Guided bone regeneration in the alveolar bone relies on the colonization and differentiation of immune cells within the defect area.The absence of osteoinductive and osteoimmune properties of currently available scaff...Guided bone regeneration in the alveolar bone relies on the colonization and differentiation of immune cells within the defect area.The absence of osteoinductive and osteoimmune properties of currently available scaffolds hinders to achieve optimal repair outcomes in clinical settings.Thus,we aimed to enhance the bone repair ability of polycaprolactone(PCL)scaffolds by incorporating osteoinductive amorphous calcium phosphate(ACP)with immune-regulating zinc ions(ACP(Zn),ACZP),to create a favorable immunomodulatory microenvironment.After one day of co-culture with PCL-ACZP,the spreading area of macrophage cells was significantly higher than that from the original PCL scaffold.Additionally,over 32.1%of macrophages exhibited M2 polarization within three days of co-culture.The PCLACZP/macrophage-conditioned medium significantly boosted osteogenic gene expression in MC3T3-E1 cells.After eight weeks of implantation in a rat femoral condyle defect,the BV/TV from the PCL-ACZP group reached 32.9%,1.4 times of that from the PCL group.Furthermore,the PCL-ACZP-GelMA biphasic module as prepared successfully achieved complete regeneration of three-walled alveolar bone defects in rabbits,resulting in arch-shaped alveolar bone repair and providing greater convenience in the clinical settings.This study showcased the effectiveness of PCL-ACZP-GelMA biphasic module as bioactive scaffolds in the morphological restoration of alveolar bone.展开更多
Although much effort has been focused on the preparation of stable amorphous calcium phosphate （ACP） nanoparticles in aqueous solution, the redispersibility and long-term stability of ACP nanoparticles in aqueous so...Although much effort has been focused on the preparation of stable amorphous calcium phosphate （ACP） nanoparticles in aqueous solution, the redispersibility and long-term stability of ACP nanoparticles in aqueous solution remains an unresolved problem. In this work, stable colloidal ACPs were prepared by using an organic bisphosphonate （BP） as a sterically hindered agent in aqueous solution. The harvested calcium phosphate nanoparticles were characterized by inductively coupled plasma atomic emission spectrometry （ICP-AES）, Fourier transform infrared （FTIR）, X-ray diffraction （XRD）, dynamic light scattering （DLS） and transmission electron microscopy （TEM）. ICP-AES, FTIR and XRD results suggested the particles were ACP. DLS and TEM results indicated that the size of the ACP nanoparticles were in the range of 60 nm with a spherical morphology. The resulting calcium phosphate nanoparticles retained its amorphous nature in aqueous solution for at least 6 months at room temperature due to the stabilizing effect of the organic bisphosphonate. Moreover, the surface of the ACP nanoparticles adsorbed with the organic bisphosphate used showed good redispersibility and high colloid stability both in organic and aqueous solutions.展开更多
Recently,multifunctional nanoparticles have shown great prospects in cancer treatment,which have the ability to simultaneously deliver the drug,image and target tumor cells.In this paper,we designed a luminescent nano...Recently,multifunctional nanoparticles have shown great prospects in cancer treatment,which have the ability to simultaneously deliver the drug,image and target tumor cells.In this paper,we designed a luminescent nanoparticles platform based on hydrothermal hyaluronic acid/amorphous calcium phosphate(HA-FCNs/ACP)with multifunctional properties for drug delivery,bio-imaging,and targeting treatment.HA-FCNs/ACP shows an ability to load curcumin(Cur)with pH-sensitive responsive drug release behavior and excellent biocompatibility.HA-FCNs/ACP dispersed in the cytoplasm through the overexpressed CD44 receptor that is actively targeted into human lung cancer cells(A549 cells).Meanwhile,the viability of A549 cells was significantly inhibited in vitro.The prepared HA-FCNs and HA-FCNs/ACP both exhibit excellent targeted bioimaging performance on cancer cells.Hence,the as-prepared nanoparticles have promising applications in treating tumor disease.展开更多
Regenerating critical-sized long bone defects poses substantial challenges due to limitations of autografts and processed allografts.Biomaterial scaffolds offer versatile alternatives,yet their effectiveness is often ...Regenerating critical-sized long bone defects poses substantial challenges due to limitations of autografts and processed allografts.Biomaterial scaffolds offer versatile alternatives,yet their effectiveness is often constrained by their limited innate osteoinductivity.While growth factors and cells can enhance osteoinduction,the inclusion of biologics in biomaterial scaffolds creates regulatory challenges for clinical translation.To address this,here we describe three-dimensional(3D)printed polycaprolactone(PCL)scaffolds for temporally controlled delivery of osteoimmunomodulatory amorphous calcium phosphate-chitosan nanoparticles(ACPC-NP).In vitro,the ACPC-NP exhibit concentration dependent effects on osteoblasts,monocytes,and osteoclasts.At increasing concen-trations up to 500μg/ml,these nanoparticles stimulate osteogenesis,modulate M2/M1 macrophage polarization,and inhibit osteoclast maturation and activity.Leveraging these concentration-dependent effects in vivo through temporally controlled release of ACPC-NP from 3D-printed PCL scaffolds,we observe the complete regeneration and the restoration of biomechanical strength of critically sized radial defects in rats.Such healing is absent in defects implanted with bare PCL scaffolds or those loaded with calcium-phosphate microparticles.The tunable osteoimmunomodulation by the NP underscores the translational potential of this technology to yield struc-turally sound and functionally robust bone regeneration outcomes.展开更多
The repair of alveolar bone defects continues to pose a significant challenge within the field of stomatology.As the primary implant material utilized in clinical treatment,the mechanisms by which calcium phosphate-ba...The repair of alveolar bone defects continues to pose a significant challenge within the field of stomatology.As the primary implant material utilized in clinical treatment,the mechanisms by which calcium phosphate-based materials promote bone formation necessitate further in-depth exploration.Single-cell RNA sequencing was employed to characterize the immune microenvironment surrounding hydroxyapatite(HA)-mediated alveolar bone regeneration,confirming the macrophage-dependent enhancement of regenerative outcomes.Based on this finding,amorphous calcium zinc phosphate(ACZP)nanoparticles were developed as immunomodulatory nanomaterials.ACZP can accelerate bone regeneration via anti-inflammatory phenotype polarization,specif-ically by inhibiting endoplasmic reticulum-mitochondria coupling,reducing pathological Ca2+transfer,and shifting macrophage metabolism from glycolysis to oxidative phosphorylation(OXPHOS),thereby enhancing bioenergetics.Our results demonstrated that ACZP can inhibit the IP3R/MCU pathway in macrophages,restoring their anti-inflammatory capabilities and ultimately achieving significant effects in the alveolar bone defects of New Zealand white rabbits.Twelve weeks post-surgery,the defects in the ACZP group were filled with nearly 70%newly formed bone tissue.This study elucidated the immunomodulatory role of ACZP materials in the dy-namic process of alveolar bone healing,providing novel insights and methodologies for the design of materials in the fields of tissue engineering and regenerative medicine.展开更多
