Osteogenic Effect Research Articles

Influence of content of silicon nitride nanoparticles into micro-arc oxidation coating of titanium on bactericidal capability and osteoblastic differentiation

Bone implants with osteogenic and bactericidal capability are particularly promising for orthopedic applications. Herein, micro-arc oxidation (MAO) coatings containing silicon nitride (Si3N4) on titanium (Ti) surface (MSN) were fabricated by dispersing different content of Si3N4 nanoparticles in the electrolyte. Compared with pure Ti and MAO coating, incorporation of Si3N4 nanoparticles into the MAO coating caused significant change in surface characters (e.g., nano-topography, hydrophilicity and surface energy) of MSN, and the change depended on the content of Si3N4 nanoparticles. MSN with the changed surface characters exhibited remarkable improvement of cell response (e.g., multiplication and osteoblastic differentiation), which significantly enhanced with the increase of Si3N4 content. Furthermore, MSN displayed excellent bactericidal ability, which improved with the increase of Si3N4 content. As a result, the enhancements of cellular response and bactericidal capability were ascribed to the increase of Si3N4 content in the coating, and MSN with high content of Si3N4 possessed outstanding osteogenic and anti-bacterial effects. The study demonstrated that incorporation of Si3N4 nanoparticles into the MAO coating led to novel implantable materials of MSN, which exhibited excellent cytocompatibility, osteogenic bioactivity, bactericidal ability, suggesting that MSN possessed a promising potential for applications in orthopedics.

Impact of a Static Magnetic Field on Early Osseointegration: A Pilot Study in Canines.

A static magnetic field generated by neodymium-iron-boron (NdFeB) magnets placed in the inner cavity of dental implants can enhance bone regeneration in rabbits. It is, however, unknown whether static magnetic fields support osseointegration in a canine model. We therefore determined the potential osteogenic effect of implants carrying NdFeB magnets inserted in the tibia of six adult canines in the early stages of osseointegration. Here, we report that after 15 days of healing, magnetic and regular implants showed a high variation with a median new bone-to-implant contact (nBIC) in the cortical (41.3% and 7.3%) and the medullary (28.6% and 44.8%) region, respectively. Consistently, the median new bone volume/tissue volume (nBV/TV) in the cortical (14.9% and 5.4%) and the medullary (22.2% and 22.4%) region were not significantly different. One week of healing only resulted in negligible bone formation. These findings suggest that considering the large variation and the pilot nature of this study, magnetic implants failed to support peri-implant bone formation in a canine model.

Disease-Modifying Adjunctive Therapy of Osteopenia and Osteoporosis with a Multimineral Marine Extract, LithoLexal® Bone

There is evidence to suggest that restoration of major/rare biominerals by supplementation can produce osteogenic and anti-resorptive effects in humans. LithoLexal® is a natural extract harvested from a marine alga, Lithothamnion sp., with a porous microstructure and multimolecular composition rich in calcium (32% w/w) and magnesium (2.2% w/w) together with ~72 trace bioelements. In vitro, LithoLexal® demonstrated cellular-level osteogenic efficacy through enhancing the maturation and activity of pre-osteoblasts. This extract also expressed the ability to suppress osteoclastogenesis by downregulating the pro-resorptive cytokines TNF-α and IL-1β and the master regulator of inflammation NF-κB. Parathyroid hormone inhibition of parathyroid hormone secretion is another bioactivity of LithoLexal® Bone reported with both short- and long-term administration at a longer duration and higher magnitude than what calcium carbonate could induce. Due to these bioactivities that affect pathogenetic factors of osteoporosis, LithoLexal® Bone is referred to as a disease-modifying adjunctive therapy (DMAT). In postmenopausal animal models, LithoLexal® monotherapy preserved bone mineral density, microarchitecture, and biomechanical properties, while calcium carbonate failed to produce significant outcomes. The pro-resorptive effect of a high-fat diet was also efficiently counteracted in vivo by supplementary LithoLexal®. A large clinical trial on postmenopausal women verified the mitigating effects of LithoLexal® Bone on bone resorption and turnover rate. The characteristic composition of LithoLexal® together with its lattice microstructure are suggested to underlie its in vivo bioactivities. In conclusion, adjunctive therapy with LithoLexal® Bone is an attractive option for clinical prevention and treatment of osteopenia/osteoporosis.

