Search

Background: Retention is an essential element of orthodontic treatment. In the past two decades, numerous biological treatments have been developed to alleviate orthodontic relapse. Pharmacologic bone modulation is a viable approach to mitigate relapse. The aim of this investigation was to determine whether administering nanoemulsion carbonated hydroxyapatite-statin (CHA-statin) would increase Runx-2 expression and decrease Acp 5 expression in rats experiencing experimental orthodontic relapse., Materials & Methods: Forty-eight rats (n = 48) were assigned to four groups: control, CHA, statin, and CHA-statin, with 12 rats in each group. A 30 g mesial traction was applied for 7 days via a closed-coil spring that connected the first maxillary molar to the maxillary incisor. To maintain the moved teeth, CHA, statin hydrogel, and nanoemulsion CHA-statin were administered intrasulcularly every 3 days for a period of 7 days. The removal of the devices facilitated the occurrence of relapse. The expression of Acp 5 and Runx-2 was evaluated using the immunohistochemistry method. The collected data were evaluated using analysis of variance and post hoc tests, with p  < 0.05., Results: A significant reduction in Acp 5-positive cells in the CHA-statin group was observed on days 7 and 14 of relapse movement compared with the other groups ( p  < 0.05), whereas the average Runx-2 expressions in the CHA-statin groups were significantly higher than in the other groups on days 1, 7, and 14 during the relapse phase ( p  < 0.05)., Conclusion: The nanoemulsion CHA-statin increased Runx-2 expression and decreased Acp 5 expression, thereby potentially preventing orthodontic relapse in rats., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objectives: This study aims to determine the effect of gelatin-simvastatin hydrogel application on bone remodelling during relapse., Materials and Methods: Twenty-four rabbits (Oryctolagus cuniculus) were divided into a control group (n = 12) and a treatment group (n = 12). The lower incisors were subjected to orthodontic force and moved distally by an open coil spring. The force (50 cN) was extended for 1 week and retained in a new position for 2 weeks (stabilisation period). The treatment group received a local gelatin-simvastatin hydrogel administration during stabilisation, and the control group received only gelatin hydrogel. The springs were debonded after the stabilisation phase from both groups to facilitate a relapse. The percentage of relapse was measured in a model study using digital callipers. Levels of OPG and RANKL were analysed using ELISA., Results: The local application of gelatin-simvastatin hydrogel in the treatment group significantly decreases the relapse percentage and RANKL level. Additionally, the gelatin-simvastatin hydrogel significantly increases the level of OPG and ratio of OPG/RANKL., Conclusions: Applying gelatin-simvastatin hydrogel in the retention period can induce bone formation, inhibit orthodontic relapse and increase tooth stability (in vivo)., (© 2024 John Wiley & Sons A/S.)

The use of biogenic calcium ions for the source of hydroxyapatite (HAp or HA) are very common and have been being explored extensively. However, it usually results high crystalline HA, due to high reaction and decomposition temperatures. In this study, strontium (Sr 2+ ) doped HA from the golden apple snail shells (Pomacea canaliculate L) was successfully synthesized. It was indicated that Sr ions completely replaced calcium (Ca) ions, increased the lattice constant, and consecutively reduced HA crystallinity. Smaller crystal size and β-type carbonate (CO 3 2- ) ions substitution with Ca/P close to 1.67 molar ratio that mimic bone crystals were observed in Sr-doped HA, with significant increased rate of MC3T3-E1 cells viability and higher IC 50 values. It was proven that Sr ions substitution resolved challenges on the use of biogenic sources for HA fabrication. Further in vivo study is needed to continue to valorise the results into real biomedical and clinical applications.

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.

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Emmanuela et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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 ., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

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., Competing Interests: The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed., (© 2023 The Authors.)

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 CO 3 2- 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.

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.

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.

