Isolation of plant-derived exosome-like nanoparticles (PDENs) from Solanum nigrum L. berries and Their Effect on interleukin-6 expression as a potential anti-inflammatory agent.

Inflammation is a temporary response of the immune system that can be treated using common anti-inflammatory drugs. However, prolonged use of these drugs increases the risk of adverse side effects. Accordingly, there is an increasing need for alternative treatments for inflammation with fewer side effects. Exosomes are extracellular vesicles secreted by most eukaryotic cells and have been studied as a candidate for cell-free therapy for inflammatory diseases due to their immunomodulatory and anti-inflammatory properties. In recent years, the focus of exosome research has shifted from animal cell-derived exosomes to plant-derived exosome-like nanoparticles (PDENs). Plant-derived exosome-like nanoparticles (PDENs) are easier to obtain, have minimal safety concerns, and can be produced in higher quantities and lower cost than exosomes derived from animal cells. In this study, the isolation and analysis of the anti-inflammatory potential of PDENs from black nightshade berries (Solanum nigrum L.) were carried out. The results of isolation and characterization showed that PDENs had a spherical morphology, measuring around 107 nm with zeta potential of -0.6 mV, and had a protein concentration of 275.38 µg/mL. PDENs were also shown to be internalized by RAW264.7 macrophage cell line after 2 hours of incubation and had no cytotoxicity effect up to the concentration of 2.5 µg/mL. Furthermore, exposure to several doses of PDENs to the LPS-stimulated RAW264.7 cell significantly decreased the expression of pro-inflammatory cytokine gene IL-6, as well as the expression of IL-6 protein up to 97,28%. GC-MS analysis showed the presence of neral, a monoterpene compound with known anti-inflammatory properties, which may contribute to the anti-inflammatory activity of PDENs isolated from Solanum nigrum L. berries. Taken together, the present study was the first to isolate and characterize PDENs from Solanum nigrum L. berries. The results of this study also demonstrated the anti-inflammatory activity of PDEN by suppressing the production of IL-6 in LPS-stimulated RAW264.7 cells.

Advances in In Vitro Blood-Air Barrier Models and the Use of Nanoparticles in COVID-19 Research.

Respiratory infections caused by coronaviruses (CoVs) have become a major public health concern in the past two decades as revealed by the emergence of SARS-CoV in 2002, MERS-CoV in 2012, and SARS-CoV-2 in 2019. The most severe clinical phenotypes commonly arise from exacerbation of immune response following the infection of alveolar epithelial cells localized at the pulmonary blood-air barrier. Preclinical rodent models do not adequately represent the essential genetic properties of the barrier, thus necessitating the use of humanized transgenic models. However, existing monolayer cell culture models have so far been unable to mimic the complex lung microenvironment. In this respect, air-liquid interface models, tissue engineered models, and organ-on-a-chip systems, which aim to better imitate the infection site microenvironment and microphysiology, are being developed to replace the commonly used monolayer cell culture models, and their use is becoming more widespread every day. On the contrary, studies on the development of nanoparticles (NPs) that mimic respiratory viruses, and those NPs used in therapy are progressing rapidly. The first part of this review describes in vitro models that mimic the blood-air barrier, the tissue interface that plays a central role in COVID-19 progression. In the second part of the review, NPs mimicking the virus and/or designed to carry therapeutic agents are explained and exemplified.

The enhanced properties and bioactivity of poly-ε-caprolactone/poly lactic-co-glycolic acid doped with carbonate hydroxyapatite-egg white.

