Nanoscale calcium-deficient hydroxyapatite (CDHA) has attracted significant attention due to its chemical and structural similarity to biological apatite in natural bone. However, synthetic CDHA still exhibits inferior bioactivity compared to native bone apatite, with trace elements being a critical differentiating factor. In this study, Zn2+ was incorporated into the CDHA lattice via chemical precipitation, followed by ceramic processing, to systematically investigate the effects of Zn2+ doping concentration on the physicochemical properties and cellular responses of CDHA ceramics. Material characterization confirmed the successful fabrication of Zn-doped CDHA ceramics with varying Zn2+ concentrations. Zn2+ incorporation enhanced sintering densification (increased shrinkage rate, reduced porosity) while accelerating degradation kinetics and ion release. Notably, higher Zn2+ doping levels significantly promoted the proliferation and osteogenic differentiation of mouse bone marrow stromal cells (mBMSCs), as evidenced by key osteogenic markers. This study demonstrates that precise control of Zn2+ doping optimizes both the material properties and biological performance of CDHA ceramics, providing a promising bone graft alternative for clinical applications andfundamental insights into trace element engineering of bioactive ceramics.

This study addresses the issue of alveolar bone defects by exploring the effects of various active ion dopants (Sr2+, Mg2+, Zn2+, and SiO44-) on the physicochemical properties, degradation, and osteogenic capacity of low-crystalline carbonated hydroxyapatite (L-CHA) ceramics. The potential of these materials as fillers for alveolar bone augmentation was analyzed. In vitro experiments revealed that active ion doping did not markedly alter the phase composition or microstructure of L-CHA ceramics. However, optimal doping concentrations—5 mol.% for Sr2+, 0.5 mol.% for Mg2+, 3 mol.% for Zn2+, and 2 mol.% for SiO44-—enhanced the degradation rate and facilitated the sustained release of active ions, effectively promoting the osteogenic differentiation of mesenchymal bone marrow stem cells. Furthermore, magnesium, zinc, and strontium doping significantly improved the osteoconductivity of L-CHA microspheres, with zinc and strontium also enhancing in vivo degradation activity, thereby aiding new bone formation and replacement of the material. These findings suggest that optimized ion doping can enhance the efficacy of alveolar bone augmentation procedures and reduce postoperative waiting periods. This research offers new insights into improving strategies for alveolar bone regeneration.

Rapid induction of angiogenesis is crucial for the treatment of large bone defects and accelerating the material-mediated bone defect repair process. In this study, we employed a negative pressure infiltration method to coat the surface of porous BCP scaffolds with dopamine-modified hyaluronic acid (HA-DA) hydrogel and magnesium-doped calcium silicate (Mg-CS). In vitro results demonstrated that HA-DA hydrogel coating with an appropriate degree of dopamine grafting significantly improved the in vitro angiogenic activity of BCP scaffolds without affecting their osteogenic activity. The Mg-CS coating, heat-treated to ensure good combination with the BCP matrix, could sustainably release angiogenic silicon ions and osteogenic magnesium ions. Results from rat cranial defect repair showed that the implanted BCP@HA-DA-2 and BCP@10 Mg-CS scaffolds further accelerated the occurrence and development of neovascularization at the defect site, facilitating new bone formation. Among them, BCP@10 Mg-CS scaffold exhibited the best bone defect repair effect and has the potential for clinical application.

