Additive manufacturing and in vitro study of biological characteristics of sulfonated polyetheretherketone-bioactive glass porous bone scaffolds.

Polyetheretherketone (PEEK), a high-performance special engineering plastic, has gradually been used in bone substitutes due to its wear resistance, acid and alkali resistance, non-toxicity, radiolucency, and modulus close to that of human bone. However, its stable biphenyl structure determines strong biological inertness, thus artificial interventions are required to improve the biological activity of fabricated PEEK parts for better clinical applications. This study developed a novel strategy for grafting bioactive glass (BAG) onto the surface of PEEK through sulfonation reaction with concentrated sulfuric acid (H2SO4), aiming to improve the bioactivity of printed porous bone scaffolds manufactured by fused deposition modeling (FDM) to meet clinical individual needs. In vitro biological study was conducted on sulfonated polyetheretherketone-bioactive glass (SPEEK-BAG) scaffolds obtained by this strategy. The results demonstrated that the optimal modification condition was a 4-hour sulfonation reaction with 1 mol/L concentrated H2SO4 at high temperature and high pressure. The scaffold obtained under this condition showed minimal cytotoxicity, and the Ca/P molar ratio, yield compressive strength, and compressive modulus of this scaffold were 2.94 ± 0.02, 62.78 MPa, and 0.186 GPa respectively. The hydrophilicity and the biomineralization ability of PEEK modified by the proposed strategy were substantially improved. The SPEEK-BAG bone scaffolds exhibited excellent biocompatible properties, suggesting that the sulfonation reaction and BAG effectively enhanced the proliferation and differentiation of osteoblasts. The presented method provides an innovative, highly effective, and customized strategy to improve the biocompatibility and bone repair ability of printed PEEK bone scaffolds for virous biomedical applications.

Effect of pH and hydroxyapatite-like layer formation on the antibacterial properties of borophosphate bioactive glass incorporated poly(methyl methacrylate) bone cement.

Infection is a leading cause of total joint arthroplasty failure. Current preventative measures incorporate antibiotics into the poly (methyl methacrylate) (PMMA) bone cement that anchors the implant into the natural bone. With bacterial resistance to antibiotics on the rise, the development of alternative antibacterial materials is crucial to mitigate infection. Borate bioactive glass, 13-93-B3, has been studied previously for use in orthopedic applications due to its ability to be incorporated into bone cements and other scaffolds, convert into hydroxyapatite (HA)-like layer, and enhance the osseointegration and antibacterial properties of the material. The purpose of this study is to better understand how glass composition and change in surrounding pH effects the composite's antibacterial characteristics by comparing the incorporation of 30% wt/wt 13-93-B3 glass and pH neutral borophosphate bioactive glass into PMMA bone cement. We also aim to elucidate how HA-like layer formation on the cement's surface may affect bacterial adhesion. These studies showed that 13-93-B3 incorporated cements had significant reduction of bacterial growth surrounding the composite beyond 24 h of exposure when compared to a neutral borate bioactive glass incorporated cement (p < 0.01) and cement only (p < 0.0001). Additionally, through soaking cement composites in simulated body fluid and then exposing them to a bioluminescent strand of staphylococcus aureus, we found that the presence of a HA-like layer on the 13-93-B3 or pH neutral glass incorporated cement disks resulted in an increase in bacterial attachment on the composite cement's surface, where p < 0.001, and p < 0.05 respectively. Overall, our studies demonstrated that borate bioactive glass incorporated PMMA bone cement has innate antimicrobial properties that make it a promising material to prevent infection in total joint arthroplasties.

Laser powder bed fusion printed poly-ether-ether-ketone/bioactive glass composite scaffolds with dual-scale pores for enhanced osseointegration and bone ingrowth.

