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

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*

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

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

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⁺, HPO₄^2-, 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

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

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

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

OBJECTIVETo evaluate the effect of 2-methacryloyloxyethyl phosphorylcholine (MPC) and nanoparticles of amorphous calcium phosphate (NACP) on the protein-repellent property of dental adhesive.

METHODSMPC and NACP were incorporated into SBMP as the test group. Scotchbond Multi-Purpose (SBMP) was used as control group. Human dentin shear bond strengths were measured. Protein adsorption onto samples was determined by micro bicinchoninic acid (BCA) method. A dental plaque microcosm biofilm model with human saliva as inoculum was used to investigate biofilm viability.

RESULTSThe dentin bond strength of modified group was (28.7±2.2) MPa, which was not significantly different from that of the SBMP control group. The amount of protein adsorption in the modified group and the SBMP control group were (0.21±0.02) µg/cm(2) and (4.17±0.45) µg/cm(2) respectively. Lactic acid production of biofilms in modified group and SBMP control were (7.71 ± 1.01) mmol/L and (19.18 ± 2.34) mmol/L repectively.

CONCLUSIONSMPC-NACP based dental adhesive greatly reduce the protein adsorption and bacterial adhesion, without compromising dentin shear bond strength. This novel bonding agent may have wide application.

Adsorption ; Biofilms ; drug effects ; growth & development ; Calcium Phosphates ; pharmacology ; Dental Cements ; pharmacology ; Dental Plaque ; Dentin ; chemistry ; Humans ; Lactic Acid ; biosynthesis ; Methacrylates ; pharmacology ; Nanoparticles ; Phosphorylcholine ; analogs & derivatives ; pharmacology ; Resin Cements ; pharmacology ; Saliva ; Tensile Strength

PURPOSETo develop a novel injectable strontium-containing calcium phosphate cement with collagen.

METHODSA novel calcium phosphate bone cement (CPC) was prepared with the addition of strontium element, collagenl, and modified starch; the injectability, solidification time, microstructure, phase composition, compressive strength, anti-collapsibility and histological properties of material were evaluated.

RESULTSThe results showed that the material could be injected with an excellent performance; the modified starch significantly improved the anti-washout property of cement; with the liquid to solid ratio of 0.3, the largest compressive strength of cement was obtained (48.0 MPa ± 2.3 MPa); histological examination of repair tissue showed that the bone was repaired after 16 weeks; the degradation of cement was consistent with the new bone growth.

CONCLUSIONA novel injectable collagen-strontium-containing CPC with excellent compressive strength and suitable setting time was prepared, with addition of modified starch. The CPC showed a good anti-washout property and the degradation time of the cement met with the new bone growing. This material is supposed to be used in orthopedic and maxillofacial surgery for bone defects.

Animals ; Bone Cements ; chemistry ; therapeutic use ; Calcium Phosphates ; chemistry ; Collagen ; chemistry ; Compressive Strength ; Histocompatibility Testing ; Injections ; Rabbits ; Strontium ; chemistry