Background: Health professionals are known to use various combinations of knowledge and skills, such as critical thinking, clinical reasoning, clinical judgment, problem-solving, and decision-making, in conducting clinical practice. Clinical reasoning development is influenced by knowledge and experience, the more knowledge and experience, the more sophisticated clinical reasoning will be. However, clinical reasoning research in dentistry shows varying results ., Aims: This study aims to observe the clinical reasoning pattern of undergraduate dental students when solving oral health problems, and their accordance with their knowledge acquisition., Material and Methods: This qualitative study employed the think-aloud method and the result was assessed through verbal protocol analyses. Five respondents from final year dental undergraduate students were agreed to participate. A unique hypothetical clinical scenario was used as a trigger. The audio data were transcribed, interpreted, and categorized as a clinical reasoning pattern; and the concept maps created were assessed by a Structure of Learning Outcomes (SOLO) taxonomy as knowledge acquisition., Results: Observations on clinical reasoning patterns and the level of knowledge acquisition in five undergraduate dental students showed varying results. They applied clinical reasoning patterns according to their knowledge acquisition during didactical phase. Learners with inadequate knowledge relied on guessing, meanwhile learners with adequate knowledge applied more sophisticated reasoning pattern when solving problems., Conclusions: Various problem-solving strategies were encountered in this study, which corresponded to the level of knowledge acquisition. Dental institutions must set minimum standards regarding the acquisition of conceptual knowledge accompanied by improvement of clinical reasoning skills, as well as refinement of knowledge and procedural skills., (© 2023. The Author(s).)

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.

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.

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 IC 50 values, the samples were also shown to be highly biocompatible. In particular, peroxidated apatite was the safest material tested, with the lowest IC 50 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.

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., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Korean Vaccine Society.)

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.

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 PO 4 3- 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.

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., (© 2022 Wiley Periodicals LLC.)

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 (IC 50 ) 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).

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-1β (IL-1β), caspase-3, and caspase-9 for both PC12 and SH-SY5Y cells. The results showed that BUVEC-CM could significantly reduce IL-1β 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-1β 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.

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., Competing Interests: Financial & competing interests disclosure This work was supported by Indonesian Collaboration Research program from World Class University (WCU) – Institut Teknologi Bandung, contract no. 012/IT1.B07.1/SPP-LPPM/II/2021. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. English language editing was provided by Enago, funded by the authors., (© 2021 Anggraini Barlian.)

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., Competing Interests: Financial & competing interests disclosure This study is supported by Indonesia Collaborative Research (RKI) Funding Scheme under World Class University Acceleration Program from the Ministry of Education, Culture, Research, and Technology of the Republic of Indonesia, with a contract number 810/UN1/Ditlit/Dit-Lit/PT/2020. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2021 Ika Dewi Ana.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 King Saud University.)

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., (© 2021 Institute of Food Technologists®.)

Background: The application of bioceramic hydroxyapatite (HA) derived from materials high in calcium to tissue engineering has been of concern, namely scaffold. Scaffold pores allow for cell mobility metabolic processes, and delivery of oxygen and nutrients by blood vessel. Thus, pore architecture affects cell seeding efficiency, cell viability, migration, morphology, cell proliferation, cell differentiation, angiogenesis, mechanical strength of scaffolds, and, eventually, bone formation. Therefore, to improve the efficacy of bone regeneration, several important parameters of the pore architecture of scaffolds must be carefully controlled, including pore size, geometry, orientation, uniformity, interconnectivity, and porosity, which are interrelated and whose coordination affects the effectiveness of bone tissue engineering. The honeycomb (HCB) as natural polymeric porogen is used to pore forming agent of scaffolds. It is unique for fully interconnected and oriented pores of uniform size and high mechanical strength in the direction of the pores. The aim of this study was therefore to evaluate the effect of HCB concentration on macropore structure of the scaffolds., Methods: Bioceramic hydroxyapatite (HA) was synthesized from abalone mussel shells (Halioitis asinina) using a precipitation method, and HA-based scaffolds were fabricated with honeycomb (HCB) as the porogen agent. Pore structure engineering was successfully carried out using HCB at concentrations of 10, 20, and 30 wt%., Results: The Energy Dispersive X-Ray Spectroscopy (EDS) analysis revealed that the Ca/P molar ratio of HA was 1.67 (the stoichiometric ratio of HA). The Fourier Transform Infrared Spectroscopy (FTIR) spectra results for porous HA-based scaffolds and synthesized HA showed that no chemical decomposition occurred in the HA-based scaffold fabrication process. The porosity of the scaffold tended to increase when higher concentrations of HCB were added. XRD data show that the HCB was completely degraded from the scaffold material. The cell metabolic activity and morphology of the HA + HCB 30 wt% scaffold enable it to facilitate the attachment of MC3T3E1 cells on its surface., Conclusion: HCB 30 wt% is the best concentration to fabricate the scaffold corresponding to the criteria for pores structure, crystallographic properties, chemical decomposition process and cell viability for bone tissue engineering.

