1.Research progress of bioactive scaffolds in repair and regeneration of osteoporotic bone defects.
Yuangang WU ; Kaibo SUN ; Yi ZENG ; Bin SHEN
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(1):100-105
OBJECTIVE:
To summarize the research progress of bioactive scaffolds in the repair and regeneration of osteoporotic bone defects.
METHODS:
Recent literature on bioactive scaffolds for the repair of osteoporotic bone defects was reviewed to summarize various types of bioactive scaffolds and their associated repair methods.
RESULTS:
The application of bioactive scaffolds provides a new idea for the repair and regeneration of osteoporotic bone defects. For example, calcium phosphate ceramics scaffolds, hydrogel scaffolds, three-dimensional (3D)-printed biological scaffolds, metal scaffolds, as well as polymer material scaffolds and bone organoids, have all demonstrated good bone repair-promoting effects. However, in the pathological bone microenvironment of osteoporosis, the function of single-material scaffolds to promote bone regeneration is insufficient. Therefore, the design of bioactive scaffolds must consider multiple factors, including material biocompatibility, mechanical properties, bioactivity, bone conductivity, and osteogenic induction. Furthermore, physical and chemical surface modifications, along with advanced biotechnological approaches, can help to improve the osteogenic microenvironment and promote the differentiation of bone cells.
CONCLUSION
With advancements in technology, the synergistic application of 3D bioprinting, bone organoids technologies, and advanced biotechnologies holds promise for providing more efficient bioactive scaffolds for the repair and regeneration of osteoporotic bone defects.
Humans
;
Tissue Scaffolds/chemistry*
;
Bone Regeneration
;
Osteoporosis/therapy*
;
Tissue Engineering/methods*
;
Biocompatible Materials/chemistry*
;
Printing, Three-Dimensional
;
Calcium Phosphates/chemistry*
;
Osteogenesis
;
Ceramics
;
Cell Differentiation
;
Hydrogels
;
Bioprinting
;
Bone and Bones
2.Research progress on strontium modified β-tricalcium phosphate composite biomaterials with immune regulatory properties.
Huanxi LI ; Xingyu SHAN ; Hongda WANG ; Zhimin TIAN ; Chunnuo HE ; Haoqiang ZHANG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(4):511-517
OBJECTIVE:
To review the research progress of strontium (Sr) modified β-tricalcium phosphate composite biomaterials (SrTCP) promoting osteogenesis through immune regulation, and provides reference and theoretical support for the further development and research of SrTCP bone repair materials in bone tissue engineering in the future.
METHODS:
The literature about SrTCP promoting osteogenesis through immune regulation at home and abroad in recent years was extensively reviewed, and the preparation methods, immune mechanism and application of promoting osteogenesis were summarized and analyzed.
RESULTS:
The preparation methods of SrTCP include solid-state reaction sintering method, solution combustion quenching method, direct doping method, ion substitution method, etc. SrTCP has immune regulatory effects, which can play an immune regulatory role in inducing macrophage polarization, inducing angiogenesis and anti oxidative stress to promote osteogenesis.
CONCLUSION
At present, studies have shown that SrTCP can promote bone defect repair through immune regulation. Subsequent studies can start from the control of the optimal repair concentration and release rate of Sr, and further clarify the specific mechanism of SrTCP in promoting angiogenesis and anti oxidative stress, which is helpful to develop new materials for bone defect repair.
Calcium Phosphates/pharmacology*
;
Strontium/pharmacology*
;
Biocompatible Materials/pharmacology*
;
Humans
;
Osteogenesis/drug effects*
;
Tissue Engineering/methods*
;
Bone Substitutes/pharmacology*
;
Bone Regeneration/drug effects*
;
Animals
;
Tissue Scaffolds/chemistry*
;
Neovascularization, Physiologic/drug effects*
;
Macrophages/immunology*
3.Preparation of calcium phosphate nanoflowers and evaluation of their antioxidant and osteogenic induction capabilities in vitro.
