Chromium nanoparticles improve bone turnover regulation in rats fed a high-fat, low-fibre diet.

The aim of the study was to investigate the effect of returning to a balanced diet combined with chromium picolinate (CrPic) or chromium nanoparticles (CrNPs) supplementation at a pharmacologically relevant dose of 0.3 mg/kg body weight on the expression level of selected genes and bone turnover markers in the blood and bones of rats fed an obese diet. The results of the study showed that chronic intake of a high-fat obesogenic diet negatively affects bone turnover by impairing processes of both synthesis and degradation of bones. The switch to a healthy diet proved insufficient to regulate bone metabolism disorders induced by an obesogenic diet, even when it was supplemented with chromium, irrespective of its form. Supplementation with CrPic with no change in diet stimulated bone metabolism only at the molecular level, towards increased osteoclastogenesis (bone resorption). In contrast, CrNPs added to the high-fat diet effectively regulated bone turnover by increasing both osteoblastogenesis and osteoclastogenesis, with these changes directed more towards bone formation. The results of the study suggest that unfavourable changes in bone metabolism induced by chronic intake of a high-fat diet can be mitigated by supplementation with CrNPs, whereas a change in eating habits fails to achieve a similar effect.

Fluorinated hydroxyapatite conditions a favorable osteo-immune microenvironment via triggering metabolic shift from glycolysis to oxidative phosphorylation.

BACKGROUND: Biological-derived hydroxyapatite is widely used as a bone substitute for addressing bone defects, but its limited osteoconductive properties necessitate further improvement. The osteo-immunomodulatory properties hold crucial promise in maintaining bone homeostasis, and precise modulation of macrophage polarization is essential in this process. Metabolism serves as a guiding force for immunity, and fluoride modification represents a promising strategy for modulating the osteoimmunological environment by regulating immunometabolism. In this context, we synthesized fluorinated porcine hydroxyapatite (FPHA), and has demonstrated its enhanced biological properties and osteogenic capacity. However, it remains unknown whether and how FPHA affects the immune microenvironment of the bone defects. METHODS: FPHA was synthesized and its composition and structural properties were confirmed. Macrophages were cultured with FPHA extract to investigate the effects of FPHA on their polarization and the related osteo-immune microenvironment. Furthermore, total RNA of these macrophages was extracted, and RNA-seq analysis was performed to explore the underlying mechanisms associated with the observed changes in macrophages. The metabolic states were evaluated with a Seahorse analyzer. Additionally, immunohistochemical staining was performed to evaluate the macrophages response after implantation of the novel bone substitutes in critical size calvarial defects in SD rats. RESULTS: The incorporation of fluoride ions in FPHA was validated. FPHA promoted macrophage proliferation and enhanced the expression of M2 markers while suppressing the expression of M1 markers. Additionally, FPHA inhibited the expression of inflammatory factors and upregulated the expression of osteogenic factors, thereby enhancing the osteogenic differentiation capacity of the rBMSCs. RNA-seq analysis suggested that the polarization-regulating function of FPHA may be related to changes in cellular metabolism. Further experiments confirmed that FPHA enhanced mitochondrial function and promoted the metabolic shift of macrophages from glycolysis to oxidative phosphorylation. Moreover, in vivo experiments validated the above results in the calvarial defect model in SD rats. CONCLUSION: In summary, our study reveals that FPHA induces a metabolic shift in macrophages from glycolysis to oxidative phosphorylation. This shift leads to an increased tendency toward M2 polarization in macrophages, consequently creating a favorable osteo-immune microenvironment. These findings provide valuable insights into the impact of incorporating an appropriate concentration of fluoride on immunometabolism and macrophage mitochondrial function, which have important implications for the development of fluoride-modified immunometabolism-based bone regenerative biomaterials and the clinical application of FPHA or other fluoride-containing materials.

Compositional, Structural, and Biomechanical Properties of Three Different Soft Tissue-Hard Tissue Insertions: A Comparative Review.