Background Enamel decalcification in orthodontics is a concern for dentists and methods to remineralize these lesions are the focus of intense research. The aim of this study was to evaluate the remineralizing effect ...Background Enamel decalcification in orthodontics is a concern for dentists and methods to remineralize these lesions are the focus of intense research. The aim of this study was to evaluate the remineralizing effect of casein phosphopeptide amorphous calcium phosphate （CPP-ACP） nanocomplexes on enamel decalcification in orthodontics. Methods Twenty orthodontic patients with decalcified enamel lesions during fixed orthodontic therapy were recruited to this study as test group and twenty orthodontic patients with the similar condition as control group. GC Tooth Mousse, the main component of which is CPP-ACP, was used by each patient of test group every night after tooth-brushing for six months. For control group, each patient was asked to brush teeth with toothpaste containing 1100 parts per million （ppm） of fluoride twice a day. Standardized intraoral images were taken for all patients and the extent of enamel decalcification was evaluated before and after treatment over this study period. Measurements were statistically compared by t test. Results After using CPP-ACP for six months, the enamel decalcification index （EDI） of all patients had decreased; the mean EDI before using CPP-ACP was 0.191＋0.025 and that after using CPP-ACP was 0.183＋0.023, the difference was significant （t=5.169, P 〈0.01）. For control group, the mean EDI before treatment was 0.188±0.037 and that after treatment was 0.187±0.046, the difference was not significant （t=1.711, P 〉0.05）. Conclusion CPP-ACP can effectively improve the demineralized enamel lesions during orthodontic treatment, so it has some remineralization potential for enamel decalcification in orthodontics.展开更多
Biological mineral generation via an amorphous precursor is a topic of great current interest.Various factors such as the temperature,solution composition and presence of organic molecules can influence this important...Biological mineral generation via an amorphous precursor is a topic of great current interest.Various factors such as the temperature,solution composition and presence of organic molecules can influence this important inorganic process.Here we demonstrate that this mineral transformation can actually readily be regulated by solution viscosity,a fundamental but often overlooked property.In our experiment,amorphous calcium carbonate(ACC),a key model compound in biomimetic mineralization studies,is synthesized and dispersed into inert dispersants with different viscosities and the crystallization process is examined by using FT-IR spectroscopy and XRD.It is found that the inhibition of the transformation of ACC becomes more significant with increasing fluid viscosity.This phenomenon can be explained by the differences in ion diffusion in different media.Furthermore,the resulting crystals always have different morphologies and size distributions although they all have the calcite structure.This study implies that the importance of the fluid medium cannot be ignored in building a complete understanding of biological control of biomimetic crystallizations.展开更多
Background The initial osteoblastic adhesion to materials characterizes the first phase of cell-material interactions and influences all the events leading to the formation of new bone. In a previous work, we develope...Background The initial osteoblastic adhesion to materials characterizes the first phase of cell-material interactions and influences all the events leading to the formation of new bone. In a previous work, we developed a novel amorphous calcium phosphate （ACP）/poly（L-lactic acid） （PLLA） material that demonstrated morphologic variations in its microstructure. The aim of this study was to investigate the initial interaction between this material and osteoblastic cells. Cellular attachment and the corresponding signal transduction pathways were investigated. Methods A porous ACP/PLLA composite and PLLA scaffold （as a control） were incubated in fetal bovine serum （FBS） containing phosphate-buffered saline （PBS）, and the protein adsorption was determined. Osteoblastic MG63 cells were seeded on the materials and cultured for 1, 4, 8, or 24 hours. Cell attachment was evaluated using the MTS method. Cell morphology was examined using scanning electron microscopy （SEM）. The expression levels of the genes encoding integrin subunits αl, α5, αv, β1, focal adhesion kinase （FAK）, and glyceraldehyde-3-phosphate dehydrogenase （GAPDH） were determined using real-time reverse transcription polymerase chain reaction （RT-PCR）. Results The ACP/PLLA material significantly increased the protein adsorption by 6.4-fold at 1 hour and 2.4-fold at 24 hours, compared with the pure PLLA scaffold. The attachment of osteoblastic cells to the ACP/PLLA was significantly higher than that on the PLLA scaffold. The SEM observation revealed a polygonal spread shape of cells on the ACP/ PLLA, with the filopodia adhered to the scaffold surface. In contrast, the cells on the PLLA scaffold exhibited a spherical or polygonal morphology. Additionally, real-time RT-PCR showed that the genes encoding the integrin subunits αl, αv, β1, and FAK were expressed at higher levels on the ACP/PLLA composite. Conclusions The ACP/PLLA composite promoted protein adsorption and osteoblastic adhesion. The enhanced cell adhesion may be mediated by the binding of integrin subunits αl, αv, and β1, and subsequently may be regulated through the FAK signal transduction pathways.展开更多
Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability.Calcium-based materials can also deliver contrast agents,which can ...Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability.Calcium-based materials can also deliver contrast agents,which can enhance real-time imaging and exert a Ca^(2+)-interfering therapeutic effect.Based on these characteristics,amorphous calcium carbonate(ACC),as a brunch of calcium-based biomaterials,has the potential to become a widely used biomaterial.Highly functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However,the standalone presence of ACC is unstable in vivo.Additives are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its destination.ACC has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo,such as Ca^(2+) with an immune-regulating ability and CO_(2) with an imaging-enhancing ability.Owing to these characteristics,ACC has been studied for selfsacrificing templates of carrier construction,targeted delivery of oncology drugs,immunomodulation,tumor imaging,tissue engineering,and calcium supplementation.Emphasis in this paper has been placed on the origin,structural features,and multiple applications of ACC.Meanwhile,ACC faces many challenges in clinical translation,and long-term basic research is required to overcome these challenges.We hope that this study will contribute to future innovative research on ACC.展开更多
