Calcium phosphate (Ca-P) ceramics are promising bioactive material that can be used for the remodeling and regeneration of bone tissue. However, it's sintering temperature-dependent mechanical strength, which is negatively correlated with its bioactivity, causes difficulties in improving the comprehensive performance of Ca-P ceramics. Here, the femtosecond laser (FSL) with low-temperature plasma effect was adopted to modify the hydroxyapatite (HA) ceramics after high temperatures (1250 °C) sintering, pursuing higher mechanical strength along with better osteogenic activity. The changes in the physicochemical properties of the materials and the osteogenic activity were characterized and investigated. Cell evaluations and in vivo experiments were performed to assess and verify the effect of FSL processing on the osteogenic capability of HA ceramics. The results indicated that α- and β-tricalcium phosphate (TCP) multiphase components were formed on the HA ceramic surfaces after laser treatment, simultaneously bringing about surface micro-nano porous structure, accelerated release of calcium (Ca) and phosphate (Pi) ions, enhancement of roughness, hydrophilicity and surface energy. Their synergistic effect facilitated apatite precipitation on the HA surface, promoted osteogenic differentiation and osteogenic/angiogenic gene expression. In vivo results also confirmed the enhancement of HA ceramic osteogenic activity by FSL treatment. This study presents an effective strategy of introducing FSL etching to high-temperature sintered Ca-P ceramics to improve the bone regeneration of HA ceramics and attain satisfactory mechanical strength at the same time. It will further promote the clinical application of HA ceramics in the field of bone regenerative repair. STATEMENT OF SIGNIFICANCE: This study introduces a method that uses the low-temperature plasma effect of the femtosecond laser (FSL) to modify the surfaces of high-temperature sintered hydroxyapatite (HA) ceramics, enhancing their osteogenic activity while maintaining the original mechanical strength. FSL processing induces the formation of bioactive multiphase of tricalcium phosphate (α-TCP and β-TCP) on the surfaces, creates micro-nano topographies, improves hydrophilicity and surface energy, promoting osteoblast differentiation and osteogenic gene expression for faster bone regeneration. This method overcomes the issue that high-temperature sintered HA ceramics have high strength but low osteogenic activity. It provides a modification method for HA ceramics with well-characterized performance enhancements, offering a convenient and effective strategy for high quality bone regenerative repair.

This study aimed to compare the regenerative effect of autogenous micro-dentin and nano-dentin particles on bone regeneration in rabbits' mandibular defects. Sixty adult New Zealand rabbits were randomly divided into three groups: a control group, a micro-dentin group, and a nano-dentin group. A critical-sized bony defect was created at the lower border of the mandible. Bone regeneration was evaluated at two, four, and eight weeks using light microscopy, cone beam computed tomography (CBCT) scans, and histomorphometric analysis.

Nano-dentin significantly enhanced bone density and defect closure, as evidenced by CBCT and histological analyses. At eight weeks, it promoted extensive new bone formation, nearly bridging the defect, with minimal residual graft material compared to the micro-dentin group. Histomorphometric analysis confirmed its superior osteogenic potential, demonstrating enhanced bone regeneration and graft resorption. These findings highlight nano-dentin as a highly effective biomaterial for mandibular bone repair.

Periodontitis and bone loss in the maxillofacial and dental areas pose considerable challenges for both functional and aesthetic outcomes. To date, implantable dental barrier membranes, designed to prevent epithelial migration into defects and create a favorable environment for targeted cells, have garnered significant interest from researchers. Consequently, a variety of materials and fabrication methods have been explored in extensive research on regenerative dental barrier membranes.

This review focuses on dental barrier membranes, summarizing the various biomaterials used in membrane manufacturing, fabrication methods, and state-of-the-art applications for dental tissue regeneration. Based on a discussion of the pros and cons of current membrane strategies, future research directions for improved membrane designs are proposed.

To endow dental membranes with various biological properties that accommodate different clinical situations, numerous biomaterials and manufacturing methods have been proposed. These approaches provide theoretical support and hold promise for advancements in dental tissue regeneration.

Bioactive glass (BG) is a class of biocompatible, biodegradable, multifunctional inorganic glass materials, which is successfully used for orthopedic and dental applications, with several products already approved for clinical use. Apart from exhibiting osteogenic properties, BG is also known to be angiogenic and antibacterial. Recently, BG's role in immunomodulation has been gradually revealed. While the therapeutic effect of BG is mostly reported in the context of bone and skin-related regeneration, its application in regenerating other tissues/organs, such as muscle, cartilage, and gastrointestinal tissue, has also been explored recently. The strategies of applying BG have also expanded from powder or cement form to more advanced strategies such as fabrication of composite polymer-BG scaffold, 3D printing of BG-loaded scaffold, and BG-induced extracellular vesicle production. This review presents a concise overview of the recent applications of BG in regenerative medicine. Various regenerative strategies of BG will be first introduced. Next, the applications of BG in regenerating various tissues/organs, such as bone, cartilage, muscle, tendon, skin, and gastrointestinal tissue, will be discussed. Finally, clinical applications of BG for tissue regeneration will be summarized, and future challenges and directions for the clinical translation of BG will be outlined.

White detection remains a critical limitation in using colorimetry to determine substances with microfluidic paper-based analytical devices (µPADs). Here, we introduced a simple, safe alcohol ink-modified µPAD for the straightforward and facile detection of white color in precipitation reactions. Although absolute alcohol ink was found to cause device leakage, dilution of the ink with water was the key to successfully precoat wax-created µPADs. Device utility was demonstrated through simultaneous detection of sulfate, phosphate, and water hardness via precipitation reactions. While phosphate interfered with sulfate detection by Ba2+, in situ distance-based quantification of phosphate was implemented. Aside from anions, the modified µPADs could be extended to detect cationic analytes such as total hardness. The limits of detection (LODs) for sulfate, phosphate, and hardness were 0.005 mmol L-1, 0.005 mmol L-1, and 0.5 mmol L-1, respectively, with the linear ranges of 0.01-10.0 mmol L-1, 0.005-1.0 mmol L-1, and 0.001-0.5 mol L-1. The µPADs were applied to real water samples, demonstrating results that were consistent with standard methods at a 95% confidence level. By incorporating white detection, these alcohol ink-modified µPADs offer enhanced versatility for addressing a broader array of analytical challenges in real-world settings.