Zirconia ceramics exhibit numerous advantageous properties, including excellent biocompatibility, corrosion resistance, superior mechanical strength, and desirable aesthetic characteristics. However, as a typical bioinert material, zirconia demonstrates limited osseointegration and soft tissue healing capabilities, posing a significant clinical challenge for its application in dental implants. To address this limitation while preserving its mechanical integrity, we developed a novel porous surface layer composed of akermanite (Ca2MgSi2O7, AKT) on zirconia ceramics using a dip-coating process combined with negative pressure infiltration. This study systematically investigated the influence of AKT content on the morphology, phase composition, mechanical properties, and surface characteristics of the modified zirconia. Furthermore, we evaluated the material's bioactivity, cell viability, cellular adhesion and differentiation, and in vivo osteogenic potential. Following immersion in simulated body fluid (SBF), AKT-modified zirconia ceramics exhibited enhanced bioactivity, as evidenced by the formation of hydroxyapatite on their surfaces. Compared to unmodified zirconia, the AKT-modified samples demonstrated significantly improved hydrophilicity and apatite mineralization. In vitro cell culture experiments revealed that the modified ceramics promoted the adhesion, spreading, and osteogenic differentiation of mouse bone marrow stromal stem cells (mBMSCs), as well as the early adhesion, proliferation, and fibroblast differentiation of human gingival fibroblasts (HGFs). In vivo studies using a rabbit model confirmed the enhanced bone-implant integration capacity of AKT-modified specimens. Finite element analysis further revealed an optimized stress-strain distribution in peri-implant bone tissue due to surface modification. To our knowledge, this study provides the first comprehensive evidence that AKT-modified zirconia ceramics represent a promising dental implant material capable of simultaneously fulfilling the requirements for osseointegration and soft tissue compatibility.

This study investigates the effects of crystallization via heat treatment on the physicochemical and biological properties of yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) ceramics modified through the infiltration of bioactive glasses (BGs) with different compositions. Y-TZP ceramics underwent a dip-coating process to construct a porous surface layer, followed by BG sol infiltration and subsequent heat treatment. The results demonstrate that infiltration and heat treatment led to the formation of distinct crystalline phases within the BGs, while preserving the tetragonal phase of Y-TZP. Surface modification significantly enhanced protein adsorption, optimized ion release behavior, and promoted cell proliferation. Among the various BG compositions, Y-TZP ceramics infiltrated with 77S BG exhibited superior performance in promoting rapid osteogenic differentiation of mouse bone marrow mesenchymal stem cells (mBMSCs). These findings suggest that the construction of surface porous Y-TZP layer and the integration of BGs into Y-TZP ceramics hold potential for enhancing the bioactivity and clinical performance of dental implants.

Although biphasic calcium phosphate (BCP) has been widely used in bone defect repair, single functionality, however, fails to address the problems of insufficient angiogenesis and frequent bacterial infections during bone repair. Therefore, functional modification of BCP is crucial to achieve angiogenic and antibacterial effects. In this study, we fabricated a multifunctional coating system on biphasic calcium phosphate (BCP) ceramics. This was achieved by first generating an apatite whisker layer via in situ alkali heat treatment, subsequently coating it with the thermosensitive gelatin-based hydrogel, and finally incorporating mesoporous magnetic Fe3O4 nanoparticles for antibiotic delivery. By combining them with the hydrogel, a drug-loaded hydrogel coating with magnetic response characteristics was constructed. Materials characterization results indicated that BCP ceramics with multiple surface features were successfully prepared. The hydrogel coating and magnetic hydrogel coating significantly enhanced the angiogenic ability of HUVECs cells. In vitro antibacterial experiments showed that under alternating magnetic field (AMF) stimulation, the magnetic response drug-loaded hydrogel coating exhibited a more efficient and controllable drug release rate and corresponding antibacterial effect. The above results confirmed that the multiple surface modification strategy could synergistically enhance the angiogenic induction and antibacterial properties of BCP ceramics, providing a new idea for the design of biomaterials for complex bone defect repair.

Both silicon (Si) and magnesium (Mg) ions play essential roles in bone health. However, the precise mechanisms by which these two ions enhance osteogenic differentiation remain to be fully elucidated. Herein, a Si-Mg dual-ion system was designed to investigate the effects of Si and Mg ions on the cytological behavior of mouse bone marrow mesenchymal stem cells (mBMSCs). The molecular mechanism of the Si-Mg dual-ion system regulating osteogenic differentiation of mBMSCs was investigated by transcriptome sequencing technology. In the single-ion system, the Si group with concentrations of 1.5 and 0.75 mM exhibited good combined effects (cell proliferation, alkaline phosphatase (ALP) activity, and osteogenic differentiation gene expression (Runx2, OPN, and Col-I)) of mBMSCs. The Mg group with concentrations of 5 and 2.5 mM showed better combined effects (cell proliferation, ALP activity, and osteogenic differentiation gene expression) of mBMSCs. In the dual-ion system, the silicon (0.75 mM)-magnesium (2.5 mM) experimental group significantly enhanced the proliferation, ALP activity, and osteogenesis-related gene expression (Runx2, OPN, and Col-I) of mBMSCs. The analysis of transcriptome sequencing results showed that Mg ions had a certain pro-stem cell osteogenic differentiation regulatory effect. Si ions had a stronger regulation on osteogenic differentiation than the Mg ions. The regulation of osteogenic differentiation by Si-Mg dual ions was synergistically enhanced compared to that of a single ion. In addition, the transforming growth factor beta (TGF-β) signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway were involved in mediating the pro-stem cell osteogenic differentiation by Si-Mg dual ions. This study sheds light on investigating the molecular mechanism of dual-ion regulation of the osteogenic differentiation of mBMSCs and enriches the theory of ion-regulating osteogenic differentiation.