It would certainly be an advantage of resin-modified glass ionomer cement (RMGIC) if it can possess bioactivity. However, research related to that is still very limited. Hybridization of RMGIC was predicted to increase mechanical properties and resistance to disintegration, and low content of polyacrylic acid induces cement bioactivity. This study investigated the effect of BAG obtained from the CaSiO 3 -Ca 3 (PO 4 ) 2 system on RMGIC bioactivity. BAG samples containing 10%, 15%, and 20% P 2 O 5 (denoted as "CSP10," "CSP15," and "CSP20," respectively) were used to modify RMGIC powder, and apatite wollastonite was used for comparison. Surface bioactivity was assessed using XRD pattern, infrared spectroscopy, and SEM microstructure after specimen immersion in simulated body fluid (SBF). Contents of Ca, P, F, Sr, and Al were measured in the remaining SBF. Cell attachment, proliferation, and differentiation on the RMGIC containing BAG were evaluated and compared with those on the RMGIC without BAG. Sr and Al analyses revealed that the addition of BAG may not influence the matrix stability of the cement. Moreover, the addition of BAG was a positive factor indicating excellent ion exchange in SBF and spontaneous growth of apatite by consuming the Ca and P ions in the surrounding fluid. Osteoblast differentiation was higher on the four types of bioactive cements than on the RMGIC without BAG. The results of these studies provide novel insights into the development of a new generation of osteoconductive biomedical materials., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors.)

A scaffold that mimics physicochemical structure of nerve and supplies calcium ions in axonal environment is an attractive alternative for nerve regeneration, especially when applied in critical nerve defect. Various scaffold material, design, including their combination with several growth-induced substances and cells application have been being investigated and used in the area of nerve tissue engineering. However, the development remains challenges today because they are still far from ideal concerning their stability, reproducibility, including complicated handling related to the poor mechanical strength. In view of the current basis, in this study, the introduction of carbonated hydroxyapatite (CHA) as promising candidate to increase mechanical properties of nerve scaffold is reported. The incorporation of CHA was not only expected to provide better mechanical properties of the scaffold. Under physiological condition, CHA is known to be the most stable phases of calcium phosphate compound. Therefore, CHA was expected to provide controlled release calcium for better axonal environment and promote fasten nerve regeneration. This study shows that CHA incorporated gelatin membrane has ideal microstructure to prevent fibrous tissue ingrowth into the injury site, while retaining its capability to survive nerve tissue by allowing adequate glucose and specific proteins diffusion. The provided Ca 2+ release to the environment promoted neuronal growth, without suppressing acetylcholine esterase release activity. Neurite elongation was dramatically higher in the gelatin membrane incorporated with CHA. Introduction of CHA into gelatin membrane represents a new generation medical device for nerve reconstruction, with CHA was considered as a promising factor., (© 2020 Wiley Periodicals, Inc.)

