AIM:Dental pulp stem cells (DPSCs) regulate immune responses; however, their heterogeneity in deep caries remains unclear. This study aimed at investigating the role of intercellular adhesion molecule 1-positive DPSCs (ICAM1+ DPSCs) within the immune microenvironment of deep carious pulp tissue to develop therapeutic strategies. METHODOLOGY:Single-cell sequencing was used to compare cellular profiles between deep caries and healthy pulp tissues. ICAM1+ DPSCs were quantified using immunofluorescence/flow cytometry in human/mouse models and sorted for functional analyses. Odontogenic differentiation was assessed using alkaline phosphatase/Alizarin Red staining, while inflammatory mediator production was assessed using RT-qPCR, Western Blot, ELISA, SCENIC and RNA-seq. THP-1 was cultured in conditioned media from ICAM1+ DPSCs and ICAM1- DPSCs. RT-qPCR, Western Blot and flow cytometry were used to assess the proportion of proinflammatory to reparative THP-1. Macrophage-derived cytokines (IL-1β/4/6/10 and TNF-α) were tested for DPSCs to ICAM1+ differentiation induction. RESULTS:Cellular profiling showed a significant increase in ICAM1+ DPSCs and proinflammatory monocytes in deep carious dental pulp tissue, with ICAM1+ DPSCs closely interacting with mononuclear macrophages. Immunofluorescence and flow cytometry confirmed the increase in ICAM1+ DPSCs in deep caries in the affected human and mouse pulp tissue. Alkaline phosphatase and Alizarin Red staining, SCENIC, RT-qPCR, Western Blot and ELISA revealed decreased odontogenic differentiation in ICAM1+ DPSCs and increased expression of CEBPD, IL-6, CCL2 and CXCL10 in ICAM1+ DPSC cells. RT-qPCR, Western Blot and flow cytometry indicated an elevated proinflammatory to reparative THP-1 ratio for THP-1 that was cultured in ICAM1+ DPSC-conditioned media for 1-3 days. CONCLUSIONS:During deep caries progression, TNF-α drives the transformation of DPSCs into inflammatory ICAM1+ DPSCs. This subcluster exhibits impaired odontogenic differentiation capacity, secretes proinflammatory cytokines and chemokines, and enhances macrophage inflammatory activity, contributing to the advancement of deep caries lesions.
Pursuing high-performance conductive hydrogels is still hot topic in development of advanced flexible wearable devices. Herein, a tough, self-healing, adhesive double network (DN) conductive hydrogel (named as OSA-(Gelatin/PAM)-Ca, O-(G/P)-Ca) was prepared by bridging gelatin and polyacrylamide network with functionalized polysaccharide (oxidized sodium alginate, OSA) through Schiff base reaction. Thanks to the presence of multiple interactions (Schiff base bond, hydrogen bond, and metal coordination) within the network, the prepared hydrogel showed outstanding mechanical properties (tensile strain of 2800 % and stress of 630 kPa), high conductivity (0.72 S/m), repeatable adhesion performance and excellent self-healing ability (83.6 %/79.0 % of the original tensile strain/stress after self-healing). Moreover, the hydrogel-based sensor exhibited high strain sensitivity (GF = 3.66) and fast response time (<0.5 s), which can be used to monitor a wide range of human physiological signals. Based on this, excellent compression sensitivity (GF = 0.41 kPa-1 in the range of 90-120 kPa), a three-dimensional (3D) array of flexible sensor was designed to monitor the intensity of pressure and spatial force distribution. In addition, a gel-based wearable sensor was accurately classified and recognized ten types of gestures, achieving an accuracy rate of >96.33 % both before and after self-healing under three machine learning models (the decision tree, SVM, and KNN). This paper provides a simple method to prepare tough and self-healing conductive hydrogel as flexible multifunctional sensor devices for versatile applications in fields such as healthcare monitoring, human-computer interaction, and artificial intelligence.
Correction for 'Phosphorylation of collagen fibrils enhances intrafibrillar mineralization and dentin remineralization' by Bo Zheng et al., Nanoscale, 2024, https://doi.org/10.1039/d4nr00652f.