Connective tissue attaches to bone across an insertion with spatial gradients in components, microstructure, and biomechanics. Due to regional stress concentrations between two mechanically dissimilar materials, the insertion is vulnerable to mechanical damage during joint movements and difficult to repair completely, which remains a significant clinical challenge. Despite interface stress concentrations, the native insertion physiologically functions as the effective load-transfer device between soft tissue and bone. This review summarizes tendon, ligament, and meniscus insertions cross-sectionally, which is novel in this field. Herein, the similarities and differences between the three kinds of insertions in terms of components, microstructure, and biomechanics are compared in great detail. This review begins with describing the basic components existing in the four zones (original soft tissue, uncalcified fibrocartilage, calcified fibrocartilage, and bone) of each kind of insertion, respectively. It then discusses the microstructure constructed from collagen, glycosaminoglycans (GAGs), minerals and others, which provides key support for the biomechanical properties and affects its physiological functions. Finally, the review continues by describing variations in mechanical properties at the millimeter, micrometer, and nanometer scale, which minimize stress concentrations and control stretch at the insertion. In summary, investigating the contrasts between the three has enlightening significance for future directions of repair strategies of insertion diseases and for bioinspired approaches to effective soft-hard interfaces and other tough and robust materials in medicine and engineering.

Predictive value of bone turnover markers and thyroid indicators for bone metabolism in GD patients after treatment.

Purpose: To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively. Methods: We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT3 and FT4 before and after treatment (FT3-P/FT3-A, FT4-P/FT4-A) on whether BTMs recovered. Results: The levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT3-P/FT3-A and FT4-P/FT4-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05). Conclusion: BTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT3 decreased more than 51% and FT4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD.

Reservoir Computing Based on Oxygen-Vacancy-Mediated X-ray Optical Synaptic Device for Medical CT Bone Diagnosis.

Recognition and judgment of X-ray computed tomography (CT) images play a crucial role in medical diagnosis and disease prevention. However, the storage and calculation of the X-ray imaging system applied in the traditional CT diagnosis is separate, and the pathological judgment is based on doctors' experience, which will affect the timeliness and accuracy of decision-making. In this paper, a simple-structured reservoir computing network (RC) is proposed based on Ga2O3 X-ray optical synaptic devices to recognize medical skeletal CT images with high accuracy. Through oxygen vacancy engineering, Ga2O3 X-ray optical synaptic devices with adjustable photocurrent gain and a persistent photoconductivity effect were obtained. By using the Ga2O3 X-ray optical synaptic device as a reservoir, we constructed an RC network for medical skeletal CT diagnosis and verified its image recognition capability using the MNIST data set with an accuracy of 78.08%. In the elbow skeletal CT image recognition task, the recognition rate is as high as 100%. This work constructs a simple-structured RC network for X-ray image recognition, which is of great significance in applications in medical fields.

SIRT1 maintains bone homeostasis by regulating osteoblast glycolysis through GOT1.

The silent information regulator T1 (SIRT1) is linked to longevity and is a crucial mediator of osteoblast function. We investigated the direct role of Sirt1 during bone modeling and remodeling stages in vivo using Tamoxifen-inducible osteoblast-specific Sirt1 conditional knockout (cKO) mice. cKO mice exhibited lower trabecular and cortical bone mass in the distal femur. These phenotypes were coupled with lower bone formation and bone resorption. Metabolomics analysis revealed that the metabolites involved in glycolysis were significantly decreased in cKO mice. Further analysis of the quantitative acetylome revealed 11 proteins with upregulated acetylation levels in both the femur and calvaria of cKO mice. Cross-analysis identified four proteins with the same upregulated lysine acetylation site in both the femur and calvaria of cKO mice. A combined analysis of the metabolome and acetylome, as well as immunoprecipitation, gene knockout, and site-mutation experiments, revealed that Sirt1 deletion inhibited glycolysis by directly binding to and increasing the acetylation level of Glutamine oxaloacetic transaminase 1 (GOT1). In conclusion, our study suggested that Sirt1 played a crucial role in regulating osteoblast metabolism to maintain bone homeostasis through its deacetylase activity on GOT1. These findings provided a novel insight into the potential targeting of osteoblast metabolism for the treatment of bone-related diseases.