Although poly-ether-ether-ketone (PEEK) implants hold significant medical promise, their bioinert nature presents challenges in osseointegration and bone ingrowth within clinical contexts. To mitigate these challenges, the present study introduces Diamond PEEK/bioactive glass (BG) composite scaffolds, characterized by macro/micro dual-porous structures, precisely fabricated via laser powder bed fusion (LPBF) technology. The findings indicate that an increase in BG content within these scaffolds significantly augments their hydrophilicity and hydroxyapatite formation capacities. Stress-strain curve analysis demonstrates reliable load-bearing stability across all scaffold types. In vitro assessments confirmed the non-cytotoxicity of PEEK/BG samples and demonstrated improved osteogenic differentiation and mineralization with increased BG incorporation. Further, in vivo experiments illustrated that the Diamond porous structure of these scaffolds facilitated bone growth, an effect notably amplified with higher BG content. Particularly in groups with 15 wt% and 25 wt% BG scaffolds, new bone formation was observed not only within the macropores of the Diamond structure but also within the micropores inside the scaffold rod, suggesting an almost seamless fusion with the new bone. This demonstrates the scaffolds' effective osteointegration and bone ingrowth properties. This study conclusively established the effectiveness of Diamond-structured PEEK/BG composite scaffolds, fabricated via LPBF, in bone repair. It highlights the crucial role of BG in enhancing osteogenic potential through interaction with the macro/micro pores of the scaffold. STATEMENT OF SIGNIFICANCE: This study addresses the bioinert nature of PEEK implants by developing Diamond-structured PEEK/bioactive glass (BG) composite scaffolds by laser powder bed fusion. The dual-porous macro/microstructure enhances hydrophilicity and hydroxyapatite formation, vital for bone regeneration. By adjusting the BG content, we controlled the melt viscosity and sintering rate, leading to the formation of beneficial microscale pores. These pores resolve the issue of ineffective bioactive fillers in previous LPBF-fabricated scaffolds, enhancing the osteogenic potential of BG and inducing superior bone ingrowth and osseointegration. In vitro and in vivo analyses show enhanced osteogenic differentiation, mineralization, and bone growth, underscoring the clinical potential of these scaffolds for bone repair.

Enhancing craniofacial bone tissue engineering strategy: integrating rapid wet chemically synthesised bioactive glass with photopolymerized resins.

BACKGROUND: Craniofacial bone regeneration represents a dynamic area within tissue engineering and regenerative medicine. Central to this field, is the continual exploration of new methodologies for template fabrication, leveraging established bio ceramic materials, with the objective of restoring bone integrity and facilitating successful implant placements. METHODS: Photopolymerized templates were prepared using three distinct bio ceramic materials, specifically a wet chemically synthesized bioactive glass and two commercially sourced hydroxyapatite variants. These templates underwent comprehensive characterization to assess their physicochemical and mechanical attributes, employing techniques including Fourier transform infrared spectroscopy, scanning electron microscopy, and nano-computed tomography. Evaluation of their biocompatibility was conducted through interaction with primary human osteoblasts (hOB) and subsequent examination using scanning electron microscopy. RESULTS: The results demonstrated that composite showed intramolecular hydrogen bonding interactions with the photopolymer, while computerized tomography unveiled the porous morphology and distribution within the templates. A relatively higher porosity percentage (31.55 ± 8.70%) and compressive strength (1.53 ± 0.11 MPa) was noted for bioactive glass templates. Human osteoblast cultured on bioactive glass showed higher viability compared to other specimens. Scanning micrographs of human osteoblast on templated showed cellular adhesion and the presence of filopodia and lamellipodia. CONCLUSION: In summary these templates have the potential to be used for alveolar bone regeneration in critical size defect. Photopolymerization of bioceramics may be an interesting technique for scaffolds fabrication for bone tissue engineering application but needs more optimization to overcome existing issues like the ideal ratio of the photopolymer to bioceramics.

Determination of the Optimum Architecture of Additively Manufactured Magnetic Bioactive Glass Scaffolds for Bone Tissue Engineering and Drug-Delivery Applications.