The hierarchical assembly of nanoapatite within a type I collagen matrix was achieved through biomimetic mineralization in vitro, cooperatively regulated by non-collagenous proteins and small biomolecules. Here, we demonstrated that IP6 could significantly promote intrafibrillar mineralization in two- and three-dimensional collagen models through binding to collagen fibrils via hydrogen bonds (the interaction energy similar to 10.21 kJ mol-1), as confirmed by the FTIR spectra and isothermal experimental results. In addition, we find that IP6 associated with dental collagen fibrils can also enhance the remineralization of calcium-depleted dentin and restore its mechanical properties similar to the natural dentin within 4 days. The promoting effect is mainly due to the chemical modification of IP6, which alters the interfacial physicochemical properties of collagen fibrils, strengthening the interaction of calcium phosphate minerals and mineral ions with collagen fibrils. This strategy of interfacial regulation to accelerate the mineralization of collagen fibrils is essential for dental repair and the development of a clinical product for the remineralization of hard tissue. Intrafibrillar mineralization of collagen fibrils was significantly improved by increasing interfacial wetting through modification of IP6.
优化支架结构的设计促进骨再生一直是骨组织工程的研究重点.近年来,许多研究表明微孔结构对生物陶瓷支架的成骨具有重要作用.本文从微孔生物陶瓷支架的力学性能、促成骨的机制和其作为载体在骨修复中的应用三方面总结微孔生物陶瓷支架在骨组织工程中的研究进展.
This paper studied the influence of brace-to-chord angle (BCA) on the in-plane flexural behavior of circular hollow section (CHS) tubular X-joints. The study begins with three CHS tubular X-joint specimens (one orthogonal joint with BCA of 90, two skew joints with BCA of 70 and 55 respectively) under cyclic in-plane bending moment (IPBM). The test results showed that specimens mainly failed in tearing of the chord wall near the brace/chord intersection after experienced large plastic development, and the crack propagation rate of the chord wall of the skew specimens under negative IPBM is obviously faster than that under positive IPBM, while the propagation rates of the orthogonal specimen under two IPBM is similar. The ductility, strength and energy dissipation of the X-joints are deeply affected by BCA. Decreasing BCA is beneficial to the ductility ratio under positive IPBM, but it is not conducive to the ductility ratio under negative IPBM; decreasing BCA can increasing the flexural strength; both the skew joint with large BCA and the orthogonal joint exhibit higher energy dissipation behavior than that of the skew joint with small BCA. These observations is further confirmed by a simple load transferring model proposed in this study. Finite element (FE) parametric analysis is then carried out to verify test and the load transferring mechanism analysis results. Moreover, FE and test results showed that the negative strength Miu- (under negative IPBM) and the positive strength Miu+ (under positive IPBM) of the orthogonal joints are close, but Miu- of the skew joints are larger than the counterpart of Miu+, and the ratio of Miu-/Miu+ is increased (from slightly more than 1.0 to above 1.2) as BCA decreased (from 70 degrees to 35 degrees).
Mineralized collagen is an organic–inorganic composite material, which is the building unit of bones and teeth. This review aims to provide an in-depth study of the collagen biomineralization and applications relating to hard tissue regeneration.
Cu-Fe in situ composites with different Fe contents were prepared by casting and cold drawing deformation. The microstructure was observed, and the mechanical and electrical properties were measured during the deformation process. The composites with a higher Fe content show a higher strength but a lower electrical conductivity because the Fe content is high enough to produce sufficient dendrite structures, resulting in strengthening and electronic scattering effects. The strain hardening of the Cu matrix mainly results in the strengthening of Cu-3 wt.% Fe. The strengthening of Cu-6 wt.% Fe is mainly attributed to the strain hardening of the Cu matrix at a lower draw ratio and the increased interface density at a higher draw ratio. A larger amount of Fe precipitates and a higher interface density lead to an improvement in the strength of Cu-12 wt.% Fe. The conductivities of the Cu-3 wt.% Fe and Cu-6 wt.% Fe alloys are similar due to the continuous Cu matrix or similar electron transmission in the Cu matrix, while that of Cu-12 wt.% Fe is much lower due to the smaller dendrite spacing and the larger amount of Fe precipitates.
It is still a challenge to optimize the component distribution and microporous structures in scaffolds for tailoring biodegradation (ion releasing) and enhancing bone defect repair within an expected time stage. Herein, the core-shell-typed nonstoichiometric wollastonite (4% and 10% Mg-doping calcium silicate; CSiMg4, CSiMg10) macroporous scaffolds with microporous shells (adding ∼10 μm PS microspheres into shell-layer slurry) were fabricated via 3D printing. The initial mechanical properties and bio-dissolution (ion releasing) in vitro, and osteogenic capacity in vivo of the bioceramic scaffolds were evaluated systematically. It was shown that endowing high-density micropores in the sparingly dissolvable CSiMg10 or dissolvable CSiMg4 shell layer inevitably led to nearly 30% reduction of compressive strength, but such micropores could readily tune the ion release behaviour of the scaffolds (CSiMg4@CSiMg10 vs. CSiMg4@CSiMg10-p; CSiMg10@CSiMg4 vs. CSiMg10@CSiMg4-p). Based on the in rabbit femoral bone defect repair model, the 3D μCT reconstruction and histological observation demonstrated that the CSiMg4@CSiMg10-p scaffolds displayed markedly higher osteogenic capability than the other scaffolds after 12 weeks of implantation. It demonstrated that core-shell bioceramic 3D printing technique can be developed to fabricate single-phase or biphasic bioactive ceramic scaffolds with accurately tailored filament biodegradation for promoting bone defect regeneration and repair in some specific pathological conditions.