Study of biphasic calcium phosphate (BCP) ceramics of tilapia fish bones by age.

Biphasic calcium phosphate (BCP), consisting of bioceramics such as HAp + ß-TCP and Ca10(PO4)6(OH)2 + Ca3(PO4)2, is a popular choice for optimizing performance due to its superior biological reabsorption and osseointegration. In this study, BCP was produced by calcining the bones of tilapia fish (Oreochromis niloticus) reared in net cages and slaughtered at an age ranging from 15 to 420 days. The bones were cleaned and dried, calcined at 900 °C for 8 h, and then subjected to high-energy grinding for 3 h to produce BCP powders. After the calcination process, the crystalline phase's hydroxyapatite (HAp) and/or beta-tricalcium phosphate (ß-TCP) were present in the composition of the bioceramic. The age-dependent variation in phase composition was confirmed by complementary vibrational spectroscopy techniques, revealing characteristic peaks and bands of the bioceramic. This variation was marked by an increase in HAp phase and a decrease in ß-TCP phase. Thermogravimetric Analysis (TGA) and Differential Thermal Analysis (DTA) from 25 to 1400 °C showed the characteristic mass losses of the material, with a greater loss observed for younger fish, indicating the complete removal of organic components at temperatures above 600 °C. Comparison of the results obtained by X-Ray Diffraction (XRD) and Rietveld refinement with Raman spectroscopy showed excellent agreement. These results showed that with temperature and environment control and adequate fish feeding, it is possible to achieve the desired amounts of each phase by choosing the ideal age of the fish. This bioceramic enables precise measurement of HAp and ß-TCP concentrations and Ca/P molar ratio, suitable for medical orthopedics and dentistry.

Methods to Enable Spatial Transcriptomics of Bone Tissues.

Understanding the relationship between the cells and their location within each tissue is critical to uncover the biological processes associated with normal development and disease pathology. Spatial transcriptomics is a powerful method that enables the analysis of the whole transcriptome within tissue samples, thus providing information about the cellular gene expression and the histological context in which the cells reside. While this method has been extensively utilized for many soft tissues, its application for the analyses of hard tissues such as bone has been challenging. The major challenge resides in the inability to preserve good quality RNA and tissue morphology while processing the hard tissue samples for sectioning. Therefore, a method is described here to process freshly obtained bone tissue samples to effectively generate spatial transcriptomics data. The method allows for the decalcification of the samples, granting successful tissue sections with preserved morphological details while avoiding RNA degradation. In addition, detailed guidelines are provided for samples that were previously paraffin-embedded, without demineralization, such as samples collected from tissue banks. Using these guidelines, high-quality spatial transcriptomics data generated from tissue bank samples of primary tumor and lung metastasis of bone osteosarcoma are shown.

Non-Classical Effects of FGF23: Molecular and Clinical Features.

This article reviews the role of fibroblast growth factor 23 (FGF23) protein in phosphate metabolism, highlighting its regulation of vitamin D, parathyroid hormone, and bone metabolism. Although it was traditionally thought that phosphate-calcium homeostasis was controlled exclusively by parathyroid hormone (PTH) and calcitriol, pathophysiological studies revealed the influence of FGF23. This protein, expressed mainly in bone, inhibits the renal reabsorption of phosphate and calcitriol formation, mediated by the α-klotho co-receptor. In addition to its role in phosphate metabolism, FGF23 exhibits pleiotropic effects in non-renal systems such as the cardiovascular, immune, and metabolic systems, including the regulation of gene expression and cardiac fibrosis. Although it has been proposed as a biomarker and therapeutic target, the inhibition of FGF23 poses challenges due to its potential side effects. However, the approval of drugs such as burosumab represents a milestone in the treatment of FGF23-related diseases.