Ruminants can recycle nitrogen (N) and phosphorus (P), which are essential for vital body processes. Reduced N- and P-intake in ruminants is desirable for economic and ecologic reasons. Simultaneous modulation of mineral homoeostasis and bone metabolism occurs in young goats. This study aimed to investigate potential effects of dietary N- and/or P-restriction on molecular changes in bone metabolism. The twenty-eight young male goats were fed a control diet, an N-reduced diet, a P-reduced diet or a combined N- and P-reduced diet for 6-8 weeks. The N-restricted goats had lower plasma Ca concentration and higher plasma osteocalcin (OC) and CrossLaps concentrations. The P-restricted goats had reduced plasma inorganic phosphate (Pi) concentrations and increased plasma Ca concentrations. Due to the initiation of a signalling pathway that inhibits the fibroblast growth factor 23 (FGF23) expression, this was lower with P-restriction. Consequently, lower Pi concentrations were the main factor influencing the reduction in FGF23. The changes in mineral homoeostasis associated with P-restriction led to a reduction in OC, bone mineral content and mineral density. Simultaneously, bone resorption potentially increased with P-restriction as indicated by an increased receptor activator of NF-κB ligand/osteoprotegerin (OPG) ratio and an increase in OPG mRNA expression. Additionally, the increased mRNA expression of the calcitonin receptor during P-restriction points to a higher number of osteoclasts. This study demonstrates an impairment of bone remodelling processes in young goats by N- or P-restriction. With P-restriction, bone mineralisation rate was potentially reduced and bone quality impaired, while with N-restriction, bone remodelling increased.

Transcription initiation is a vital step in the regulation of eukaryotic gene expression. It can be dysregulated in response to various cellular stressors which is associated with numerous human diseases including cancer. Transcription initiation is facilitated via many gene-specific trans-regulatory elements such as transcription factors, activators, and coactivators through their interactions with transcription pre-initiation complex (PIC). These trans-regulatory elements can uniquely facilitate PIC formation (hence, transcription initiation) in response to cellular nutrient stress. Cellular nutrient stress also regulates the activity of other pathways such as target of rapamycin (TOR) pathway. TOR pathway exhibits distinct regulatory mechanisms of transcriptional activation in response to stress. Like TOR pathway, the cell cycle regulatory pathway is also found to be linked to transcriptional regulation in response to cellular stress. Several transcription factors such as p53, C/EBP Homologous Protein (CHOP), activating transcription factor 6 (ATF6α), E2F, transforming growth factor (TGF)-β, Adenomatous polyposis coli (APC), SMAD, and MYC have been implicated in regulation of transcription of target genes involved in cell cycle progression, apoptosis, and DNA damage repair pathways. Additionally, cellular metabolic and oxidative stressors have been found to regulate the activity of long non-coding RNAs (lncRNA). LncRNA regulates transcription by upregulating or downregulating the transcription regulatory proteins involved in metabolic and cell signaling pathways. Numerous human diseases, triggered by chronic cellular stressors, are associated with abnormal regulation of transcription. Hence, understanding these mechanisms would help unravel the molecular regulatory insights with potential therapeutic interventions. Therefore, here we emphasize the recent advances of regulation of eukaryotic transcription initiation in response to cellular stress.

The biological performance of aluminum oxide-titanium (Al2O3-Ti) composites requires special attention to achieve improved osteoblastic differentiation, and subsequent osseointegration/strong anchorage with the surrounding bone. Therefore, the aim of this study was to improve them by providing calcium phosphate (Ca-P)/bovine serum albumin (BSA) coating on their surfaces.

Ca-P/BSA coatings were prepared on the surfaces of 75vol.%Ti composites (75Ti-BSA) and pure Ti (100Ti-BSA as a control). The surface characteristics, phase analysis, micro-hardness, BSA release profile and biological responses including cytotoxicity, cell viability, differentiation, mineralization, and cell adhesion were evaluated.

The results showed that lower cytotoxicity% and higher mitochondrial activity or viability % were associated with the samples with Ca-P/BSA coatings (particularly 75Ti-BSA having 21.3% cytotoxicity, 111.4% and 288.6% viability at day 1 and 7, respectively). Furthermore, the Ca-P/BSA coating could highly enhance the differentiation of pre-osteoblast cells into osteoblasts in 75Ti-BSA group (ALP concentration of 4.8 ng/ml). However, its influence on cell differentiation in 100Ti-BSA group was negligible. Similar results were also obtained from mineralization assay. The results on cell adhesion revealed that the Ca-P/BSA coated samples differently interacted with MC3T3-E1 cells; enlarged flat cells on 75Ti-BSA vs more spindle-shaped cells on 100Ti-BSA.

Ca-P/BSA coated Al2O3-Ti provided promising biological performance, superior to that of uncoated composites. Therefore, they have the potential to improve implant osseointegration.

Physiological processes within the human body are regulated in approximately 24-h cycles known as circadian rhythms, serving to adapt to environmental changes. Bone rhythms play pivotal roles in bone development, metabolism, mineralization, and remodeling processes. Bone rhythms exhibit cell specificity, and different cells in bone display various expressions of clock genes. Multiple environmental factors, including light, feeding, exercise, and temperature, affect bone diurnal rhythms through the sympathetic nervous system and various hormones. Disruptions in bone diurnal rhythms contribute to the onset of skeletal disorders such as osteoporosis, osteoarthritis and skeletal hypoplasia. Conversely, these bone diseases can be effectively treated when aimed at the circadian clock in bone cells, including the rhythmic expressions of clock genes and drug targets. In this review, we describe the unique circadian rhythms in physiological activities of various bone cells. Then we summarize the factors synchronizing the diurnal rhythms of bone with the underlying mechanisms. Based on the review, we aim to build an overall understanding of the diurnal rhythms in bone and summarize the new preventive and therapeutic strategies for bone disorders.

We aimed to determine the onset time of hypophosphatemic rickets and investigate the mechanism of motility impairment through adenosine triphosphate (ATP) production in goslings. Two hundred and sixteen 1-day-old male Jiangnan white geese were randomly divided into 3 groups, with 6 replicates and 12 geese per replicate. Birds were fed on 3 diets: a control diet (nonphytic phosphorus, NPP, 0.38%), a P-deficient diet (PD; NPP, 0.08%), and a high P diet (HP; NPP, 0.80%) for 14 d. Subsequently, all birds were shifted to the control diet for an additional 14 d. The cumulative incidence of lameness increased significantly (P < 0.01) starting on d 4, reaching over 80% on d 7 and 100% on d 12 in the PD group. Drinking and eating frequency decreased from d 4 and d 5, respectively, in the PD group compared to the other groups (most P < 0.01). The PD group exhibited shorter and narrower beaks, higher (worse) curvature scores of the beak and costochondral junctions, swelling caput costae, and dirtier feathers since d 4, in contrast to the control and HP groups (most P < 0.01). The HP had bigger (P < 0.05) beak and sternum sizes than the control groups on d 4 to 11. Leg muscle ATP levels were lower (P < 0.01 or 0.05) on d 4 to 11; in contrast, adenosine diphosphate (d 7-11) was higher in PD compared to the control (P < 0.05). Leg muscle ATP level had positive linear (R2 > 0.40) correlations (r > 0.60) with eating and drinking frequencies on d 7 and 11 (P < 0.01). Bone stiffness, feather cleanliness, and ATP levels recovered (P > 0.05) to the control level, whereas bone size did not recover (P < 0.05) in PD and HP after eating the control diet for 2 wk. The onset time of hypophosphatemic rickets was around 4 d in goslings, and insufficient leg muscle ATP was related to the impaired motility observed in early P-deficient geese.

Hypoxia and acidosis are recognized tumor microenvironment (TME) biomarkers of cancer progression. Alterations in cancer redox status and metabolism are also associated with elevated levels of intracellular glutathione (GSH) and interstitial inorganic phosphate (Pi). This study aims to evaluate the capability of these biomarkers to discriminate between stages and inform on a switch to malignancy.