A scaffold that mimics the physicochemical structure of bone at the nanoscale level is an attractive alternative to conventional bone grafts, but its development remains a main challenge in bone tissue engineering today. This work describes the fabrication of a nanofibrous poly(vinyl alcohol)/chitosan/carbonated hydroxyapatite (PVA/CS/CHAp) scaffold. CHAp nanoparticles were synthesized using a co-precipitation method, and nanofibrous PVA/CS/CHAp scaffolds were fabricated by electrospinning using CHAp concentrations of 0, 5, 10, 15, and 20 wt%. The physicochemical properties of the scaffolds were evaluated by SEM, XRD, FTIR, and EDS, and the mechanical properties were determined by tensile strength tests. Swelling behavior, protein adsorption onto the scaffold surfaces, surface biomineralization, and cells viability were also evaluated in vitro. The addition of CHAp to the composite decreased the fiber diameter from ∼160 nm at 0 wt% to ∼139 nm at 15 wt% and great agglomerations were evident at 20 wt%. XRD, FTIR, and EDS showed effective incorporation of CHAp into the nanofibrous structure. This CHAp incorporation significantly increased the modulus of the scaffold at PVA/CS/CHAp 15 wt%, with an average 103.86 MPa, but tensile strength was not significantly altered. However, the elongation at break was decreased as the CHAp concentration increased. Swelling capacity of scaffold increases due to CHAp addition. Protein adsorption onto the scaffold increased 2.3fold at 20 wt% when compared to 0 wt%. The PVA/CS/CHAp 15 wt% showed a better bioactivity when compared to PVA/CS/CHAp 0 wt% after immersion of the scaffolds in a simulated body fluid solution for 7 days. Cell viability and cell morphology results reveal that PVA/CS/CHAp able to facilitate osteoblast cells to attach and proliferate. Introducing higher CHAp into the scaffold could increase the cell viability of the scaffold. PVA/CS/CHAp has potential to serve as an alternative scaffold material for bone tissue engineering., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: We determined and structurally analyzed the reported effect of hydroxyapatite (HA) bone substitute on alveolar bone regeneration. To the best of our knowledge, no systematic reviews have previously reported the bone regenerative effect of the HA bone substitute., Materials and Methods: A literature search was performed for articles published up to August 2015 using MEDLINE with the search terms "hydroxyapatite," "bone regeneration," and "alveolar bone" as well as their known synonyms. The inclusion criteria were set up for human trials with at least five patients. The literature search, eligible article selection, and data extraction were independently performed by two readers, and their agreement was reported by κ value., Results: Of the 504 studies found using the MEDLINE literature search, 241 were included for further steps (inter-reader agreement, κ = 0.968). Abstract screening yielded 74 studies (κ = 0.910), with 42 completely fulfilling the inclusion criteria (κ = 0.864). In a final step, 42 studies were further analyzed, with 17 and 25 studies with and without statistical analysis, respectively. The 17 studies reporting similar outcome measures were compared using the calculated 95% confidence intervals. The effect of HA on ridge preservation could not be evaluated., Conclusions: The use of the HA bone substitute interfered with the normal healing process, with significant differences found for sinus augmentation but not for periodontal bone defects. Thus, a bone substitute with optimal bone regenerative properties for alveolar ridge or socket preservation, sinus augmentation, and periodontal bony defect should be developed.

Objective: To evaluate the effect of carbonated hydroxyapatite-incorporated advanced platelet-rich fibrin on relapse and bone remodelling in rabbits., Materials and Methods: Forty-five rabbits were divided into 3 groups (n = 15): a control group, carbonated hydroxyapatite (CHA) and carbonated hydroxyapatite-incorporated advanced platelet-rich fibrin (CHA-aPRF) group. The lower incisors were subjected to an orthodontic force of 50 cN. During the retention period, CHA and CHA-aPRF hydrogel were gently injected in the mesial gingival sulcus every 7 days. Next, the appliances were debonded to allow relapse. At 5 subsequent time points (0, 3, 7, 14 and 21 days after debonding), the distance between the mesial tips of rabbits incisors was measured using a digital calliper, osteoblast quantity was evaluated using haematoxylin-eosin staining and osteoclast activity was examined using tartrate-resistant acid phosphatase (TRAP) staining., Results: The relapse rate of CHA-aPRF group was lower than that of the other groups, and the relapse distances were significantly lower on days 14 and 21 (P < .05). Histological analysis revealed that the number of osteoblasts was significantly higher and that the osteoclast activity was significantly lower in the CHA-aPRF group compared with the other groups (P < .05)., Conclusions: Intrasulcular injection of hydrogel CHA incorporated aPRF can locally reduce orthodontic relapse in rabbits., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Bioceramics represent functional ceramics with significant interest in regenerative medicine area. In orthopedics as well as in oral and maxillofacial surgery, bioceramics have been widely used as bone reconstructive materials. The most common one is hydroxyapatite which have been in the market and clinical applications since the mid of 1970s. Nowadays, a lot of works have been being in the pipeline to develop bioceramics for various clinical applications in regenerative medicine area, including dentistry. Bioceramics have been used and considered promising candidate for periodontal treatment, prevention of relapse, nerve regeneration, vaccine adjuvant, drug delivery technology, even for esthetic medicine and cosmetics. In this chapter, the advantages of bioceramics for regenerative therapy especially in dentistry is discussed. The overview of bioceramics classification is also explained. The future perspective and challenges on the use of bioceramics for next generation regenerative therapy is also discussed.