Combined computational analysis and cytology show limited depth osteogenic effect on bone defects in negative pressure wound therapy.

Background: The treatment of bone defects remains a clinical challenge. The effect of negative pressure wound therapy (NPWT) on osteogenesis in bone defects has been recognized; however, bone marrow fluid dynamics under negative pressure (NP) remain unknown. In this study, we aimed to examine the marrow fluid mechanics within trabeculae by computational fluid dynamics (CFD), and to verify osteogenic gene expression, osteogenic differentiation to investigate the osteogenic depth under NP. Methods: The human femoral head is scanned using micro-CT to segment the volume of interest (VOI) trabeculae. The VOI trabeculae CFD model simulating the bone marrow cavity is developed by combining the Hypermesh and ANSYS software. The effect of trabecular anisotropy is investigated, and bone regeneration effects are simulated under NP scales of -80, -120, -160, and -200mmHg. The working distance (WD) is proposed to describe the suction depth of the NP. Finally, gene sequence analysis, cytological experiments including bone mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation are conducted after the BMSCs are cultured under the same NP scale. Results: The pressure, shear stress on trabeculae, and marrow fluid velocity decrease exponentially with an increase in WD. The hydromechanics of fluid at any WD inside the marrow cavity can be theoretically quantified. The NP scale significantly affects the fluid properties, especially those fluid close to the NP source; however, the effect of the NP scale become marginal as WD deepens. Anisotropy of trabecular structure coupled with the anisotropic hydrodynamic behavior of bone marrow; An NP of -120mmHg demonstrates the majority of bone formation-related genes, as well as the most effective proliferation and osteogenic differentiation of BMSCs compared to the other NP scales. Conclusion: An NP of -120mmHg may have the optimal activated ability to promote osteogenesis, but the effective WD may be limited to a certain depth. These findings help improve the understanding of fluid mechanisms behind NPWT in treating bone defects.

Synergism of silver/CEM drug on novel proteinaceous silk fibroin/mesoporous silica based sandwich-layered nanofibrous scaffolds for osteoregenerative applications

Osteoregeneration and bacterial infection remains a major challenge in current clinical practice despite, many advanced strategies significantly developed so far. The combination of bioactive molecules and nano topology design can favour osteoinducivity that holds a greater potential as a bone substitute and minimize implant failure due to burst antibacterial effect. Here, we have reported a novel design of sandwich-like layered silver doped mesoporous silica nanofibers stuffed with an antibiotic drug combined with silk fibroin to boost the synergistic effect. We have investigated the physiochemical property of CEM incorporated sandwiched scaffolds by in vitro biomineralization, tensile strength, antibacterial efficacy against Escherichia coli and Staphylococcus aureus bacterial strains, in vitro degradation, osteogenic effects (MTT assay using MG63 cell line and ARS staining). In conclusion, the faster degradation of monolayered nanofibrous scaffold by incorporating the sandwich technique was minimized. The combination of CEM/SF embedded Ag@mesoporous silica sandwich layered nanofibers showed a synergistic antibacterial effect due to the sustained release of drug from the middle layer with no burst release. The development of sandwich technique for the nanofibrous scaffolds could be a viable candidate for bone regeneration and defect repair.

Osteogenic effect of magnesium oxychloride cement modified with phytic acid and loaded with strontium ranelate

BackgroundMagnesium oxychloride cement has good mechanical properties, but poor water resistance.MethodsPhytic acid, which can form chelate with Mg2+, was used to modify magnesium oxychloride cement, and the effects of phytic acid on the strength, in vitro degradation and biological activity of magnesium oxychloride cement were studied. Based on the preparation of phytic acid modified magnesium oxychloride cement with good water resistance and biological activity, osteoporosis treatment strontium ranelate was loaded on phytic acid- magnesium oxychloride cement, strontium ranelate/phytic acid-magnesium oxychloride cement was prepared.ResultsIt was found that the compressive strength of 1.25 wt% phytic acid-magnesium oxychloride cement after soaking in SBF for 28 d could reach 40.5 ± 2.0 MPa, 13.33% higher than that of the control group (when phytic acid was 0 wt%), and the mass loss rate of all ages was lower than that of the control group. The water resistance of magnesium oxychloride cement was effectively improved by phytic acid. After loading with strontium ranelate, the water resistance of 1.25 wt% phytic acid-magnesium oxychloride cement was improved. Cell experiments showed that strontium ranelate could effectively promote cell proliferation and improve the expression of osteoblast-related proteins. When strontium ranelate/phytic acid-magnesium oxychloride cement samples were implanted subcutaneously in rats for 4 w, no obvious inflammatory response was observed, and the material was tightly bound to the surrounding tissues. When bone cement was implanted into rat femur for 4 w, the bone cement was gradually wrapped and absorbed by new bone tissue, which grew from the outside to the inside, indicating that the bone cement containing strontium ranelate/phytic acid-magnesium oxychloride cement had excellent bone-forming ability.ConclusionsIn conclusion, the results indicated that strontium ranelate/phytic acid-magnesium oxychloride cement composite bone cement had a potential application prospect in clinical bone repair.Graphical