Natural Compounds for Bone Remodeling: A Computational and Experimental Approach Targeting Bone Metabolism-Related Proteins.

Osteoporosis, characterized by reduced bone density and increased fracture risk, affects over 200 million people worldwide, predominantly older adults and postmenopausal women. The disruption of the balance between bone-forming osteoblasts and bone-resorbing osteoclasts underlies osteoporosis pathophysiology. Standard treatment includes lifestyle modifications, calcium and vitamin D supplementation and specific drugs that either inhibit osteoclasts or stimulate osteoblasts. However, these treatments have limitations, including side effects and compliance issues. Natural products have emerged as potential osteoporosis therapeutics, but their mechanisms of action remain poorly understood. In this study, we investigate the efficacy of natural compounds in modulating molecular targets relevant to osteoporosis, focusing on the Mitogen-Activated Protein Kinase (MAPK) pathway and the gut microbiome's influence on bone homeostasis. Using an in silico and in vitro methodology, we have identified quercetin as a promising candidate in modulating MAPK activity, offering a potential therapeutic perspective for osteoporosis treatment.

Vitamin A - discovery, metabolism, receptor signaling and effects on bone mass and fracture susceptibility.

The first evidence of the existence of vitamin A was the observation 1881 that a substance present in small amounts in milk was necessary for normal development and life. It was not until more than 100 years later that it was understood that vitamin A acts as a hormone through nuclear receptors. Unlike classical hormones, vitamin A cannot be synthesized by the body but needs to be supplied by the food as retinyl esters in animal products and ß-carotene in vegetables and fruits. Globally, vitamin A deficiency is a huge health problem, but in the industrialized world excess of vitamin A has been suggested to be a risk factor for secondary osteoporosis and enhanced susceptibility to fractures. Preclinical studies unequivocally have shown that increased amounts of vitamin A cause decreased cortical bone mass and weaker bones due to enhanced periosteal bone resorption. Initial clinical studies demonstrated a negative association between intake of vitamin A, as well as serum levels of vitamin A, and bone mass and fracture susceptibility. In some studies, these observations have been confirmed, but in other studies no such associations have been observed. One meta-analysis found that both low and high serum levels of vitamin A were associated with increased relative risk of hip fractures. Another meta-analysis also found that low levels of serum vitamin A increased the risk for hip fracture but could not find any association with high serum levels of vitamin A and hip fracture. It is apparent that more clinical studies, including large numbers of incident fractures, are needed to determine which levels of vitamin A that are harmful or beneficial for bone mass and fracture. It is the aim of the present review to describe how vitamin A was discovered and how vitamin A is absorbed, metabolized and is acting as a ligand for nuclear receptors. The effects by vitamin A in preclinical studies are summarized and the clinical investigations studying the effect by vitamin A on bone mass and fracture susceptibility are discussed in detail.

Circadian Regulation of Bone Remodeling.

Adult bones are continuously remodeled by the balance between bone resorption by osteoclasts and subsequent bone formation by osteoblasts. Many studies have provided molecular evidence that bone remodeling is under the control of circadian rhythms. Circadian fluctuations have been reported in the serum and urine levels of bone turnover markers, such as digested collagen fragments and bone alkaline phosphatase. Additionally, the expressions of over a quarter of all transcripts in bones show circadian rhythmicity, including the genes encoding master transcription factors for osteoblastogenesis and osteoclastogenesis, osteogenic cytokines, and signaling pathway proteins. Serum levels of calcium, phosphate, parathyroid hormone, and calcitonin also display circadian rhythmicity. Finally, osteoblast- and osteoclast-specific knockout mice targeting the core circadian regulator gene Bmal1 show disrupted bone remodeling, although the results have not always been consistent. Despite these studies, however, establishing a direct link between circadian rhythms and bone remodeling in vivo remains a major challenge. It is nearly impossible to repeatedly collect bone materials from human subjects while following circadian changes. In addition, the differences in circadian gene regulation between diurnal humans and nocturnal mice, the main model organism, remain unclear. Filling the knowledge gap in the circadian regulation of bone remodeling could reveal novel regulatory mechanisms underlying many bone disorders including osteoporosis, genetic diseases, and fracture healing. This is also an important question for the basic understanding of how cell differentiation progresses under the influence of cyclically fluctuating environments.