Strontium (Sr) modified biomaterials are testified to be beneficial for bone regeneration. The form of Sr incorporated in calcium phosphate cement (CPC) plays a vital role in the ion release behavior and osteogenesis of cement. In this study, four kinds of Sr-containing compounds, SrCO3 (SrC), SrHPO4 (SrP), SrSiO3 (SrSi) and SrSO4 (SrS) were incorporated into CPC, respectively. The effects on the physicochemical and biological properties of Sr-CPCs were comparatively investigated. The results showed that all Sr-containing compounds shortened the setting time and increased the injectability of CPC. The phases of CPC changed a little and the hydrated crystals became thinner. All CPCs modified by Sr compounds could release Sr in a long-term behavior. Moreover, all Sr compounds significantly promoted the adhesion and proliferation behaviors of mouse bone marrow mesenchymal stem cells (mBMSCs) on the surface of CPC. Compared to CPC alone, cells cultured on CPC containing SrC and SrSi exhibited higher expression levels of osteogenic genes, including ALP, Runx2, OCN, OPN, Col-I, and BSP, than those on the other two CPCs containing Sr compounds. In addition, SrSi/CPC showed higher ALP activity. In summary, CPCs incorporated with SrCO3 and SrSiO3 demonstrated enhanced osteogenic performance. This finding is expected to provide a theoretical foundation and practical guideline for the development of Sr-modified calcium phosphate cements (CPCs) with optimized setting time, improved injectability, and enhanced osteogenic performance.

The effective restoration of local bone homeostasis is a key factor in successfully treating pathological bone defects, which can be attributed to conditions such as osteoporosis or bone tumors. To address this challenge, we prepared a strontium calcium phosphate (SrCaP) ceramic using an ion doping method that demonstrated both osteogenic promotion and osteoclastic inhibition. In this study, we systematically evaluated the physicochemical properties, in vitro cell responses and in vivo osteogenesis for this material. Our results demonstrate that a higher purity SrCaP can be obtained when the strontium doping content in hydroxyapatite is equal to or greater than 25 mol.%. The long-term release of strontium ions from SrCaP significantly promoted osteogenic differentiation of stem cells. Furthermore, in vitro experiments revealed that SrCaP scaffolds doped with 30 mol.% of strontium (Sr30-S) demonstrated the most effective performance in promoting osteogenic differentiation and inhibiting osteoclast formation, thus providing effective support for the restoration of local bone homeostasis. Although Sr30-S inhibited the formation of osteoclasts, which hindered active material absorption, its faster passive degradation rate ensured a more rapid in vivo degradation rate than that of hydroxyapatite scaffold, thereby promoting the generation and growth of new bones. In summary, the innovative SrCaP ceramic scaffolds synthesized in this study demonstrate superior capabilities in promoting osteogenic differentiation and inhibiting osteoclastic resorption activity. These scaffolds not only hold potential in facilitating the restoration of local bone homeostasis but also exhibit a degradation rate that aligns with new bone growth. As a result, they represent an excellent candidate for repairing pathological bone defects characterized by high osteoclastic absorption activity, offering promising clinical applications.