These studies were performed using MMTV-PyMT( +) female transgenic mice that spontaneously develop breast cancer and emulate human tumor staging. In vivo assessment of oxygen concentration (pO2), extracellular acidity (pHe), Pi, and GSH was performed using L-band electron paramagnetic resonance spectroscopy and multifunctional trityl and GSH-sensitive nitroxide probes.

Profiling of the TME showed significant deviation of measured biomarkers upon tumor progression from pre-malignancy (pre-S4) to the malignant stage (S4). For the combined marker, HOP: (pHe × pO2)/Pi, a value > 186 indicated that the tumors were pre-malignant in 85% of the mammary glands analyzed, and when < 186, they were malignant 42% of the time. For GSH, a value < 3 mM indicated that the tumors were pre-malignant 74% of the time, and when > 3 mM, they were malignant 80% of the time. The only marker that markedly deviated as early as stage 1 (S1) from its value in pre-S1 was elevated Pi, followed by a decrease of pHe and pO2 and increase in GSH at later stages.

Molecular TME profiling informs on alteration of tumor redox and metabolism during tumor staging. Early elevation of interstitial Pi at S1 may reflect tumor metabolic alterations that demand elevated phosphorus supply in accordance with the high rate growth hypothesis. These metabolic changes are supported by the following decrease of pHe due to a high tumor reliance on glycolysis and increase of intracellular GSH, a major intracellular redox buffer. The appreciable decrease in TME pO2 was observed only at malignant S4, apparently as a consequence of tumor mass growth and corresponding decrease in perfusion efficacy and increase in oxygen consumption as the tumor cells proliferate.

The suprachiasmatic nucleus (SCN) encodes time of day through changes in daily firing; however, the molecular mechanisms by which the SCN times behavior are not fully understood. To identify factors that could encode day/night differences in activity, we combine patch-clamp recordings and single-cell sequencing of individual SCN neurons in mice. We identify PiT2, a phosphate transporter, as being upregulated in a population of Vip+Nms+ SCN neurons at night. Although nocturnal and typically showing a peak of activity at lights off, mice lacking PiT2 (PiT2-/-) do not reach the activity level seen in wild-type mice during the light/dark transition. PiT2 loss leads to increased SCN neuronal firing and broad changes in SCN protein phosphorylation. PiT2-/- mice display a deficit in seasonal entrainment when moving from a simulated short summer to longer winter nights. This suggests that PiT2 is responsible for timing activity and is a driver of SCN plasticity allowing seasonal entrainment.

The kidney controls systemic inorganic phosphate (Pi) levels by adapting reabsorption to Pi intake. Renal Pi reabsorption is mostly mediated by sodium-phosphate cotransporters NaPi-IIa (SLC34A1) and NaPi-IIc (SLC34A3) that are tightly controlled by various hormones including parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). PTH and FGF23 rise in response to Pi intake and decrease NaPi-IIa and NaPi-IIc brush border membrane abundance enhancing phosphaturia. Phosphaturia and transporter regulation occurs even in the absence of PTH and FGF23 signaling. The calcium-sensing receptor (CaSR) regulates PTH and FGF23 secretion, and may also directly affect renal Pi handling. Here, we combined pharmacological and genetic approaches to examine the role of the CaSR in the acute phosphaturic response to Pi loading. Animals pretreated with the calcimimetic cinacalcet were hyperphosphatemic, had blunted PTH levels upon Pi administration, a reduced Pi-induced phosphaturia, and no Pi-induced NaPi-IIa downregulation. The calcilytic NPS-2143 exaggerated the PTH response to Pi loading but did not abolish Pi-induced downregulation of NaPi-IIa. In mice with a dominant inactivating mutation in the Casr (CasrBCH002), baseline NaPi-IIa expression was higher, whereas downregulation of transporter expression was blunted in double CasrBCH002/PTH knockout (KO) transgenic animals. Thus, in response to an acute Pi load, acute modulation of the CaSR affects the endocrine and renal response, whereas chronic genetic inactivation, displays only subtle differences in the downregulation of NaPi-IIa and NaPi-IIc renal expression. We did not find evidence that the CaSR impacts on the acute renal response to oral Pi loading beyond its role in regulating PTH secretion.NEW & NOTEWORTHY Consumption of phosphate-rich diets causes an adaptive response of the body leading to the urinary excretion of phosphate. The underlying mechanisms are still poorly understood. Here, we examined the role of the calcium-sensing receptor (CaSR) that senses both calcium and phosphate. We confirmed that the receptor increases the secretion of parathyroid hormone involved in stimulating urinary phosphate excretion. However, we did not find any evidence for a role of the receptor beyond this function.

Phosphate is an essential anion in the human body, comprising approximately 1% of the total body weight, and playing a vital role in metabolism, cell membranes, and bone formation. We have recently provided spectroscopic, microscopic, and computational evidence indicating that phosphates can aggregate much more readily in solution than previously thought. This prior work provided indirect evidence through the observation of unusual31 P NMR relaxation and line-broadening effects with increasing temperature. Here, we show that, under conditions of slow exchange and selective RF saturation, additional features become visible in chemical exchange saturation transfer (CEST) experiments, which appear to be related to the previously reported phosphate clustering. In particular, CEST shows pronounced dips several ppm upfield of the main phosphate resonance at low temperatures, while direct31 P spectroscopy does not produce any signals in that range. We study the pH dependence of these new spectroscopic features and present exchange and spectroscopic parameters based on fitting the CEST data. These findings could be of importance in the investigation of phosphate dynamics, especially in the biological milieu.

The creation of a suitable scaffold is a crucial step in the process of bone tissue engineering (BTE). The scaffold, acting as an artificial extracellular matrix, plays a significant role in determining the fate of cells by affecting their proliferation and differentiation in BTE. Therefore, careful consideration should be given to the fabrication approach and materials used for scaffold preparation. Natural polypeptides such as gelatin and collagen have been widely used for this purpose. The unique properties of nanoparticles, which vary depending on their size, charge, and physicochemical properties, have demonstrated potential in solving various challenges encountered in BTE. Therefore, nanocomposite biomaterials consisting of polymers and nanoparticles have been extensively used for BTE. Gelatin has also been utilized in combination with other nanomaterials to apply for this purpose. Composites of gelatin with various types of nanoparticles are particularly promising for creating scaffolds with superior biological and physicochemical properties. This review explores the use of nanocomposite biomaterials based on gelatin and various types of nanoparticles together for applications in bone tissue engineering.

