The effect of 90, 180 and 270 mEq/kg of the calcium sequestering salts (CSS) disodium phosphate (DSP), trisodium citrate (TSC) and sodium hexametaphosphate (SHMP) on the solubilisation of proteins and minerals and the rheological and textural properties of processed cheese (PC) prepared from Gouda cheese ripened for 30-150 d at 8°C was studied. The solubilisation of individual caseins and Ca and the maximum loss tangent during temperature sweeps of PC made from Gouda cheese increased, while hardness of PC decreased with ripening duration of the Gouda cheese. Levels of soluble Ca in PC increased with increasing concentration of TSC and SHMP, but decreased with increasing concentration of DSP. The solubilisation of casein and Ca due to ripening of Gouda cheese used for manufacturing PC could explain the changes in texture and loss tangent of PC. The results suggest that DSP, TSC or SHMP in PC formulation can form insoluble Ca-phosphate, soluble Ca-citrate or insoluble casein-Ca-HMP complexes, respectively, that influence casein solubilisation differently and together with levels of residual intact casein determine the functional attributes of PC.

Only few excipients are known to be suitable as pelletization aids. In this study, the potential use of croscarmellose sodium (CCS) as pelletization aid was investigated. Furthermore, the impact of cations on extrusion-spheronization (ES) of CCS was studied and different grades of CCS were tested. The influence of different cations on the swelling of CCS was investigated by laser diffraction. Mixtures of CCS with lactose monohydrate as filler with or without the inclusion of different cations were produced. The mixtures were investigated by mixer torque rheometry and consequently extruded and spheronized. Resulting pellets were analyzed by dynamic image analysis. In addition, mixtures of different CCS grades with dibasic calcium phosphate anhydrous (DP) and a mixture with praziquantel (PZQ) as filler were investigated. Calcium and magnesium cations caused a decrease of the swelling of CCS and influenced the use of CCS as pelletization aid since they needed to be included for successful ES. Aluminum, however, led to an aggregation of the CCS particles and to failure of extrusion. The inclusion of cations decreased the uptake of water by the mixtures which also reduced the liquid-to-solid-ratio (L/S) for successful ES. This was shown to be dependent on the amount of divalent cations in the mixture. With DP or PZQ as filler, no addition of cations was necessary for a successful production of pellets, however the optimal L/S for ES was dependent on the CCS grade used. In conclusion, CCS can be used as a pelletization aid.

BACKGROUND: Dental caries is a dynamic process. By using therapeutic agents, early, noncavitated lesions and caries limited to the enamel can be stopped or even remineralized. For the remineralization of the initial carious lesion, many nonfluoridated remineralizing agents were investigated.
OBJECTIVE: An observational study to assess the remineralizing efficacy of tricalcium phosphate (TCP), nano-hydroxyapatite (nHAp) and ozone remineralizing agents on the artificial carious lesion.
METHODS: In this observational research, the artificial carious lesion was produced on extracted 40 premolar teeth. Later, remineralizing agents (Group A: nHAp, Group B: TCP, Group C: Ozone remineralizing agents, Group D: Control group (Deionized water) were used to remineralize demineralized teeth. Utilizing the Vickers Hardness Number, the level of demineralization and remineralization was assessed. Later these readings were statistically assessed using the Tukey\'s HSD (honestly significant difference) and ANOVA tests in SPSS version 21.0. The P value was set at 0.05 or less.
RESULTS: After demineralization, there was a decrease in enamel microhardness values, with 32% in Group A, 26% in Group B, 22% in Group C, and 21% in Group D, respectively. From the baseline to demineralization, there was a statistically significant decrease in microhardness across all groups. After remineralization, Groups A, B, and C experienced an increase in microhardness while Group D experienced no changes. This showed that Group A had the highest remineralization percentage, followed by Group B and Group C.
CONCLUSIONS: nHAp and TCP had the greater remineralizing ability, which can be used to manage initial carious lesions.