Calcium carbonate crystals with various morphologies have been found in a variety of biospecimens and artificially synthesized structures. Usually, the diversity in morphology can be attributed to different types of i...Calcium carbonate crystals with various morphologies have been found in a variety of biospecimens and artificially synthesized structures. Usually, the diversity in morphology can be attributed to different types of interactions between the specific crystal faces and the environment or the templates used for the growth of CaCO3 crystals. On the other hand, isotropic amorphous calcium carbonate （ACC） has been recognized as the precursor of other crystalline calcium carbonate forms for both in vivo and in vitro systems. However, here we propose a self-confined amorphous template process leading to the anisotropic growth of single-crystalline calcite nanowires. Initiated by the assembly of precipitated nanoparticles, the calcite nanowires grew via the continuous precipitation of partly crystallized ACC nanodroplets onto their tips. Then, the crystalline domains in the tip, which were generated from the partly crystallized nanodroplets, coalesced in the interior of the nanowire to form a single-crystalline core. The ACC domains were left outside and spontaneously formed a protective shell to retard the precipitation of CaCO3 onto the side surface of the nanowire and thus guided the highly anisotropic growth of nanowires as a template.展开更多
Hydrothermal treatment has been widely applied in the synthesis of well crystalline calcium silicate hydrate（CSH）, such as tobermorite and xonotlite. However, both morphology and crystallinity of CSH are greatly aff...Hydrothermal treatment has been widely applied in the synthesis of well crystalline calcium silicate hydrate（CSH）, such as tobermorite and xonotlite. However, both morphology and crystallinity of CSH are greatly affected by the conditions of hydrothermal treatment including siliceous materials, temperature increase rate and isothermal periods. In this study, the influence of hydrothermal conditions on the growth of nano-crystalline CSH was investigated based on XRD analysis. Results showed that siliceous materials with amorphous nature（i e, nano silica powder） are beneficial to synthesize pure amorphous CSH, while the use of more crystallized siliceous materials（i e, diatomite and quartz powder） leads to producing crystalline CSH. Results also indicate that the formation of tobermorite and xonotlite is greatly affected by the temperature rise rate during hydrothermal treatment.展开更多
Calcium phosphate(CaP)has been widely used for bone defect repair due to good biocompatibility and osteoconductivity.Additive manufacture of calcium phosphate bioceramics with tailored architectures and improved mecha...Calcium phosphate(CaP)has been widely used for bone defect repair due to good biocompatibility and osteoconductivity.Additive manufacture of calcium phosphate bioceramics with tailored architectures and improved mechanical properties has recently attracted great attention.Herein,calcium phosphate nanoparticles with the size of~89-164 nm were synthesized by the hydrothermal treatment of amorphous calcium phosphate(ACP)precursors at 180°C for 24 h.Biofunctional elements including Mg,Sr and Zn have been doped into these calcium phosphate nanoparticles.Our results revealed that Mg^(2+)ions played critical roles in formation of whitlockite-type calcium phosphate(not hydroxyapatite)from ACP precursors.Moreover,gyroid scaffolds with bionic triply periodic minimal surface structures were fabricated using stereolithography printing of these calcium phosphate nanoparticles,which are likely used as biofunctional scaffolds for bone repair.展开更多
Using a titration setup to accurately control the reaction conditions and in situ monitor the reaction,we showed that fluoride exhibited negligible effects on the ion association process of calcium and phosphate and t...Using a titration setup to accurately control the reaction conditions and in situ monitor the reaction,we showed that fluoride exhibited negligible effects on the ion association process of calcium and phosphate and the formation of ACP nanospheres in a buffer solution with constant ionic strength.However,the stability of ACP increased with increasing fluoride concentration,which was ascribed to the inhibitory effect of fluoride on the aggregation of ACP nanospheres and the nucleation of nanocrystals on the surface of ACP nanospheres.Furthermore,fluoride could inhibit the lateral growth of HAP nanosheets and promote the formation of rod-like crystals.These results further improve our understanding of the crystallization pathway of HAP crystals and the regulatory effects of fluoride.展开更多
Bone and teeth are derived from intrafibrillarly mineralized collagen fibrils as the second level of hierarchy.According to polymer-induced liquid-precursor process,using amorphous calcium phosphate precursor(ACP)is a...Bone and teeth are derived from intrafibrillarly mineralized collagen fibrils as the second level of hierarchy.According to polymer-induced liquid-precursor process,using amorphous calcium phosphate precursor(ACP)is able to achieve intrafibrillar mineralization in the case of bone biomineral in vitro.Therefore,ACP precursors might be blended with any osteoconductive scaffold as a promising bone formation supplement for in-situ remineralization of collagens in bone.In this study,mesoporous silica nanoparticles with carboxyl-functionalized groups and ultra large-pores have been synthesized and used for the delivery of liquid like biomimetic precursors(ACP).The precursor delivery capacity of the nanoparticles was verified by the precursor release profile and successful mineralization of 2D and 3D collagen models.The nanoparticles could be completely degraded in 60 days and exhibited good biocompatibility as well.The successful translational strategy for biomineralization precursors showed that biomineralization precursor laden ultra large pore mesoporous silica possessed the potential as a versatile supplement in demineralized bone formation through the induction of intrafibrillar collagen mineralization.展开更多
3D porous scaffold could provide suitable bone-like structure for cell adhesion and proliferation;however,surgical suffering from large volume implantation is a great challenge for patients.In this study,a shape progr...3D porous scaffold could provide suitable bone-like structure for cell adhesion and proliferation;however,surgical suffering from large volume implantation is a great challenge for patients.In this study,a shape programmable porous poly(ε-caprolactone)(PCL)-based polyurethane scaffold with memory effect was synthesized via gas foaming method,using Citrate modified Amorphous calcium Phosphate(CAP)as bioactive factor.The bending experiments indicated that the scaffolds achieved excellent shape-memory effect,which could be influenced by particle weight content.In vitro mineralization results suggested that the deposition of hydroxyapatite was promoted by scaffolds.Additionally,cell assay showed that composite scaffolds presented good cell toxicity and osteogenicity by the differentiation of rat Mesenchymal Stem Cells(rMSCs)into the osteogenic lineage.In the model of rat cranial implantation,the reparative tissue covered the defect site and bone-like structure deposited on the scaffold due to the formation of new bones.In summary,the porous smart shape-memory composite scaffolds could be a potential candidate in future distinctive bone repair applications.展开更多
