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The oral cavity and oropharynx are complex environments that are susceptible to physical, chemical, and microbiological insults. They are also common sites for pathological and cancerous changes. The effectiveness of conventional locally‐administered medications against diseases affecting these oral milieus may be compromised by constant salivary flow. For systemically‐administered medications, drug resistance and adverse side‐effects are issues that need to be resolved. New strategies for drug delivery have been investigated over the last decade to overcome these obstacles. Synthesis of nanoparticle‐containing agents that promote healing represents a quantum leap in ensuring safe, efficient drug delivery to the affected tissues. Micro/nanoencapsulants with unique structures and properties function as more favorable drug‐release platforms than conventional treatment approaches. The present review provides an overview of newly‐developed nanocarriers and discusses their potential applications and limitations in various fields of dentistry and oral medicine. A wide variety of micro/nanoscale platforms are employed for oral and dental applications including tissue regeneration, infection control, and cancer management. Such micro and nanocarriers deliver ions (e.g., fluoride, calcium, strontium), antibiotic, antiviral, antifungal compounds, as well as genes and proteins.

Identifying the changes in endogenous metabolites in response to intrinsic and extrinsic factors has excellent potential to obtain an understanding of cells, biofluids, tissues, or organisms’ functions and interactions with the environment. The advantages provided by the metabolomics strategy have promoted studies in bone research fields, including an understanding of bone cell behaviors, diagnosis and prognosis of diseases, and the development of treatment methods such as implanted biomaterials. This review article summarizes the metabolism changes during osteogenesis, osteoclastogenesis, and immunoregulation in hard tissue. The second section of this review is dedicated to describing and discussing metabolite changes in the most relevant bone diseases: osteoporosis, bone injuries, rheumatoid arthritis, and osteosarcoma. We consolidated the most recent finding of the metabolites and metabolite pathways affected by various bone disorders. This collection can serve as a basis for future metabolomics-driven bone research studies to select the most relevant metabolites and metabolic pathways. Additionally, we summarize recent metabolic studies on metabolomics for the development of bone disease treatment including biomaterials for bone engineering. With this article, we aim to provide a comprehensive summary of metabolomics in bone research, which can be helpful for interdisciplinary researchers, including material engineers, biologists, and clinicians.

Background/Objectives: We evaluated serum and urinary biomarkers of bone and energy metabolism in an ovine osteoporosis model (Control, OVX, OVXD, OVXDS) at 0/3/8 months (M). Methods: Morning sampling; DXA (ROI ‘abdominal width’) and linear mixed models for repeated measures. Results: Only OVXDS showed severe DXA loss (Z-scores −3.29 at 3 M; −4.86 at 8 M), with ≈20% and ≈30% BMD reductions at 3 M and 8 M versus controls. OVX and OVXD remained within age-expected Z-score ranges at 8 M. At 3 M, OVXDS had hypocalcemia, markedly elevated UFEP, near-zero 25-OH-vitamin-D, and suppressed osteocalcin/NTX (depressed turnover). By 8 M, osteocalcin rose in OVXDS while NTX stayed low, consistent with altered coupling under chronic glucocorticoids and vitamin D deficiency. OVXD showed milder, later changes. Fructosamine and insulin were transiently higher in OVXDS at 3 M; IGF-1 was stable across groups/time. Conclusions: Combined ovariectomy, calcium/vitamin-D-deficient diet, and glucocorticoids produce the clearest biomarker signature and DXA loss. Assay cross-reactivity limited PTH/DKK-1/cathepsin-K measurement in sheep; we summarize DXA outcomes and expand assay limitations and future validation plans.

The musculoskeletal (MS) system consists of bone, cartilage, tendon, ligament, and skeletal muscle, which forms the basic framework of the human body. This system plays a vital role in appropriate body functions, including movement, the protection of internal organs, support, hematopoiesis, and postural stability. Therefore, it is understandable that the damage or loss of MS tissues significantly reduces the quality of life and limits mobility. Tissue engineering and its applications in the healthcare industry have been rapidly growing over the past few decades. Tissue engineering has made significant contributions toward developing new therapeutic strategies for the treatment of MS defects and relevant disease. Among various biomaterials used for tissue engineering, natural polymers offer superior properties that promote optimal cell interaction and desired biological function. Natural polymers have similarity with the native ECM, including enzymatic degradation, bio-resorb and non-toxic degradation products, ability to conjugate with various agents, and high chemical versatility, biocompatibility, and bioactivity that promote optimal cell interaction and desired biological functions. This review summarizes recent advances in applying natural-based scaffolds for musculoskeletal tissue engineering.