Mingyu JIA ; Zhihong CHEN ; Huajian ZHOU ; Yukang ZHANG ; Min WU
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(9):1203-1211
OBJECTIVE:
To investigate the antioxidant and osteogenic induction capabilities of calcium phosphate nanoflowers (hereinafter referred to as nanoflowers) in vitro at different concentrations.
METHODS:
Nanoflowers were prepared using gelatin, tripolyphosphate, and calcium chloride. Their morphology, microstructure, elemental composition and distribution, diameter, and molecular constitution were characterized using scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and energy-dispersive spectroscopy. Femurs and tibias were harvested from twelve 4-week-old Sprague Dawley rats, and bone marrow mesenchymal stem cells (BMSCs) were isolated and cultured using the whole bone marrow adherent method, followed by passaging. The third passage cells were identified as stem cells by flow cytometry and then co-cultured with nanoflowers at concentrations of 0, 0.4, 0.8, 1.2, 1.6, 2.0, 2.4, 2.8, 3.2, and 3.6 mg/mL. Cell counting kit 8 (CCK-8) assay was performed to screen for the optimal concentration that demonstrated the best cell viability, which was subsequently used as the experimental concentration for further studies. After co-culturing BMSCs with the screened concentration of nanoflowers, the biocompatibility of the nanoflowers was verified through live/dead cell staining, scratch assay, and cytoskeleton staining. The antioxidant capacity was assessed by using reactive oxygen species (ROS) fluorescence staining. The in vitro osteoinductive ability was evaluated via alkaline phosphatase (ALP) staining, alizarin red staining, and immunofluorescence staining of osteocalcin (OCN) and Runt-related transcription factor 2 (RUNX2). All the above indicators were compared with the control group of normally cultured BMSCs without the addition of nanoflowers.
RESULTS:
Scanning electron microscopy revealed that the prepared nanoflowers exhibited a flower-like structure; transmission electron microscopy scans discovered that the nanoflowers possessed a multi-layered structure, and high-magnification images displayed continuous atomic arrangements, with the nanoflower diameter measuring (2.00±0.25) μm; energy-dispersive spectroscopy indicated that the nanoflowers contained elements such as C, N, O, P, and Ca, which were uniformly distributed across the flower region; Fourier transform infrared spectroscopy analyzed the absorption peaks of each component, demonstrating the successful preparation of the nanoflowers. Through CCK-8 screening, the concentrations of 0.8, 1.2, and 1.6 mg/mL were selected for subsequent experiments. The live/dead cell staining showed that nanoflowers at different concentrations exhibited good cell compatibility, with the 1.2 mg/mL concentration being the best (P<0.05). The scratch assay results indicated that the cell migration ability in the 1.2 mg/mL group was superior to the other groups (P<0.05). The cytoskeleton staining revealed that the cell morphology was well-extended in all concentration groups, with no significant difference compared to the control group. The ROS fluorescence staining demonstrated that the ROS fluorescence in all concentration groups decreased compared to the control group after lipopolysaccharide induction (P<0.05), with the 1.2 mg/mL group showing the weakest fluorescence. The ALP staining showed blue-purple nodular deposits around the cells in all groups, with the 1.2 mg/mL group being significantly more prominent. The alizarin red staining displayed orange-red mineralized nodules around the cells in all groups, with the 1.2 mg/mL group having more and denser nodules. The immunofluorescence staining revealed that the expressions of RUNX2 and OCN proteins in all concentration groups increased compared to the control group, with the 1.2 mg/mL group showing the strongest protein expression (P<0.05).
CONCLUSION
The study successfully prepares nanoflowers, among which the 1.2 mg/mL nanoflowers exhibits excellent cell compatibility, antioxidant properties, and osteogenic induction capability, demonstrating their potential as an artificial bone substitute material.