Synthetic polymers, such as PCL and PLGA, are among the main material choices in tissue engineering because of their stable structures and strong mechanical properties. In this study, we designed polycaprolactone (PCL)/polylactic-co-glycolate acid (PLGA) nanofibers doped with carbonate hydroxyapatite (CHA) and egg white (EW) with enhanced properties. The addition of CHA and EW significantly influenced the properties and morphology of PCL/PLGA nanofibers; whereby the CHA substitution (PCL/PLGA/CHA) greatly increased the mechanical properties related to the Young's modulus and EW doping (PCL/PLGA/CHA/EW) increased the elongation at break. Bioactivity tests of PCL/PLGA/CHA/EW after immersion in the SBF for 3 to 9 days showed increased fiber diameters and a good swelling capacity that could improve cell adhesion, while biocompatibility tests with NIH-3T3 fibroblast cells showed good cell proliferation (85%) after 48 h and antibacterial properties against S. aureus.

A microfluidic organ-on-a-chip: into the next decade of bone tissue engineering applied in dentistry.

A comprehensive understanding of the complex physiological and pathological processes associated with alveolar bones, their responses to different therapeutics strategies, and cell interactions with biomaterial becomes necessary in precisely treating patients with severe progressive periodontitis, as a bone-related issue in dentistry. However, existing monolayer cell culture or pre-clinical models have been unable to mimic the complex physiological, pathological and regeneration processes in the bone microenvironment in response to different therapeutic strategies. In this point, 'organ-on-a-chip' (OOAC) technology, specifically 'alveolar-bone-on-a-chip', is expected to resolve the problems by better imitating infection site microenvironment and microphysiology within the oral tissues. The OOAC technology is assessed in this study toward better approaches in disease modeling and better therapeutics strategy for bone tissue engineering applied in dentistry.

Bone-related issues have been widely focused on in the field of dentistry due to oral cancers, trauma, injuries and the high incidence of periodontitis (a serious gum infection which causes bone damage and tooth loss). To overcome this condition, several strategies have been developed involving tissue engineering approaches and drug discovery. To provide better drugs for periodontitis, it is important to study the ways in which tissues and cells work together as well as the disease mechanisms, and cell interactions with drugs, other therapeutics agents, or biomaterials. For this, cell studies are needed, but the current research cannot replicate the disease environment and therefore cannot show exactly what happens in real sick areas. In this review, a new idea is explored called organ-on-a-chip technology, where scientists make small models that work like our organs, which could help them find better ways to treat dental and bone problems.

Fibrous PVA Matrix Containing Strontium-Substituted Hydroxyapatite Nanoparticles from Golden Apple Snail (Pomacea canaliculata L.) Shells for Bone Tissue Engineering.

A scaffold that replicates the physicochemical composition of bone at the nanoscale level is a promising replacement for conventional bone grafts such as autograft, allograft, or xenograft. However, its creation is still a major challenge in bone tissue engineering. The fabrication of a fibrous PVA-HA/Sr matrix made of strontium (Sr)-substituted hydroxyapatite from the shell of Pomecea canaliculate L. (golden apple snail) is reported in this work. Since the fabrication of HAp from biogenic resources such as the shell of golden apple snail (GASs) should be conducted at very high temperature and results in high crystalline HAp, Sr substitution to Ca was applied to reduce crystallinity during HAp synthesis. The resulted HAp and HA/Sr nanoparticles were then combined with PVA to create fibrous PVA-HAp or PVA-HA/Sr matrices in 2 or 4 mol % Sr ions substitution by electrospinning. The nanofiber diameter increased gradually by the addition of HAp, HA/Sr 2 mol %, and HA/Sr 4 mol %, respectively, into PVA. The percentage of the swelling ratio increased and reached the maximum value in PVA-HA/Sr-4 mol %, as well as in its protein adsorption. Furthermore, the matrices with HAp or HA/Sr incorporation exhibited good bioactivity, increased cell viability and proliferation. Therefore, the fibrous matrices generated in this study are considered potential candidates for bone tissue engineering scaffolds. Further in vivo studies become an urgency to valorize these results into real clinical application.

Synthesis of Biocompatible Silver-Doped Carbonate Hydroxyapatite Nanoparticles Using Microwave-Assisted Precipitation and In Vitro Studies for the Prevention of Peri-Implantitis.