Biphasic calcium phosphate (BCP) ceramics are valued for their osteoconductive properties but have limited osteogenic and angiogenic activities, which restricts their clinical utility in bone defect repair. Silicon doping has emerged as an effective strategy to enhance these biological functions of BCP. However, the biological impact of BCP is influenced by the level of silicon doping, necessitating determination of the optimal concentration to maximize efficacy in bone repair. This study investigated the effects of silicon doping on both the physicochemical and biological properties of BCP, with a specific focus on osteogenic and angiogenic potentials. Results indicated that silicon doping exceeding 4 mol.% led to the formation of alpha-TCP, accelerating BCP degradation, enhancing silicon ion release, and promoting mineralization product formation. Simultaneously, silicon doping increased the porosity of BCP scaffolds, which typically reduces their compressive strength. Nevertheless, scaffolds doped with <= 4 mol.% silicon maintained compressive strengths exceeding 2 MPa. In vitro biological experiments indicated that higher levels of silicon doping (>= 6 mol.%) partially inhibited the successful differentiation of stem cells and the vascularization of endothelial cells. Optimal conditions for promoting osteogenic differentiation and angiogenesis were identified between 2 and 4 mol.% silicon doping, with an optimal level of approximately 4 mol.%. Subsequent in vivo experiments confirmed that BCP scaffolds doped with 4 mol.% silicon effectively promoted vascularization and new bone formation, highlighting their potential for clinical bone defect repair.

Zinc ions have shown promising osteogenic activity, while silicon ions promote angiogenesis. In this study, the effects of silicon doping, zinc doping, and their co‐doping on the physicochemical properties, as well as the in vitro angiogenic and osteogenic activities of β‐tricalcium phosphate (β‐TCP), are investigated. In the findings, it is revealed that silicon doping primarily occurs on the P1 site, leading to lattice stability disruption in β‐TCP and favoring its transformation into α‐TCP (α‐TCP). Notably, a significant portion of silicon ions is distributed on the particle surface. As a result, silicon‐doped TCP (Si–TCP) exhibits remarkable in vitro mineralization activity. Conversely, zinc doping contributes to stabilizing the β‐TCP phase, even at a sintering temperature of 1200 °C, preventing the formation of α‐TCP. Silicon/zinc‐co‐doped TCP (Si/Zn–TCP) displays comparable physicochemical properties to zinc‐doped TCP (Zn–TCP), thus demonstrating higher thermal stability than pure β‐TCP. Cell response evaluations indicate excellent biocompatibility for Si–TCP, Zn–TCP, and Si/Zn–TCP. Silicon doping significantly enhances in vitro angiogenic capability, while zinc doping notably improves osteogenic potential of β‐TCP. Furthermore, the bifunctional ion‐co‐doping approach in Si/Zn–TCP results in combined angiogenic promoting from Si–TCP and osteogenic stimulation from Zn–TCP. In these results, the considerable potential of Si/Zn–TCP is highlighted for bone defect repair applications.

Both silicon (Si) and zinc (Zn) ions are essential elements to bone health and their mechanisms for promoting osteogenesis have aroused the extensive attention of researchers. Thereinto, the mechanism by which dual ions promote osteogenic differentiation remains to be elucidated. Herein, the effects of Si and Zn ions on the cytological behaviors of mBMSCs were firstly studied. Then, the molecular mechanism of Si-Zn dual ions regulating the osteogenic differentiation of mBMSCs was investigated via transcriptome sequencing technology. In the single-ion system, Si ion at the concentration of 1.5 mM (Si-1.5) had better comprehensive effects of cell proliferation, ALP activity and osteogenesis-related gene expression levels (ALP, Runx2, OCN, Col-I and BSP); Zn ion at the concentration of 50 μM (Zn-50) demonstrated better combining effects of cell proliferation, ALP activity and same osteogenic genes expression levels. In the dual-ion system, the Si (1.5 mM)-Zn (50 μM) group (Si1.5-Zn50) synthetically enhanced ALP activity and osteogenesis genes compared with single-ion groups. Analysis of the transcriptome sequencing results showed that Si ion had a certain effect on promoting the osteogenic differentiation of mBMSCs; Zn ion had a stronger effect of contributing to a better osteogenic differentiation of mBMSCs than that of Si ion; the Si-Zn dual ions had a synergistic enhancement on conducting to the osteogenic differentiation of mBMSCs compared to single ion (Si or Zn). This study offers a blueprint for exploring the regulation mechanism of osteogenic differentiation by dual ions.