Animals
;
Osteogenesis/drug effects*
;
Mesenchymal Stem Cells/drug effects*
;
Calcium Phosphates/pharmacology*
;
Rats, Sprague-Dawley
;
Rats
;
Antioxidants/chemistry*
;
Cells, Cultured
;
Cell Differentiation/drug effects*
;
Nanostructures/chemistry*
;
Tissue Engineering/methods*
;
Bone Marrow Cells/cytology*
;
Coculture Techniques
;
Tissue Scaffolds/chemistry*
;
Male
;
Biocompatible Materials/chemistry*
;
Cell Survival
;
Core Binding Factor Alpha 1 Subunit/metabolism*
;
Cell Proliferation
4.Three-dimensional (3D) printing-assisted freeze-casting of processed pyritum-doped β-tricalcium phosphate biomimetic scaffold with angiogenesis and bone regeneration capability.
Chenxu WEI ; Zongan LI ; Xiaoyun LIANG ; Yuwei ZHAO ; Xingyu ZHU ; Haibing HUA ; Guobao CHEN ; Kunming QIN ; Zhipeng CHEN ; Changcan SHI ; Feng ZHANG ; Weidong LI
Journal of Zhejiang University. Science. B 2025;26(9):863-880
Bone repair remains an important target in tissue engineering, making the development of bioactive scaffolds for effective bone defect repair a critical objective. In this study, β-tricalcium phosphate (β-TCP) scaffolds incorporated with processed pyritum decoction (PPD) were fabricated using three-dimensional (3D) printing-assisted freeze-casting. The produced composite scaffolds were evaluated for their mechanical strength, physicochemical properties, biocompatibility, in vitro pro-angiogenic activity, and in vivo efficacy in repairing rabbit femoral defects. They not only demonstrated excellent physicochemical properties, enhanced mechanical strength, and good biosafety but also significantly promoted the proliferation, migration, and aggregation of pro-angiogenic human umbilical vein endothelial cells (HUVECs). In vivo studies revealed that all scaffold groups facilitated osteogenesis at the bone defect site, with the β-TCP scaffolds loaded with PPD markedly enhancing the expression of neurogenic locus Notch homolog protein 1 (Notch1), vascular endothelial growth factor (VEGF), bone morphogenetic protein-2 (BMP-2), and osteopontin (OPN). Overall, the scaffolds developed in this study exhibited strong angiogenic and osteogenic capabilities both in vitro and in vivo. The incorporation of PPD notably promoted the angiogenic-osteogenic coupling, thereby accelerating bone repair, which suggests that PPD is a promising material for bone repair and that the PPD/β-TCP scaffolds hold great potential as a bone graft alternative.
Calcium Phosphates/chemistry*
;
Animals
;
Bone Regeneration
;
Rabbits
;
Tissue Scaffolds
;
Printing, Three-Dimensional
;
Humans
;
Human Umbilical Vein Endothelial Cells
;
Neovascularization, Physiologic
;
Osteogenesis
;
Tissue Engineering/methods*
;
Biomimetic Materials
;
Cell Proliferation
;
Angiogenesis
5.Process parameter optimization and immunogenicity evaluation of calcium phosphate-coated foot-and-mouth disease virus-like particles.