A carbonate-hydroxyapatite-based antibacterial implant material with low cytotoxicity was synthesized. The silver ion (Ag+) was incorporated into CHA material, resulting in silver-doped carbonate hydroxyapatite (CHA-Ag). The microwave-assisted precipitation method was used to synthesize the CHA-Ag material. The amount of Ag+ was varied at 0.005, 0.010, and 0.015 mol fractions (χAg). The XRD results showed that the diffractograms corresponded with hydroxyapatite (ICSD 98-05-1414), without any additional phase. The presence of carbonate ions was indicated by vibrations at wavenumber of 871, 1411, and 1466 cm-1 in the infrared spectra. The CHA-Ag materials were agglomerates of nanosized particles with low crystallinity. The particle size and crystallinity of the materials decreased due to the incorporation of CO32- and Ag+. The incorporated Ag+ successfully inhibited peri-implant-associated bacterial growth. The antibacterial ability increased alongside the increase in the Ag+ amount. The pre-osteoblast MC3T3E1 cell could grow up to >70% in the MTT assay, despite the use of Ag+ as a dopant. The cell viability was higher in the CHA-Ag-containing media than in the CHA-containing media. The MTT assay also revealed that the CHA-Ag cytotoxicity decreased even though the Ag+ amount increased. The CHA-Ag-15 had the lowest cytotoxicity and highest antibacterial activity. Therefore, the optimal amount of Ag+ in the CHA-Ag formulation was χAg = 0.015.

Plant-Derived Exosome-like Nanoparticles for Biomedical Applications and Regenerative Therapy.

Plant-derived exosome-like nanoparticles (PDENs) comprise various bioactive biomolecules. As an alternative cell-free therapeutic approach, they have the potential to deliver nano-bioactive compounds to the human body, and thus lead to various anti-inflammatory, antioxidant, and anti-tumor benefits. Moreover, it is known that Indonesia is one of the herbal centers of the world, with an abundance of unexplored sources of PDENs. This encouraged further research in biomedical science to develop natural richness in plants as a source for human welfare. This study aims to verify the potential of PDENs for biomedical purposes, especially for regenerative therapy applications, by collecting and analyzing data from the latest relevant research and developments.

Development of mucosal vaccine delivery: an overview on the mucosal vaccines and their adjuvants.

Currently, mucosal infectious diseases are still a very high global health burden, but there are few effective vaccines to prevent mucosal-borne diseases. The development of mucosal vaccines requires the selection of appropriate antigens, delivery system strategies, and adjuvants to increase vaccine efficacy but limited studies have been conducted. The aim of this review is to describe the mucosal immune system, as well as the potential for the development of vaccines and mucosal adjuvants, and their challenges. The study was conducted by applying inclusion criteria for the articles, and a review was conducted by two readers with the agreement. It was known that mucosal vaccination is a potential route to be applied in future preventive efforts through vaccination. However, limited studies have been conducted so far and limited mucosal vaccination has been approved. New technological approaches such as material development involving nano- and micro-patterning are important to intensively open and investigate the potential area of development to provide better vaccination methods.

Safe-by-Design Antibacterial Peroxide-Substituted Biomimetic Apatites: Proof of Concept in Tropical Dentistry.