For better bone regeneration, precise control over the architecture of the scaffolds is necessary. Because the shape of the pore may affect the bone regeneration, therefore, additive manufacturing has been used in this study to fabricate magnetic bioactive glass (MBG) scaffolds with three different architectures, namely, grid, gyroid, and Schwarz D surface with 15 × 15 × 15 mm3 dimensions and 70% porosity. These scaffolds have been fabricated using an in-house-developed material-extrusion-based additive manufacturing system. The composition of bioactive glass was selected as 45% SiO2, 20% Na2O, 23% CaO, 6% P2O5, 2.5% B2O3, 1% ZnO, 2% MgO, and 0.5% CaF2 (wt %), and additionally 0.4 wt % of iron carbide nanoparticles were incorporated. Afterward, MBG powder was mixed with a 25% (w/v) Pluronic F-127 solution to prepare a slurry for fabricating scaffolds at 23% relative humidity. The morphological characterization using microcomputed tomography revealed the appropriate pore size distribution and interconnectivity of the scaffolds. The compressive strengths of the fabricated grid, gyroid, and Schwarz D scaffolds were found to be 14.01 ± 1.01, 10.78 ± 1.5, and 12.57 ± 1.2 MPa, respectively. The in vitro study was done by immersing the MBG scaffolds in simulated body fluid for 1, 3, 7, and 14 days. Darcy's law, which describes the flow through porous media, was used to evaluate the permeability of the scaffolds. Furthermore, an anticancer drug (Mitomycin C) was loaded onto these scaffolds, wherein these scaffolds depicted good release behavior. Overall, gyroid-structured scaffolds were found to be the most suitable among the three scaffolds considered in this study for bone tissue engineering and drug-delivery applications.

Multifunctional Bionic Periosteum with Ion Sustained-Release for Bone Regeneration.

In this study, a novel bionic periosteum (BP)-bioactive glass fiber membrane (BGFM) is designed. The introduction of magnesium ion (Mg2+) and zinc ion (Zn2+) change the phase separation during the electrospinning (ES) jet stretching process. The fiber's pore structure transitions from connected to closed pores, resulting in a decrease in the rapid release of metal ions while also improving degradation via reducing filling quality. Additionally, the introduction of magnesium (Mg) and zinc (Zn) lead to the formation of negative charged tetrahedral units (MgO4 2- and ZnO4 2-) in the glass network. These units effectively trap positive charged metal ions, further inhibiting ion release. In vitro experiments reveal that the deigned bionic periosteum regulates the polarization of macrophages toward M2 type, thereby establishing a conducive immune environment for osteogenic differentiation. Bioinformatics analysis indicate that BP enhanced bone repair via the JAK-STAT signaling pathway. The slow release of metal ions from the bionic periosteum can directly enhance osteogenic differentiation and vascularization, thereby accelerating bone regeneration. Finally, the bionic periosteum exhibits remarkable capabilities in angiogenesis and osteogenesis, demonstrating its potential for bone repair in a rat calvarial defect model.

Osteogenic and angiogenic potential of molybdenum-containing mesoporous bioactive glass nanoparticles: An ionic approach to bone tissue engineering.

Biomaterials intended for application in bone tissue engineering (BTE) ideally stimulate osteogenesis and angiogenesis simultaneously, as both mechanisms are of critical importance for successful bone regeneration. Mesoporous bioactive glass nanoparticles (MBGNs) can be tailored towards specific biological needs, for example by addition of ions like Molybdenum (Mo). While Mo has been shown to enhance osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (BMSCs) as well as their ability to form and mature a primitive osseous extracellular matrix (ECM), there are contradictory findings regarding its impact on angiogenesis. In this study, the effects of Mo-MBGNs (mol%: 70 SiO2, 25 CaO, 5 MoO3) on viability, proliferation, osteogenic differentiation, ECM formation and angiogenic response of BMSCs were compared to undoped MBGNs (in mol%: 70 SiO2, 30 CaO) and a control group of BMSCs. Furthermore, a human umbilical vein endothelial cells tube formation assay and a chorioallantoic membrane-assay using fertilized chicken eggs were used to analyze angiogenic properties. Mo-MBGNs were cytocompatible and promoted the proliferation of BMSCs. Furthermore, Mo-MBGNs showed promising osteogenic properties as they enhanced osteogenic differentiation, ECM formation and maturation as well as the gene expression and protein production of relevant osteogenic factors in BMSCs. However, despite the promising outcome on osteogenic properties, the addition of Mo to MBGNs resulted in anti-angiogenic effects. Due to the high relevance of vascularization in-vivo, the anti-angiogenic properties of Mo-MBGNs might hamper their osteogenic properties and therefore might restrict their performance in BTE applications. These limitations can be overcome by the addition of ions with distinct pro-angiogenic properties to the Mo-MBGNs-composition. Due to their promising osteogenic properties, Mo-MBGNs constitute a suitable basis for further research in the field of ionic (growth factor free) BTE.