Regenerative capacity of trophoblast stem cell-derived extracellular vesicles on mesenchymal stem cells

BackgroundHuman mesenchymal stem cells (MSCs) are therapeutic for clinical applications because of their excellent immunomodulatory and multiple lineage differentiation abilities at tissue injury sites. However, insufficient number of cells and lack of regenerative properties during in vitro expansion still limit the clinical applicability of MSC therapies. Here, we demonstrated a preconditioning strategy with trophoblast stem cell-derived extracellular vesicles (TSC-EVs) to boost the proliferation and regenerative capacity of MSCs.MethodsWe employed cell proliferation analyses such as CCK8 and BrdU assays to determine the proliferation-promoting role of TSC-EVs on MSCs. Osteogenic effects of TSC-EVs on MSCs were assessed by alkaline phosphatase (ALP) activity, calcium assays, and calvarial bone defect animal models. For skin regenerative effects, skin wound mice model was exploited to analyze wound-healing rate in this study, as well as immunofluorescence and histological staining evaluates. We also performed the small RNA profiling and RNA-sequencing analyzes to understand the cellular mechanism of TSC-EVs on MSCs.ResultsTSC-EVs significantly promoted MSC proliferation under xeno-free conditions and facilitated the therapeutic effects of MSCs, including osteogenesis, anti-senescence, and wound healing. Transcriptomic analysis also provided evidence that specific microRNAs in TSC-EVs and differentially expressed genes (DEGs) in TSC-EV-treated MSCs showed the possibility of TSC-EVs triggering the regenerative abilities of MSCs with cytokine interaction. Hence, we found that NGF/Akt signaling mediated the regenerative effects of TSC-EVs on MSCs as a particular cellular signaling pathway.ConclusionThe results of this study demonstrated the functional properties of TSC-EVs on MSCs for MSC-based therapeutic applications, suggesting that TSC-EVs may serve as a potential preconditioning source for MSC therapy in the clinical field of regenerative medicine.Graphical abstract

LncRNA MEG3 Promotes PDK4/GSK-3β/β-Catenin Axis in MEFs by Targeting miR-532-5p.

Studies reported the positive and negative osteogenic effects of MEG3 in mesenchymal stem cells (MSCs). This study aims at clarifying the osteogenic potential of MEG3 and the underlying mechanism. Bone morphogenetic protein 9- (BMP9-) transfected MSCs were recruited as an osteogenic model in vitro, and ectopic bone formation were used in vivo to explore the effect of MEG3 on osteogenesis. We found that overexpression of MEG3 facilitated BMP9-induced osteogenic markers, ALP activities, and matrix mineralization. However, knockdown of MEG3 attenuated BMP9-induced osteogenic markers. MEG3 increased the phosphorylation of GSK-3β and the protein level of β-catenin. Pyruvate dehydrogenase kinase 4 (PDK4) can also combine with GSK-3β and increase the latter phosphorylation. Moreover, MEG3 increased the mRNA level of PDK4. The ceRNA analysis showed that MEG3 may regulate the expression of PDK4 via microRNA 532-5p (miR-532-5p). The MEG3-enhanced GSK-3β/β-catenin axis can be attenuated by miR-532-5p, and miR-532-5p inhibitor partly rescued endogenous PDK4 and MEG3-mediated expression of PDK4. MEG3 may potentiate PDK4 and GSK-3β/β-catenin by inhibiting miR-532-5p.