Bone infections are a key health challenge with dramatic consequences for affected patients. In dentistry, periodontitis is a medically compromised condition for efficient dental care and bone grafting, the success of which depends on whether the surgical site is infected or not. Present treatments involve antibiotics associated with massive bacterial resistance effects, urging for the development of alternative antibacterial strategies. In this work, we established a safe-by-design bone substitute approach by combining bone-like apatite to peroxide ions close to natural in vivo oxygenated species aimed at fighting pathogens. In parallel, bone-like apatites doped with Ag+ or co-doped Ag+/peroxide were also prepared for comparative purposes. The compounds were thoroughly characterized by chemical titrations, FTIR, XRD, SEM, and EDX analyses. All doped apatites demonstrated significant antibacterial properties toward four major pathogenic bacteria involved in periodontitis and bone infection, namely Porphyromonas gingivalis (P. gingivalis), Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Fusobacterium nucleatum (F. nucleatum), and S. aureus. By way of complementary tests to assess protein adsorption, osteoblast cell adhesion, viability and IC50 values, the samples were also shown to be highly biocompatible. In particular, peroxidated apatite was the safest material tested, with the lowest IC50 value toward osteoblast cells. We then demonstrated the possibility to associate such doped apatites with two biocompatible polymers, namely gelatin and poly(lactic-co-glycolic) acid PLGA, to prepare, respectively, composite 2D membranes and 3D scaffolds. The spatial distribution of the apatite particles and polymers was scrutinized by SEM and µCT analyses, and their relevance to the field of bone regeneration was underlined. Such bio-inspired antibacterial apatite compounds, whether pure or associated with (bio)polymers are thus promising candidates in dentistry and orthopedics while providing an alternative to antibiotherapy.

Induction of protein specific antibody by carbonated hydroxy apatite as a candidate for mucosal vaccine adjuvant.

Buccal mucosae are considered as a site for vaccine delivery since they are relatively abundant with antigen-presenting dendritic cells, mainly Langerhans cells. In this study, we formulated carbonated hydroxy apatite (CHA) with ovalbumin (OVA) (denoted as CHA-OVA), incorporated it into bilayer buccal membrane to form hydrogel films containing CHA-OVA complex for vaccination via buccal mucosae. Ethylcellulose blend with polyethylene glycol 400 were used as impermeable backing layer. Physical properties of all tested buccal membranes were found suitable for mucosal application. In vitro and ex vivo release study showed there was no burst release of OVA found from all tested formula. From the in vivo examination, rabbit buccal mucosae vaccinated by mucoadhesive membranes containing CHA-OVA complex demonstrated mucosal specific antibody induction, represented the potential of CHA as a candidate of needle-free vaccine adjuvant. Future research is awaiting to investigate proper CHA crystallinity in complex with protein against targeted diseases.

Cell Viability Assay and Surface Morphology Analysis of Carbonated Hydroxyapatite/Honeycomb/Titanium Alloy Coatings for Bone Implant Applications.

In this work, carbonated hydroxyapatite/titanium alloy (CHA/Ti) and carbonated hydroxyapatite/honeycomb/titanium alloy (CHA/HCB/Ti) plates were coated using the electrophoretic deposition dip coating (EP2D) method. Analysis of cell viability and surface morphology of CHA/Ti and CHA/HCB/Ti coatings were carried out using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and scanning electron microscopy (SEM), respectively. In a previous study, the thickness and average compressive strength values for the CHA/Ti and CHA/HCB/Ti plates were about 63−89 µm and 54−75 MPa, respectively. The result for thickness and compressive strength in this research followed the thickness and compressive strength parameters for coating in bone implants. In this work, the cell viability for incubation times during 24 h and 48 h of CHA/Ti plates is demonstrably superior to that of CHA/HCB/Ti plates, respectively, where the cell viability for CHA/Ti plates increased to ((67 ± 2)%) after incubation for 48 h. According to the one-way analysis of variance (ANOVA), the p-value was <0.05, indicating a significant difference in the average cell viability value across the three groups. Furthermore, the surface of CHA/Ti is not changed after the coating process. These results will yield many positive biomedical applications, especially in bone implants. Overall, CHA/Ti and CHA/HCB/Ti plates can be considered candidates for biomedical applications based on an analysis of surface morphology and cell viability.

Dual functional carbonate-hydroxyapatite nanocomposite from Pinctada maxima and egg-white for bone tissue engineering.