A novel injectable boron doped-mesoporous nano bioactive glass loaded-alginate composite hydrogel as a pulpotomy filling biomaterial for dentin regeneration.

BACKGROUND: Different materials have been used as wound dressings after vital pulp therapies. Some of them have limitations such as delayed setting, difficult administration, slight degree of cytotoxicity, crown discoloration and high cost. Therefore, to overcome these disadvantages, composite scaffolds have been used in regenerative dentistry. This study aims to construct and characterize the physicochemical behavior of a novel injectable alginate hydrogel loaded with different bioactive glass nanoparticles in various concentrations as a regenerative pulpotomy filling material. METHODS: Alginate hydrogels were prepared by dissolving alginate powder in alcoholic distilled water containing mesoporous bioactive glass nanoparticles (MBG NPs) or boron-doped MBG NPs (BMBG NPs) at 10 and 20 wt% concentrations. The mixture was stirred and incubated overnight in a water bath at 50 0 C to ensure complete solubility. A sterile dual-syringe system was used to mix the alginate solution with 20 wt% calcium chloride solution, forming the hydrogel upon extrusion. Then, constructed hydrogel specimens from all groups were characterized by FTIR, SEM, water uptake percentage (WA%), bioactivity and ion release, and cytotoxicity. Statistical analysis was done using One-Way ANOVA test for comparisons between groups, followed by multiple pairwise comparisons using Bonferroni adjusted significance level (p < 0.05). RESULTS: Alginate/BMBG loaded groups exhibited remarkable increase in porosity and pore size diameter [IIB1 (168), IIB2 (183) (µm)]. Similarly, WA% increased (~ 800%) which was statistically significant (p < 0.05). Alginate/BMBG loaded groups exhibited the strongest bioactive capability displaying prominent clusters of hydroxyapatite precipitates on hydrogel surfaces. Ca/P ratio of precipitates in IIA2 and IIB1 (1.6) were like Ca/P ratio for stoichiometric pure hydroxyapatite (1.67). MTT assay data revealed that the cell viability % of human gingival fibroblast cells have declined with increasing the concentration of both powders and hydrogel extracts in all groups after 24 and 48 h but still higher than the accepted cell viability % of (˃70%). CONCLUSIONS: The outstanding laboratory performance of the injectable alginate/BMBGNPs (20 wt%) composite hydrogel suggested it as promising candidate for pulpotomy filling material potentially enhancing dentin regeneration in clinical applications.

Quantitative study of early-stage transient bacterial adhesion to bioactive glass and glass ceramics: atomic force microscopic observations.

Antimicrobial potential of bioactive glass (BAG) makes it promising for implant applications, specifically overcoming the toxicity concerns associated with traditional antibacterial nanoparticles. The 58S composition of BAG (with high Ca and absence of Na) has been known to exhibit excellent bioactivity and antibacterial behaviour, but the mechanisms behind have not been investigated in detail. In this pioneering study, we are using Atomic Force Microscopy (AFM) to gain insights into 58S BAG's adhesive interactions with planktonic cells of both gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria; along with the impact of crystallinity on antibacterial properties. We have recorded greater bacterial inhibition by amorphous BAG compared to semi-crystalline glass-ceramics and stronger effect against gram-negative bacteria via conventional long-term antibacterial tests. AFM force distance curves has illustrated substantial bonding between bacteria and BAG within the initial one second (observed at a gap of 250 ms) of contact, with multiple binding events. Further, stronger adhesion of BAG with E.coli (~ 6 nN) compared to S. aureus (~ 3 nN) has been found which can be attributed to more adhesive nano-domains (size effect) distributed uniformly on E.coli surface. This study has revealed direct evidence of impact of contact time and 58S BAG's crystalline phase on bacterial adhesion and antimicrobial behaviour. Current study has successfully demonstrated the mode and mechanisms of initial bacterial adhesion with 58S BAG. The outcome can pave the way towards improving the designing of implant surfaces for a range of biomedical applications.

Osteogenic potency of dental stem cell-composite scaffolds in an animal cleft palate model.