With respect to other fields, bone tissue engineering has significantly expanded in recent years, leading not only to relevant advances in biomedical applications but also to innovative perspectives. Polycaprolactone (PCL), produced in the beginning of the 1930s, is a biocompatible and biodegradable polymer. Due to its mechanical and physicochemical features, as well as being easily shapeable, PCL-based constructs can be produced with different shapes and degradation kinetics. Moreover, due to various development processes, PCL can be made as 3D scaffolds or fibres for bone tissue regeneration applications. This outstanding biopolymer is versatile because it can be modified by adding agents with antimicrobial properties, not only antibiotics/antifungals, but also metal ions or natural compounds. In addition, to ameliorate its osteoproliferative features, it can be blended with calcium phosphates. This review is an overview of the current state of our recent investigation into PCL modifications designed to impair microbial adhesive capability and, in parallel, to allow eukaryotic cell viability and integration, in comparison with previous reviews and excellent research papers. Our recent results demonstrated that the developed 3D constructs had a high interconnected porosity, and the addition of biphasic calcium phosphate improved human cell attachment and proliferation. The incorporation of alternative antimicrobials-for instance, silver and essential oils-at tuneable concentrations counteracted microbial growth and biofilm formation, without affecting eukaryotic cells\' viability. Notably, this challenging research area needs the multidisciplinary work of material scientists, biologists, and orthopaedic surgeons to determine the most suitable modifications on biomaterials to design favourable 3D scaffolds based on PCL for the targeted healing of damaged bone tissue.

The pathology of medication-related osteonecrosis of the jaw (MRONJ), often associated with antiresorptive therapy, is still not fully understood. Osteocyte networks are known to play a critical role in maintaining bone homeostasis and repair, but the exact condition of these networks in MRONJ is unknown. On the other hand, the local application of E-coli-derived Recombinant Human Bone Morphogenetic Protein 2/β-Tricalcium phosphate (E-rhBMP-2/β-TCP) has been shown to promote bone regeneration and mitigate osteonecrosis in MRONJ-like mouse models, indicating its potential therapeutic application for the treatment of MRONJ. However, the detailed effect of BMP-2 treatment on restoring bone integrity, including its osteocyte network, in an MRONJ condition remains unclear. Therefore, in the present study, by applying a scanning electron microscope (SEM) analysis and a 3D osteocyte network reconstruction workflow on the alveolar bone surrounding the tooth extraction socket of an MRONJ-like mouse model, we examined the effectiveness of BMP-2/β-TCP therapy on the alleviation of MRONJ-related bone necrosis with a particular focus on the osteocyte network and alveolar bone microstructure (microcrack accumulation). The 3D osteocyte dendritic analysis showed a significant decrease in osteocyte dendritic parameters along with a delay in bone remodeling in the MRONJ group compared to the healthy counterpart. The SEM analysis also revealed a notable increase in the number of microcracks in the alveolar bone surface in the MRONJ group compared to the healthy group. In contrast, all of those parameters were restored in the E-rhBMP-2/β-TCP-treated group to levels that were almost similar to those in the healthy group. In summary, our study reveals that MRONJ induces osteocyte network degradation and microcrack accumulation, while application of E-rhBMP-2/β-TCP can restore a compromised osteocyte network and abrogate microcrack accumulation in MRONJ.

Zr-50Ti alloys are promising biomaterials due to their excellent mechanical properties and low magnetic susceptibility. However, Zr-50Ti alloys do not inherently bond well with bone. This study aims to enhance the bioactivity and bonding strength of Zr-50Ti alloys for orthopedic implant materials. Initially, the surface of Zr-50Ti alloys was treated with a sulfuric acid solution to create a microporous structure, increasing surface roughness and area. Subsequently, low crystalline calcium phosphate (L-CaP) precipitation was controlled by adding Mg2+ and/or CO32- ions in modified simulated body fluid (m-SBF). The treated Zr-50Ti alloys were then subjected to cold isostatic pressing to force m-SBF into the micropores, followed by incubation to allow L-CaP formation. The apatite-forming process was tested in simulated body fluid (SBF). The results demonstrated that the incorporation of Mg2+ and/or CO32- ions enabled the L-CaP to cover the entire surface of Zr-50Ti alloys within only one day. After short-term soaking in SBF, the L-CaP layer, modulated by Mg2+ and/or CO32- ions, formed a uniform hydroxyapatite (HA) coating on the surface of the Zr-50Ti alloys, showing potential for optimized bone integration. After soaking in SBF for 14 days, the bonding strength between the apatite layer and alloy has the potential to meet the orthopedic application requirement of 22 MPa. This study demonstrates an effective method to enhance the bioactivity and bonding strength of Zr-50Ti alloys for orthopedic applications.

Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair.

UNASSIGNED: To investigate the physicochemical properties, osteogenic properties, and osteogenic ability in rabbit model of femoral condylar defect of acellular dermal matrix (ADM)/dicalcium phosphate (DCP) composite scaffold.
UNASSIGNED: ADM/DCP composite scaffolds were prepared by microfibril technique, and the acellular effect of ADM/DCP composite scaffolds was detected by DNA residue, fat content, and α-1，3-galactosyle (α-Gal) epitopes; the microstructure of scaffolds was characterized by field emission scanning electron microscopy and mercury porosimetry; X-ray diffraction was used to analyze the change of crystal form of scaffold; the solubility of scaffolds was used to detect the pH value and calcium ion content of the solution; the mineralization experiment in vitro was used to observe the surface mineralization. Twelve healthy male New Zealand white rabbits were selected to prepare the femoral condylar defect models, and the left and right defects were implanted with ADM/DCP composite scaffold (experimental group) and skeletal gold ® artificial bone repair material (control group), respectively. Gross observation was performed at 6 and 12 weeks after operation; Micro-CT was used to detect and quantitatively analyze the related indicators [bone volume (BV), bone volume/tissue volume (BV/TV), bone surface/bone volume (BS/BV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), bone mineral density (BMD)], and HE staining and Masson staining were performed to observe the repair of bone defects and the maturation of bone matrix.
UNASSIGNED: Gross observation showed that the ADM/DCP composite scaffold was a white spongy solid. Compared with ADM, ADM/DCP composite scaffolds showed a significant decrease in DNA residue, fat content, and α-Gal antigen content ( P<0.05). Field emission scanning electron microscopy showed that the ADM/DCP composite scaffold had a porous structure, and DCP particles were attached to the porcine dermal fibers. The porosity of the ADM/DCP composite scaffold was 76.32%±1.63% measured by mercury porosimetry. X-ray diffraction analysis showed that the crystalline phase of DCP in the ADM/DCP composite scaffolds remained intact. Mineralization results in vitro showed that the hydroxyapatite layer of ADM/DCP composite scaffolds was basically mature. The repair experiment of rabbit femoral condyle defect showed that the incision healed completely after operation without callus or osteophyte. Micro-CT showed that bone healing was complete and a large amount of new bone tissue was generated in the defect site of the two groups, and there was no difference in density between the defect site and the surrounding bone tissue, and the osteogenic properties of the two groups were equivalent. There was no significant difference in BV, BV/TV, BS/BV, Tb.Th, Tb.N, and BMD between the two groups ( P>0.05), except that the Tb.Sp in the experimental group was significantly higher than that in the control group ( P<0.05). At 6 and 12 weeks after operation, HE staining and Masson staining showed that the new bone and autogenous bone fused well in both groups, and the bone tissue tended to be mature.
UNASSIGNED: The ADM/DCP composite scaffold has good biocompatibility and osteogenic ability similar to the artificial bone material in repairing rabbit femoral condylar defects. It is a new scaffold material with potential in the field of bone repair.
UNASSIGNED: 探讨脱细胞真皮基质（acellular dermal matrix，ADM）/磷酸氢钙（dicalcium phosphate，DCP）复合支架的理化特性、成骨性能及在兔股骨髁缺损模型中的成骨能力。.
UNASSIGNED: 采用微纤维化技术制备ADM/DCP复合支架，行DNA残留、脂肪含量及α-半乳糖基抗原（α-1，3-galactosyle，α-Gal）抗原表位数检测ADM/DCP复合支架的脱细胞效果；场发射扫描电镜观察及压汞仪测定支架孔隙率行支架微观结构表征；行支架X射线衍射分析晶型是否发生变化；支架溶解性检测溶液pH值和钙离子含量；支架体外矿化实验观察表面矿化物。选取健康雄性新西兰大白兔12只，制备兔股骨髁缺损模型，左、右侧缺损处分别植入ADM/DCP复合支架（实验组）和骼金 ®人工骨修复材料（对照组）。术后6、12周取材行大体观察；行Micro-CT检测并定量分析相关指标 ［骨体积（bone volume，BV）、骨体积分数（bone volume/tissue volume，BV/TV）、骨表面积和骨体积之比（bone surface/bone volume，BS/BV）、骨小梁厚度（trabecular thickness，Tb.Th）、骨小梁数目（trabecular number，Tb.N）、骨小梁间隙（trabecular separation，Tb.Sp）、骨密度（bone mineral density，BMD）］；行HE染色和Masson染色，观察骨缺损修复及骨基质成熟情况。.
UNASSIGNED: 大体观察示ADM/DCP复合支架为白色海绵状固体。与ADM相比，ADM/DCP复合支架的DNA残留、脂肪含量和α-Gal抗原含量均大幅降低（ P<0.05）。场发射扫描电镜观察示ADM/DCP复合支架具有多孔联通结构，猪真皮纤维上附着DCP颗粒；压汞仪测得ADM/DCP复合支架孔隙率为76.32%±1.63%。X射线衍射分析示，ADM/DCP复合支架中的DCP晶相保持完整。体外矿化结果示ADM/DCP复合支架的羟基磷灰石层基本成熟。兔股骨髁缺损修复实验示，术后12周切口完全愈合，无骨痂、骨赘。术后12周，Micro-CT观察示两组材料缺损部位已完成骨性愈合且生成大量新生骨组织，密度与周围骨组织无差异，两组材料成骨性能相当；除实验组Tb.Sp 显著大于对照组（ P<0.05）外，两组BV、BV/TV、BS/BV、Tb.Th、Tb.N、BMD比较差异均无统计学意义（ P>0.05）。术后6、12周HE染色和Masson染色示两组新生骨和自体骨融合良好，骨组织均趋于成熟。.
UNASSIGNED: ADM/DCP复合支架具有良好生物相容性，修复兔股骨髁缺损具有与人工骨修复材料相似的成骨能力，是骨修复领域具有应用潜力的新型支架材料。.

