ACS Omega
·
2025
·
IF 4.3
Jing Ru,Xiaochen Xu,Yuxuan Cheng,Nan Luo,Shuo Tan,Xi Chen,Feng Chen,Bing-Qiang Lu
Dental minerals are in an equilibrium state of demineralization and remineralization, which can be disrupted by pathogenic bacteria to cause dental caries. While the inorganic polymer polyphosphate (polyP) is ubiquitous in living organisms and is also widely involved in mineralization regulations, its specific influence on the mineralization balance of teeth remains unclear. As a concept-and-proof study, the effects of polyP on the demineralization and remineralization of teeth are investigated on dental enamel (the highly mineralized outer covering tissue of teeth) from the perspective of mineralization balance. We found that a high concentration (containing 1.0–20 mM P element, comparable to and higher than the free phosphate ions in body fluids) of polyP has the capability to demineralize enamel in the aqueous solution, yet this effect is absent in the simulated biological environments including simulated body fluid and MEM (α-minimum essential medium) solutions. More importantly, polyP with a very low concentration (containing ≥5.0 μM P) is able to inhibit enamel mineralization significantly. This suggests that polyP could impact the mineralization balance of enamel by preferentially inhibiting the remineralization process, thereby disrupting the equilibrium necessary for maintaining enamel health.
研究领域:
口腔医学
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生物材料学
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DOI
PubMed
高影响因子
BMC Oral Health
·
2025
·Vol. 25
·期 1
·1-15
·
IF 3.1
Li Huanying,Liu Gengbo,Liu Xiaohao,Wu Buling
Section
Background
Currently, many biomimetic mineralization materials fail to bind effectively to collagen, which significantly limits their remineralization efficacy. To address this limitation, we designed MMP2-derived peptides (MDPs) on the basis of the strong affinity domain of collagen: MDP-a and MDP-3DSS.
Section
Methods
Surface plasmon resonance (SPR) was used to measure the binding force of MDPs to collagen. Inductively coupled plasma-mass spectrometer (ICP-MS) was used to evaluate the effects of peptides on the adsorption of calcium ions by collagen. Transmission electron microscopy (TEM) and thermogravimetric analysis (TGA) were employed to analyze the stabilizing effect of MDPs on amorphous calcium phosphate (ACP) and the mineralization effect on collagen. Scanning electron microscopy (SEM), mechanical tests, and the CCK-8 assay were employed to evaluate the remineralization effect of MDPs on demineralized dentin and their biocompatibility.
Section
Results
The results of the present study demonstrated that MDPs strongly bind to collagen (18 µM for MDP-a and 18.9 µM for MDP-3DSS) and can promote calcium ion adsorption by collagen (p < 0.0001). Furthermore, MDPs have been shown to stabilize ACP and induce intrafibrillar mineralization. In vitro studies revealed that both surface and cross-sectional dentin slices treated with MDPs presented dense mineral deposition. This deposition effectively occluded the dentinal tubules and resulted in enhanced mechanical properties. The tubule plugging rate, the elastic modulus and microhardness of the MDPs group were greater than those of the control group (p < 0.01). Moreover, MDP-3DSS demonstrated the most significant remineralization potential. Additionally, MDPs treatment did not affect the activity of human dental pulp stem cells (hDPSCs) (p > 0.05).
Section
Conclusion s
The present study successfully developed and evaluated two novel biomimetic mineralized peptides, MDP-a and MDP-3DSS. It is necessary to conduct further research to explore the possibility of clinical transformation of MDPs.
研究领域:
口腔生物学
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生物材料学
·
牙体牙髓病学
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2020
·
IF 4.152
Yinan Qu,Tianyi Gu,Qiaolin Du,Changyu Shao,Jing Wang,Biao Jin,Weijing Kong,Jian Sun,Chaoqun Chen,Haihua Pan,Ruikang Tang,Xinhua Gu
Biomineralization has intrigued researchers for decades. Although mineralization of type I collagen has been universally investigated, this process remains a great challenge due to the lack of mechanistic understanding of the roles of biomolecules. In our study, dentine was successfully repaired using the biomolecule polydopamine (PDA), and the remineralized dentine exhibited mechanical properties comparable to those of natural dentine. Detailed analyses of the collagen mineralization process facilitated by PDA showed that PDA can promote intrafibrillar mineralization with a decreased heterogeneous nucleation barrier for hydroxyapatite (HAP) by reducing the interfacial energy between collagen fibrils and amorphous calcium phosphate (ACP), resulting in the conversion of an increasing amount of nanoprecursors into collagen fibrils. The present work highlights the importance of interfacial control in dentine remineralization and provides profound insight into the regulatory effect of biomolecules in collagen mineralization as well as the clinical application of dentine restoration.