This study aims to design a 3D carbonate-hydroxyapatite (CHA)/sago (S) based egg white (EW) microstructure with antibacterial properties to improve the performance of bone grafts for bone tissue engineering. In this study, Pinctada maxima (P. maxima) shell was used as a calcium (Ca) source in CHA synthesis. The annealing temperature of CHA at 900, 1000, and 1100 °C affected microstructural and lattice parameters, with stoichiometry 1.72-1.77, and B-type CHA was identified. CHA/S with various concentrations of EW (10 and 30 wt.%) effectively increased pore size and porosity. XRD spectra confirmed that sago and EW in CHA nanocomposite stable the crystal structure. FTIR spectrum shows protein phosphorylation in CHA nanocomposite due to PO43- ion exchange. In-vitro bioactivity of CHA-S10 (MTT assay) showed increased cell viability and optical density (OD; 24-48 h) to control. Antibacterial activity of CHA-S10 and CHA/S (control) against bacteria associated with periodontal disease and bone infection (Actinobacillus actinomycetemcomitans [A. actinomycetemcomitans], Porphyromonas gingivalis [P. gingivalis], Fusobacterium nucleatum [F. nucleatum; gram negative], and Staphylococcus aureus [S. aureus; gram positive]) by disc diffusion method showed that CHA-S10 and CHA/S had strong antibacterial activity. In conclusion, EW's properties had proven the CHA/S/EW as bone grafts, effectively increasing pore size, porosity, biocompatibility, and strong antibacterial properties.

In Vitro Neuroprotective Effect of the Bovine Umbilical Vein Endothelial Cell Conditioned Medium Mediated by Downregulation of IL-1ß, Caspase-3, and Caspase-9 Expression.

Mesenchymal stem cells (MSCs) and conditioned medium (CM) derived from human umbilical blood cord stem cells (HUBSC) are now being extensively utilized. Human umbilical vein endothelial cells (HUVECs) have the same ability as HUBSC as an option for autologous therapy. In addition, cell therapy using HUVECs may produce protective signals for cerebral vessels and promote neuronal survival after hypoxic-ischemic damage. HUVECs have the same anatomical and physiological structure as bovine umbilical vein endothelial cells (BUVECs). In this study, we aim to determine the ability of BUVEC-CM to reduce inflammation and apoptosis on in vitro neurodegeneration models (PC12 and SH-SY5Y cell lines). BUVEC-CM obtained from the third and fourth passages were analyzed using liquid chromatography-mass spectrometry (LC-MS) and high-resolution mass spectrometry (HR-MS), while the other part was used as a treatment for in vitro model neurodegeneration. The PC12 and SH-SY5Y cell lines were cultured and grouped into seven different treatments, including untreated cells. As the treatment group, cells were given TMT 10 µM in the presence of different doses of CM (25%, 50%, 75%, and 100%); as a control comparison of recent therapy, donepezil was used. In addition, cells with the administration of TMT 10 µM were run as a positive control. Cell viability assay (CCK-8) and enzyme-linked immunosorbent assay (ELISA) were performed to identify the viability and expression of interleukin-1ß (IL-1ß), caspase-3, and caspase-9 for both PC12 and SH-SY5Y cells. The results showed that BUVEC-CM could significantly reduce IL-1ß expression and downregulate caspase-3 and caspase-9, as well as when compared to the donepezil group. Taken together, these results indicate that BUVEC-CM can be used as a potential candidate for neuroprotective agents by reducing the activity of IL-1ß and the expression of caspase-9 and caspase-3 in PC12 and SH-SY5Y cells induced by TMT. However, further research still needs to be conducted.

In vitro bioactivity of 3D microstructure hydroxyapatite/collagen based-egg white as an antibacterial agent.