Bone, a mineralized tissue, continuously undergoes remodeling. It is a process that engages the mineralization and demineralization of the bone matrix, orchestrated by the interactions among cells and cell-secreted biomolecules under the bone ionic microenvironment (BIE). The osteoinductive properties of the demineralized organic bone matrix and many biological factors have been well-investigated. However, the impact of the bone ionic environment on cell differentiation and osteogenesis remains largely unknown. In this study, we extracted and isolated inorganic bone components (bone-derived monetite, BM) using a low-temperature method and, for the first time, investigated whether the BIE could actively affect cell differentiation and regulate osteoimmune reactions. It was evidenced that the BIE could foster the osteogenesis of human bone marrow stromal cells (hBMSCs) and promote hBMSCs mineralization without using osteogenic inductive agents. Interestingly, it was noted that BIE resulted in intracellular mineralization, evidenced by intracellular accumulation of carbonate hydroxyapatite similar to that oberved in osteoblasts cultured in osteoinductive media. Additionally, BIE was found to enhance osteogenesis by generating a favorable osteoimmune environment. In a rat calvarial bone defect model, the osteogenic capacity of BIE was evaluated using a collagen type I-impregnated BM (Col-BM) composite. It showed that Col-BM significantly promoted new bone formation in the critical-size bone defect areas. Taken together, this is the first study that investigated the influence of the BIE on osteogenesis, osteoimmunology, and in situ bone tissue engineering. The innate osteoinductive potential of inorganic bone components, both in vitro and in vivo, not only expands the understanding of the BIE on osteogenesis but also benefits future biomaterials engineering for bone tissue regeneration.

Background: Kashin-Beck disease (KBD) is a distinct osteoarthropathy in China with an unclear pathogenesis. This study aims to explore whether perturbations in the intestine metabolome could be linked to KBD individuals. Methods: An investigation was conducted in KBD endemic villages and fecal samples were collected. After applying inclusion and exclusion criteria, a total of 75 subjects were enrolled for this study, including 46 KBD (including 19 Grade I KBD and 27 Grade II KBD) and 29 controls. Untargeted metabolomics analysis was performed on the platform of UHPLC-MS. PLS-DA and OPLS-DA were conducted to compare the groups and identify the differential metabolites (DMs). Pathway analysis was conducted on MPaLA platform to explore the functional implication of the DMs. Results: Metabolomics analysis showed that compared with the control group, KBD individuals have a total of 584 differential metabolites with dysregulated levels such as adrenic acid (log2FC = -1.87, VIP = 4.84, p = 7.63 × 10-7), hydrogen phosphate (log2FC = -2.57, VIP = 1.27, p = 1.02 × 10-3), taurochenodeoxycholic acid (VIP = 1.16, log2FC = -3.24, p = 0.03), prostaglandin E3 (VIP = 1.17, log2FC = 2.67, p = 5.61 × 10-4), etc. Pathway analysis revealed several significantly perturbed pathways associated with KBD such as selenium micronutrient network (Q value = 3.11 × 10-3, Wikipathways), metabolism of lipids (Q value = 8.43 × 10-4, Reactome), free fatty acid receptors (Q value = 3.99 × 10-3, Reactome), and recycling of bile acids and salts (Q value = 2.98 × 10-3, Reactome). Subgroup comparisons found a total of 267 differential metabolites were shared by KBD vs. control, KBD II vs. control, and KBD I vs. control, while little difference was found between KBD II and KBD I (only one differential metabolite detected). Conclusions: KBD individuals showed distinct metabolic features characterized by perturbations in lipid metabolism and selenium-related bioprocesses. Our findings suggest that the loss of nutrients metabolism balance in intestine was involved in KBD pathogenesis. Linking the nutrients metabolism (especially selenium and lipid) to KBD cartilage damage should be a future direction of KBD study.

The integrated repair of cartilage and bone involves the migration and differentiation of cells, which has always been a difficult problem to be solved. We utilize the natural biomaterial gelatin to construct gelatin methacryloyl (GelMA), a hydrogel scaffold with high cell affinity. GelMA is mixed with different components to print a bi-layer porous hydrogel scaffold with different modulus and composition in upper and lower layers through three-dimensional (3D) printing technology. The upper scaffold adds black phosphorus (BP) and human umbilical cord mesenchymal stem cells (hUMSCs) exosomes (exos) in GelMA, which has a relatively lower elastic modulus and is conducive to the differentiation of BMSCs into cartilage. In the lower scaffold, in addition to BP and hUMSCs exos,β-tricalcium phosphate (β-TCP), which has osteoconductive and osteoinductive effects, is added to GelMA. The addition ofβ-TCP significantly enhances the elastic modulus of the hydrogel scaffold, which is conducive to the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).In vitroexperiments have confirmed that the bi-layer scaffolds can promote osteogenesis and chondrogenic differentiation respectively. And in the rabbit cartilage-bone injury model, MRI and micro-CT results show that the 3D printed bi-layer GelMA composite scaffold has a repair effect close to normal tissue.

Guided bone regeneration (GBR) is a widely used technique in preclinical and clinical studies due to its predictability. Its main purpose is to prevent the migration of soft tissue into the osseous wound space, while allowing osseous cells to migrate to the site. GBR is classified into two main categories: resorbable and non-resorbable membranes. Resorbable membranes do not require a second surgery but tend to have a short resorption period. Conversely, non-resorbable membranes maintain their mechanical strength and prevent collapse. However, they require removal and are susceptible to membrane exposure. GBR is often used with bone substitute graft materials to fill the defect space and protect the bone graft. The membrane can also undergo various modifications, such as surface modification and biological factor loading, to improve barrier functions and bone regeneration. In addition, bone regeneration is largely related to osteoimmunology, a new field that focuses on the interactions between bone and the immune system. Understanding these interactions can help in developing new treatments for bone diseases and injuries. Overall, GBR has the potential to be a powerful tool in promoting bone regeneration. Further research in this area could lead to advancements in the field of bone healing. This review will highlight resorbable and non-resorbable membranes with cellular responses during bone regeneration, provide insights into immunological response during bone remodeling, and discuss antibacterial features.

In the last several years, zinc and its alloys have come into focus as bioabsorbable materials by qualifying themselves with an excellent corrosion rate, mechanical properties, anti-bacterial effects. and considerable biocompatibility. In this study, the biocompatibility of zinc-silver alloys containing 3.3 wt% silver (ZnAg3) was assessed by evaluating their cell viability, the proliferation rate, and the cell toxicity. Two alloys were investigated in which one was phosphated and the other was non-phosphated. The alloys were tested on human osteoblasts (hOb), which are, to a large extent, responsible for bone formation and healing processes. The performance of the phosphated alloy did not differ significantly from the non-phosphated alloy. The results showed a promising biocompatibility with hOb for both alloys equally in all conducted assays, qualifying ZnAg3 for further investigations such as in vivo studies.

Bone is capable of adjusting size, shape, and quality to maintain its strength, toughness, and stiffness and to meet different needs of the body through continuous remodeling. The balance of bone homeostasis is orchestrated by interactions among different types of cells (mainly osteoblasts and osteoclasts), extracellular matrix, the surrounding biological milieus, and waste products from cell metabolisms. Inorganic ions liberated into the localized microenvironment during bone matrix degradation not only form apatite crystals as components or enter blood circulation to meet other bodily needs but also alter cellular activities as molecular modulators. The osteoinductive potential of inorganic motifs of bone has been gradually understood since the last century. Still, few have considered the naturally generated ionic microenvironment's biological roles in bone remodeling. It is believed that a better understanding of the naturally balanced ionic microenvironment during bone remodeling can facilitate future biomaterial design for bone tissue engineering in terms of the modulatory roles of the ionic environment in the regenerative process.

