthesis, all of these resulting in long-term rehabilitation. This is a huge burden to the public health system resulting in increased healthcare costs. Current technologies e.g. co-delivery systems, where antibacterial and osteoinductive agents are delivered encounter challenges such as site-specific delivery, sustained and prolonged release, and biocompatibility. In this review, these aspects are highlighted to promote the invention of the next generation biomaterials to prevent and/or treat bone infections and promote tissue regeneration.

Correction to: Evolution of PVA gels prepared without crosslinking agents as a cell adhesive surface.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The Binary Effect on Methicillin-Resistant Staphylococcus aureus of Polymeric Nanovesicles Appended by Proline-Rich Amino Acid Sequences and Inorganic Nanoparticles.

Prevalent research underscores efforts to engineer highly sophisticated nanovesicles that are functionalized to combat antibiotic-resistant bacterial infections, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA), and that aid with wound healing or immunomodulation. This is especially relevant for patients who are susceptible to Staphylococcus aureus infections postoperatively. Here, antibacterial formulations are incorporated into polymeric, biocompatible vesicles called polymersomes (PsNPs) that self-assemble via hydrophobic interactions of admixed aqueous and organic substances. Nano-PsNPs are synthesized using a high molecular weight amphiphilic block copolymer, and are conjugated to include antimicrobial peptides (AMPs) along the peripheral hydrophilic region and silver nanoparticles (AgNPs) inside their hydrophobic corona. In vitro testing on bacterial and human cell lines indicates that finely tuned treatment concentrations of AMP and AgNPs in PsNPs synergistically inhibits the growth of MRSA without posing significant side effects, as compared with other potent treatment strategies. A ratio of silver-to-AMP of about 1:5.8 corresponding to ≈11.6 µg mL-1 of silver nanoparticles and 14.3 × 10-6 m of the peptide, yields complete MRSA inhibition over a 23 h time frame. This bacteriostatic activity, coupled with nominal cytotoxicity toward native human dermal fibroblast cells, extends the potential for AMP/AgNP polymersome therapies to replace antibiotics in the clinical setting.