Enhancement of critical-sized bone defect regeneration by magnesium oxide-reinforced 3D scaffold with improved osteogenic and angiogenic properties

• 3D bio-nanocomposite scaffold which have an ideal magnesium ionic microenvironment was developed for critical-sized bony tissue repairing. • Significantly enhanced osteogenic effects were observed over the bio-nanocomposite as compare to the polycaprolactone control. • The rodent femoral and critical-sized cranial defect models were applied to characterize the osteogenesis in vivo . • Magnesium enriched scaffold exhibited remarkably increased bone volume, enhanced angiogenesis, and almost recovered critical-sized defect after an 8-week implantation. The healing of critical-sized bone defects (CSD) remains a challenge in orthopaedic medicine. In recent years, scaffolds with sophisticated microstructures fabricated by the emerging three-dimensional (3D) printing technology have lighted up the treatment of the CSD due to the elaborate microenvironments and support they may build. Here, we established a magnesium oxide-reinforced 3D-printed biocomposite scaffold to investigate the effect of magnesium-enriched 3D microenvironment on CSD repairing. The composite was prepared using a biodegradable polymer matrix, polycaprolactone (PCL), and the dispersion phase, magnesium oxide (MgO). With the appropriate surface treatment by saline coupling agent, the MgO dispersed homogeneously in the polymer matrix, leading to enhanced mechanical performance and steady release of magnesium ion (Mg 2+ ) for superior cytocompatibility, higher cell viability, advanced osteogenic differentiation, and cell mineralization capabilities in comparison with the pure PCL. The in-vivo femoral implantation and critical-sized cranial bone defect studies demonstrated the importance of the 3D magnesium microenvironment, as a scaffold that released appropriate Mg 2+ exhibited remarkably increased bone volume, enhanced angiogenesis, and almost recovered CSD after 8-week implantation. Overall, this study suggests that the magnesium-enriched 3D scaffold is a potential candidate for the treatment of CSD in a cell-free therapeutic approach.

Titanium dioxide nanotubes increase purinergic receptor P2Y6 expression and activate its downstream PKCα-ERK1/2 pathway in bone marrow mesenchymal stem cells under osteogenic induction.

Titanium dioxide (TiO2) nanotubes can improve the osseointegration of pure titanium implants, but this exact mechanism has not been fully elucidated. The purinergic receptor P2Y6 is expressed in bone marrow mesenchymal stem cells (BMSCs) and participates in the regulation of bone metabolism. However, it is unclear as to whether P2Y6 is involved in the osteogenic differentiation of BMSCs induced by TiO2 nanotubes. TiO2 nanotubes were prepared on the surface of titanium specimens using the anodizing method and characterized their features. Quantitative reverse transcriptase polymerase chain reaction and western blotting were used to detect the expression of P2Y6, markers of osteogenic differentiation, and PKCα-ERK1/2. A rat femoral defect model was established to evaluate the osseointegration effect of TiO2 nanotubes combined with P2Y6 agonists. The results showed that the average inner diameter of the TiO2 nanotubes increased with an increase in voltage (voltage range of 30-90V), and the expression of P2Y6 in BMSCs could be upregulated by TiO2 nanotubes in osteogenic culture. Inhibition of P2Y6 expression partially inhibited the osteogenic effect of TiO2 nanotubes and downregulated the activity of the PKCα-ERK1/2 pathway. When using in vitro and in vivo experiments, the osteogenic effect of TiO2 nanotubes when combined with P2Y6 agonists was more pronounced. TiO2 nanotubes promoted the P2Y6 expression of BMSCs during osteogenic differentiation and promoted osteogenesis by activating the PKCα-ERK1/2 pathway. The combined application of TiO2 nanotubes and P2Y6 agonists may be an effective new strategy to improve the osseointegration of titanium implants. STATEMENT OF SIGNIFICANCE: Titanium dioxide (TiO2) nanotubes can improve the osseointegration of pure titanium implants, but this exact mechanism has not been fully elucidated. The purinergic receptor P2Y6 is expressed in bone marrow mesenchymal stem cells (BMSCs) and participates in the regulation of bone metabolism. However, it is unclear as to whether P2Y6 is involved in the osteogenic differentiation of BMSCs induced by TiO2 nanotubes. For the first time, this study revealed the relationship between TiO2 nanotubes and purine receptor P2Y6, and further explored its mode of action, which may provide clues as to the regulatory role of TiO2 nanotubes on osteogenic differentiation of BMSCs. These findings will help to develop novel methods for guiding material design and biosafety evaluation of nano implants.