The determination of phosphate ions in biological testing is critical for environmental safety. A reliable and accurate method is required to measure the true phosphate ion concentrations; in this regard, the electrochemical method is preferable because of its simple operation, fast response, and high sensitivity. By compiling existing electroanalytical techniques, researchers can compare the advantages and disadvantages of each method. This review examines the progress and recent advances in electrochemical sensing strategies adapted for the determination of phosphate ions in the environmental and during biological monitoring. We first discuss the history of phosphorus and the development of methods to detect phosphates. The recognition elements of phosphate ion sensors for environmental applications include metal-based, nanomaterial-based, carbon-based, and enzymatic electrodes. Phosphate determination in biological samples, such as blood serum, drugs, and other biological fluids, such as urine and saliva, as well as phosphate esters, is also discussed. The final part of our review addresses the current challenges that phosphate sensing technology faces and illustrates future opportunities for more reliable phosphate detection.

Traumatic, tumoral, and infectious bone defects are common in clinics, and create a big burden on patient's families and society. Calcium phosphate (CaP)-based biomaterials have superior properties and have been widely used for bone defect repair, due to their similarities to the inorganic components of human bones. The biological performance of CaPs, as a determining factor for their applications, are dependent on their physicochemical properties. Hydroxyapatite (HAP) as the most thermally stable crystalline phase of CaP is mostly used in the form of ceramics or composites scaffolds with polymers. Nanostructured CaPs with large surface areas are suitable for drug/gene delivery systems. Additionally, CaP scaffolds with hierarchical nano-/microstructures have demonstrated excellent ability in promoting bone regeneration. This review focuses on the relationships and interactions between the physicochemical/biological properties of CaP biomaterials and their species, sizes, and morphologies in bone regeneration, including synthesis strategies, structure control, biological behavior, and the mechanisms of CaP in promoting osteogenesis. This review will be helpful for scientists and engineers to further understand CaP-based biomaterials (CaPs), and be useful in developing new high-performance biomaterials for bone repair.

In this study, we synthesized polyacrylic acid (PAA)-Ca (Eu) nanoclusters as a luminescence sensor of phosphate ion by a complex method, and we aimed to achieve the quantitative detection of PO43− based on the sensitivity of the charge transfer band of Eu3+ to anionic ligand. The resulting PAA-Ca(Eu) nanoclusters showed a well-dispersed and a dot-like morphology, with an ultra-small diameter (the average size of 2.17 nm) under high resolution transmission electron microscopy(HRTEM) observation. A dynamic light scattering particle size analyzer (DLS) showed a hydrodynamic size of 2.39 nm. The (PAA)-Ca (Eu) nanoclusters as a luminescence sensor showed a significantly higher sensitivity for PO43− than other anions (CO32−, SiO32−, SO42−, SO32−, Br−, Cl−, F−). The luminescence intensity displayed a linear increase (y = 19.32x + 74.75, R2 > 0.999) in a PO43 concentration range (0−10 mM) with the concentration of PO43− increase, and the limit of detection was 0.023 mM. The results showed good recovery rates and low relative standard deviations. These (PAA)-Ca (Eu) nanoclusters are hopeful to become a luminescence sensor for quantitatively detecting PO43−.

In patients with chronic kidney disease (CKD), hyperphosphatemia is associated with several adverse outcomes, including bone fragility and progression of kidney and cardiovascular disease. However, there is a knowledge gap regarding phosphate balance in CKD. This review explores its current state, depending on the stage of CKD, dialysis modalities, and the influence of kidney transplantation.

Adequate phosphate control is one of the goals of treatment for CKD-mineral and bone disorder. However, ongoing studies are challenging the benefits of phosphate-lowering treatment. Nevertheless, the current therapy is based on dietary restriction, phosphate binders, and optimal removal by dialysis. In the face of limited adherence, due to the high pill burden, adjuvant options are under investigation. The recent discovery that intestinal absorption of phosphate is mostly paracellular when the intraluminal concentration is adequate might help explain why phosphate is still well absorbed in CKD, despite the lower levels of calcitriol.

Future studies could confirm the benefits of phosphate control. Greater understanding of the complex distribution of phosphate among the body compartments will help us define a better therapeutic strategy in patients with CKD.

In this work, a novel fluorescence method for the detection of phosphate anions (PO₄^3-) was developed based on porphyrin metalation. Through catalysis by G-quadruplex (G4), Cu²⁺ could insert into the porphyrins to quench their fluorescence. G4 simultaneously improved the fluorescence of the porphyrins but not that of Cu²⁺-porphyrin. In the absence of PO₄^3-, the porphyrins were metallized by Cu²⁺, and no fluorescence was observed. In the presence of PO₄^3-, PO₄^3- could coordinate with Cu²⁺ to prevent porphyrin metalation. Free porphyrin could bind with G4 to emit strong fluorescence. By comparing four common porphyrins, we found that G4 had the greatest effect on increasing the fluorescence intensity of N-methylmesoporphyrin IX (NMM). Thus, NMM/G4 was chosen for the design of a biosensor. Under optimal experimental conditions, this method showed high sensitivity and satisfactory selectivity for PO₄^3- with a detection limit of 44 nM in a linear range of 0.01-1.0 μM. The recovery experiments showed recovery rates of 93.75-106.00%, suggesting a great potential for measuring PO₄^3- in real samples.

Dietary inorganic phosphate (Pi) modulates renal Pi reabsorption by regulating the expression of the NaPi-IIa and NaPi-IIc Pi transporters. Here, we aimed to clarify the role of several Pi-regulatory mechanisms including parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23) and inositol hexakisphosphate kinases (IP6-kinases) in the acute regulation of NaPi-IIa and NaPi-IIc.

Wildtype (WT) and PTH-deficient mice (PTH-KO) with/without inhibition of FGF23 signalling were gavaged with Pi/saline and examined at 1, 4 and 12 h.

Pi-gavage elevated plasma Pi and decreased plasma Ca²⁺ in both genotypes after 1 h Within 1 h, Pi-gavage decreased NaPi-IIa abundance in WT and PTH-KO mice. NaPi-IIc was downregulated 1 h post-administration in WT and after 4 h in PTH-KO. PTH increased after 1 h in WT animals. After 4 h Pi-gavage, FGF23 increased in both genotypes being higher in the KO group. PTHrp and dopamine were not altered by Pi-gavage. Blocking FGF23 signalling blunted PTH upregulation in WT mice and reduced NaPi-IIa downregulation in PTH-KO mice 4 h after Pi-gavage. Inhibition of IP6-kinases had no effect.

(1) Acute downregulation of renal Pi transporters in response to Pi intake occurs also in the absence of PTH and FGF23 signalling, (2) when FGF23 signalling is blocked, a partial contribution of PTH is revealed, (3) IP6 kinases, intracellular Pi-sensors in yeast and bacteria, are not involved, and (4) Acute Pi does not alter PTHrp and dopamine. Thus, signals other than PTH, PTHrp, FGF23 and dopamine contribute to renal adaption.