Objective: To evaluate the osteogenic potency of stem cells isolated from human exfoliated deciduous teeth (SHED) in polycaprolactone with gelatin surface modification (PCL-GE) and poly (lactic-co-glycolic acid)-bioactive glass composite (PLGA-bioactive glass (BG)) scaffolds after implantation in a rat cleft model. Methods: Cleft palate-like lesions were induced in Sprague-Dawley rats by extracting the right maxillary first molars and drilling the intact alveolar bone. Rats were then divided into five groups: Control, PCL-GE, PCL-GE-SHED, PLGA-BG, and PLGA-BG-SHED, and received corresponding composite scaffolds with/without SHED at the extraction site. Tissue samples were collected at 2, 3, and 6 months post-implantation (4 rats per group). Gross and histological analyses were conducted to assess osteoid or bone formation. Immunohistochemistry for osteocalcin and human mitochondria was performed to evaluate bone components and human stem cell viability in the tissue. Results: Bone tissue formation was observed in the PCL-GE and PLGA-BG groups compared to the control, where no bone formation occurred. PLGA-BG scaffolds demonstrated greater bone regeneration potential than PCL-GE over 2-6 months. Additionally, scaffolds with SHED accelerated bone formation compared to scaffolds alone. Osteocalcin expression was detected in all rats, and positive immunoreactivity for human mitochondria was observed in the regenerated bone tissue with PCL-GE-SHED and PLGA-BG-SHED. Conclusion: PCL-GE and PLGA-BG composite scaffolds effectively repaired and regenerated bone tissue in rat cleft palate defects. Moreover, scaffolds supplemented with SHED exhibited enhanced osteogenic potency. Clinical significance: PCL-GE and PLGA-BG scaffolds, augmented with SHED, emerge as promising biomaterial candidates for addressing cleft repair and advancing bone tissue engineering endeavors.

The anti-biofilm efficacy of copper and zinc doped borate bioactive glasses.

Aim: Healthcare-acquired infections (HAIs) pose significant challenges in medical settings due to their resistance to conventional treatment methods. The role of bacterial biofilms in exacerbating these infections is well-documented, making HAIs particularly difficult to eradicate. Despite numerous research efforts, an effective solution to combat these infections remains elusive. This study aims to explore the potential of metal-ion (copper and zinc) doped borate bioactive glasses (BBGs) as a novel treatment modality to inhibit bacterial species commonly implicated in HAIs: Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa.Methods: The study analyzed the efficacy of both direct and indirect applications of BBGs on severe biofilms pre-formed under static and dynamic growth conditions; a comprehensive predictive modeling was developed, simulating diverse clinically relevant conditions.Results: Results demonstrate more than 4 log reduction in bacterial growth within 2 days for direct application and 3 days for indirect application of copper and zinc-doped BBGs. These findings were consistent across the three bacterial species, in both static and dynamic conditions.Conclusion: Copper and zinc-doped BBGs can be an effective approach in combating HAIs complicated by biofilms.

Hospital-acquired infections (HAIs) are common in medical settings and can be difficult to treat because they often involve biofilms ­ communities of bacteria that are hard to eliminate with antibiotics. Our study examines the use of a biomaterials called borate bioactive glasses (BBGs) enhanced with copper and zinc, which are metals are known for killing bacteria. We tested these materials against common bacteria found in HAIs to determine if they could prevent and break down biofilms. Our experiments showed that these metal-enhanced glasses could significantly reduce bacterial growth within a few days in a various of clinically-relevant scenarios, making them a promising solution for controlling infections in clinical settings. This research could lead to new ways to prevent and treat infections resistant to standard treatments.

Multifunctional bioactive glass nanoparticles: surface-interface decoration and biomedical applications.

Developing bioactive materials with multifunctional properties is crucial for enhancing their biomedical applications in regenerative medicine. Bioactive glass nanoparticle (BGN) is a new generation of biomaterials that demonstrate high biocompatibility and tissue-inducing capacity. However, the hard nanoparticle surface and single surface property limited their wide biomedical applications. In recent years, the surface functional strategy has been employed to decorate the BGN and improve its biomedical applications in bone tissue repair, bioimaging, tumor therapy and wound repair. This review summarizes the progress of surface-interface design strategy, customized multifunctional properties and biomedical applications in detail. We also discussed the current challenges and further development of multifunctional BGN to meet the requirements of various biomedical applications.