研究领域:
牙科材料学
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生物医学工程
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口腔医学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Weisin Chen,Juan Li,Dehua Meng,Fangrui Liu,Lei Huang,Ning Wang,Guokang Mo,Haifeng Liang,Dihan Su,Jian Zhang,Libo Jiang
With four levels of formations and functional properties similar to biological tissues, protein hydrogel attracts great attention from researchers and clinical practitioners for broad applications. However, hydrogels with high water content usually exhibit poor mechanical properties, which limit their widespread application. In the study, a general and feasible approach was used to enhance the regenerated silk fibroin (RSF) hydrogel's mechanical strength by mimicking the human skeleton biomineralization process in vitro. The final mechanical strength was around 4.5 MPa, and the compressive modulus was around 0.90 MPa after combining the effects of ethanol induction of β-sheet and mineralization by SBF, reaching 3 times higher strength than the original RSF hydrogel. The mineral composition and chemical structure proved that the biomineralization of HAp apposition within amorphous hydrophilic domains enhanced the mechanical properties of RSF hydrogel. In vivo RSF hydrogel mineralization was observed after subcutaneous implantation in rats. The femoral bone defect model demonstrated that the biomineralized RSF hydrogel maintained the bone structure from collapse in the early phase. In summary, a straightforward method for fabricating high-strength biomineralized RSF hydrogel through a slow-and-low approach, i.e., low SBF concentration and longer immersion time, was developed and is promising for treating bone diseases.
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高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-15
·
IF 15.7
Xie Chang,Li Wenyue,Yao Xudong,Wu Boxuan,Fang Jinghua,Mao Renwei,Yan Yiyang,Meng Hongxu,Wu Yan,Zhang Xianzhu,Li Rui,Zhang Jie,Duan Wangping,Dai Xuesong,Wang Xiaozhao,Ouyang Hongwei
Growth plate (GP), a critical cartilaginous structure in amniotes, underpins longitudinal bone growth, yet the intricate mechanisms behind its polarized mineralization during evolution remain unclear. Herein, employing high-resolution analytical techniques, we reveal that the GP-epiphysis interface displays a sharp transition in tissue modulus, acting as a protective shell for the underlying GP, whereas the GP-metaphysis interface exhibits a gradual modulus increase, enabling efficient load redistribution to the metaphysis. This mechanical microenvironment contributes to unique microstructural and compositional transformations from GP to epiphysis and metaphysis. Notably, the GP-epiphysis interface acts as a mineralization inhibition zone while the GP-metaphysis serves as a mineralization promotion zone, orchestrated by a complex network of proteins. Proteins such as secreted phosphoprotein 1 (SPP1) and alpha-2-HS-glycoprotein (AHSG) at the GP-epiphysis interface inhibit mineralization, forming a defense line; while ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and alkaline phosphatase, biomineralization associated (ALPL), coexisting with SPP1 and AHSG, promote a sequential nucleation and assembly of calcium phosphate minerals at the GP-metaphysis. Such polarized mineralization patterns maintain the homeostasis of GPs and drive polarized bone elongation. Replicating this process in vitro, we synthesize stable amorphous calcium phosphate which shows highly controlled transformation into hydroxyapatite. This work provides a more comprehensive view of the structural integrity of human bone in development and offers strategies for controlled biomineralization.
研究领域:
发育生物学
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生物力学
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生物矿化
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分子生物学
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骨骼生物学
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DOI
PubMed
高影响因子
Nanoscale
·
2018
·Vol. 10
·期 40
·18980-18987
·
IF 7.233
Zhe Wang,Yan Ouyang,Zhifang Wu,Leiqing Zhang,Changyu Shao,Jiayan Fan,Ling Zhang,Ying Shi,Zihuai Zhou,Haihua Pan,Ruikang Tang,Baiping Fu
We propose a novel fluorescent adhesive-assisted biomimetic mineralization strategy, based on which 1 wt% of sodium fluorescein and 25 wt% of polyacrylic acid stabilized amorphous calcium phosphate (PAA-ACP) nanoparticles were incorporated into a mild self-etch adhesive (Clearfil S3 Bond) as a fluorescent mineralizing adhesive. The characterization of the PAA-ACP nanoparticles indicates that they were spherical particles clustered together, each particle with a diameter of approximately 20–50 nm, in a metastable phase with two characteristic absorption peaks (1050 cm−1 and 580 cm−1). Our results suggest that the fluorescent mineralizing adhesive was non-cytotoxic with minimal esthetic interference and its fluorescence intensity did not significantly decrease within 6 months. Our data reveal that the fluorescent mineralizing adhesive could induce the extra- and intra-fibrillar remineralization of the reconstituted type I collagen, the demineralized enamel and dentin substrate. Our data demonstrate that a novel fluorescent adhesive-assisted biomimetic mineralization strategy will pave the way to design and produce anti-carious materials for the prevention of dental caries.