The blood level of phosphate is tightly regulated in a narrow range. Hyperphosphatemia and hypophosphatemia both lead to the development of diseases, such as hyperphosphatemic tumoral calcinosis and rickets/osteomalacia, respectively. Although several humoral factors have been known to affect blood phosphate levels, fibroblast growth factor 23 (FGF23) is the principal hormone involved in the regulation of blood phosphate. This hormone is produced by bone, particularly by osteocytes and osteoblasts, and has the effect of lowering the blood level of phosphate in the renal proximal tubules. Therefore, some phosphate-sensing mechanism should exist, at least in the bone. However, the mechanisms through which bone senses changes in the blood level of phosphate, and through which the bone regulates FGF23 production remain to be fully elucidated. Our recent findings demonstrate that high extracellular phosphate phosphorylates FGF receptor 1c (FGFR1c). Its downstream extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling pathway regulates the expression of several transcription factors and the GALNT3 gene, which encodes GalNAc-T3, which plays a role in the regulation of posttranslational modification of FGF23 protein, which in turn enhances FGF23 production. The FGFR1c-GALNT3 gene axis is considered to be the most important mechanism for regulating the production of FGF23 in bone in the response to a high phosphate diet. Thus-in the regulation of FGF23 production and blood phosphate levels-FGFR1c may be considered to function as a phosphate-sensing molecule. A feedback mechanism, in which FGFR1c and FGF23 are involved, is present in blood phosphate regulation. In addition, other reports indicate that PiT1 and PiT2 (type III sodium-phosphate cotransporters), and calcium-sensing receptor are also involved in the phosphate-sensing mechanism. In the present chapter, we summarize new insights on phosphate-sensing mechanisms.

The development of highly bioactive engineered scaffolds is required to promote bone regeneration and the success of bone tissue engineering treatment approaches. This study attempts to fabricate a biofunctional magnetic scaffold based on new phosphorylated polycaprolactone combined with gelatin (MNPs-PCL-P/gelatin). Phosphorylated polymer and magnetic nanoparticles (MNPs) were synthesized and characterized by NMR, FT-IR, TEM, and DLS instruments. The synthetic polymer, MNPs, and biopolymer were mixed then freeze-dried to prepare a porous scaffold. Physiochemical assessments showed that a scaffold with well-developed porous morphology, and stable structure was obtained. MNPs-PCL-P/gelatin scaffold had no toxicity on human dental pulp stem cells (hDPSCs). The use of phosphorous-containing polymer resulted in improvement of the scaffold's osteoconductivity to support proper cell attachment and promote cell proliferation. Phosphate group by mimicking function of bone phosphate groups stimulate bone mineralization that reflected by alizarin red S staining assay. The presence of MNPs resulted in higher ALP activity and increased expression level of RUNX2, BMP2 osteogenic biomarkers. Also, phosphorylation enhanced osteoinductivity of scaffold and upregulate RUNX2, BMP2, COL1A1, and OCN genes in phosphors-containing scaffold test groups. It seems that biocompatible MNPs-PCL-P/gelatin scaffold possesses the potential of applications in bone tissue engineering.

Large injuries to bones are still one of the most challenging musculoskeletal problems. Tissue engineering can combine stem cells, scaffold biomaterials, and biofactors to aid in resolving this complication. Therefore, this review aims to provide information on the recent advances made to utilize the potential of biomaterials for making bone scaffolds and the assisted stem cell therapy and use of biofactors for bone tissue engineering. The requirements and different types of biomaterials used for making scaffolds are reviewed. Furthermore, the importance of stem cells and biofactors (growth factors and extracellular vesicles) in bone regeneration and their use in bone scaffolds and the key findings are discussed. Lastly, some of the main obstacles in bone tissue engineering and future trends are highlighted.

2-Ethoxy-6-[1-(phenyl-pyridin-2-yl-methyl)-1H-benzoimidazol-2-yl]-phenol (HL) selectively serves as a sensitive 'turn on' Zn²⁺ sensor in 9 : 1 (v/v) DMSO/H₂O (HEPES buffer, pH = 7.4) medium in the presence of sixteen other cations at the limit of detection (LOD) of 3.2 nM. The strong blue emission of the complex, {[Zn(L¹)OAc]} (HL¹ = benzimidazolyl ring-opening structure of HL) (λ_em, 461 nm), is quenched by H₂PO₄^- in the presence of eighteen other anions and the LOD is 0.238 μM. The emission of the complex is due to restricted intramolecular rotation (RIR) followed by chelation-enhanced fluorescence (CHEF). The quenching of the emission of [Zn(L¹)OAc] by H₂PO₄^- (in the presence of other P^Vs (inorganic and biological) as well as additional anions) is due to the 'turn off' fluorescence via the demetallation and release of the nonfluorescent ligand, HL, and [Zn(H₂PO₄)]⁺. An INHIBIT logic gate memory circuit of the probe HL was devised with Zn²⁺ and H₂PO₄^- as two consecutive inputs. The percentage of H₂PO₄^- recovery was excellent and was obtained from distilled, tap, and drinking water sources. The bright blue emission of [Zn(L¹)OAc] further triggered the fabrication of ready-made portable thin films of the Zn-complex, which executed a cost-effective 'on-site' solid-state contact mode detection of H₂PO₄^- with selectivity at the picogram level (10.97 pg cm^-2) by monitoring the intensities of quenched spots under UV light upon varying the analyte concentration from 10^-8 to 10^-3 M. Finally, taking advantage of reversible fluorescence switching, a simple and definite ion-responsive security feature was successfully embedded into a "use" and "throw" solution-coated paper strip of the Zn(II)-pyridyl-benzimidazolyl-phenolato-based chemosensor, which efficiently detected H₂PO₄^- in water by a successive 'ON-OFF' fluorescence switching-driven security activity without any exhaustion of the emission phenomenon.

The regulatory functions of the immune response in tissue healing, repair, and regeneration have been evidenced in the last decade. Immune cells play central roles in immune responses toward inducing favorable tissue regenerative processes. Modulating and controlling the immune cell responses (particularly macrophages) is an emerging approach to enhance tissue regeneration. Bioactive glasses (BGs) are multifunctional materials exhibiting osteogenic, angiogenic, and antibacterial properties, being increasingly investigated for various tissue regeneration scenarios, including bone regeneration and wound healing. On the other hand, the immunomodulatory effects of BGs in relation to regenerating tissues have started to be understood, and key knowledge is emerging. This is the first review article summarizing the immunomodulatory effects of BGs for tissue repair and regeneration. The immune response to BGs is firstly introduced, discussing potential mechanisms regarding the immunomodulation effects induced by BGs. Moreover, the interactions between the immune cells involved in the immunomodulation process and BGs (dissolution products) are summarized in detail. Particularly, a well-regulated and timely switch of macrophage phenotype from pro-inflammatory to anti-inflammatory is crucial to constructive tissue regeneration through modulating osteogenesis, osteoclastogenesis, and angiogenesis. The influence of BG characteristics on macrophage responses is discussed. We highlight the strategies employed to harness macrophage responses for enhanced tissue regeneration, including the incorporation of active ions, surface functionalization, and controlled release of immunomodulatory molecules. Finally, we conclude with our perspectives on future research challenges and directions in the emerging field of immunomodulatory BGs for tissue regeneration. STATEMENT OF SIGNIFICANCE: Immunomodulatory effects of bioactive glasses (BGs) in relation to bone regeneration and wound healing have started to be understood. We summarize those studies which have focused on immunomodulatory BGs for tissue regeneration. We first introduce the potential mechanisms of the immunomodulation effects induced by BGs. Interactions between the cells involved in immunomodulation processes and BGs (and their dissolution products, biologically active ions) are elaborated. We highlight the strategies employed to modulate macrophage responses for enhancing tissue regeneration, including incorporation of active ions, surface functionalization, and controlled release of immunomodulatory agents. This is the first review article summarizing and outlining the immunomodulatory effects of BGs for tissue regeneration. We anticipate that increasing research efforts will start to emerge in the area of immunomodulatory BGs.