Lihua REN ; Wei GUO ; Qianqian XIE ; Ruipeng LIU ; Shiqi SUN ; Hu DONG ; Yun ZHANG ; Manyuan BAI ; Huichen GUO ; Zhidong TENG
Chinese Journal of Biotechnology 2025;41(7):2672-2681
Bio-mineralization has emerged as a promising strategy to enhance vaccine immunogenicity. This study optimized the calcium phosphate (CaP) mineralization process of foot-and-mouth disease virus-like particles (FMD VLPs) to achieve high mineralization efficiency and scalability. Key parameters, including concentrations of Ca2+, HPO42-, NaCl, and VLPs, as well as stirring speed, were systematically optimized. Stability of the scaled-up reaction system and immunogenicity of the mineralized vaccine were evaluated. Optimal conditions [25.50 mmol/L Ca(NO3)2, 15 mmol/L Na2HPO4, 300 mmol/L NaCl, 0.75 mg/mL VLPs, and 1 500 r/min] yielded CaP-mineralized VLPs (VLPs-CaP) with high mineralization efficiency, uniform morphology, and a favorable particle size. Scaling up the reaction by 25 folds maintained consistent mineralization efficiency and particle characteristics. Immunization in mice demonstrated that VLPs-CaP induced higher titers of specific antibodies and neutralizing antibodies than unmineralized VLPs (P < 0.05). Higher IgG2a/IgG1 ratio and enhanced IFN-γ secretion (P < 0.05) further indicated robust cellular immune responses. We establish a stable and scalable protocol for VLPs-CaP, providing a theoretical and technical foundation for developing high-efficacy VLPs-CaP vaccines.
Vaccines, Virus-Like Particle/immunology*
;
Immunogenicity, Vaccine
;
Calcium Phosphates/chemistry*
;
Foot-and-Mouth Disease Virus
;
Biomineralization
;
Particle Size
;
Animals
;
Mice
;
Antibodies, Neutralizing/blood*
;
Antibodies, Viral/blood*
;
Immunity, Cellular
6.Quality assessment of soil fertility of planting Chrysanthemum morifolium areas of Macheng city based on minimum data set.
Yin LIU ; Hong-Yuan YAN ; Xiao-Hong OU ; Lan-Ping GUO ; Da-Hui LIU
China Journal of Chinese Materia Medica 2019;44(24):5382-5389
A minimal data set( MDS) for soil fertility evaluation of Chrysanthemum plantation areas of Macheng city was established by principal component analysis( PCA) combined with Norm values of soil fertility indices and correlation coefficients among indices. A radar map was used to visually reflect the fertility level of individual indicators. Then,the comprehensive index model was used to calculate the soil fertility quality index( SFQI),and the values of SFQI was used to cluster,and the results showed that MDS was composed of five indicators: organic matter( OM),total phosphate( TP),available phosphorus( Av P),available magnesium( Av Mg) and available ferrum( Av Fe). Radar maps showed that the fertility of available phosphorus( Av P) and available copper( Av Cu) was mostly different in the two town,and the fertility of available ferrum( Av Fe) is smallest different. Except for the effective manganese( Av Mn) fertility level of Huangtugang town was higher than that of Futianhe town,the rest were lower than that of Futianhe town. Through analysis,the sensitivity of SFQI value calculated by taking the contribution rate of MDS index in the principal component of the whole data set( TDS) as the weight was the highest,MDS could better replace TDS. The value of SFQI-MDS ranged from 0. 353 to 0. 833,with an average value of 0. 604 and a coefficient of variation of 22%. The results of SFQI-MDS clustering showed that soil fertility could be divided into four categories: grade Ⅰ( 0. 727-0. 833) was superior,accounting for 25. 0%,grade Ⅱ( 0. 615-0. 681)was good,accounting for 29. 2%,mainly distributed in Futianhe Town,grade Ⅲ( 0. 494-0. 589) was medium,accounting for29. 1%,and grade Ⅳ( 0. 353-0. 419) was poor,accounting for 16. 7%,mainly distributed in Huangtugang town. Soil fertility of Futianhe town was better than that of Huangtugang town. It is suggested that boron fertilizer and potassium fertilizer should be supplemented to Chrysanthemum morifolium in production practice,and the amount of phosphate fertilizer,magnesium fertilizer and nitrogen fertilizer should be increased appropriately. At the same time,the amount of organic fertilizer should be increased to enhance soil fertility and improve soil physical and chemical properties.