Type I collagen and non-collagen proteins are the main organic components of dentin. This study aimed to investigate the biomimetic remineralization of demineralized dentin by aspartic acid (Asp), which is abundant in non-collagenous proteins (NCPs). Asp was added to a mineralizing solution containing polyacrylic acid (PAA) to explore the mechanism of Asp regulating the pure amorphous calcium phosphate (ACP) phase transition process. The remineralization process and superstructure of the remineralized layer of demineralized dentin were evaluated and analyzed by transmission electron microscope (TEM) and scanning electron microscope (SEM), and the biological stability of the remineralized layer was investigated by collagenase degradation experiment. It demonstrated that Asp promoted the crystallization kinetics of PAA-stabilized amorphous calcium phosphate to hydroxyapatite (HAP), and shortened the remineralization time of demineralized dentin from 7 days to 2 days. The newly formed remineralized dentin had similar morphology and biological stability to the natural dentin layer. The presence of a large number of Asp residues in NCPs promoted the phase transformation of ACP, and further revealed the mechanism of action of NCPs in dentin biomineralization. This experiment also showed that Asp promoted the biomimetic remineralization of dentin; the morphology and hierarchical structure of remineralized layer was similar to that of natural teeth, and had good biological properties.
Biodegradable ceramic (composite) scaffolds have inspired worldwide efforts in bone regenerative medicine. However, balancing the biodegradation with the bone's natural healing time scale remains difficult; in particularl, there is a lack of strategy to control component distribution and bioactive ion release favorable for stimulating alveolar bone tissue ingrowth in situ within an expected time window. Here we aimed to develop the robocasting core-shell bioceramic scaffolds and investigate their physicochemical properties and osteostimulative capability in beagle alveolar bone defect model. The β-tircalcium phosphate (TCP) and 5% Mg-doped calcium silicate (CSi-Mg5) were used to fabricate the core-shell-typed TCP@TCP, CSi-Mg5@CSi-Mg5 and TCP@CSi-Mg5 porous scaffolds. Both in vitro and in vivo studies show that the CSi-Mg5 shell readily contributed to the initial mechanical strength and early-stage osteogenic activity of the TCP@CSi-Mg5 scaffolds, including tunable ion release, enhanced biodegradation, and outstanding osteogenesis capacity in comparison with the CSi-Mg5@CSi-Mg5 scaffolds and clinically available Bio-Oss granules in alveolar bone defects. Therefore, the presented core-shell robocasting of bioceramic technology and porous scaffold biomaterials enables an accurate preparation of highly bioactive and biodegradable scaffolds with a large freedom of design, and thereby may be beneficial for fabricating osteostimulation-tuned porous scaffolds for the challengeable alveolar bone defect reconstruction medicine.
The purpose of this study was to induce a biomimetic remineralization process by using glutaraldehyde (GA) to reconstruct the mechanical properties and biostability of demineralized collagen. Demineralized dentin disks (35% phosphoric acid, 10s) were pretreated with a 5% GA solution for 3min and then cultivated in a calcium phosphate remineralization solution. The remineralization kinetics and superstructure of the remineralization layer were evaluated by Raman spectroscopy, transmission electron microscopy, scanning electron microscopy and nanoindentation tests. The biostability was examined by enzymatic degradation experiments. A significant difference was found in dentin remineralization process between dentin with and without GA pretreating. GA showed a specific affinity to dentin collagen resulting in the formation of a cross-linking superstructure. GA pretreating could remarkably shorten remineralization time from 7days to 2days. The GA-induced remineralized collagen fibrils were well encapsulated by newly formed hydroxyapatite mineral nanocrystals. With the nano-hydroxyapatite coating, both the mechanical properties (elastic modulus and hardness) and the biostability against enzymatic degradation of the collagen were significantly enhanced, matching those of natural dentin. The results indicated that GA cross-linking of dentin collagen could promote dentin biomimetic remineralization, resulting in an improved mechanical properties and biostability. It may provide a promising tissue-engineering technology for dentin repair.