Background: Phenamil (PH) is a small molecule that induces bone formation through upregulation of the TRB3 gene in the bone-regeneration process. [beta]-Cyclodextrins ([beta]CDs) with hydrophilic surfaces and a relatively hydrophobic cavity can form inclusion complexes with primarily hydrophobic small molecules such as PH, and increase their apparent solubility and dissolution rate. The hydrophilic surface of [beta]CDs prevents their interaction with the hydrophobic lipids of the cell membrane for penetration. Therefore, binding of penetrative groups, such as lysine, arginine, and histidine (His), to [beta]CDs for cell penetration is required. Aim: The aim of this study was to investigate the effect of His-conjugated [beta]CD on cellular uptake of PH for bone differentiation. Methods: In this study, His-[beta]CDs were synthesized and used to prepare an inclusion complex of His-[beta]CD-PH. A hydroxypropyl-[beta]CD-PH (HP-[beta]CD-PH) inclusion complex for increasing PH solubility without a penetrative group was prepared for comparison. 3-D geometry of [beta]CD derivatives and PH-inclusion complexes was investigated by Fourier-transform infrared spectroscopy and molecular docking. Alizarin red staining and real-time PCR were performed to compare bone differentiation of His-[beta]CD-PH and HP-[beta]CD-PH. Results: The results suggested that the benzene ring of PH was inserted into the wide side of both His-[beta]CD and HP-[beta]CD. Alizarin red staining at 14 days postculture in the presence of His-[beta]CD-PH at total concentration of 50 [micro]M for PH showed that bone-matrix mineralization increased significantly compared with free PH and HP-[beta]CD-PH. Real-time PCR confirmed this result, and showed gene expression increased significantly (OPN 1.84-fold, OCN 1.69-fold) when stem cells were cultured with His-[beta]CD-PH. Conclusion: The overall results indicated that His-[beta]CD-PH is a promising carrier for osteoinductive PH with possible penetration ability and sustained release that reduces BMP2 consumption for differentiation of mesenchymal stem cells to bone tissue. Keywords: phenamil, [beta]-cyclodextrin, inclusion complex, histidine, cell penetration, bone regeneration

Phenamil (PH) is a small molecule that induces bone formation through upregulation of the gene in the bone-regeneration process. β-Cyclodextrins (βCDs) with hydrophilic surfaces and a relatively hydrophobic cavity can form inclusion complexes with primarily hydrophobic small molecules such as PH, and increase their apparent solubility and dissolution rate. The hydrophilic surface of βCDs prevents their interaction with the hydrophobic lipids of the cell membrane for penetration. Therefore, binding of penetrative groups, such as lysine, arginine, and histidine (His), to βCDs for cell penetration is required. The aim of this study was to investigate the effect of His-conjugated βCD on cellular uptake of PH for bone differentiation. In this study, His-βCDs were synthesized and used to prepare an inclusion complex of His-βCD-PH. A hydroxypropyl-βCD-PH (HP-βCD-PH) inclusion complex for increasing PH solubility without a penetrative group was prepared for comparison. 3-D geometry of βCD derivatives and PH-inclusion complexes was investigated by Fourier-transform infrared spectroscopy and molecular docking. Alizarin red staining and real-time PCR were performed to compare bone differentiation of His-βCD-PH and HP-βCD-PH. The results suggested that the benzene ring of PH was inserted into the wide side of both His-βCD and HP-βCD. Alizarin red staining at 14 days postculture in the presence of His-βCD-PH at total concentration of 50 μM for PH showed that bone-matrix mineralization increased significantly compared with free PH and HP-βCD-PH. Real-time PCR confirmed this result, and showed gene expression increased significantly ( 1.84-fold, 1.69-fold) when stem cells were cultured with His-βCD-PH. The overall results indicated that His-βCD-PH is a promising carrier for osteoinductive PH with possible penetration ability and sustained release that reduces BMP2 consumption for differentiation of mesenchymal stem cells to bone tissue.