The role of the thermal history of the precursor was studied for amorphous and crystalline calcium carbon- ate phases synthesized from calcium nitrate. The X-ray diffraction patterns of these phases are influenced by ...The role of the thermal history of the precursor was studied for amorphous and crystalline calcium carbon- ate phases synthesized from calcium nitrate. The X-ray diffraction patterns of these phases are influenced by their annealing temperature of 0, 300, 400, and 500 ℃. However, the effect of the precursor thermal history on the X-ray diffraction pattern of the resulting calcium carbonate phase is negligible. Transmis- sion electron microscopy indicates that materials annealed at 400 ℃ consist of amorphous aggregates, irrespective of the precursor thermal history. The crystallite size of crystalline calcium carbonate is influ- enced by the precursor thermal history, and ranges from 23 to 26 rim. Near-edge X-ray absorption fine structure measurements indicate that the annealing temperature plays an important role in determining the local electronic structure. The role of the thermal history of the precursor is also important for the resultinu electronic structure.展开更多
Recently,a de novo synthetic calcium-responsive self-assemblyβ-sheet peptide ID8(Ile-Asp-Ile-Asp-Ile-Asp-Ile-Asp)has been developed to serve as the template inducing hydroxyapatite nucleation.The aim of this study wa...Recently,a de novo synthetic calcium-responsive self-assemblyβ-sheet peptide ID8(Ile-Asp-Ile-Asp-Ile-Asp-Ile-Asp)has been developed to serve as the template inducing hydroxyapatite nucleation.The aim of this study was to evaluate the effect of ID8 on intrafibrillar mineralization of collagen making full use of its self-assembly ability.The mineralization experiments were carried out in vitro on both bare TypeⅠcollagen and fully demineralized dentin samples.The calcium-responsive self-assembly of ID8 was revealed by circular dichroism spectrum,8-anilino-1-naphthalenesulfonic acid ammonium salt hydrate assay,attenuated total reflection Fourier transform infrared spectrum(ATR-FTIR)and transmission electron microscope(TEM).Polyacrylic acid(450 kDa)with a concentration of 100μg ml^(-1)was selected as the nucleation inhibitor based on the determination of turbidimetry and TEM with selected area electron diffraction(TEM-SAED).The results showed that collagen intrafibrillar mineralization was significantly promoted with the pretreatment of self-assembly ID8 detected by TEM-SAED,SEM,X-ray diffraction and ATRFTIR.The pretreatment of collagen utilizing self-assembly ID8 not only enhanced intermolecular hydrogen bonding but also contributed to calcium retention inside collagen and significantly increased the hydrophilicity of collagen.These results indicated that peptides with self-assembly properties like ID8 are expected to be potential tools for biomimetic mineralization of collagen.展开更多
Amyloid deposits are widely presented in ectopic calcification associated with many degenerative diseases,such as calcific aortic valve disease and Alzheimer’s disease.Recently,amyloid-like secondary structures have ...Amyloid deposits are widely presented in ectopic calcification associated with many degenerative diseases,such as calcific aortic valve disease and Alzheimer’s disease.Recently,amyloid-like secondary structures have also been observed in matrix proteins during physiological mineralization processes.With advancing observational apparatus,the mineral-templating role of amyloid has been increasingly investigated;nevertheless,it is still challenging to elucidate the explicit contribution of amyloid-like proteins in both pathological and physiological calcification.In this review,we discuss the potential roles of amyloid-forming proteins in both pathological and physiological mineralization,the nature of the interactions between the amyloid-like structure and the mineral ions,as well as the mechanisms underlying hierarchical mineralization templated by amyloid proteins.Taking inspiration from nature’s book,we summarize the cutting-edge developments in amyloid-based materials for hard tissue repair.Spanning from mechanisms to applications,this review provides valuable insights for further interdisciplinary research.展开更多
As a global public health focus,oral health plays a vital role in facilitating overall health.Defected teeth characterized by exposure of dentin generally increase the risk of aggravating oral diseases.The exposed den...As a global public health focus,oral health plays a vital role in facilitating overall health.Defected teeth characterized by exposure of dentin generally increase the risk of aggravating oral diseases.The exposed dentinal tubules provide channels for irritants and bacterial invasion,leading to dentin hypersensitivity and even pulp inflammation.Cariogenic bacterial adhesion and biofilm formation on dentin are responsible for tooth demineralization and caries.It remains a clinical challenge to achieve the integration of tubule occlusion,collagen mineralization,and antibiofilm functions for managing exposed dentin.To address this issue,an epigallocatechin-3-gallate(EGCG)and poly(allylamine)-stabilized amorphous calcium phosphate(PAH-ACP)co-delivery hollow mesoporous silica(HMS)nanosystem(E/PA@HMS)was herein developed.The application of E/PA@HMS effectively occluded the dentinal tubules with acid-and abrasion-resistant stability and inhibited the biofilm formation of Streptococcus mutans.Intrafibrillar mineralization of collagen fibrils and remineralization of demineralized dentin were induced by E/PA@HMS.The odontogenic differentiation and mineralization of dental pulp cells with high biocompatibility were also promoted.Animal experiments showed that E/PA@HMS durably sealed the tubules and inhibited biofilm growth up to 14 days.Thus,the development of the E/PA@HMS nanosystem provides promising benefits for protecting exposed dentin through the coordinated manipulation of dentin caries and hypersensitivity.展开更多
Magnesium calcite(Mg-calcite)mesocrystal is widespread in the biominerals with specific functions.Until now,it remains challenging to obtain Mg-calcite mesocrystals without organic additives and the formation mechanis...Magnesium calcite(Mg-calcite)mesocrystal is widespread in the biominerals with specific functions.Until now,it remains challenging to obtain Mg-calcite mesocrystals without organic additives and the formation mechanism of Mg-calcite mesocrystals in the ocean is not clear yet.We report here the synthesis of corn-like Mg-calcite mesocrystals from pure amorphous calcium carbonate(ACC)via a facile method only by using Ca^(2+)and Mg^(2+).The obtained Mg-calcite is composed of many nanocubes with common crystallographic orientation,which shows very good single crystal feature.In the crystallizing procedure,the ACC nanospheres rapidly agglomerate into Mg-calcite corn-like mesocrystal by oriented attachment(OA)in a certain direction,which belongs to the non-classical nucleation.By this method,the molar ratio of Ca^(2+)and Mg^(2+)plays a vital role in the whole crystallization procedure,which may shed a new light on disclosing the mechanism behind for the effect of seawater in the formation of biological Mg-calcite in nature.展开更多
基金financially supported by the National Natural Science Foundation of China(Nos.82203680 and 52273278)the Natural Scientific Foundation of Liaoning Province(No.2021-MS-176)+1 种基金Shenyang Bureau of Science and Technology(No.RC230527)the Central Guidance Funding for Local Scientific and Techno-logical Development in Liaoning(No.2023JH6/100100029).