This study aimed to enhance the bone-forming performance of (3-TCP ceramic scaffolds by incorporating porosity-generating polystyrene microspheres. The microspheres were blended with the (3-TCP powder and sintered to produce porous ceramics with varying porosities and mesopore sizes. Optimal conditions for manufacturing scaffolds with hierarchical pore structures were identified, and their impact on ectopic bone formation and bone defect repair was assessed. Increasing the volume of microspheres enhanced porosity while reducing compressive strength. The optimal microsphere content was determined to be 20 %, which resulted in increased alkaline phosphatase (ALP) activity and up-regulated expression of osteogenesis-related genes. Introduction of microspheres of different sizes (10, 20, 40, and 70 mu m) effectively yielded porous (3-TCP ceramics with mesopores that promoted cell attachment and spreading. Scaffolds with 40 mu m mesopores demonstrated superior cell attachment and enhanced osteogenic differentiation. The integration of microspheres and 3D printing enabled the fabrication of hierarchical porous (3-TCP ceramic scaffolds, featuring mm-scale macropores between struts, mesopores ranging from 10 to 100 mu m within the struts, and micropores smaller than 10 mu m. Stem cells cultured on scaffolds with 500 mu m macropores exhibited elevated osteogenic gene expression compared to those with 300 mu m macropores. Both 40 mu m mesopores and 500 mu m macropores accelerated in vivo degradation of the scaffolds, with the macropores exerting a more pronounced effect. New bone tissue can grow into the mesopores within the struts of the scaffold. Moreover, the (3-TCP ceramic scaffold with 40 mu m mesopores and 500 mu m macropores demonstrated superior ectopic osteogenic performance and bone defect repair efficacy. These findings hold significance in addressing the challenges linked to the absence of mesopores and suboptimal osteogenic effects in conventional (3-TCP ceramics. It is anticipated that these outcomes will contribute to the expanded utilization of (3-TCP ceramic scaffolds in clinical bone repair applications.

The rapid repair of bone defects remains a significant clinical challenge to this day. To address this issue, a 3D-printed biphasic calcium phosphate (BCP) scaffold consisting of 40 wt % hydroxyapatite (HA) and 60 wt % beta-tricalcium phosphate (beta-TCP) was created. Silicon and zinc were incorporated into HA and beta-TCP, respectively, to enhance the angiogenic and osteogenic properties of the BCP scaffold. The physicochemical properties, in vitro cell responses, and bone defect repair efficacy of the modified BCP scaffold were comprehensively investigated. Results showed that the fabricated scaffold possessed a 3D interconnected pore structure. Zinc doping enhanced the sintering of the BCP scaffold, increased its density and strength, but decreased its degradation rate. Conversely, silicon doping had the opposite effect. The modified scaffold was capable of a gradual release of zinc/silicon ions, which promoted the proliferation and differentiation of cells. Specifically, the scaffold doped with zinc significantly promoted the osteogenic differentiation of stem cells. Moreover, co-doping with silicon and zinc synergistically promoted in vitro angiogenesis, with BCP-3 (doped with 2.5 mol % zinc and 4 mol % silicon) exhibiting the best pro-angiogenic activity. BCP-3 significantly induced regeneration of blood vessels and bone tissue in vivo, indicating its potential to accelerate the process of bone defect repair.

Hydroxyapatite (HA), a commonly used material for bone repair, can enhance its biological properties through the modulation of its crystallinity. Exploring the variations in physicochemical and biological properties associated with different degrees of crystallinity is crucial for advancing the applications of HA. In this study, stoichiometric nano-apatite precursors were initially synthesized using chemical precipitation. Subsequently, four groups of HA ceramics with varying degrees of crystallinity (24 %, 42 %, 72 %, 100 %) were produced by adjusting the calcination temperature, as confirmed through comprehensive characterizations. A systematic investigation was then conducted to examine the impact of crystallinity on the physicochemical, cytological, and in vivo osteogenic properties of HA ceramics, elucidating the influence of crystallinity on the osteogenic potential of HA. Results indicated that higher crystallinity in HA ceramics enhanced mechanical strength and hardness while reducing surface roughness, hydrophilicity, and protein affinity. Cytological studies revealed that decreased crystallinity led to lower cell proliferation rates but facilitated cell adhesion, spreading, and increased expression of osteogenic genes. Moreover, cell experiments with extracts further supported the significant role of surface properties of HA ceramics in modulating cell behavior. In vivo osteogenic assays demonstrated that reduced crystallinity notably stimulated new bone formation. Overall, by integrating the results of in vitro and in vivo experiments, it can be concluded that reducing the crystallinity of HA ceramics, the biological properties of HA ceramics can be significantly enhanced while maintaining a certain level of mechanical strength, such as HA2 group (42 % crystallinity). This study highlights the substantial impact of crystallinity and surface characteristics of HA ceramics on cell behavior, offering valuable insights and strategies for enhancing and optimizing bone repair materials in future applications.