Purpose: to investigate the use of NaOH solution as storage medium on dentin micro-tensile bond strengths (MTBS) and the micromorphology of resin-dentin interfaces. Materials and Methods: mid-coronal dentin was exposed for 45 human third molars. One of five dentin adhesives investigated was applied to each dentin surface, followed by placement of a resin composite from the same manufacturer (Clearfil S3 Bond+Clearfil Majesty, Clearfil SE Bond+Clearfil Majesty, Kuraray Co. Ltd; Adper Easy One+Z250, Adper Single Bond 2+Z250, 3M ESPE; Gluma Comfort Bond+Charisma, Heraeus Kulzer). Bonded specimens were sectioned through resin-dentin interfaces into multiple beams with a cross-sectional area of about 1mm(2). The beams were kept in 10wt% NaOH solution at 37 degrees C for 0, 2, 4, 6, 8, 10, or 12h respectively prior to MTBS evaluation. The MTBS data were analyzed statistically. Failure modes were determined by stereomicroscopy. Representative fractured surfaces and resin-dentin interfaces were examined by scanning electron microscopy. Resin-dentin interfaces were also analyzed by transmission electron microscopy (TEM). Results: dentin MTBS decreased significantly with increased storage time in NaOH. Micro-gaps appeared along the resin-dentin interfaces after NaOH treatment and became wider over time. An electron-dense hybrid layer was observed by TEM in the control group, while an electron-lucent band was detected at the resin-dentin interfaces of specimens treated with NaOH for 8h. Conclusion: aging of resin-dentin bonds in NaOH solution may be used as an expedited chemical aging method for evaluating degradation of dentin bond.
目的:探索Cu-Fe合金中纳米尺寸和微米尺寸的Fe相的变形行为及区别。方法:1.通过热处理在Cu-2.5%Fe-0.2%Cr合金中得到纳米级的Fe析出相,在Cu-6%Fe中得到微米级的Fe析出相;2.通过冷拉拔手段使铜合金从棒状逐步变形成线材;3.使用光学显微镜、扫描电镜和透射电镜观察微观组织,并用万能电子试验机测量抗拉强度,用标准四点法测量电阻率。结论:1.通过热处理在Cu-6%Fe合金中得到尺寸约50 nm的初生Fe颗粒,在Cu-2.5%Fe-0.2%Cr合金中得到尺寸约50 nm的次生Fe颗粒;2.初生Fe颗粒在冷拉拔过程中转变成丝带状纤维,Cu/Fe相界面密度随变形量增加而增加,从而使Cu-6%Fe合金的强度和电阻率都随之增大;3.次生Fe颗粒即使在η=6的时候也难以变形,保持着球形的形貌,同时高密度的位错环绕着Fe颗粒;Cu-2.5%Fe-0.2%Cr合金的强度随变形量增加而增大,遵循Orowan强化机制;Cu-2.5%Fe-0.2%Cr合金的电阻率几乎保持不变,因为Cu/Fe相界面密度在冷拉拔过程中几乎不变;4.尺寸效应和Fe析出颗粒与Cu基体的非共格界面对Fe析出颗粒在冷拉拔过程中不变形起到重要作用。
High strength and high conductivity Cu-based materials are key requirements in high-speed railway and high-field magnet systems. Cu-Fe alloys represent one of the most promising candidates due to the cheapness of Fe compared to Cu-Ag and Cu-Nb alloys. The high strength of Cu-Fe alloys primarily relies on the high density of the Cu/Fe phase interface, which is controlled by the co-deformation of the Cu matrix and Fe phase. In this study, our main attention was focused on the deformation behavior of the Fe phase using different scales. Cu-2.5% Fe-0.2% Cr (in weight) and Cu-6% Fe alloys were cast, annealed, and cold drawn into wires to investigate their microstructure and properties evolution. Cu-6% Fe contains Cu matrix and Fe, which become the primary particles in the micrometer scale after solution treatment. Cu-2.5% Fe-0.2% Cr contains Cu matrix and Fe precipitate particles in a nanometer scale after solution and aging treatment. The Fe primary particles were elongated and evolved into ribbons in a nanometer scale while the Fe precipitate particles were hardly deformed even at a drawing strain of 6. The reason for the unchanging characteristics of Fe precipitate particles is due to the size effect and incoherent phase interface of Cu matrix and Fe precipitate particles. The strength of both Cu-6% Fe and Cu-2.5% Fe-0.2% Cr alloys increases with the increase in the drawing strain. The electrical resistivity of Cu-6% Fe gradually increases and that of Cu-2.5% Fe-0.2% Cr keeps almost constant with the increase in the drawing strain.