Calcium sulfate (CS), also known as POP (Plaster of Paris) is a self-setting, biocompatible, and osteoconductive biomaterial with a long history for the treatment of skeletal defects. However, CS cements show a too fast resorption rate and are unable to provide a long-term 3D framework during the osteogenesis process. In our previous studies, it was found that the incorporation of CaCO 3 and CaCO 3 hydrogel provided enhanced mechanical and degradation properties of POP composites. Furthermore, it was also found that the use of cinnamaldehyde to crosslink CaCO 3 hydrogel may have some advantages, for example to crosslink the hydrogel and to act as anti-inflammatory control agent. The objective of the current study was to evaluate the effect of adding cinnamaldehyde crosslinked CaCO 3 hydrogel into POP on the diametral tensile strength, weight loss, age swelling, degradation, cinnamaldehyde release, and porosity. The following composites were prepared: POP/HCin-025 (25% addition of hydrogel microsphere) and POP/HCin-050 (50% addition of hydrogel microsphere). The composites were assessed on their diametral tensile strength, weight loss of the POP composite, age swelling, degradation of the hydrogel CaCO 3 , cinnamaldehyde release, and porosity, as well as XRD-patterns and FT-IR spectra. It was confirmed from the study that incorporation of cinnamaldehyde into CaCO 3 hydrogel system significantly increased the mechanical strength of the POP composite. Weight loss, swelling ratio in both acid to neutral pH, and biodegradability of the POP composites were controllable by the addition of cinnamaldehyde-CaCO 3 hydrogel. Moreover, the cinnamaldehyde incorporated into the hydrogel was proven to be released in a controlled manner. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1055-1062, 2017., (© 2017 Wiley Periodicals, Inc.)

The incorporation of CaCO 3 hydrogel has been proven to enhance the bone biological activity of Plaster of Paris (POP) and to decrease its degradability. However, the installation of this bone substitute in a bone defect will still be associated with an inflammatory response. In this study, the influence of cinnamaldehyde as anti-inflammatory agent, was investigated. In addition, it is known that aldehyde chains of cinnamaldehyde may also act as crosslinking agent and function as a plastisizer to the CaCO 3 hydrogel construct. Therefore, different concentrations of cinnamaldehyde were added to CaCO 3 hydrogel and the effect on the diametral tensile strength, age swelling, gel fractination, cinnamaldehyde release, antimicrobial effect, and cell cytotoxycity were investigated. The incorporation of cinnamaldehyde was found to decrease the age swelling and degradation rate of CaCO 3 hydrogel and to have no toxic effect to human gingival fibroblast cells. Moreover, the incorporation of cinnamaldehyde essential oil into the CaCO 3 hydrogel was beneficial and acted as an antiinflammatory agent. Further research in vivo is warranted to determine the final favorable effect of cinnamaldehyde incorporated CaCO 3 hydrogel in POP to provide a bone substitute. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 768-774, 2016., (© 2015 Wiley Periodicals, Inc.)

Gypsum or calcium sulfate (CS) or plaster of Paris (POP) is considered as a fast degradable material that usually resorbs before the bone defect area is completely filled by new bone. In this study, the incorporation of CaCO3 hydrogel into POP in different compositions was proposed to enhance the bone biological activity of POP and to decrease its degradability. The mechanical and degradation properties of the various materials were characterized by in vitro analysis. Subsequently, the materials were inserted into cylindrically sized bone defects as created into the femoral condyle of rats and left in situ for 1, 4, and 8 weeks. Histological analysis of the retrieved specimens indicated that the addition of CaCO3 hydrogel into POP increased bone formation, angiogenesis and collagen density and resulted into faster bone formation and maturation. It was also confirmed that the degradation rate of the POP decreased by the addition of CaCO3 hydrogel. The in vivo findings did corroborate with the in vitro analysis. In conclusion, the incorporation of CaCO3 hydrogel provides a promising technology to improve the properties of POP, the oldest biomaterial used for bone grafting., (© 2015 Wiley Periodicals, Inc.)