China
;
Chrysanthemum/growth & development*
;
Fertilizers
;
Magnesium
;
Nitrogen
;
Phosphates
;
Phosphorus
;
Plants, Medicinal/growth & development*
;
Soil/chemistry*
7.Dental remineralization via poly(amido amine) and restorative materials containing calcium phosphate nanoparticles.
Kunneng LIANG ; Suping WANG ; Siying TAO ; Shimeng XIAO ; Han ZHOU ; Ping WANG ; Lei CHENG ; Xuedong ZHOU ; Michael D WEIR ; Thomas W OATES ; Jiyao LI ; Hockin H K XU
International Journal of Oral Science 2019;11(2):15-15
Tooth decay is prevalent, and secondary caries causes restoration failures, both of which are related to demineralization. There is an urgent need to develop new therapeutic materials with remineralization functions. This article represents the first review on the cutting edge research of poly(amido amine) (PAMAM) in combination with nanoparticles of amorphous calcium phosphate (NACP). PAMAM was excellent nucleation template, and could absorb calcium (Ca) and phosphate (P) ions via its functional groups to activate remineralization. NACP composite and adhesive showed acid-neutralization and Ca and P ion release capabilities. PAMAM+NACP together showed synergistic effects and produced triple benefits: excellent nucleation templates, superior acid-neutralization, and ions release. Therefore, the PAMAM+NACP strategy possessed much greater remineralization capacity than using PAMAM or NACP alone. PAMAM+NACP achieved dentin remineralization even in an acidic solution without any initial Ca and P ions. Besides, the long-term remineralization capability of PAMAM+NACP was established. After prolonged fluid challenge, the immersed PAMAM with the recharged NACP still induced effective dentin mineral regeneration. Furthermore, the hardness of pre-demineralized dentin was increased back to that of healthy dentin, indicating a complete remineralization. Therefore, the novel PAMAM+NACP approach is promising to provide long-term therapeutic effects including tooth remineralization, hardness increase, and caries-inhibition capabilities.
Amines
;
pharmacology
;
Calcium
;
Calcium Phosphates
;
chemistry
;
pharmacology
;
Dentin
;
chemistry
;
Humans
;
Nanocomposites
;
chemistry
;
Nanoparticles
;
Tooth Remineralization
;
methods
8.Effects of different external carbon sources and electron acceptors on interactions between denitrification and phosphorus removal in biological nutrient removal processes.
Xiang HU ; Dominika SOBOTKA ; Krzysztof CZERWIONKA ; Qi ZHOU ; Li XIE ; Jacek MAKINIA
Journal of Zhejiang University. Science. B 2018;19(4):305-316
The effects of two different external carbon sources (acetate and ethanol) and electron acceptors (dissolved oxygen, nitrate, and nitrite) were investigated under aerobic and anoxic conditions with non-acclimated process biomass from a full-scale biological nutrient removal-activated sludge system. When acetate was added as an external carbon source, phosphate release was observed even in the presence of electron acceptors. The release rates were 1.7, 7.8, and 3.5 mg P/(g MLVSS·h) (MLVSS: mixed liquor volatile suspended solids), respectively, for dissolved oxygen, nitrate, and nitrite. In the case of ethanol, no phosphate release was observed in the presence of electron acceptors. Results of the experiments with nitrite showed that approximately 25 mg NO2-N/L of nitrite inhibited anoxic phosphorus uptake regardless of the concentration of the tested external carbon sources. Furthermore, higher denitrification rates were obtained with acetate (1.4 and 0.8 mg N/(g MLVSS·h)) compared to ethanol (1.1 and 0.7 mg N/ (g MLVSS·h)) for both anoxic electron acceptors (nitrate and nitrite).
Biomass
;
Bioreactors
;
Carbon/chemistry*
;
Denitrification
;
Electrons
;
Nitrates
;
Nitrites
;
Oxygen
;
Phosphates
;
Phosphorus/chemistry*
;
Sewage
;
Waste Disposal, Fluid/methods*
;
Wastewater
;
Water Pollutants, Chemical
;
Water Purification/methods*
9.Biomechanical and biocompatible enhancement of reinforced calcium phosphate cement via RGD peptide grafted chitosan nanofibers.