研究领域:
材料科学
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口腔医学
·
生物医学工程
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Songzhe Shan,Zhenhang Tang,Kaida Sun,Wenjing Jin,Haihua Pan,Ruikang Tang,Wei Yin,Zhijian Xie,Zhuo Chen,Changyu Shao
Despite significant efforts utilizing advanced technologies, the contentious debate surrounding the intricate mechanism underlying collagen fibril mineralization, particularly with regard to amorphous precursor infiltration and phase transformation, persists. This work proposes an amorphous calcium phosphate (ACP)-mediated pathway for collagen fibril mineralization and utilizing stochastic optical reconstruction microscopy technology, and has experimentally confirmed for the first time that the ACP nanoparticles can infiltrate inside collagen fibrils. Subsequently, the ACP-mediated phase transformation occurs within collagen fibrils to form HAP crystallites, and significantly enhances the mechanical properties of the mineralized collagen fibrils compared to those achieved by the calcium phosphate ion (CPI)-mediated mineralization and resembles the natural counterpart. Furthermore, demineralized dentin can be effectively remineralized through ACP-mediated mineralization, leading to complete restoration of its mechanical properties. This work provides a new paradigm of collagen mineralization via particle-mediated phase transformation, deepens the understanding of the mechanism behind the mineralization of collagen fibrils, and offers a new strategy for hard tissue repair.
研究领域:
生物材料学
·
骨生物学
·
再生医学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Leiqing Zhang,Zihuai Zhou,Zhiwen Liu,Ying Shi,Yingjie Mao,Baiping Fu,Zhe Wang
Alendronate (ALN), a potent bisphosphonate, plays a significant role in both bone formation and osteoporosis therapy. However, its potential to promote biomimetic mineralization of type I collagen fibrils and demineralized dentin remains unclear. This study reveals that ALN-pretreated collagen fibrils form ester bonds between the hydroxyl groups of ALN and the carboxyl groups of collagen, accompanied by a reduction in collagen surface potential. Additionally, an adsorption equilibrium of ALN to collagen was achieved at 25 mM ALN. ALN pretreatment facilitates intrafibrillar mineralization of type I collagen fibrils in a dose-dependent manner, as well as mineralization of demineralized dentin in synergy with polyelectrolyte-stabilized Amorphous Calcium Phosphate (ACP) nanoparticles. This process effectively restores the mechanical properties of demineralized dentin to levels comparable to natural dentin. Thus, ALN holds potential for localized applications aimed at promoting remineralization of demineralized dentin.
研究领域:
口腔医学
·
材料科学
·
生物医学工程
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Haiyan Wu,Changyu Shao,Jue Shi,Zihe Hu,Yanyan Zhou,Zhuo Chen,Ruikang Tang,Zhijian Xie,Wenjing Jin
Non-collagenous proteins (NCPs) in the extracellular matrix (ECM) of bone and dentin are known to play a critical regulatory role in the induction of collagen fibril mineralization and are embedded in hyaluronic acid (HA), which acts as a water-retaining glycosaminoglycan and provides necessary biochemical and biomechanical cues. Our previous study demonstrated that HA could regulate the mineralization degree and mechanical properties of collagen fibrils, yet its kinetics dynamic mechanism on mineralization is under debate. Here, we further investigated the role of HA on collagen fibril mineralization and the possible mechanism. The HA modification can significantly promote intrafibrillar collagen mineralization by reducing the electronegativity of the collagen surface to enhance calcium ions (Ca 2+ ) binding capacity to create a local higher supersaturation . In addition, the HA also provides additional nucleation sites and shortens the induction time of amorphous calcium phosphate (ACP)-mediated hydroxyapatite (HAP) crystallization, which benefits mineralization. The acceleration effect of HA on intrafibrillar collagen mineralization is also confirmed in collagen hydrogel and in vitro dentin remineralization. These findings offer a physicochemical view of the regulation effect of carbohydrate polymers in the body on biomineralization , the fine prospect for an ideal biomaterial to repair collagen-mineralized tissues.