Liquid-transmission electron microscopy (liquid-TEM) provides exciting potential for capturing mineralization events at biomaterial interfaces, though it is largely unexplored. To address this, we established a unique approach to visualize calcium phosphate (CaP)-titanium (Ti) interfacial mineralization events by combining the nanofabrication of Ti lamellae by focused ion beam with in situ liquid-TEM. Multiphasic CaP particles were observed to nucleate, adhere, and form different assemblies onto and adjacent to Ti lamellae. Here, we discuss new approaches for exploring the interaction between biomaterials and liquids at the nanoscale. Driving this technology is crucial for understanding and controlling biomineralization to improve implant osseointegration and direct new pathways for mineralized tissue disease treatment in the future.

UNASSIGNED: For safe and effective gene therapy, the ability to deliver the therapeutic nucleic acid to the target sites is crucial. In this study, lactosylated lipid phosphate calcium nanoparticles (lac-LCP) were developed for targeted delivery of pDNA to the hepatocyte cells. The lac-LCP formulation contained lactose-modified cholesterol (CHL), a ligand that binds to the asialoglycoprotein receptor (ASGR) expressed on hepatocytes, and polyethyleneimine (PEI) in the core.
UNASSIGNED: Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) were used to monitor the chemical modification, and the physicochemical properties of NPs were studied using dynamic light scattering (DLS) and transmission electron microscopy (TEM). To evaluate transfection efficiency, cellular uptake and GFP expression were assessed using fluorescence microscopy and flow cytometry.
UNASSIGNED: The results revealed that lactose-targeted particles (lac-LCP) had a significant increase in cellular uptake by hepatocytes. The inclusion of a low molecular weight PEI (1.8 KDa) with a low PEI/pDNA ratio of 1 in the core of LCP, elicited high degrees of GFP protein expression (by 5 and 6-fold), which exhibited significantly higher efficiency than PEI 1.8 KDa and Lipofectamine.
UNASSIGNED: The successful functionalization and nuclear delivery of LCP NPs described here indicate its promise as an efficient delivery vector to hepatocyte nuclei.