Life histories in Fiji as reconstructed from first millennium CE Sigatoka Sand Dune burials using isotopes.

This paper aims to re-examine the dietary practices of individuals buried at Sigatoka Sand Dunes site (Fiji) in Burial Ground 1 excavated by Simon Best in 1987 and 1988 using two approaches and a reassessment of their archaeological, bioarchaeological and chronological frame. First, stable carbon and nitrogen isotope analysis was applied to document dietary changes between childhood and adulthood using an intra-individual approach on paired bone-tooth. Second, the potential adaptation of the individuals to their environment was evaluated through regional and temporal comparisons using inter-individual bone analysis. Ten AMS radiocarbon dates were measured directly on human bone collagen samples, placing the series in a range of approximately 600 years covering the middle of the first millennium CE (1,888 to 1,272 cal BP). δ13C and δ15N ratios were measured on bone and tooth collagen samples from 38 adult individuals. The results show that δ15N values from tooth are higher than those s from bone while bone and tooth δ13C values are similar, except for females. Fifteen individuals were included in an intra-individual analysis based on paired bone and tooth samples, which revealed six dietary patterns distinguished by a differential dietary intake of marine resources and resources at different trophic levels. These highlight sex-specific differences not related to mortuary practices but to daily life activities, supporting the hypothesis of a sexual division of labour. Compared to other Southwest Pacific series, Sigatoka diets show a specific trend towards marine food consumption that supports the hypothesis of a relative food self-sufficiency requiring no interactions with other groups.

O-GlcNAcylation: roles and potential therapeutic target for bone pathophysiology.

O-linked N-acetylglucosamine (O-GlcNAc) protein modification (O-GlcNAcylation) is a critical post-translational modification (PTM) of cytoplasmic and nuclear proteins. O-GlcNAcylation levels are regulated by the activity of two enzymes, O-GlcNAc transferase (OGT) and O­GlcNAcase (OGA). While OGT attaches O-GlcNAc to proteins, OGA removes O-GlcNAc from proteins. Since its discovery, researchers have demonstrated O-GlcNAcylation on thousands of proteins implicated in numerous different biological processes. Moreover, dysregulation of O-GlcNAcylation has been associated with several pathologies, including cancers, ischemia-reperfusion injury, and neurodegenerative diseases. In this review, we focus on progress in our understanding of the role of O-GlcNAcylation in bone pathophysiology, and we discuss the potential molecular mechanisms of O-GlcNAcylation modulation of bone-related diseases. In addition, we explore significant advances in the identification of O-GlcNAcylation-related regulators as potential therapeutic targets, providing novel therapeutic strategies for the treatment of bone-related disorders.

Alterations in regulators of the renal-bone axis, inflammation and iron status in older people with early renal impairment and the effect of vitamin D supplementation.