Improved drug incorporation and in vitro osteogenic effect of baicalin coating on different modified titanium surfaces

Improved drug incorporation and in vitro osteogenic effect of baicalin coating on different modified titanium surfaces

Nanotherapy for bone repair: milk-derived small extracellular vesicles delivery of icariin

Icariin (ICA) played an important role in the treatment of inflammatory bone defects. However, pharmacokinetic studies have shown that its poor bioavailability limited its application. In this context, we isolated bovine milk-derived sEV and prepared sEV-ICA to improve the osteogenic effect of ICA. In this study, we successfully constructed sEV-ICA. sEV-ICA was found to have significantly higher osteogenic efficiency than ICA in cell culture and cranial bone defect models. Mechanistically, bioinformatics analysis predicted that signal transducers and activators of transcription 5 (STAT5a) may bind to the GJA1 promoter, while luciferase activity assays and chromatin immunoprecipitation (ChIP) experiments confirmed that STAT5a directly binded to the GJA1 promoter to promote osteogenesis. We proved that compared with ICA, sEV-ICA showed a better effect of promoting bone repair in vivo and in vitro. In addition, sEV-ICA could promote osteogenesis by promoting the combination of STAT5a and GJA1 promoter. In summary, as a complex drug delivery system, sEV-ICA constituted a rapid and effective method for the treatment of bone defects and could improve the osteogenic activity of ICA.

Osteogenic and anti-inflammatory effect of the multifunctional bionic hydrogel scaffold loaded with aspirin and nano-hydroxyapatite.

Although tissue engineering offered new approaches to repair bone defects, it remains a great challenge to create a bone-friendly microenvironment and rebuild bone tissue rapidly by a scaffold with a bionic structure. In this study, a multifunctional structurally optimized hydrogel scaffold was designed by integrating polyvinyl alcohol (PVA), gelatin (Gel), and sodium alginate (SA) with aspirin (ASA) and nano-hydroxyapatite (nHAP). The fabrication procedure is through a dual-crosslinking process. The chemical constitution, crystal structure, microstructure, porosity, mechanical strength, swelling and degradation property, and drug-release behavior of the hydrogel scaffold were analyzed. Multi-hydrogen bonds, electrostatic interactions, and strong "egg-shell" structure contributed to the multi-network microstructure, bone tissue-matched properties, and desirable drug-release function of the hydrogel scaffold. The excellent performance in improving cell viability, promoting cell osteogenic differentiation, and regulating the inflammatory microenvironment of the prepared hydrogel scaffold was verified using mouse pre-osteoblasts (MC3T3-E1) cells. And the synergistic osteogenic and anti-inflammatory functions of aspirin and nano-hydroxyapatite were also verified. This study provided valuable insights into the design, fabrication, and biological potential of multifunctional bone tissue engineering materials with the premise of constructing a bone-friendly microenvironment.

3D-printed porous functional composite scaffolds with polydopamine decoration for bone regeneration.

Large size bone defects affect human health and remain a worldwide health problem that needs to be solved immediately. 3D printing technology has attracted substantial attention for preparing penetrable multifunctional scaffolds to promote bone reconditioning and regeneration. Inspired by the spongy structure of natural bone, novel porous degradable scaffolds have been printed using polymerization of lactide and caprolactone (PLCL) and bioactive glass 45S5 (BG), and polydopamine (PDA) was used to decorate the PLCL/BG scaffolds. The physicochemical properties of the PLCL/BG and PLCL/BG/PDA scaffolds were measured, and their osteogenic and angiogenic effects were characterized through a series of experiments both in vitro and in vivo. The results show that the PLCL/BG2/PDA scaffold possessed a good compression modulus and brilliant hydrophilicity. The proliferation, adhesion and osteogenesis of hBMSCs were improved in the PDA coating groups, which exhibited the best performance. The results of the SD rat cranium defect model indicate that PLCL/BG2/PDA obviously promoted osteointegration, which was further confirmed through immunohistochemical staining. Therefore, PDA decoration and the sustained release of bioactive ions (Ca, Si, P) from BG in the 3D-printed PLCL/BG2/PDA scaffold could improve surface bioactivity and promote better osteogenesis and angiogenesis, which may provide a valuable basis for customized implants in extensive bone defect repair applications.

A multifunctional nanocomposite hydrogel with controllable release behavior enhances bone regeneration.