文摘Guided bone regeneration in the alveolar bone relies on the colonization and differentiation of immune cells within the defect area.The absence of osteoinductive and osteoimmune properties of currently available scaffolds hinders to achieve optimal repair outcomes in clinical settings.Thus,we aimed to enhance the bone repair ability of polycaprolactone(PCL)scaffolds by incorporating osteoinductive amorphous calcium phosphate(ACP)with immune-regulating zinc ions(ACP(Zn),ACZP),to create a favorable immunomodulatory microenvironment.After one day of co-culture with PCL-ACZP,the spreading area of macrophage cells was significantly higher than that from the original PCL scaffold.Additionally,over 32.1%of macrophages exhibited M2 polarization within three days of co-culture.The PCLACZP/macrophage-conditioned medium significantly boosted osteogenic gene expression in MC3T3-E1 cells.After eight weeks of implantation in a rat femoral condyle defect,the BV/TV from the PCL-ACZP group reached 32.9%,1.4 times of that from the PCL group.Furthermore,the PCL-ACZP-GelMA biphasic module as prepared successfully achieved complete regeneration of three-walled alveolar bone defects in rabbits,resulting in arch-shaped alveolar bone repair and providing greater convenience in the clinical settings.This study showcased the effectiveness of PCL-ACZP-GelMA biphasic module as bioactive scaffolds in the morphological restoration of alveolar bone.
基金financial supports from the Natural Science Foundation of China(No.50973069)the project of Postgraduate Degree Construction,Southwest University for Nationalities(No.2013XWD-S0703)
文摘Although much effort has been focused on the preparation of stable amorphous calcium phosphate （ACP） nanoparticles in aqueous solution, the redispersibility and long-term stability of ACP nanoparticles in aqueous solution remains an unresolved problem. In this work, stable colloidal ACPs were prepared by using an organic bisphosphonate （BP） as a sterically hindered agent in aqueous solution. The harvested calcium phosphate nanoparticles were characterized by inductively coupled plasma atomic emission spectrometry （ICP-AES）, Fourier transform infrared （FTIR）, X-ray diffraction （XRD）, dynamic light scattering （DLS） and transmission electron microscopy （TEM）. ICP-AES, FTIR and XRD results suggested the particles were ACP. DLS and TEM results indicated that the size of the ACP nanoparticles were in the range of 60 nm with a spherical morphology. The resulting calcium phosphate nanoparticles retained its amorphous nature in aqueous solution for at least 6 months at room temperature due to the stabilizing effect of the organic bisphosphonate. Moreover, the surface of the ACP nanoparticles adsorbed with the organic bisphosphate used showed good redispersibility and high colloid stability both in organic and aqueous solutions.
基金financially supported by the National Natural Science Foundation of China (31700689)Natural Science Foundation of Shanxi Province (201901D111115)+1 种基金Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi (172040098-S)Transformation of Scientific and Technological Achievements Programs of Higher Education Institutions in Shanxi (2020CG015)
文摘Recently,multifunctional nanoparticles have shown great prospects in cancer treatment,which have the ability to simultaneously deliver the drug,image and target tumor cells.In this paper,we designed a luminescent nanoparticles platform based on hydrothermal hyaluronic acid/amorphous calcium phosphate(HA-FCNs/ACP)with multifunctional properties for drug delivery,bio-imaging,and targeting treatment.HA-FCNs/ACP shows an ability to load curcumin(Cur)with pH-sensitive responsive drug release behavior and excellent biocompatibility.HA-FCNs/ACP dispersed in the cytoplasm through the overexpressed CD44 receptor that is actively targeted into human lung cancer cells(A549 cells).Meanwhile,the viability of A549 cells was significantly inhibited in vitro.The prepared HA-FCNs and HA-FCNs/ACP both exhibit excellent targeted bioimaging performance on cancer cells.Hence,the as-prepared nanoparticles have promising applications in treating tumor disease.
基金supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award numbers P50AR072000(HAA),P30AR069655(HAA)the Musculoskeletal Transplant Foundation(HAA)the AO Foundation Clinical Priority Program(HAA).
文摘Regenerating critical-sized long bone defects poses substantial challenges due to limitations of autografts and processed allografts.Biomaterial scaffolds offer versatile alternatives,yet their effectiveness is often constrained by their limited innate osteoinductivity.While growth factors and cells can enhance osteoinduction,the inclusion of biologics in biomaterial scaffolds creates regulatory challenges for clinical translation.To address this,here we describe three-dimensional(3D)printed polycaprolactone(PCL)scaffolds for temporally controlled delivery of osteoimmunomodulatory amorphous calcium phosphate-chitosan nanoparticles(ACPC-NP).In vitro,the ACPC-NP exhibit concentration dependent effects on osteoblasts,monocytes,and osteoclasts.At increasing concen-trations up to 500μg/ml,these nanoparticles stimulate osteogenesis,modulate M2/M1 macrophage polarization,and inhibit osteoclast maturation and activity.Leveraging these concentration-dependent effects in vivo through temporally controlled release of ACPC-NP from 3D-printed PCL scaffolds,we observe the complete regeneration and the restoration of biomechanical strength of critically sized radial defects in rats.Such healing is absent in defects implanted with bare PCL scaffolds or those loaded with calcium-phosphate microparticles.The tunable osteoimmunomodulation by the NP underscores the translational potential of this technology to yield struc-turally sound and functionally robust bone regeneration outcomes.
基金supported partly by the National Key R&D Program of China(No.2024YFC2418600)the Natural Science Foundation of China(No.82370987)the Natural Science Foundation of Liaoning Prov-ince(No.2024-MSBA-66).
文摘The repair of alveolar bone defects continues to pose a significant challenge within the field of stomatology.As the primary implant material utilized in clinical treatment,the mechanisms by which calcium phosphate-based materials promote bone formation necessitate further in-depth exploration.Single-cell RNA sequencing was employed to characterize the immune microenvironment surrounding hydroxyapatite(HA)-mediated alveolar bone regeneration,confirming the macrophage-dependent enhancement of regenerative outcomes.Based on this finding,amorphous calcium zinc phosphate(ACZP)nanoparticles were developed as immunomodulatory nanomaterials.ACZP can accelerate bone regeneration via anti-inflammatory phenotype polarization,specif-ically by inhibiting endoplasmic reticulum-mitochondria coupling,reducing pathological Ca2+transfer,and shifting macrophage metabolism from glycolysis to oxidative phosphorylation(OXPHOS),thereby enhancing bioenergetics.Our results demonstrated that ACZP can inhibit the IP3R/MCU pathway in macrophages,restoring their anti-inflammatory capabilities and ultimately achieving significant effects in the alveolar bone defects of New Zealand white rabbits.Twelve weeks post-surgery,the defects in the ACZP group were filled with nearly 70%newly formed bone tissue.This study elucidated the immunomodulatory role of ACZP materials in the dy-namic process of alveolar bone healing,providing novel insights and methodologies for the design of materials in the fields of tissue engineering and regenerative medicine.