CONTEXT: Chronic kidney disease (CKD) leads to alterations in fibroblast growth factor 23 (FGF23) and the renal-bone axis. This may be partly driven by altered inflammation and iron status. Vitamin D supplementation may reduce inflammation. OBJECTIVE AND METHODS: Older adults with early CKD (estimated glomerular filtration rate (eGFR) 30-60 ml/min/1.73 m2; CKDG3a/b; n = 35) or normal renal function (eGFR >90 ml/min/1.73 m2; CKDG1; n = 35) received 12,000, 24,000 or 48,000 IU D3/month for 1 year. Markers of the renal-bone axis, inflammation and iron status were investigated pre- and post-supplementation. Predictors of c-terminal and intact FGF23 (cFGF23; iFGF23) were identified by univariate and multivariate regression. RESULTS: Pre-supplementation, comparing CKDG3a/b to CKDG1, plasma cFGF23, iFGF23, PTH, sclerostin and TNFα were significantly higher and Klotho, 1,25-dihydroxyvitamin D and iron were lower. Post-supplementation, only cFGF23, 25(OH)D and IL6 differed between groups. The response to supplementation differed between eGFR groups. Only in the CKDG1 group, phosphate decreased, cFGF23, iFGF23 and procollagen type I N-propeptide increased. In the CKDG3a/b group, TNFα significantly decreased, and iron increased. Plasma 25(OH)D and IL10 increased, and carboxy-terminal collagen crosslinks decreased in both groups. In univariate models cFGF23 and iFGF23 were predicted by eGFR and regulators of calcium and phosphate metabolism at both time points; IL6 predicted cFGF23 (post-supplementation) and iFGF23 (pre-supplementation) in univariate models. Hepcidin predicted post-supplementation cFGF23 in multivariate models with eGFR. CONCLUSION: Alterations in regulators of the renal-bone axis, inflammation and iron status were found in early CKD. The response to vitamin D3 supplementation differed between eGFR groups. Plasma IL6 predicted both cFGF23 and iFGF23 and hepcidin predicted cFGF23.

Carrion insects living within the bones of large mammals: insect conservation and forensic entomology implications.

Succession patterns of carrion insects on large mammal's carrion has been widely studied, notably to estimate the post-mortem interval in forensic investigations as accurately as possible. However, little attention has been paid to the carrion insects living inside these bones once a carcass is skeletonized. One very recent study documented flies emerging from pig carcasses, and only scarce authors reported the presence of other carrion insects taking advantage of the bone marrow. We, thus, aimed to (1) estimate the frequency of inner-bone space colonization by carrion insects, with particular attention to bone-skipper flies; (2) identify the insects living inside the carrion bones; and (3) determine whether or not carrion insects found within the bones can successfully exit the bones and complete their development. We extensively sampled 185 large mammals' bones collected from twelve vulture feeding stations and four isolated carcasses in southwest France and northern Spain. Sampled bones were opened, and the insects found inside were identified. For two bones, foramen, i.e., the holes providing a natural entrance and exit to the bone's inner cavity, was monitored with a camera to assess the insect's putative exit. We describe the entomofauna, i.e., the set of insect species, living within the bones, and illustrate insects' ability to exit the bones for their subsequent development and maturity. These results are discussed in the framework of carrion insect conservation and forensic entomology perspectives.

Unravelling social status in the first medieval military order of the Iberian Peninsula using isotope analysis.

Medieval Iberia witnessed the complex negotiation of religious, social, and economic identities, including the formation of religious orders that played a major role in border disputes and conflicts. While archival records provide insights into the compositions of these orders, there have been few direct dietary or osteoarchaeological studies to date. Here, we analysed 25 individuals discovered at the Zorita de los Canes Castle church cemetery, Guadalajara, Spain, where members of one of the first religious orders, the Order of Calatrava knights, were buried between the 12th to 15th centuries CE. Stable carbon (δ13C) and nitrogen (δ15N) isotope analyses of bone collagen reveal dietary patterns typical of the Medieval social elite, with the Bayesian R model, 'Simmr' suggesting a diet rich in poultry and marine fish in this inland population. Social comparisons and statistical analyses further support the idea that the order predominantly comprised the lower nobility and urban elite in agreement with historical sources. Our study suggests that while the cemetery primarily served the order's elite, the presence of individuals with diverse dietary patterns may indicate complexities of temporal use or wider social interaction of the medieval military order.

Diets, stress, and disease in the Etruscan society: Isotope analysis and infantile skeletal palaeopathology from Pontecagnano (Campania, southern Italy, 730-580 BCE).