The release behavior and in vitro osteogenesis of quercetin-loaded bioactive glass/hyaluronic acid/sodium alginate nanocomposite paste.

Injectable pastes based on bioactive compounds and natural polymers are of interest in non-invasive bone surgeries. Several quantities of quercetin (100, 150, and 200 µM) were added to a sol-gel derived mesoporous bioactive glass. Injectable pastes based on quercetin-loaded bioactive glass, sodium alginate, and hyaluronic acid were prepared. Aggregated nanoparticles of bioactive glass and quercetin-loaded bioactive glass with mesoporous morphologies were confirmed by TEM and BET techniques. The quercetin release study was assessed in phosphate-buffered solution medium over 200 h and the obtained data were fitted by different eqs. A sustained release of quercetin was found, in which a better regression coefficient was achieved using Weibull equation. Human-derived mesenchymal stem cells were utilized to determine alkaline phosphatase activity and bone-related protein expression by western blotting and real-time PCR evaluations. Quercetin-loaded pastes increased the levels of alkaline phosphatase activity and the expression of Collagen-1, Osteopontin, Osteocalcin, and Runx2 proteins in a concentration-dependent manner. Due to the mesoporous architecture and high specific surface area of bioactive glass, the paste made of these particles and sodium alginate/hyaluronic acid macromolecules is appropriate matrix for quercetin release, resulting in promoted osteogenesis. The further in vivo studies can support the osteogenesis capacity of the quercetin-loaded paste.

Advancements in reliability of mechanical performance of 3D PRINTED Ag-doped bioceramic antibacterial scaffolds for bone tissue engineering.

The current gold-standard approach for addressing bone defects in load-bearing applications sees the use of either autographs or allographs. These solutions, however, have limitations as autographs and allographs carry the risk of additional trauma, the threat of disease transmission, and potential donor rejection. An attractive candidate for overcoming the challenges associated with the use of autographs and allographs is a 3D porous scaffold displaying the needed mechanical competency for use in load-bearing applications that can stimulate bone tissue regeneration and provide antibacterial capabilities. To date, no reports document a 3D porous scaffold that fully meets the criteria specified above. In this work, we show how the use of fused filament fabrication (FFF) 3D printing technology in combination with a bimodal distribution of Ag-doped bioactive glass-ceramic (Ag-BG) micro-sized particles can successfully deliver porous 3D scaffolds with attractive and reliable mechanical performance characteristics capable of stimulating bone tissue regeneration and the ability to provide inherent antibacterial properties. To characterize the reliability of the mechanical performance of the FFF-printed Ag-BG scaffolds, Weibull statistics were evaluated for both the compressive (N = 25; m = 13.6 ± 0.9) and flexural (N = 25; m = 7.3 ± 0.7) strengths. Methicillin-resistant Staphylococcus aureus (MRSA) was used both in planktonic and biofilm forms to highlight the advanced antibacterial characteristics of the FFF-printed Ag-BG scaffolds. Biological performance was evaluated in vitro through indirect exposure to human marrow stromal cells (hMSCs), where the FFF-printed Ag-BG scaffolds were found to provide an attractive environment for cell infiltration and mineralization. Our work demonstrates how fused filament fabrication technology can be used with bioactive and antibacterial materials such as Ag-BG to deliver mechanically competent porous 3D scaffolds capable of stimulating bone tissue regeneration while simultaneously providing antibacterial performance capabilities.

Flexible and high-strength bioactive glass fiber membrane for bone regeneration with the aid of alkoxysilane sol spinnability.

In this research, the spinnability of bioactive glass (BG) precursor solution was supplied by alkoxysilane sol with appropriate molar ratio of H2O/silicon (R) to prepare bioactive glass fiber membrane (BFM) using electrospinning (ES) technique. Alkoxysilane could form a linear or chain-like colloidal aggregation in hydrolysis-polycondensation with R = 2 or so, thereby exhibiting good spinnability. Therefore, the role of polymer binders could be largely replaced. Due to the significant decrease of polymer binder, the defects within the fibers are largely reduced and degree of fiber densification was improved after calcination, leading to BFM drastically enhanced strength and flexibility. The effect of R and calcination temperature on mechanical performance were investigated in detail. The tensile strength could reach the highest value 2.31 MPa with R = 2 and calcination at 700 °C. In addition, under this preparation condition, the BFM also possessed good flexibility with bending rigidity 37.7 mN. Furthermore, the great performance of promoting cell proliferation and osteogenesis could be observed from in vitro cellular experiment. The BFM calcined at 750 °C exhibited the best promoting osteogenic differentiation ability. The rat skull defect model revealed BFM could perform well in osteogenesis in vivo.

