负载氯喹的骨靶向纳米颗粒打破肿瘤细胞增殖与骨吸收之间的恶性循环

肿瘤细胞增殖与骨吸收之间的恶性循环加剧了骨肿瘤的进展和转移风险.为此,我们设计并制备了聚乙二醇-阿仑膦酸钠修饰的聚多巴胺(PPA)纳米粒子,并在其表面负载自噬抑制剂氯喹(CQ),期望利用该治疗载体(PPA/CQ)打破肿瘤细胞增殖与骨吸收之间的恶性循环,从而有效地治疗骨肿瘤.实验证明,PPA/CQ可以有效地富集到骨组织,...     

Nutritional Calcium Supply Dependent Calcium Balance,Bone Calcification and Calcium Isotope Ratios in Rats

Serum calcium isotopes (δ^44/42Ca) have been suggested as a non-invasive and sensitive Ca balance marker. Quantitative δ^44/42Ca changes associated with Ca flux across body compartment barriers relative to the dietary Ca and the correlation of δ^44/42Ca_Serum with bone histology are unknown. We analyzed Ca and δ^44/42Ca by mass-spectrometry in rats after two weeks of standard-Ca-diet (0.5%) and after four subsequent weeks of standard- and of low-Ca-diet (0.25%). In animals on a low-Ca-diet net Ca gain was 61 ± 3% and femur Ca content 68 ± 41% of standard-Ca-diet, bone mineralized area per section area was 68 ± 15% compared to standard-Ca-diet. δ^44/42Ca was similar in the diets, and decreased in feces and urine and increased in serum in animals on low-Ca-diet. δ^44/42Ca_Bone was higher in animals on low-Ca-diet, lower in the diaphysis than the metaphysis and epiphysis, and unaffected by gender. Independent of diet, δ^44/42Ca_Bone was similar in the femora and ribs. At the time of sacrifice, δ^44/42Ca_Serum inversely correlated with intestinal Ca uptake and histological bone mineralization markers, but not with Ca content and bone mineral density by µCT. In conclusion, δ^44/42Ca_Bone was bone site specific, but mechanical stress and gender independent. Low-Ca-diet induced marked changes in feces, serum and urine δ^44/42Ca in growing rats. δ^44/42Ca_Serum inversely correlated with markers of bone mineralization.     

Morphological and Biological Evaluations of Human Periodontal Ligament Fibroblasts in Contact with Different Bovine Bone Grafts Treated with Low-Temperature Deproteinisation Protocol

Several types of deproteinised bovine bone mineral (DBBM) are available on the market, and each one is obtained with a thermic and chemical process that can differ, achieving different results. Currently, several protocols using low temperature are suggested to reduce the possible particle crystallisation during the production process. This study aimed to evaluate the biomorphological reaction of periodontal fibroblast cultures in contact with different DBBM particles treated with a low-temperature protocol (Thermagen^®) and without exposure to sodium hydroxide (NaOH). Morphological evaluation was performed using light, confocal laser, and scanning electron microscopy, and the biological reaction in terms of proliferation was performed using an XTT proliferation assay at 24 h (T1), 72 h (T2), and 7 days (T3). The morphological analysis highlighted how the presence of the materials stimulated a change in the morphology of the cells into a polygonal shape, surface reactions with the thickening of the membrane, and expression of actin. In particular, the morphological changes were appreciable from T1, with a progressive increase in the considered morphological characteristics at T2 and T3 follow-ups. The proliferation assay showed a statistical significance between the different experimental materials and the negative control in T2 and T3 follow-ups. The post hoc analysis did not reveal any differences between the materials. In conclusion, the grafts obtained with the low-temperature extractions protocol and not exposed to NaOH solution showed positive morphological reactions with no differences in the sizes of particles.     

Structural Analysis of Mitochondrial Dynamics—From Cardiomyocytes to Osteoblasts: A Critical Review

Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options.     