The balance between porosity and compressive strength, as well as the pro-osteogenic and pro-angiogenesis effects of beta-tricalcium phosphate (beta-TCP) are not satisfactory in the clinical application even though it has good biocompatibility, osseointegration and osteoconductivity. Herein, different contents (10, 20 and 30 wt%) of magnesium silicate (Mg2SiO4, MS) and beta-TCP composite bioceramic scaffolds (MS/beta-TCP) were fabricated by three-dimensional fiber deposition (3DF) technology. The physicochemical, in vitro osteogenic and angiogenic properties, the early (6 weeks) cranium defect repair effects in rats and the underlying molecular mechanism on accelerating osteogenic differentiation of MS/beta-TCP were systematically investigated. The results showed that MS compounding not only promoted the sintering of beta-TCP and significantly enhanced the compressive strength, but also greatly improved its osteogenic and angiogenic performances, such as the viability, adhesion, and proliferation of mouse bone marrow mesenchymal stem cells (mBMSCs) and human umbilical vein endothelial cells (HUVECs), ALP activity and the expression of adhesion-related, osteogenesis-related and angiogenesisrelated genes. The in vivo experiments presented that 10MS/beta-TCP had more new bone formation and better angiogenesis compared to beta-TCP and Blank. Analysis of the transcriptome sequencing results confirmed that the Wnt signaling pathway was involved in the regulation of osteogenic differentiation in mBMSCs by the MS/beta-TCP composite bioceramic scaffold. The MS/beta-TCP holds great potential in bone repair and regeneration.

Rapid bone regeneration in implants is important for successful transplantation. In this regard, we report the development of calcium silicate/zinc silicate (CS/ZS) dual-compound-incorporated calcium phosphate cement (CPC) scaffolds with a three-dimensional poly (lactic-co-glycolic acid) network that synergistically promote bone regeneration. In vitro results demonstrated that the incorporation of CS/ZS dual compounds into the CPC significantly promoted the osteogenic differentiation of stem cells compared to the addition of CS or ZS alone. Moreover, the bone-regeneration efficacy of the composite scaffolds was validated by filling in femur condyle defects in rabbits, which showed that the scaffolds with CS and ZS possessed a great bone repair effect, as evidenced by more new bone formation and a faster scaffold biodegradation compared to the scaffold with CS alone.

Most bone filler materials currently achieve bone regeneration by mimicking the natural bone extracellular matrix. However, it is difficult for these materials to replicate the structural functions and bioactivities, including immunomodulation, of natural bone perfectly to reduce inflammation and promote bone regeneration synergistically. Repairing bone defects with scaffolds using a decellularised extracellular matrix (dECM) as a matrix material is an important clinical application and research direction. Here, we processed bovine cancellous bone via an optimised combination of decellularisation methods and preferred dECM, which has the shortest processing time and lowest immunogenicity. Hexagonal mesoporous silica (HMS)/poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with bone morphogenetic protein-2 (BMP-2) were prepared using the complex emulsion method. The HMS/PLGA microspheres had longer cytokine release periods than did the separate HMS and PLGA microspheres. Composite BMP-2/HMS/PLGA microspheres were used to prepare dual-loaded cytokine scaffolds with bone immunomodulatory capacity, which were prepared from composite BMP-2/HMS/PLGA microspheres to increase the osteogenic activity of the dECM and to adsorb interleukin-4 (IL-4) on the surface of the scaffolds. The results showed that the dECM had good cytocompatibility and mechanical strength, and the composite microspheres and IL-4 further endowed the dECM with an ordered spatiotemporally controlled release function, which could release BMP-2 for more than 4 months in the long term and release IL-4 for approximately 10 days in the short term. The composite scaffold not only effectively promoted the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) but also immunomodulated the M1 to M2 polarisation of macrophages (MPs) and mediated the M2 polarisation of MPs, which in turn promoted the osteogenic differentiation of BMSCs, creating a favourable immune microenvironment for bone regeneration. In vivo, the dual drug-loaded scaffolds also exhibited good biocompatibility and significantly superior immunomodulatory bone-enhancing properties compared with those of the other groups. In summary, the combination of dECM scaffolds with cytokine-carrying microspheres and immunomodulatory factors can promote the orderly spatiotemporal release of cytokines, which significantly enhances the bone regeneration and repair effects of dECM scaffolds and is a promising bone filler material for clinical application.