Yang HUANG ; Jinsong KONG ; Xiaokang GONG ; Xin ZHENG ; Haibao WANG ; Jianwei RUAN
Journal of Zhejiang University. Medical sciences 2017;46(6):593-599
Objective: To analysis the biomechanical and biocompatible properties of calcium phosphate cement (CPC) enhanced by chitosan short nanofibers(CSNF) and Arg-Gly-Asp (RGD). Methods: Chitosan nanofibers were prepared by electrospinning, and cut into short fibers by high speed dispersion. CPC with calcium phosphorus ratio of 1.5:1 was prepared by Biocement D method. The composition and structure of CPC, CSNF, RGD modified CSNF (CSNF-RGD), CSNF enhanced CPC (CPC-CSNF), RGD modified CPC-CSNF (CPC-CSNF-RGD) were observed by infrared spectrum, X-ray diffraction (XRD) and scan electron microscopy (SEM). The mechanical properties were measured by universal mechanical testing instrument. The adhesion and proliferation of MC3T3 cells were assessed using immunofluorescence staining and MTT method. Results: The distribution of CSNF in the scaffold was homogeneous, and the porous structure between the nanofibers was observed by SEM. The infrared spectrum showed the characteristic peaks at 1633 nm and 1585 nm, indicating that RGD was successfully grafted on chitosan nanofibers. The XRD pattern showed that the bone cement had a certain curability. The stain-stress test showed that break strengths were (17.74±0.54) MPa for CPC-CSNF and (16.67±0.56) MPa for CPCP-CSNF-RGD, both were higher than that of CPC(all P<0.05). The immunofluorescence staining and MTT results indicated that MC3T3 cells grew better on CPC-CSNF-RGD after 240 min of culture(all P<0.05). Conclusion: CSNF-RGD can improve the biomechanical property and biocompatibility of CPC, indicating its potential application in bone tissue repair.
3T3 Cells
;
Animals
;
Biocompatible Materials
;
Bone Cements
;
chemistry
;
metabolism
;
pharmacology
;
Calcium Phosphates
;
metabolism
;
Cell Proliferation
;
drug effects
;
Chitosan
;
chemistry
;
pharmacology
;
Mice
;
Nanofibers
;
chemistry
;
Oligopeptides
;
chemistry
10.Effect of a lithium-doped calcium phosphate cement in promoting tibial bone defect repair in rats.
Li LI ; Yong-Bao QIN ; Gang MA ; Bing LI
Journal of Southern Medical University 2016;36(6):824-828
OBJECTIVETo evaluate the effects a lithium chloride-doped calcium phosphate cement (Li/CPC) on promoting tibial defect repair in rats.
METHODSTwenty 6-month-old female SD rats randomized into Li/CPC (n=10) and CPC control (n=10) groups. Surgery was performed to create bone defects at the bilateral tibia, which were filled with either of the cement. Five rats from each group were sacrificed at 1 and 2 months after the surgery for micro-CT examination and HE staining of the tibia.
RESULTSMicro-CT showed better repair of bone defects in Li/CPC group, which had a significantly higher new bone volume fraction (BV/TV) and a lower trabecular separation/spacing (Tb.Sp) than the control group (P<0.05). HE staining showed an earlier appearance of fiber and osteoid callus in Li/CPC group than CPC control group. The number and quality of bone healing was significantly higher in Li/CPC group than in CPC group.
CONCLUSIONLi/CPC possessed better osteoinductivity and can significantly promote bone defect repair in rats.
Animals ; Bone Cements ; chemistry ; Calcium Phosphates ; chemistry ; Female ; Lithium ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tibia ; pathology

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