The EPH/Ephrin System in Bone and Soft Tissue Sarcomas’ Pathogenesis and Therapy: New Advancements and a Literature Review

Musculoskeletal sarcomas represent rare heterogenous malignancies of mesenchymal origin that can be divided in two distinct subtypes, bone and soft tissue sarcomas. Current treatment options combine the surgical excision of local tumors and multidrug chemotherapy to prevent metastatic widespread disease. Due to the grim prognosis that usually accompanies such tumors, researchers have attempted to shed light on the molecular pathways implicated in their pathogenesis in order to develop novel, innovative, personalized therapeutic strategies. Erythropoietin-producing human hepatocellular receptors (EPHs) are tyrosine-kinase transmembrane receptors that, along with their ligands, ephrins, participate in both tumor-suppressive or tumor-promoting signaling pathways in bone and soft tissue sarcomas. The EPH/ephrin axis orchestrates cancerous processes such as cell–cell and cell–substrate adhesion and enhances the remodeling of the intracellular cytoskeleton to stimulate the motility and invasiveness of sarcoma cells. The purpose of our study was to review published PubMed literature to extract results from in vitro, in vivo and clinical trials indicative of the role of EPH/ephrin signaling in bone and soft tissue sarcomas. Based on these reports, significant interactions between the EPH/ephrin signaling pathway and a plethora of normal and abnormal cascades contribute to molecular mechanisms enhancing malignancy during sarcoma progression. In addition, EPHs and ephrins are prospective candidates for diagnostic, monitoring and therapeutic purposes in the clinical setting against bone and soft tissue sarcomas.     

A Hierarchical 3D Graft Printed with Nanoink for Functional Craniofacial Bone Restoration

An ideal craniofacial bone repair graft shall not only focus on the repair ability but also the regeneration of natural architecture with occlusal loads-related function restoration. However, such functional bone tissue engineering scaffold has rarely been reported. Herein, a hierarchical 3D graft is proposed for rebuilding craniofacial bone with both natural structure and healthy biofunction reconstruction. Inspired by the bone healing process, an organic–inorganic nanoink with ultrasmall calcium phosphate oligomers and bone morphogenetic protein-2 incorporated is developed for spatiotemporal guidance of new bone. Based on such homogeneous nanoink, a biomimetic graft, including a cortical layer containing Haversian system, and a cancellous layer featured with triply periodic minimum surface macrostructures, is fabricated via projection-based 3D printing method, and the layers are loaded with distinct concentrations of bioactive factors for regenerating new bone with gradient density. The graft exhibits excellent osteogenic and angiogenic potential in vitro, and accelerates revascularization and reconstructs neo-bone with original morphology in vivo. Benefiting from such natural architecture, loading force is widely transferred with reduced stress concentration around the inserted dental implant. Taken from native physiochemical and structural cues, this wstudy provides a novel strategy for functional tissue engineering through designing function-oriented biomaterials.     

喷雾热解法制备功能材料研究进展

综合评述了喷雾热解技术在超导陶瓷、介质材料、固体燃料电池电极、催化剂、磁性材料、人工骨材料以及气体传感器薄膜等领域的研究进展,并指出了进一步发展的方向。     

海珊瑚在不同酸性条件处理下的微结构研究

本文利用扫描电镜（ＳＥＭ）观察了滨珊瑚和角孔现瑚及它们在不同酸性条件处理下的形貌和显微结构变化,并对角孔珊瑚进行了溶解失重分析。实验结果表明,为了保持珊瑚天然的微结构,以作为制备人工骨的材料,对其进行了处理环境的环境ｐＨ值不能小于３。     

Spatiotemporal Magnetocaloric Microenvironment for Guiding the Fate of Biodegradable Polymer Implants

The degradation behavior of implants is significantly important for bone repair. However, it is still unprocurable to spatiotemporally regulate the degradation of the implants to match bone ingrowth. In this paper, a magneto-controlled biodegradation model is established to explore the degradation behavior of magnetic scaffolds in a magnetothermal microenvironment generated by an alternating magnetic field (AMF). The results demonstrate that the scaffolds can be heated by magnetic nanoparticles (NPs) under AMF, which dramatically accelerated scaffold degradation. Especially, magnetic NPs modified by oleic acid with a better interface compatibility exhibit a greater heating efficiency to further facilitate the degradation. Furthermore, the molecular dynamics simulations reveal that the enhanced motion correlation between magnetic NPs and polymer matrix can accelerate the energy transfer. As a proof-of-concept, the feasibility of magneto-controlled degradation for implants is demonstrated, and an optimizing strategy for better heating efficiency of nanomaterials is provided, which may have great instructive significance for clinical medicine.