Immune regulation plays a crucial role during the regeneration process, and it determines the fate of inflammation after tissue injury or infection. Neutrophils serve as the primary immune cells recruited to the site of inflammation, initiating and directing the subsequent inflammatory cascade following implantation. This study investigated the effects of the in vitro standard foetal bovine serum (FBS), either in the culture medium or as a surface coating, as well as type I collagen coating on responses of neutrophils isolated from human peripheral blood using 3D-printed polycaprolactone (PCL) scaffolds. Neutrophil activity was evaluated by assessing metabolic activity and metabolomic profiles, reactive oxygen species (ROS) production, and inflammation-related markers via high throughput proximity extension assay. Type I collagen coating modified the metabolomic profile of neutrophils and MMP-9 release but had minimal effect on ROS generation. In contrast, the presence of FBS in the culture medium significantly influenced neutrophil behavior, leading to significant changes in metabolic activity, cytotoxicity, and the secretion of inflammation-associated molecules, even at concentrations as low as 1% (v/v). These findings highlight the importance of assessing the use of FBS in neutrophil culture models, particularly those isolated from humans, and emphasize the development of alternative platforms for investigating neutrophil–cell interactions in a more physiologically relevant manner. Neutrophil response to FBS(1–10%) and collagen coatings on PCL scaffolds was tested. FBS impacts neutrophil activation and alters metabolite composition of the medium. FBS increased the release of inflammation-related molecules such as NE, IL-8 and VEGFA. Collagen changed neutrophil metabolites and decreased MMP-9 release. Results addressed the FBS bias and the need for physiologically relevant culture models.

Many studies have shown that artificial neural networks (ANNs) are useful for predicting the unconfined compressive strength (UCS) of rocks. However, ANNs do have some deficiencies: they can get trapped in local minima and they have a slow learning rate. It is widely accepted that optimization algorithms such as particle swarm optimization (PSO) can improve ANN performance. This study investigated the application of a hybrid PSO-based ANN model to the prediction of rock UCS. To prepare a dataset for the predictive model, extensive laboratory tests (i.e., 160 tests in total) were conducted on 40 soft rock sample sets (mostly shale) presenting various weathering grades that were obtained from different excavation sites in Johor, Malaysia. The laboratory tests included the UCS test and other basic rock index tests (the Brazilian tensile strength test, point load index test, and ultrasonic test). When developing the predictive model of UCS, the results of the basic rock tests as well as the bulk densities of the samples were used as input parameters, while the UCS was set as the output of the predictive model. The value account for (VAF), root mean squared error (RMSE), and adjusted R 2 (coefficient of determination) were utilized to check the performances of the predictive models. The high performance indices of the proposed model highlight the superiority of the PSO-based ANN model for UCS prediction.

One of the most significant environmental issues of blasting operations is ground vibration, which can cause damage to the surrounding residents and structures. Hence, it is a major concern to predict and subsequently control the ground vibration due to blasting. This paper presents two artificial intelligence techniques, namely, adaptive neuro-fuzzy inference system (ANFIS) and artificial neural network for the prediction of ground vibration in quarry blasting site. For this purpose, blasting parameters as well as ground vibrations of 109 blasting operations were measured in ISB granite quarry, Johor, Malaysia. Moreover, an empirical equation was also proposed based on the measured data. Several AI-based models were trained and tested using the measured data to determine the optimum models. Each model involved two inputs (maximum charge per delay and distance from the blast-face) and one output (ground vibration). To control capacity performances of the predictive models, the values of root mean squared error (RMSE), value account for (VAF), and coefficient of determination (R ²) were computed for each model. It was found that the ANFIS model can provide better performance capacity in predicting ground vibration in comparison with other predictive techniques. The values of 0.973, 0.987 and 97.345 for R ², RMSE and VAF, respectively, reveal that the ANFIS model is capable to predict ground vibration with high degree of accuracy.

The durability of aggregates is an important factor that is used as an input parameter in desirable engineering properties along with resistance to exposure conditions. However, it is sometimes difficult to determine the durability of aggregates in the laboratory (with a magnesium sulfate test) because this test is time-consuming and expensive. In this paper, the physical and mechanical properties including water absorption and the Los Angeles coefficient are tailored to the specific evaluation of the durability of limestone aggregates. However, the predictive capabilities of artificial neural networks (ANN) and hybrid particle swarm optimization-based (PSO) ANN techniques have been evaluated and compared using the same input variables. To assess the reliability of the model, some performance indices such as the correlation coefficient ( R 2 ), the variance account for, and the root-mean-square error were calculated and compared for the two developed models. The results revealed that even though the two developed models reliably predict the durability value (magnesium sulfate value), the proposed PSO–ANN method displays an obvious potential for the reliable assessment of the value of magnesium sulfate according to the model performance criterion.