Autologous and allogeneic bone grafts remain the gold standard for repairing bone defects. However, donor shortages and postoperative infections contribute to unsatisfactory treatment outcomes. Tissue engineering technology that utilizes biologically active composites to accelerate the healing and reconstruction of segmental bone defects has led to new ideas for in situ bone repair. Multifunctional nanocomposite hydrogels were constructed by covalently binding silver (Ag+) core-embedded mesoporous silica nanoparticles (Ag@MSN) to bone morphogenetic protein-2 (BMP-2), which was encapsulated into silk fibroin methacryloyl (SilMA) and photo-crosslinked to form an Ag@MSN-BMP-2/SilMA hydrogel to preserve the biological activity of BMP-2 and slow its release. More importantly, multifunctional Ag+-containing nanocomposite hydrogels showed antibacterial properties. These hydrogels possessed synergistic osteogenic and antibacterial effects to promote bone defect repair. Ag@MSN-BMP-2/SilMA exhibited good biocompatibility in vitro and in vivo owing to its interconnected porosity and improved hydrophilicity. Furthermore, the multifunctional nanocomposite hydrogel showed controllable sustained-release activity that promoted bone regeneration in repairing rat skull defects by inducing osteogenic differentiation and neovascularization. Overall, Ag@MSN-BMP-2/SilMA hydrogels enrich bone regeneration strategies and show great potential for bone regeneration.

Icariin Has a Synergistic Effect on the Osteoinductivity of Bone Morphogenetic Protein 2 at Ectopic Sites.

Establishing biocompatible, biodegradable, osteoconductive, and osteoinductive bone materials remains a challenging subject in the research of bone healing and bone regeneration. Previously, we demonstrated the osteogenic and osteoconductive effects of biomimetic calcium phosphate (BioCaP) incorporating with Icariin and/or bone morphogenetic protein 2 (BMP-2) at orthotopic sites. By implanting the BioCaP granules incorporated Icariin and/or BMP-2 into the dorsal subcutaneous pockets of adult male Sprague-Dawley (S-D) rats (6-7 weeks old), we investigated the osteoinductive efficacy of the samples. Micro-computed tomography(micro-CT) observations and histological slices were used to verify the osteoinduction of this system on the 2nd and 5th week. Statistical significances was evaluated using Turkey's post hoc test of one-way analysis of variance. The osteoinduction of the BioCaP incorporated with BMP-2 or both agents was confirmed as expected. BioCaP with Icariin alone could not generate bone formation at an ectopic sites. Nevertheless, co-administration of Icariin increased bone mineral density (BMD; p < 0.01) (628mg HA/cm3 vs 570mg HA/cm3 ) and completely changed the distribution of newly formed bone when compared with the granules with BMP-2 alone, even though there was no significant difference in the volume of newly formed bone. In contrast, the BioCaP with both agents (37.86%) had significantly fewer remaining materials than the other groups by the end of the fifth week (53.22%, 53.62% and 48.22%) (p < 0.01). The co-administration of Icariin and BMP-2 increased BMD changed the distribution of newly formed bone, and reduced the amount of remaining materials. Therefore, Icariin can stimulate BMP-2 when incorporated into BioCaP granules at ectopic sites, which makes it useful for bone tissue engineering.

Design of a Haversian system-like gradient porous scaffold based on triply periodic minimal surfaces for promoting bone regeneration

IntroductionThe bone ingrowth depth in the porous scaffolds is greatly affected by the structural design, notably the pore size, pore geometry, and the pore distribution. To enhance the bone regeneration capability of scaffolds, the bionic design can be regarded as a potential solution. ObjectivesWe proposed a Haversian system-like gradient structure based on the triply periodic minimal surface architectures with pore size varying from the edge to the center. And its effects in promoting bone regeneration were evaluated in the study. MethodsThe gradient scaffold was designed using the triply periodic minimal surface architectures. The mechanical properties were analyzed by the finite element simulation and confirmed using the universal machine. The fluid characteristics were calculated by the computational fluid dynamics analysis. The bone regeneration process was simulated using a in silico computational model containing the main biological, physical, and chemical variation during the bone growth process. Finally, the in vitro and in vivo studies were carried out to verify the actual osteogenic effect. ResultsCompared to the uniform scaffold, the biomimetic gradient scaffold demonstrated better performance in stress conduction and reduced stress shielding effects. The fluid features were appropriate for cell migration and flow diffusion, and the permeability was in the same order of magnitude with the natural bone. The bone ingrowth simulation exhibited improved angiogenesis and bone regeneration. Higher expression of the osteogenesis-related genes, higher alkaline phosphatase activity, and increased mineralization could be observed on the gradient scaffold in the in vitro study. The 12-week in vivo study proved that the gradient scaffold had deeper bone inserting depth and a more stable bone-scaffold interface. ConclusionThe Haversian system-like gradient structure can effectively promote the bone regeneration. This structural design can be used as a new solution for the clinical application of prosthesis design.