The present study aims to design 3D scaffold hydroxyapatite (HA)/collagen (Coll) based egg-white (EW) as antibacterial properties. The calcium source in HA synthesis derived from the Pinctada maxima shell cultivated on Bali Island has proven biocompatibility, and the compressive strength exceeded human bone. HA synthesis by precipitation with heat treatment in oven-dried at 80°C (HA-80) and annealed at 900°C (HA-900), has crystallinity 48% and 85%, respectively, were used for scaffold design. The physicochemical properties of X-ray diffractometer spectra showed that increasing temperature affected the crystallinity and HA phase formed. Furthermore, the crystal structure of HA changed in nanocomposite due to the substitution of Coll and EW, and the Fourier transform infrared spectroscopy spectra confirmed that the absorption peak of the phosphate group (1027-1029 cm-1 ) decreased intensity, presumably by protein binding of EW and Coll. The cell viability of HA/Coll/EW in 24, 48, and 72 h incubation period was 112.34 ± 4.36, 104.89 ± 3.41, 72.88 ± 6.85, respectively. The decreases of cell viability due to high cell density and reduced nutrients in wells. Antibacterial activity of HA/Col/EW exhibited a strong zone of inhibition against bacteria causing periodontitis; Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, and Staphylococcus aureus.

Extracellular vesicles: a promising cell-free therapy for cartilage repair.

Few effective therapies for cartilage repair have been found as cartilage has a low regenerative capacity. Extracellular vesicles (EVs), including exosomes, are produced by cells and contain bioactive components such as nucleic acids, proteins, lipids and other metabolites that have potential for treating cartilage injuries. Challenges like the difficulty in standardizing targeted therapy have prevented EVs from being used frequently as a treatment option. In this review we present current studies, mechanisms and delivery strategies of EVs. Additionally, we describe the challenges and future directions of EVs as therapeutic agents for cartilage repair.

Development of a hydroxyapatite nanoparticle-based gel for enamel remineralization -A physicochemical properties and cell viability assay analysis.

Nano-hydroxyapatite (nHA) was synthesized from abalone mussel shells (Haliotis asinina) using a precipitation method, and gel HA-Abalone was developed using the carbomer materials with concentrations of 0, 10, 20, 30, and 40 wt%. The specimens used were 25 freshly extracted caries-free premolar teeth, and the treatment was done twice a day for 14 days. Gel HA-Abalone 20 wt%, with a crystallite size of 14.70±1.21 nm, was the best concentration to achieve the best remineralization (~863 VHN) of the superficial layer. Based on the results of cell viability assay on gel HA-Abalone 20 wt%, the growth of NIH/3T3 cells was inhibited beginning at a gel concentration of 1,000 µg/mL, and the half maximal inhibitory concentration (IC50) value was 1,497 µg/mL. Based on to the one-way analysis of variance (ANOVA), the result reflected statistically significant differences in the average of the cell viability and enamel surface microhardness values (p<0.05).

The Use of Polymers to Enhance Post-Orthodontic Tooth Stability.

Relapse after orthodontic treatment occurs at a rate of about 70 to 90%, and this phenomenon is an orthodontic issue that has not yet been resolved. Retention devices are one attempt at prevention, but they require a considerable amount of time. Most orthodontists continue to find it challenging to manage orthodontic relapse; therefore, additional research is required. In line with existing knowledge regarding the biological basis of relapse, biomedical engineering approaches to relapse regulation show promise. With so many possible uses in biomedical engineering, polymeric materials have long been at the forefront of the materials world. Orthodontics is an emerging field, and scientists are paying a great deal of attention to polymers because of their potential applications in this area. In recent years, the controlled release of bisphosphonate risedronate using a topically applied gelatin hydrogel has been demonstrated to be effective in reducing relapse. Simvastatin encapsulation in exosomes generated from periodontal ligament stem cells can promote simvastatin solubility and increase the inhibitory action of orthodontic relapse. Moreover, the local injection of epigallocatechin gallate-modified gelatin suppresses osteoclastogenesis and could be developed as a novel treatment method to modify tooth movement and inhibit orthodontic relapse. Furthermore, the intrasulcular administration of hydrogel carbonated hydroxyapatite-incorporated advanced platelet-rich fibrin has been shown to minimize orthodontic relapse. The objective of this review was to provide an overview of the use of polymer materials to reduce post-orthodontic relapse. We assume that bone remodeling is a crucial factor even though the exact process by which orthodontic correction is lost after retention is not fully known. Delivery of a polymer containing elements that altered osteoclast activity inhibited osteoclastogenesis and blocking orthodontic relapse. The most promising polymeric materials and their potential orthodontic uses for the prevention of orthodontic relapse are also discussed.