Wollastonite (CaSiO3, CS) has shown a great potential as a bone biomaterial due to its favorable degradation behavior and the beneficial silicon and calcium ions released during its degradation. However, the rapid degradation of CS may result in a rapid increase in local pH values and lead to cell death. To address this issue and further enhance the biocompatibility, osteogenic, angiogenic, and osteoclast differentiation inhibitory properties of CS; zinc (Zn) and strontium (Sr) ions were introduced into CS through an ion-doping method. The effects of Zn doping, Sr doping, and Zn/Sr co-doping on the crystal structure, in vitro mineralization, and cellular responses of CS were systematically investigated. The results indicated that Zn doping and Sr doping had no significant effect on the phase of CS, while Zn/Sr co-doping promoted the substitution of Zn and Sr ions for calcium ions. Moreover, the introduction of Zn and Sr ions slowed the degradation process of CS and inhibited its in vitro mineralization activity. Furthermore, while Zn doping and Sr doping significantly enhanced the cytocompatibility and osteogenesis of CS, respectively, Zn/Sr co-doping exhibited synergistic effects in enhancing the osteogenesis of CS. Interestingly, the introduction of Zn and Sr ions also improved the angiogenic properties of CS and increased its ability to inhibit osteoclast differentiation; however, there was no significant synergistic effect between Zn doping and Sr doping on these properties. In conclusion, Zn/Sr co-doped CS exhibits a more suitable degradation rate and enhanced bioactivity, presenting significant application prospects in the field of bone defect repair.

This study aimed to enhance the bone-forming performance of β-TCP ceramic scaffolds by incorporating porosity-generating polystyrene microspheres. The microspheres were blended with the β-TCP powder and sintered to produce porous ceramics with varying porosities and mesopore sizes. Optimal conditions for manufacturing scaffolds with hierarchical pore structures were identified, and their impact on ectopic bone formation and bone defect repair was assessed. Increasing the volume of microspheres enhanced porosity while reducing compressive strength. The optimal microsphere content was determined to be 20 %, which resulted in increased alkaline phosphatase (ALP) activity and up-regulated expression of osteogenesis-related genes. Introduction of microspheres of different sizes (10, 20, 40, and 70 μm) effectively yielded porous β-TCP ceramics with mesopores that promoted cell attachment and spreading. Scaffolds with 40 μm mesopores demonstrated superior cell attachment and enhanced osteogenic differentiation. The integration of microspheres and 3D printing enabled the fabrication of hierarchical porous β-TCP ceramic scaffolds, featuring mm-scale macropores between struts, mesopores ranging from 10 to 100 μm within the struts, and micropores smaller than 10 μm. Stem cells cultured on scaffolds with 500 μm macropores exhibited elevated osteogenic gene expression compared to those with 300 μm macropores. Both 40 μm mesopores and 500 μm macropores accelerated in vivo degradation of the scaffolds, with the macropores exerting a more pronounced effect. New bone tissue can grow into the mesopores within the struts of the scaffold. Moreover, the β-TCP ceramic scaffold with 40 μm mesopores and 500 μm macropores demonstrated superior ectopic osteogenic performance and bone defect repair efficacy. These findings hold significance in addressing the challenges linked to the absence of mesopores and suboptimal osteogenic effects in conventional β-TCP ceramics. It is anticipated that these outcomes will contribute to the expanded utilization of β-TCP ceramic scaffolds in clinical bone repair applications.