Regenerative engineering has pioneered several novel biomaterials to treat critical-sized bone injuries. However, despite significant improvement in synthetic materials research, some limitations still exist. The constraints correlated with the current grafting methods signify a treatment paradigm shift to osteoinductive regenerative engineering approaches. Because of their intrinsic potential, inductive biomaterials may represent alternative approaches to treating critical bone injuries. Osteoinductive scaffolds stimulate stem cell differentiation into the osteoblastic lineage, enhancing bone regeneration. Inductive biomaterials comprise polymers, calcium phosphate ceramics, metals, and graphene family materials. This review will assess the cellular behavior toward properties of inductive materials.

Rapid and accurate detection of phosphate (Pi) in complex biological fluid is of critical importance for timely warning of Pi accumulation and monitoring Pi related pathological process. Up to date, various luminescent probes have been developed for Pi determination in aqueous media. However, the huge obstacles of the current probes suffer from the inherent issues such as time-consuming, tedious preparation and unavoidable background interference during Pi detection. To circumvent this limitation, we proposed a universal and facile strategy to fabricate a novel sensitizer-Ln³⁺@surfactant micelle probe with time-resolved luminescent (TRL) superiority through the self-assembly of sensitizer, Ln³⁺ and surfactant. Through this design, the sensitizer-Ln³⁺ chelate can be encapsulated into the surfactant constructed micelle and Ln³⁺ luminescence can be substantially lighted up through the effective energy transfer from the coordinated sensitizer and the assistance of Triton X-100. Such high TRL signal can be sensitively and specifically quenched by Pi, which was attributed to the specific coordination competition between sensitizer and Pi towards Ln³⁺. Benefitting from the background-free interference and highly sensitive TRL response of the sensitizer-Ln³⁺@surfactant probe, we achieved the rapid, selective and sensitive detection of Pi in the range of 0.5-120 μM with a limit of detection (LOD) of 0.19 μM. Furthermore, the accuracy of the proposed method based on the Ln³⁺ involved micelle probes was further verified through the quantitation of Pi in real biological samples.

We have designed and synthesized a novel pyrene-naphthalene sulphonyl conjugate, 1-((1Z)-(4-((Z)-4-(pyrene-1-yl)methyleneamino)phenylsulfonyl)phenylimino)methyl)naphthalene-2-ol (PSN) through a facile two-step reactions. It was characterized by various spectral techniques. Fluorescence spectral studies showed that compound PSN featured fluorescence enhancement upon increasing the water content in THF. This can be attributed to the phenomena of aggregated induced emission (AIE), which is confirmed by SEM and AFM studies, due to the restriction of CHN isomerization of PSN. The anion sensing of PSN was examined with various anions. Among these anions, H₂PO₄^- and F^- ions were selectively sensing with a low detection limit of 3.52 × 10^-7 M and 7.23 × 10^-7 M, respectively, and an obvious color change from yellow to orange was observed by the naked eye. The mechanism of sensing involved the formation of hydrogen bonding interaction between O-H group of PSN and H₂PO₄^-/ F^- ions. The binding of PSN with LYZ was also examined by docking studies, which shows that H-bonding and hydrophobic interactions play crucial roles for the interaction of LYZ toward PSN.

Phosphorus, an essential nutrient, performs vital functions in skeletal and non-skeletal tissues and is pivotal for energy production. The last two decades of research on the physiological importance of phosphorus have provided several novel insights about its dynamic nature as a nutrient performing functions as a phosphate ion. Phosphorous also acts as a signaling molecule and induces complex physiological responses. It is recognized that phosphorus homeostasis is critical for health. The intake of phosphorus by the general population world-wide is almost double the amount required to maintain health. This increase is attributed to the incorporation of phosphate containing food additives in processed foods purchased by consumers. Research findings assessed the impact of excessive phosphorus intake on cells' and organs' responses, and highlighted the potential pathogenic consequences. Research also identified a new class of bioactive phosphates composed of polymers of phosphate molecules varying in chain length. These polymers are involved in metabolic responses including hemostasis, brain and bone health, via complex mechanism(s) with positive or negative health effects, depending on their chain length. It is amazing, that phosphorus, a simple element, is capable of exerting multiple and powerful effects. The role of phosphorus and its polymers in the renal and cardiovascular system as well as on brain health appear to be important and promising future research directions.

Nitrogen doped carbon dots (N-CDs) have been prepared via a one-pot hydrothermal method by using formamide and o-phenylenediamine as the carbon precursors. The as-fabricated N-CDs display excellent water dispersibility, good biocompatibility and anti-photobleaching properties. A strong emission band with an emission maximum (λ ^fl _max) of 556 nm is observed under 450 nm excitation, and a large Stokes shift of 106 nm is presented. However, the fluorescence is quenched by the addition of Fe³⁺; a good linearity is shown in the range of 0-65 μM with a detection limit as low as 0.85 μM. Fortunately, the quenched fluorescence could be recovered rapidly by the addition of monohydrogen phosphate (HPO₄ ^2-) due to the formation of the stable [N-CDs-Fe³⁺-HPO₄ ^2-] complex, and a good linearity is exhibited in the range of 0-60 μM with a low detection limit of 0.80 μM for HPO₄ ^2-. A novel "on-off-on" fluorescence response is seen with an obvious color change from yellow-crimson-yellow by the naked eye. In addition, the confocal microscopy images suggest that the as-synthesized N-CDs could serve as a sensitive nanosensor for Fe³⁺ and HPO₄ ^2- detection, implying the diverse potential application of N-CDs in the biomedical field.

Hyperphosphatemia, iron deficiency, and anemia are powerful stimuli of fibroblast growth factor 23 (FGF23) production and are highly prevalent complications of chronic kidney disease (CKD). In this manuscript, we put in perspective the newest insights on FGF23 regulation by iron and phosphate and their effects on CKD progression and associated outcomes. We especially focus on new studies aiming to reduce FGF23 levels, and we present new data that suggest major benefits of combined corrections of iron, phosphate, and FGF23 in CKD.