Challenges and strategy in treatment with exosomes for cell-free-based tissue engineering in dentistry.

In dentistry, problems of craniofacial, osteochondral, periodontal tissue, nerve, pulp or endodontics injuries, and osteoarthritis need regenerative therapy. The use of stem cells in dental tissue engineering pays a lot of increased attention, but there are challenges for its clinical applications. Therefore, cell-free-based tissue engineering using exosomes isolated from stem cells is regarded an alternative approach in regenerative dentistry. However, practical use of exosome is restricted by limited secretion capability of cells. For future regenerative treatment with exosomes, efficient strategies for large-scale clinical applications are being studied, including the use of ceramics-based scaffold to enhance exosome production and secretion which can resolve limited exosome secretory from the cells when compared with the existing methods available. Indeed, more research needs to be done on these strategies going forward.

The intrasulcular application effect of bisphosphonate hydrogel toward osteoclast activity and relapse movement.

INTRODUCTION: Orthodontic relapse occurs after orthodontic treatment and shifting of teeth to unfavorable positions. Bisphosphonates' effects on bone resorption and relapse prevention have been extensively investigated. However, topical administration, which results in local effect, is still a problem. OBJECTIVE: This study aimed to investigate the effect of risedronate with gelatin hydrogel as a carrier to prevent relapse movement by inhibiting osteoclast activity. METHODS: Lower incisors of 75 guinea pigs were moved distally using an orthodontic appliance until ±3 mm length. Gelatin hydrogel was fabricated to obtain a semisolid controlled release of 250 (Bis-CR250) and 500 mmol/L risedronate (Bis-CR500) and then applied intrasulcularly into the mesial subperiosteal area of 50 guinea pigs (25 in each group) every 3 days; the rest were the control (Bis-CR000). After 14 days of stabilization, the apparatus was removed. The distance decrease between incisors and the osteoclast number with TRAP staining at 0, 3, 7, 14, and 21 days were measured. ANOVA was used to determine the differences among the different time and experimental groups. RESULTS: Both treatments showed significantly less relapse movement compared to the control (p < 0.05) at 14 and 21 days. Bis-CR500 more effectively inhibited the relapse movement than Bis-CR250 on day 21, indicating a dose dependency in the inhibition. Both treatments showed less osteoclast numbers than control (p < 0.05). CONCLUSION: Controlled release of bisphosphonate risedronate with a topically administered gelatin hydrogel has shown to be effective in decreasing the tooth relapse movement and osteoclast activity.

Plant-derived exosome-like nanoparticles: A concise review on its extraction methods, content, bioactivities, and potential as functional food ingredient.

Plant-derived exosome-like nanoparticles (PDENs) are small vesicles released by multivesicular bodies mainly to communicate between cells and regulate immunity against pathogen attack. Current studies have reported that PDENs could modulate gene expression in a cross-kingdom fashion. Therefore, PDENs could be a potential future functional food ingredient as their cross-kingdom communication abilities were reported to exert multiple health benefits. Macrophage and other cells have been reported to absorb PDENs in a manner regulated by the membrane lipid and protein profile and the intactness of the PDENs lipid bilayer. PDENs could be extracted from plant materials by various techniques such as ultracentrifugation, immunoaffinity, size-based isolation, and precipitation, though each method has its pros and cons. PDENs mainly contain lipid, protein, and genetic materials, mainly micro RNAs, which could exert multiple health benefits and functionalities when consumed in sufficient amounts. However, most studies on the health functionalities of PDENs were conducted through in-vitro and in-vivo studies, and its potency to be used as a functional ingredient remains a question as PDENs are sensitive to storage and processing condition and requires costly extraction method. This concise review features various exosome extraction methods, contents of PDENs and their roles, the health functionalities of PDENs, and its potency as a functional food ingredient.