研究领域:
生物材料
·
生物矿化
·
牙科材料
·
材料科学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2023
·
IF 19
Jiaying Liu,Xiaonong Zhang,Chunsheng Xiao,Xuesi Chen
Fabrication of mineralized materials through the nature-mimicking dynamic biomineralization process has attracted great interest but remains a huge challenge till now. Here, a drug-mineralized hydrogel (DMH) with spontaneous dynamic mineralization behaviors is reported, which highly mimics the dynamic mineralization process of natural tissues. The hydrogel is facilely fabricated via directly mixing sodium hyaluronate (HA) with alendronate sodium (ADA) and CaCl 2 in deionized water. The resultant hydrogel possesses a white-to-semi-transparent transition and a soft-to-hard transition during incubation at 37 °C. Mechanism studies reveal that the spontaneous dynamic change of the hydrogel is ascribed to the HA-regulated dynamic mineralization of ADA/Ca 2+ complexes, where amorphous ADA/Ca 2+ complexes will gradually transform into mineral crystals with the prolongation of incubation time. Owing to the dynamic transformation process, the DMH shows excellent injectability and moldability at the initial stage. More importantly, the DMH exhibits a sustained release behavior of ADA in vitro, superior adhesiveness with bone, biodegradability, and good biocompatibility. As a result, the developed DMH demonstrates promising uses for accelerating bone repair in a rat cranial defect model. Overall, the research provides a general strategy to prepare drug-mineralized hydrogels with spontaneous dynamic mineralization behaviors, which may find potential uses in various biomedical fields.
研究领域:
材料科学
·
生物医学工程
·
组织工程
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DOI
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 45
·10373-10383
·
IF 5.344
Yufei Wang,Die Hu,Jingyao Cui,Yuhao Zeng,Xinyan Gan,Zhongxin Chen,Qian Ren,Linglin Zhang
Amelogenin and its various derived peptides play important roles in promoting biomimetic mineralization of enamel. Previously, an amelogenin-derived peptide named QP5 was proved to be able to repair demineralized enamel. The objective here was to interpret the mechanism of QP5 by elucidating the specific function of each domain for further sequence and efficacy improvement. Peptide QP5 was separated into domains (QPX)5 and C-tail. (QPX)3 was also synthesized to investigate how QPX repeats affect the mineralization process. Circular dichroism spectroscopy showed that two (QPX) repeats adopted a β-sheet structure, while C-tail exhibited a disordered structure. (QPX)5 showed more absorption in confocal laser scanning microscopy observation and a higher K value in Langmuir adsorption isotherms compared to C-tail, while (QPX)3 with better hydropathy had greater adsorption capability than (QPX)5. Meanwhile, calcium consumption kinetics, transmission electron microscopy and selected area electron diffraction indicated that (QPX)5, C-tail and (QPX)3 had similar inhibitory effects on the spontaneous calcium consumption and the morphology of their nucleation products were alike, while QP5 had a greater inhibitory effect than them and induced elongated plate-like crystals. X-Ray diffraction further showed that both C-tail and (QPX)3 had greater potential in improving the apatite crystal orientation degree. In conclusion, (QPX)5 was the major adsorption region, both (QPX)5 and C-tail inhibited the nucleation, and C-tail contributed more to improve the HAP orientation degree, so QP5 could exert a significant remineralization effect. By reducing two repeats, (QPX)3 showed higher hydropathicity than (QPX)5 and achieved higher binding affinity, and it was more potential in improving the HAP orientation degree with lower economic cost.
研究领域:
牙科材料
·
生物材料
·
矿化机制
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Xiangtao Liu,Sisi Zhang,Haiyan Zheng,Mengyao Bian,Linna Qian,Weijia Zhao,Ying Shi,Zhifang Wu
Dental caries, primarily induced by plaque biofilm, is a significant challenge in oral health due to the disruption of the equilibrium between mineralization and demineralization processes. The primary objective in caries management is to preserve biofilm homeostasis while promoting the repair and regeneration of dental hard tissues, thereby restoring the structural integrity and functionality of the affected teeth. This study aimed to develop a multifunctional film with mineralizing and antibacterial abilities by incorporating ultrasmall amorphous calcium phosphate (ACP) nanoclusters (~1 nm) into hydroxypropyl trimethyl ammonium chloride chitosan (HACC) matrix. The ACP nanoclusters were synthesized using polyacrylic acid and polyaspartic acid as stabilizers and were homogeneously dispersed into the HACC matrix to form ACP@HACC film. The capacity for Ca and P ions release from ACP@HACC film was evaluated by inductively coupled plasma-mass spectrometry, demonstrating a sustained ion release over a period of 7 days. The ACP@HACC film induced the mineralization of type I collagen fibrils within 4 days. In vivo studies further confirmed the occurrence of dentin remineralization after 4 days. The remineralization process mediated by the ACP@HACC film significantly restored the elastic modulus and microhardness of demineralized dentin. Additionally, cytotoxicity assessments confirmed the excellent biocompatibility of the ACP@HACC film. Dentin treated with the ACP@HACC film demonstrated antibacterial ability against Streptococcus mutans in vitro. The ACP@HACC film integrates the dual functionalities of mineralization and antibacterial activity while maintaining excellent biocompatibility. This innovative approach shows potential for the treatment of early carious lesions, offering a clinically viable supplement to conventional restorative strategies.
研究领域:
牙科
·
生物材料
·
纳米技术
·
口腔生物学
·
抗菌材料
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产品关联
DOI
PubMed
高影响因子