Calcium sulfate, also known as plaster of Paris (POP), is probably the oldest biomaterial used for bone grafting and considered to be a fast degradable material that allows complete resorption before the bone defect area is completely filled by new bone. The aim of this study was to investigate the possibility to combine POP with calcium carbonate in order to increase the the osteoconductivity of this material. Twenty four male Sprague Dawley rats, 5-months-old and weighing 300-350 g, were used in the study. Various treatment groups were created by the implantation of cylindrical samples of POP-100, POP-075 and POP-050 into the femoral condyles. After 1 and 4 weeks of implantation, rats were sacrificed and the implanted areas and the surrounding tissue were retrieved for histological analysis. The study was completed by an in vitro experiment, which included the soaking of the experimental materials into simulated body fluid. The results indicated that the composites were appropriate to be used as bone grafting material. The incorporation of CaCO3 into POP did decrease the degradation rate of the cements and induced faster bone formation, thus provides promising properties to this material., (Copyright © 2012 Wiley Periodicals, Inc.)

Although extensive efforts have been devoted to the development of polymer-ceramic composites for bone repair, those developed thus far were not able to mimic the nanostructure of bone, partly because of the aggregated, microscale organization of the mineral component. As a consequence, homogenization and intermixing of organic and inorganic components remain a major engineering challenge for the development of functional, biomimetic bone-substituting composites. In the current study, various dispersants were evaluated for their potential to be used as biocompatible dispersants in the synthesis of biomimetic composites with a nanodispersed mineral phase. Based on sedimentation experiments, tribasic sodium citrate was selected as the most effective dispersant for the stabilization of calcium phosphate (CaP) suspensions. Specific adsorption of citrate anions onto CaP nanocrystals was shown to result in a strong increase in the negative surface charge of the CaP particles and consequently increased repulsive interparticle forces that were able to overcome attractive van der Waals forces. Using sodium citrate as dispersant at a CaP/citrate ratio of 4.0, CaP-gelatin nanocomposites were fabricated which displayed a nanostructured mineral phase without occurrence of microscale CaP particles. Consequently, aggregation and sedimentation of CaP mineral phase was reduced considerably., (Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In this study, the effects of added bioactive glass on the basic setting properties of a commercially available resin-modified glass ionomer cement were investigated with respect to setting time, mechanical strength, and setting mechanism. It was found to be clinically acceptable whether the setting time was extended or shortened depending on the type of bioactive glass added. The compressive strength of the set cement containing the bioactive glass decreased and was much higher when compared with the conventional type glass ionomer cement containing bioactive glass. The Fourier-transform infrared and 13C CP/MAS-NMR spectroscopies revealed that the extent of the acid-base reaction was larger in the cements containing bioactive glass than in the commercial resin-modified glass ionomer cement because of its high basicity in the bioactive glass. The 27Al MAS-NMR showed that crosslinking of the carboxylates in the polymeric acid by Al proceeded less in the cement containing the bioactive glass.

Fluoride and various cations release from three commercial compomers (Dyract, Dyract AP and Compoglass-F) and a resin-modified glass ionomer (Fuji-II LC) as a control were measured up to 7 days in distilled water and 0.01M lactate buffer solution with pH 4.1. The surface morphological change before and after the release experiment was observed with a scanning electron microscopy. Fluoride, aluminum and strontium ions were released from Dyract, Dyract AP and Fuji-II LC much more in the lactate buffer than in the distilled water. With compoglass-F containing barium instead of strontium, barium was released in the same way. X-ray diffraction analysis confirmed that fluoride release from Dyract and Dyract AP was derived mainly from SrF(2) contained in Dyract and Dyract AP. However, fluoride release from Compoglass-F was derived from glassy phase though it contained much fluoride as YbF(3). Cumulative release amount of each species versus square root of time plot showed good linearity, indicating that the dissolution was controlled by the diffusion mechanism. The surface characteristics of disks for each material, which were immersed in the lactate buffer, were quite different from the surface before and after immersion in deionized water, especially with Dyract. After immersion in the lactate buffer, many voids which were left after dissolution of the filler particle, were seen obviously on the surface of Dyract., (Copyright 2003 Elsevier Science Ltd.)