Enhancing alginate dialdehyde-gelatin (ADA-GEL) based hydrogels for biofabrication by addition of phytotherapeutics and mesoporous bioactive glass nanoparticles (MBGNs).

This study explores the 3D printing of alginate dialdehyde-gelatin (ADA-GEL) inks incorporating phytotherapeutic agents, such as ferulic acid (FA), and silicate mesoporous bioactive glass nanoparticles (MBGNs) at two different concentrations. 3D scaffolds with bioactive properties suitable for bone tissue engineering (TE) were obtained. The degradation and swelling behaviour of films and 3D printed scaffolds indicated an accelerated trend with increasing MBGN content, while FA appeared to stabilize the samples. Determination of the degree of crosslinking validated the increased stability of hydrogels due to the addition of FA and 0.1% (w/v) MBGNs. The incorporation of MBGNs not only improved the effective moduli and conferred bioactive properties through the formation of hydroxyapatite (HAp) on the surface of ADA-GEL-based samples but also enhanced VEGF-A expression of MC3T3-E1 cells. The beneficial impact of FA and low concentrations of MBGNs in ADA-GEL-based inks for 3D (bio)printing applications was corroborated through various printing experiments, resulting in higher printing resolution, as also confirmed by rheological measurements. Cytocompatibility investigations revealed enhanced MC3T3-E1 cell activity and viability. Furthermore, the presence of mineral phases, as confirmed by an in vitro biomineralization assay, and increased ALP activity after 21 days, attributed to the addition of FA and MBGNs, were demonstrated. Considering the acquired structural and biological properties, along with efficient drug delivery capability, enhanced biological activity, and improved 3D printability, the newly developed inks exhibit promising potential for biofabrication and bone TE.

Sol-gel-derived calcium silicate cement incorporating collagen and mesoporous bioglass nanoparticles for dental pulp therapy.

OBJECTIVE: Calcium silicate cements (CSCs) are often used in endodontics despite some limitations related to their physical properties and antibacterial efficacy. This study aimed to develop and demonstrate the viability of a series of CSCs that were produced by sol-gel method and further modified with mesoporous bioactive glass nanoparticles (MBGNs) and collagen, for endodontic therapy. METHODS: Calcium silicate (CS) particles and MBGNs were synthesized by the sol-gel method, and their elemental, molecular, and physical microstructure was characterized. Three CSCs were developed by mixing the CS with distilled water (CS+H2O), 10 mg/mL collagen solution (CS+colH2O), and MBGNs (10 %) (CSmbgn+colH2O). The mixing (MT) and setting (ST) times of the CSCs were determined, while the setting reaction was monitored in real-time. Antibacterial efficacy against Enterococcus faecalis (E. faecalis) and regenerative potential on dental pulp stem cells (DPSCs) were also analyzed. RESULTS: The CS+H2O displayed a ST comparable to commercial products, while CSmbgn+colH2O achieved the longest MT of 68 s and the shortest ST of 8 min. All the experimental CSCs inhibited the growth of E. faecalis. Additionally, compared to the control group, CSCs supported cell proliferation and spreading and mineralized matrix production, regardless of their composition. SIGNIFICANCE: Tested CSCs presented potential as candidates for pulp therapy procedures. Future research should investigate the pulp regeneration mechanisms alongside rigorous antibacterial evaluations, preferably with multi-organism biofilms, executed over extended periods.

Exploratory Investigation of Zinc-Modified Borosilicate Bioactive Glass: A New Methodology for Its Biocompatibility, Immunoregulation, and Pro-Angiogenic Property Evaluation.