New studies show that simultaneously correcting iron deficiency and hyperphosphatemia in CKD reduces the magnitude of FGF23 increase. Promising therapies using iron-based phosphate binders in CKD might mitigate cardiac and renal injury and improve survival.

New strategies to lower FGF23 have emerged, and we discuss their benefits and risks in the context of CKD. Novel clinical and preclinical studies highlight the effects of phosphate restriction and iron repletion on FGF23 regulation.

Biphasic calcium phosphate (BCP) is a bioceramic material successfully used in alloplastic bone augmentation. Despite many advantages, a disadvantage of BCP seems to be a difficult application and position instability. The aim of this study was to determine how different carrier materials influence BCP-induced quantitative and qualitative bone regeneration.

A total of 70 critical size defects were set in the frontal bone of 14 domestic pigs (5 each) and filled randomly with either BCP alone (BCP), BCP in combination with nano-hydroxyapatite (BCP + NHA), BCP embedded in native porcine type I/III collagen blocks (BCP + C), autologous bone (AB), or were left empty (ED). Specimens were harvested after 4 and 8 weeks and were evaluated histologically as well as histomorphometrically.

Significantly lowest rate of new bone formation was found in ED (p = < 0.001) and BCP + NHA groups (p = 0.05). After 8 weeks, the highest percentage of new bone formation was observed in the BCP + C group. Fibrous matrix was detected highest in BCP alone. The lowest residual bone substitute material was found in BCP + C after 8 weeks.

BCP-induced bone regeneration is indeed affected by different carrier types. Surface morphology and bioactive characteristics influence osseointegration and new bone formation in vivo. The combination of type I/III collagen seems most suitable for qualitative and quantitative bone regeneration.

Stabilization of granular bone substitutes using type I/III collagen might be an alternative to granulates alone, indicating excellent volume stability, satisfactory plasticity, and easy application.

This study aimed to investigate the effect of solute carrier family 20 member 2 (SLC20A2) gene mutation (identified from a hereditary multiple exostoses family) on chondrocyte proliferation and differentiation.

ATDC5 chondrocytes were cultured in insulin-transferrin-selenium medium to induce differentiation. Cells were transfected with pcDNA3.0 plasmids with either a wild-type (WT) or mutated (MUT) SLC20A2 gene. The inorganic phosphate (Pi) concentration in the medium of cells was determined. The expression of markers of chondrocyte proliferation and differentiation, the Indian hedgehog (Ihh), and parathyroid hormone-related protein (PTHrP) pathway were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting.

The expression of SLC20A2 in MUT group was similar to WT group. The Pi concentration in the medium of cells in MUT group was significantly higher than WT group, which meant the SLC20A2 mutation inhibited Pi uptake in ATDC5 chondrocytes. The proliferation rate of ATDC5 chondrocytes in MUT group was greater than WT group. The expression of aggrecan (Acan), α-1 chain of type II collagen (COL2A1), and SRY-box transcription factor 9 (SOX9) were higher in MUT group than WT group. However, the expression of Runt-related transcription factor 2 (Runx2), α-1 chain of type X collagen (COL10A1), and matrix metallopeptidase 13 (MMP13) was significantly decreased in the MUT group. Similar results were obtained by Alcian blue and Alizarin red staining. The expression of Ihh and PTHrP in MUT group was higher than WT group. An inhibitor (cyclopamine) of Ihh/PTHrP signalling pathway inhibited the proliferation and restored the differentiation of chondrocytes in MUT group.

A mutation in SLC20A2 (c.C1948T) decreases Pi uptake in ATDC5 chondrocytes. SLC20A2 mutation promotes chondrocyte proliferation while inhibiting chondrocyte differentiation. The Ihh/PTHrP signalling pathway may play an important role in this process. Cite this article: Bone Joint Res 2020;9(11):751-760.

Bioceramics have experienced great development over the past 50 years. Modern bioceramics are designed to integrate bioactive ions within ceramic granules to trigger living tissue regeneration. Preclinical and clinical studies have shown that strontium is a safe and effective divalent metal ion for preventing osteoporosis, which has led to its incorporation in calcium phosphate-based ceramics. The local release of strontium ions during degradation results in moderate concentrations that trigger osteogenesis with few systemic side effects. Moreover, strontium has been proven to generate a favorable immune environment and promote early angiogenesis at the implantation site. Herein, the important aspects of strontium-enriched calcium phosphate bioceramics (Sr-CaPs), and how Sr-CaPs affect the osteogenic microenvironment, are described.

Ceramic materials such as calcium phosphates (CaPs) with a composition similar to the mineral phase of bones and polymeric polylactic acid (PLA) are potential candidates for the manufacturing of scaffolds to act as bone substitutes and for tissue engineering applications, due to their bioresorbability and biocompatibility. Variables such as porosity, topography, morphology, and mechanical properties play an essential role in the scaffolds response. In this paper, a polymer/ceramic composite filament of 1.7 mm in diameter based on PLA and biphasic calcium phosphates (BCPs) was obtained by hot-melt extrusion in a single screw extruder. The particles of BCP were obtained by solution-combustion synthesis, and the PLA used was commercial grade. The BCPs ceramics were characterized by X-ray diffraction (XRD), scanning electron microscopic (SEM), transmission electron microscopy (TEM), and Brunauer, Emmett, and Teller (BET). It was possible to confirm that the main inorganic phases were hydroxyapatite (HAP) and tricalcium phosphate (TCP) with grain sizes below 100 nm and with high porosity. The Filaments obtained are a bit fragile but were able to be used in fused deposition modelling (FDM) using low-cost commercial printers. The filaments were characterized by SEM and energy dispersive X-ray (EDX). The in-vitro tests of filaments showed deposition of apatite phases on their surface, non-cytotoxic behavior, adequate cell proliferation and cell adhesion.

In vitro electrochemical characterization and in vivo implantation in an animal model were employed to evaluate the degradation behaviour and the biological activity of FeMnSi and FeMnSiCa alloys obtained using UltraCast (Ar atmosphere) melting. Electrochemical characterization was based on open circuit potential measurement, electrochemical impedance spectroscopy and potentiodynamic polarization techniques while the alloys were immersed in Ringer's solution at 37 °C for 7 days. Higher corrosion rates were measured for the Ca-containing material, resulting from inefficient passivation of the metal surface by oxy-hydroxide products. In vivo osseointegration was investigated on a tibia implant model in rabbits by referring to a standard control (AISI 316 L) stainless steel using standard biochemical, histological and radiological methods of investigation. Changes in the biochemical parameters were related to the main stages of the bone defect repair, whereas implantation of the alloys in rabbit's tibia provided the necessary mechanical support to the injured bone area and facilitated the growth of the newly connective tissue, as well as osteoid formation and mineralization, as revealed by either histological sections or computed tomography reconstructed images and validated by the bone morphometric indices. The present study highlighted that the FeMnSiCa alloy promotes better osteoinduction and osseconduction processes when compared to the base FeMnSi alloy or with AISI 316 L, and in vivo degradation rates correlate well with corrosion resistance measurements in Ringer's solution.