It is widely accepted that the mechanical properties of dentin are significantly determined by its hierarchical structure. The current correlation between the mechanical properties and the hierarchical structure was mainly established by studying altered forms of dentin, which limits the potential outcome of the research. In this study, dentins with three different hierarchical structures were obtained via two different remineralization procedures and at different remineralization stages: (1) a dentin structure with amorphous minerals incorporated into the collagen fibrils, (2) a dentin with crystallized nanominerals incorporated into the collagen fibrils, and (3) a dentin with an out-of-order mineral layer filling the collagen fibrils matrix. Nanoindentation tests were performed to investigate the mechanical behavior of the remineralized dentin slides. The results showed that the incorporation of the crystallized nanominerals into the acid-etched demineralized organic fibrils resulted in a remarkable improvement of the mechanical properties of the dentin. In contrast, for the other two structures, i.e. the amorphous minerals inside the collagen fibrils and the out-of-order mineral layer within the collagen fibrils matrix, the excellent mechanical properties of dentin could not be restored.
The amorphous phase precipitates first during biomineralization and acts as the precursor for the subsequent mineralization of hard tissues including dentin. During this process, various biomineralization proteins with different, even opposite functions control the dimensions and phase states of the amorphous precursors that permeate the collagen matrix and then crystallize to form highly sophisticated organic-inorganic biological materials. In this study, a biomimetic strategy containing polyacylic acid and l-glutamic acid (l-Glu) was applied to promote the remineralization of Ca-depleted dentin collagen. Following the structural features of biomineralization-related non-collagenous proteins (NCPs), l-Glu was found to be capable of promoting the crystallization kinetics of the polyacylic acid-stabilized metastable amorphous to hydroxyapatite phase transformation. It is demonstrated that the dentin remineralization could be shortened within two days by using the cooperative effect of polyacrylic acid and l-glutamic acid. Furthermore, the resulting remineralized dentin layer has the same characteristics, including mechanical strength, as the natural ones. This biomimetic strategy highlights the combination of the two opposing factors of biomineralization components as the key to control the phase-transformation-based mineralization reactions with the organic matrix of dental tissues. In summary, a bio-inspired approach was followed to reconstruct collagen-mineralized tissues with biocompatible functions, morphologies, and characteristics.
Cu-12% Fe (in weight) composite was prepared by casting, pretreating, and cold drawing. The microstructure was observed and Vickers hardness was measured for the composite at various drawing strains. Cu and Fe grains could evolve into aligned filaments during the drawing process. X-ray diffraction (XRD) was used to analyze the orientation evolution during the drawing process. The axial direction of the filamentary structure has different preferred orientations from the radial directions. The strain of Fe grains linearly increases with an increase in the drawing strain up to 6.0, and deviates from the linear relation when the drawing strain is higher than 6.0. With an increase in the drawing strain, the microstructure scales of Fe filaments exponentially decrease. The density of the interface between Cu and Fe phases exponentially increases with an increase in the aspect ratio of Fe filaments. There is a similar Hall-Petch relationship between the hardness and Fe filament spacing. The refined microstructure from drawing deformation at drawing strains lower than 3.0 can induce a more significant hardening effect than that at drawing strains higher than 3.0.
The microstructure and thermoelectric properties of InSb-NiSb composite system are investigated. NiSb, ranging from micro- to nanoscale, is introduced as a nonsoluble second phase in the InSb matrix by using the water quenching method. The morphology of the second phase is adjusted by varying the composition from hypoeutectic to hypereutectic alloys. The eutectic composite with a semiconducting InSb matrix and a metallic NiSb fiber on the order of 100-nm diameter is obtained. Melt spinning (MS) is applied to the eutectic composition to change the NiSb dispersion phase to around 200-nm diameter sphere. Transport properties, including Seebeck coefficient, resistivity, Hall coefficient, and thermal conductivity, are measured from 80 to 630 K. Compared to the water quenched (WQ) eutectic sample, the MS process results in a slight increase in the carrier concentration but a remarkable reduction in the mobility and thermal conductivity. Compared to the InSb matrix, ZT of the samples with the NiSb second phase is lower. For the eutectic samples, ZT is significantly reduced after the MS process because of the loss in mobility. ZT of the WQ InSb matrix is the highest in all the samples, ∼0.5 at 600 K.
This work shows that the carrier mean free path of TAGS-85 thermoelectric materials is comparable to the lattice parameter, and that refining the grain size will not affect the mobility while benefiting the thermal conductivity reduction. A state-of-the-art ZT of ~ 1.6 is obtained for the fine-grained samples.