The assessment of biodegradable materials, such as bioactive glass, under the existing ISO 10993 standard test methods poses a significant challenge due to potential cell viability impairment caused by the accumulation of degraded products in a static environment. Therefore, innovative methodologies are urgently needed to tailor the unique biodegradation characteristics of these materials, providing more precise and scientific insights into biosafety and efficacy verification. Motivation by its bidirectional regulation of angiogenesis and immunity, zinc (Zn) was incorporated into sol-gel-derived borosilicate bioactive glasses (SBSGs) to fabricate Zn-incorporated borosilicate bioactive glasses (SBSG-Zn) to complement the tissue repair capabilities of bioactive glasses. Both SBSG and SBSG-Zn glasses consist of nanosized particles, slit mesoporous pores, high specific surface areas, and bioreactivity. In vitro comparative analysis, conducted according to ISO 10993 standards, demonstrates that only at suitable dilution rates─such as the 8-fold dilution employed in this study─do extracts of SBSG and SBSG-Zn glasses exhibit low cytotoxicity when cultured with human umbilical vein endothelial cells (HUVECs). Notably, SBSG-Zn glasses show optimal promotion of angiogenic gene expression in HUVECs. Furthermore, within an appropriate concentration range of released ions, SBSG-Zn glass extracts not only promote cell survival but also modulate the expression of anti-inflammatory genes while simultaneously inhibiting pro-inflammatory genes concurrently. After being implanted in rat subcutaneous defect models, both SBSG and SBSG-Zn glasses demonstrated the local immunoregulation and angiogenic effects. SBSG-Zn stands out by demonstrating superior modulation of M1/M2 polarization in macrophages as validated by altered secretion of key factors in macrophages and expression of relevant growth factors in HUVECs. These findings underscore the potential for convenient manipulation of localized angiogenic and immunoregulation through the incorporation of zinc into bioactive glass, emphasizing the importance of ensuring the appropriate ion doses are applied for achieving optimal therapeutic efficiency.

Borate bioactive glass enhances 3D bioprinting precision and biocompatibility on a sodium alginate platform via Ca2+ controlled self-solidification.

Sodium alginate (SA) has gained widespread acclaim as a carrier medium for three-dimensional (3D) bioprinting of cells and a diverse array of bioactive substances, attributed to its remarkable biocompatibility and affordability. The conventional approach for fabricating alginate-based tissue engineering constructs entails a post-treatment phase employing a calcium ion solution. However, this method proves ineffectual in addressing the predicament of low precision during the 3D printing procedure and is unable to prevent issues such as non-uniform alginate gelation and substantial distortions. In this study, we introduced borate bioactive glass (BBG) into the SA matrix, capitalizing on the calcium ions released from the degradation of BBG to incite the cross-linking reaction within SA, resulting in the formation of BBG-SA hydrogels. Building upon this fundamental concept, it unveiled that BBG-SA hydrogels greatly enhance the precision of SA in extrusion-based 3D printing and significantly reduce volumetric contraction shrinkage post-printing, while also displaying certain adhesive properties and electrical conductivity. Furthermore, in vitro cellular experiments have unequivocally established the excellent biocompatibility of BBG-SA hydrogel and its capacity to actively stimulate osteogenic differentiation. Consequently, BBG-SA hydrogel emerges as a promising platform for 3D bioprinting, laying the foundation for the development of flexible, biocompatible electronic devices.

Three-dimensional porous polycaprolactone/chitosan/bioactive glass scaffold for bone tissue engineering.

Three-dimensional (3D) porous scaffolds based on polycaprolactone (PCL)/chitosan (CS)/bioactive glass (BG) nanoparticle composites were fabricated by the freeze-drying technique for bone tissue engineering. The physiochemical properties of the developed PCL/CS/BG scaffolds were studied using FTIR, XRD, EDX and SEM. Furthermore, the swelling degree, porosity, water retention ability, compression strength, in vitro biodegradation, bioactivity and biocompatibility of the scaffolds were examined. The PCL/CS/BG scaffolds with 4 wt. % of BG content presented adequate pore size (106 µm), porosity (156%), water swelling degree (128%), water retention ability (179%), compressive strength (3.7 MPa) and controlled degradation behavior, which could be ideal for bone tissue engineering. The PCL/CS/BG composite scaffolds showed good antimicrobial activity against both test bacteria and fungi. The MTT assay demonstrated the biocompatibility of PCL/CS/BG scaffolds against C3H10T1/2 cell line. The Alizarin red staining assay confirmed the osteogenic activity of the PCL/CS/BG scaffolds.