Susceptibility to morbidity and mortality is increased in early life, yet proactive measures, such as breastfeeding and weaning practices, can be taken through specific investments from parents and wider society. The extent to which such biosocialcultural investment was achieved within 1st millennium BCE Etruscan society, of whom little written sources are available, is unkown. This research investigates life histories in non-adults and adults from Pontecagnano (southern Italy, 730-580 BCE) in order to track cross-sectional and longitudinal breastfeeding and weaning patterns and to characterize the diet more broadly. Stable carbon and nitrogen isotope analysis of incrementally-sampled deciduous and permanent dentine (n = 15), bulk bone collagen (n = 38), and tooth enamel bioapatite (n = 21) reveal the diet was largely based on C3 staple crops with marginal contributions of animal protein. Millet was found to play a role for maternal diet and trajectories of breastfeeding and feeding for some infants and children at the site. The combination of multiple isotope systems and tissues demonstrates exclusive breastfeeding was pursued until 0.6 years, followed by progressive introduction of proteanocius supplementary foods during weaning that lasted between approximately 0.7 and 2.6 years. The combination of biochemical data with macroscopic skeletal lesions of infantile metabolic diseases and physiological stress markers showed high δ15Ndentine in the months prior to death consistent with the isotopic pattern of opposing covariance.

Research progress on the application of magnesium phosphate bone cement in bone defect repair: A review.

BACKGROUND: Bone defects arising from diverse causes, such as traffic accidents, contemporary weapon usage, and bone-related disorders, present significant challenges in clinical treatment. Prolonged treatment cycles for bone defects can result in complications, impacting patients' overall quality of life. Efficient and timely repair of bone defects is thus a critical concern in clinical practice. OBJECTIVE: This study aims to assess the scientific progress and achievements of magnesium phosphate bone cement (MPC) as an artificial bone substitute material. Additionally, the research seeks to explore the future development path and clinical potential of MPC bone cement in addressing challenges associated with bone defects. METHODS: The study comprehensively reviews MPC's performance, encompassing e.g. mechanical properties, biocompatibility, porosity, adhesion and injectability. Various modifiers are also considered to broaden MPC's applications in bone tissue engineering, emphasizing drug-loading performance and antibacterial capabilities, which meet clinical diversification requirements. RESULTS: In comparison to alternatives such as autogenous bone transplantation, allograft, polymethyl methacrylate (PMMA), and calcium phosphate cement (CPC), MPC emerges as a promising solution for bone defects. It addresses limitations associated with these alternatives, such as immunological rejection and long-term harm to patients. MPC can control heat release during the curing process, exhibits superior mechanical strength, and has the capacity to stimulate new bone growth. CONCLUSION: MPC stands out as an artificial bone substitute with appropriate mechanical strength, rapid degradation, non-toxicity, and good biocompatibility, facilitating bone repair and regeneration. Modification agents can enhance its clinical versatility. Future research should delve into its mechanical properties and formulations, expanding clinical applications to create higher-performing and more medically valuable alternatives in bone defect repair.

Silk fibroin sponge impregnated with fish bone collagen: A promising wound healing scaffold and skin tissue regeneration.

In the present study, porous silk fibroin sponges (SFS) were prepared using silk fibroin (SF), fish bone collagen (FBC), and olive oil (OO). The study investigates the potential use of using this sponge as skin tissue regeneration. The sponge was characterized for its physicochemical, mechanical, antimicrobial, and drug release properties. An in vitro study was carried out using human keratinocyte cell line (HaCaT). Biodegradation study using enzymatic method was carried out. The results showed that the mechanical properties such as tensile strength (23.40 ± 0.05 MPa), elongation at break (14.25 ± 0.02%), and water absorption (30.23 ± 0.01%) of the SFS were excellent, indicating promising performance. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays proved the biocompatible nature of the SFS. The SFS exhibited outstanding antibacterial properties against E. coli (4.72 ± 0.05 mm) and S. aureus (4.98 ± 0.07 mm). The developed SFS promote a promising solution for skin tissue regeneration and wound dressing.