文摘Background Enamel decalcification in orthodontics is a concern for dentists and methods to remineralize these lesions are the focus of intense research. The aim of this study was to evaluate the remineralizing effect of casein phosphopeptide amorphous calcium phosphate （CPP-ACP） nanocomplexes on enamel decalcification in orthodontics. Methods Twenty orthodontic patients with decalcified enamel lesions during fixed orthodontic therapy were recruited to this study as test group and twenty orthodontic patients with the similar condition as control group. GC Tooth Mousse, the main component of which is CPP-ACP, was used by each patient of test group every night after tooth-brushing for six months. For control group, each patient was asked to brush teeth with toothpaste containing 1100 parts per million （ppm） of fluoride twice a day. Standardized intraoral images were taken for all patients and the extent of enamel decalcification was evaluated before and after treatment over this study period. Measurements were statistically compared by t test. Results After using CPP-ACP for six months, the enamel decalcification index （EDI） of all patients had decreased; the mean EDI before using CPP-ACP was 0.191＋0.025 and that after using CPP-ACP was 0.183＋0.023, the difference was significant （t=5.169, P 〈0.01）. For control group, the mean EDI before treatment was 0.188±0.037 and that after treatment was 0.187±0.046, the difference was not significant （t=1.711, P 〉0.05）. Conclusion CPP-ACP can effectively improve the demineralized enamel lesions during orthodontic treatment, so it has some remineralization potential for enamel decalcification in orthodontics.
基金supported by the National Natural Science Foundation of China(2061023,20871102)Zhejiang Provincial Natural Science Foun-dation(R407087)the Chinese Universities Scientific Fund and Daming Biomineralization Foundation
文摘Biological mineral generation via an amorphous precursor is a topic of great current interest.Various factors such as the temperature,solution composition and presence of organic molecules can influence this important inorganic process.Here we demonstrate that this mineral transformation can actually readily be regulated by solution viscosity,a fundamental but often overlooked property.In our experiment,amorphous calcium carbonate(ACC),a key model compound in biomimetic mineralization studies,is synthesized and dispersed into inert dispersants with different viscosities and the crystallization process is examined by using FT-IR spectroscopy and XRD.It is found that the inhibition of the transformation of ACC becomes more significant with increasing fluid viscosity.This phenomenon can be explained by the differences in ion diffusion in different media.Furthermore,the resulting crystals always have different morphologies and size distributions although they all have the calcite structure.This study implies that the importance of the fluid medium cannot be ignored in building a complete understanding of biological control of biomimetic crystallizations.
基金The present study was supported by grants from the Natural Science Foundation of China （No. 81201414 and No. 81101377）, the Doctoral Fund of the Ministry of Education of China （No. 20100101120132）, and the Natural Science Grants of the Zhejiang Province （No. LQ14H060001）.
文摘Background The initial osteoblastic adhesion to materials characterizes the first phase of cell-material interactions and influences all the events leading to the formation of new bone. In a previous work, we developed a novel amorphous calcium phosphate （ACP）/poly（L-lactic acid） （PLLA） material that demonstrated morphologic variations in its microstructure. The aim of this study was to investigate the initial interaction between this material and osteoblastic cells. Cellular attachment and the corresponding signal transduction pathways were investigated. Methods A porous ACP/PLLA composite and PLLA scaffold （as a control） were incubated in fetal bovine serum （FBS） containing phosphate-buffered saline （PBS）, and the protein adsorption was determined. Osteoblastic MG63 cells were seeded on the materials and cultured for 1, 4, 8, or 24 hours. Cell attachment was evaluated using the MTS method. Cell morphology was examined using scanning electron microscopy （SEM）. The expression levels of the genes encoding integrin subunits αl, α5, αv, β1, focal adhesion kinase （FAK）, and glyceraldehyde-3-phosphate dehydrogenase （GAPDH） were determined using real-time reverse transcription polymerase chain reaction （RT-PCR）. Results The ACP/PLLA material significantly increased the protein adsorption by 6.4-fold at 1 hour and 2.4-fold at 24 hours, compared with the pure PLLA scaffold. The attachment of osteoblastic cells to the ACP/PLLA was significantly higher than that on the PLLA scaffold. The SEM observation revealed a polygonal spread shape of cells on the ACP/ PLLA, with the filopodia adhered to the scaffold surface. In contrast, the cells on the PLLA scaffold exhibited a spherical or polygonal morphology. Additionally, real-time RT-PCR showed that the genes encoding the integrin subunits αl, αv, β1, and FAK were expressed at higher levels on the ACP/PLLA composite. Conclusions The ACP/PLLA composite promoted protein adsorption and osteoblastic adhesion. The enhanced cell adhesion may be mediated by the binding of integrin subunits αl, αv, and β1, and subsequently may be regulated through the FAK signal transduction pathways.
基金supported by Beijing Nova Program(Z211100002121127 and 20220484219,China)Beijing Natural Science Foundation(L212059,China)+1 种基金Fundamental Research Funds for the Central Universities(3332021101,China)CAMS Innovation Fund for Medical Sciences(CIFMS,2021-I2M-1-026 and 2021-I2M-1-028,China).
文摘Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability.Calcium-based materials can also deliver contrast agents,which can enhance real-time imaging and exert a Ca^(2+)-interfering therapeutic effect.Based on these characteristics,amorphous calcium carbonate(ACC),as a brunch of calcium-based biomaterials,has the potential to become a widely used biomaterial.Highly functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However,the standalone presence of ACC is unstable in vivo.Additives are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its destination.ACC has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo,such as Ca^(2+) with an immune-regulating ability and CO_(2) with an imaging-enhancing ability.Owing to these characteristics,ACC has been studied for selfsacrificing templates of carrier construction,targeted delivery of oncology drugs,immunomodulation,tumor imaging,tissue engineering,and calcium supplementation.Emphasis in this paper has been placed on the origin,structural features,and multiple applications of ACC.Meanwhile,ACC faces many challenges in clinical translation,and long-term basic research is required to overcome these challenges.We hope that this study will contribute to future innovative research on ACC.
基金Acknowledgements This work was handed by the National Natural Science Foundation of China （Nos. 21521001, 21431006, 21061160492, and J1030412）, the National Basic Research Program of China （Nos. 2014CB931800 and 2013CB933900）, the Users with Excellence and Scientific Research Grant of Hefei Science Center of CAS （Nos. 2015HSC-UE007 and 2015SRG-HSC038）, and the Chinese Academy of Sciences （No. KJZD-EW-M01-1）.
文摘Calcium carbonate crystals with various morphologies have been found in a variety of biospecimens and artificially synthesized structures. Usually, the diversity in morphology can be attributed to different types of interactions between the specific crystal faces and the environment or the templates used for the growth of CaCO3 crystals. On the other hand, isotropic amorphous calcium carbonate （ACC） has been recognized as the precursor of other crystalline calcium carbonate forms for both in vivo and in vitro systems. However, here we propose a self-confined amorphous template process leading to the anisotropic growth of single-crystalline calcite nanowires. Initiated by the assembly of precipitated nanoparticles, the calcite nanowires grew via the continuous precipitation of partly crystallized ACC nanodroplets onto their tips. Then, the crystalline domains in the tip, which were generated from the partly crystallized nanodroplets, coalesced in the interior of the nanowire to form a single-crystalline core. The ACC domains were left outside and spontaneously formed a protective shell to retard the precipitation of CaCO3 onto the side surface of the nanowire and thus guided the highly anisotropic growth of nanowires as a template.
基金Funded by the Fundamental Research Funds for the Central Universities(No.2018CDXYCL0018)the National Natural Science Foundation of China(NSFC)(No.51678093)the National Youth Fund(No.51402029)
文摘Hydrothermal treatment has been widely applied in the synthesis of well crystalline calcium silicate hydrate（CSH）, such as tobermorite and xonotlite. However, both morphology and crystallinity of CSH are greatly affected by the conditions of hydrothermal treatment including siliceous materials, temperature increase rate and isothermal periods. In this study, the influence of hydrothermal conditions on the growth of nano-crystalline CSH was investigated based on XRD analysis. Results showed that siliceous materials with amorphous nature（i e, nano silica powder） are beneficial to synthesize pure amorphous CSH, while the use of more crystallized siliceous materials（i e, diatomite and quartz powder） leads to producing crystalline CSH. Results also indicate that the formation of tobermorite and xonotlite is greatly affected by the temperature rise rate during hydrothermal treatment.
基金financially supported by the National Key Research and Development Program of China from Ministry of Science and Technology(No.2016YFC1100502)the Doctoral Research Foundation Program of Liaoning Province(No.2019-BS-256)+2 种基金the Key Research Program of Frontier Sciences(No.QYZDY-SSWJSC031)from Chinese Academy of Sciences(CAS)Key Research and Development Program of Liaoning Province(No.201703031)Shenyang Key R&D and Technology Transfer Program(No.Z17-7023)。
文摘Calcium phosphate(CaP)has been widely used for bone defect repair due to good biocompatibility and osteoconductivity.Additive manufacture of calcium phosphate bioceramics with tailored architectures and improved mechanical properties has recently attracted great attention.Herein,calcium phosphate nanoparticles with the size of~89-164 nm were synthesized by the hydrothermal treatment of amorphous calcium phosphate(ACP)precursors at 180°C for 24 h.Biofunctional elements including Mg,Sr and Zn have been doped into these calcium phosphate nanoparticles.Our results revealed that Mg^(2+)ions played critical roles in formation of whitlockite-type calcium phosphate(not hydroxyapatite)from ACP precursors.Moreover,gyroid scaffolds with bionic triply periodic minimal surface structures were fabricated using stereolithography printing of these calcium phosphate nanoparticles,which are likely used as biofunctional scaffolds for bone repair.
基金Funded by the National Natural Science Foundation of China(No.52172287)the National Key Research and Development Program of China(No.2021YFA0715700)。
文摘Using a titration setup to accurately control the reaction conditions and in situ monitor the reaction,we showed that fluoride exhibited negligible effects on the ion association process of calcium and phosphate and the formation of ACP nanospheres in a buffer solution with constant ionic strength.However,the stability of ACP increased with increasing fluoride concentration,which was ascribed to the inhibitory effect of fluoride on the aggregation of ACP nanospheres and the nucleation of nanocrystals on the surface of ACP nanospheres.Furthermore,fluoride could inhibit the lateral growth of HAP nanosheets and promote the formation of rod-like crystals.These results further improve our understanding of the crystallization pathway of HAP crystals and the regulatory effects of fluoride.
基金the National Natural Science Foundation of China(No.81600911).
文摘Bone and teeth are derived from intrafibrillarly mineralized collagen fibrils as the second level of hierarchy.According to polymer-induced liquid-precursor process,using amorphous calcium phosphate precursor(ACP)is able to achieve intrafibrillar mineralization in the case of bone biomineral in vitro.Therefore,ACP precursors might be blended with any osteoconductive scaffold as a promising bone formation supplement for in-situ remineralization of collagens in bone.In this study,mesoporous silica nanoparticles with carboxyl-functionalized groups and ultra large-pores have been synthesized and used for the delivery of liquid like biomimetic precursors(ACP).The precursor delivery capacity of the nanoparticles was verified by the precursor release profile and successful mineralization of 2D and 3D collagen models.The nanoparticles could be completely degraded in 60 days and exhibited good biocompatibility as well.The successful translational strategy for biomineralization precursors showed that biomineralization precursor laden ultra large pore mesoporous silica possessed the potential as a versatile supplement in demineralized bone formation through the induction of intrafibrillar collagen mineralization.
基金supported by the National Natural Science Foundation of China(NO.41673109)Sichuan Science and Technology Program(2021YFH0098)+2 种基金Sichuan University Panzhihua school city strategic cooperation special fund project(2019CDPZH-6)the Science and Technology Department Project of Sichuan Province(2018SZDZX0022)Key Project of Sichuan Vanadium and Titanium Industry Development Research Center(2018VTCY-Z-01).
文摘3D porous scaffold could provide suitable bone-like structure for cell adhesion and proliferation;however,surgical suffering from large volume implantation is a great challenge for patients.In this study,a shape programmable porous poly(ε-caprolactone)(PCL)-based polyurethane scaffold with memory effect was synthesized via gas foaming method,using Citrate modified Amorphous calcium Phosphate(CAP)as bioactive factor.The bending experiments indicated that the scaffolds achieved excellent shape-memory effect,which could be influenced by particle weight content.In vitro mineralization results suggested that the deposition of hydroxyapatite was promoted by scaffolds.Additionally,cell assay showed that composite scaffolds presented good cell toxicity and osteogenicity by the differentiation of rat Mesenchymal Stem Cells(rMSCs)into the osteogenic lineage.In the model of rat cranial implantation,the reparative tissue covered the defect site and bone-like structure deposited on the scaffold due to the formation of new bones.In summary,the porous smart shape-memory composite scaffolds could be a potential candidate in future distinctive bone repair applications.
文摘The role of the thermal history of the precursor was studied for amorphous and crystalline calcium carbon- ate phases synthesized from calcium nitrate. The X-ray diffraction patterns of these phases are influenced by their annealing temperature of 0, 300, 400, and 500 ℃. However, the effect of the precursor thermal history on the X-ray diffraction pattern of the resulting calcium carbonate phase is negligible. Transmis- sion electron microscopy indicates that materials annealed at 400 ℃ consist of amorphous aggregates, irrespective of the precursor thermal history. The crystallite size of crystalline calcium carbonate is influ- enced by the precursor thermal history, and ranges from 23 to 26 rim. Near-edge X-ray absorption fine structure measurements indicate that the annealing temperature plays an important role in determining the local electronic structure. The role of the thermal history of the precursor is also important for the resultinu electronic structure.
基金supported by the National Natural Science Foundation of China(Grant Nos.81470734,Grant Nos.81970931).
文摘Recently,a de novo synthetic calcium-responsive self-assemblyβ-sheet peptide ID8(Ile-Asp-Ile-Asp-Ile-Asp-Ile-Asp)has been developed to serve as the template inducing hydroxyapatite nucleation.The aim of this study was to evaluate the effect of ID8 on intrafibrillar mineralization of collagen making full use of its self-assembly ability.The mineralization experiments were carried out in vitro on both bare TypeⅠcollagen and fully demineralized dentin samples.The calcium-responsive self-assembly of ID8 was revealed by circular dichroism spectrum,8-anilino-1-naphthalenesulfonic acid ammonium salt hydrate assay,attenuated total reflection Fourier transform infrared spectrum(ATR-FTIR)and transmission electron microscope(TEM).Polyacrylic acid(450 kDa)with a concentration of 100μg ml^(-1)was selected as the nucleation inhibitor based on the determination of turbidimetry and TEM with selected area electron diffraction(TEM-SAED).The results showed that collagen intrafibrillar mineralization was significantly promoted with the pretreatment of self-assembly ID8 detected by TEM-SAED,SEM,X-ray diffraction and ATRFTIR.The pretreatment of collagen utilizing self-assembly ID8 not only enhanced intermolecular hydrogen bonding but also contributed to calcium retention inside collagen and significantly increased the hydrophilicity of collagen.These results indicated that peptides with self-assembly properties like ID8 are expected to be potential tools for biomimetic mineralization of collagen.
基金supported by the National Natural Science Foundation of China(Nos.82301138 and 82370918)the National Key R&D Program of China(No.2022YFC2402900).
文摘Amyloid deposits are widely presented in ectopic calcification associated with many degenerative diseases,such as calcific aortic valve disease and Alzheimer’s disease.Recently,amyloid-like secondary structures have also been observed in matrix proteins during physiological mineralization processes.With advancing observational apparatus,the mineral-templating role of amyloid has been increasingly investigated;nevertheless,it is still challenging to elucidate the explicit contribution of amyloid-like proteins in both pathological and physiological calcification.In this review,we discuss the potential roles of amyloid-forming proteins in both pathological and physiological mineralization,the nature of the interactions between the amyloid-like structure and the mineral ions,as well as the mechanisms underlying hierarchical mineralization templated by amyloid proteins.Taking inspiration from nature’s book,we summarize the cutting-edge developments in amyloid-based materials for hard tissue repair.Spanning from mechanisms to applications,this review provides valuable insights for further interdisciplinary research.
基金This work was financially supported by National Natural Science Foundation of China(81901043,81970918,and 82001106)J.Yu’s research conducted at the UBC Faculty of Dentistry was supported by China Scholarship Council(202006275049).
文摘As a global public health focus,oral health plays a vital role in facilitating overall health.Defected teeth characterized by exposure of dentin generally increase the risk of aggravating oral diseases.The exposed dentinal tubules provide channels for irritants and bacterial invasion,leading to dentin hypersensitivity and even pulp inflammation.Cariogenic bacterial adhesion and biofilm formation on dentin are responsible for tooth demineralization and caries.It remains a clinical challenge to achieve the integration of tubule occlusion,collagen mineralization,and antibiofilm functions for managing exposed dentin.To address this issue,an epigallocatechin-3-gallate(EGCG)and poly(allylamine)-stabilized amorphous calcium phosphate(PAH-ACP)co-delivery hollow mesoporous silica(HMS)nanosystem(E/PA@HMS)was herein developed.The application of E/PA@HMS effectively occluded the dentinal tubules with acid-and abrasion-resistant stability and inhibited the biofilm formation of Streptococcus mutans.Intrafibrillar mineralization of collagen fibrils and remineralization of demineralized dentin were induced by E/PA@HMS.The odontogenic differentiation and mineralization of dental pulp cells with high biocompatibility were also promoted.Animal experiments showed that E/PA@HMS durably sealed the tubules and inhibited biofilm growth up to 14 days.Thus,the development of the E/PA@HMS nanosystem provides promising benefits for protecting exposed dentin through the coordinated manipulation of dentin caries and hypersensitivity.
基金the National Natural Science Foundation of China(21701162,21761132008 and 51702312)Anhui Provincial Natural Science Foundation(1808085MB27)+2 种基金the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(21521001)the Key Research Program of Frontier Sciences,CAS(QYZDJ-SSW-SLH036)the Users with Excellence and Scientific Research Grant of Hefei Science Center of CAS(2015HSC-UE007)。
文摘Magnesium calcite(Mg-calcite)mesocrystal is widespread in the biominerals with specific functions.Until now,it remains challenging to obtain Mg-calcite mesocrystals without organic additives and the formation mechanism of Mg-calcite mesocrystals in the ocean is not clear yet.We report here the synthesis of corn-like Mg-calcite mesocrystals from pure amorphous calcium carbonate(ACC)via a facile method only by using Ca^(2+)and Mg^(2+).The obtained Mg-calcite is composed of many nanocubes with common crystallographic orientation,which shows very good single crystal feature.In the crystallizing procedure,the ACC nanospheres rapidly agglomerate into Mg-calcite corn-like mesocrystal by oriented attachment(OA)in a certain direction,which belongs to the non-classical nucleation.By this method,the molar ratio of Ca^(2+)and Mg^(2+)plays a vital role in the whole crystallization procedure,which may shed a new light on disclosing the mechanism behind for the effect of seawater in the formation of biological Mg-calcite in nature.