Dopamine and epigallocatechin-3-gallate cross-linked coating demonstrates improved osteointegration of polyetheretherketone in rabbits

The increasing demand for enhanced osteointegration calls for next-generation polyetheretherketone (PEEK) that can offer fast bone integration. Whether polydopamine (PDA) and epigallocatechin-3-gallate (EGCG) cross-linked coatings could improve osteointegration of PEEK remains unclear. Here, we fabricated a series of PDA and EGCG cross-linked coatings (PE coatings: P2E0.1, P2E0.5, P2E1, and P2E2 coatings) to enhance osteointegration of PEEK. The material characteristics of coatings were studied using scanning electron microscopy, X-ray photoelectron spectroscopy, micro-BCA tests, and static water contact angle tests. We evaluated the cytotoxicity, cell adhesion, and osteogenic effects of the coatings in vitro. Furthermore, the P2E0.5 coating was selected to coat porous PEEK scaffold to observe osteointegration using micro-computed tomography and histology in a rabbit. The results show that the PE coatings provide phenolic hydroxyl and amino groups and enhanced hydrophilicity of PEEK, especially in the P2E0.5 coating. Several lines of cellular evidence suggest that P2E0.5 coatings exhibit a noncytotoxic and excellent osteogenic effect. Compared with PEEK, the P2E0.5-coated PEEK shows higher values of bone volume, trabecular number, and trabecular thickness. This study suggests that the PE coating is a promising candidate for surface modification of PEEK and may lay the foundation for further application of PE coatings in clinical practice.

Calcium-Zinc Phosphate Chemical Conversion Coating Facilitates the Osteointegration of Biodegradable Zinc Alloy Implants by Orchestrating Macrophage Phenotype.

Zinc (Zn) alloys provide a new generation for orthopedic applications due to their essential physiological effects and promising degradation properties. However, excessive release of Zn ions (Zn2+ ) during degradation and the severe inflammatory microenvironment are not conducive to osseointegration, which is determined by the characteristics of the implant surface. Therefore, it is essential to modulate the release rate of Zn alloys by surface modification technology and endow them with anti-inflammatory and osteogenic effects. In this study, two kinds of phosphate chemical conversion (PCC) coatings with different compositions and morphological structures are prepared, namely Zn-P (with disk-like crystals) and Ca-Zn-P (with lamellar crystals). Although all the PCC-coated Zn implants have low cytotoxicity, Ca-Zn-P show better osteoimmunomodulation effects in several aspects: the induction of the M2-phenotype macrophage polarization and thus promotion of osteogenesis in vitro; the regulation of the bone immune microenvironment which is conducive to tissue regeneration and osseointegration in vivo; and the release of ions (through PI3K/AKT and Wnt signaling pathways) and the morphological structures (through RhoGTPase signaling pathways) act as possible mechanisms of M2 polarization. The Ca-Zn-P coating can be considered to provide new insights into bone immunomodulation and osseointegration.

Human umbilical cord mesenchymal stem cells induction in peri-implantitis Rattus norvegicus accelerates and enhances osteogenesis activity and implant osseointegration

BackgroundPeri-implantitis additional treatment generally aims to repair damaged tissue through a regenerative approach. Human umbilical cord mesenchymal stem cells (hUCMSCs) produce a high osteogenic effect and are capable of modulating the immune system by suppressing inflammatory response, modulating bone resorption, and inducing endogenous osteogenesis. Aim: This study was intended to discover the effect of hUCMSCs on an implant osseointegration process in peri-implantitis rat subjects as assessed by several markers including interleukin-10 (IL-10), transforming growth factor-β (TGF-β), receptor activator of nuclear factor kappa- β ligand (RANKL), bone morphogenic protein (BMP-2), osterix (Osx), and osteoprotegerin (OPG). Material and methods: The research design implemented during this study represented a true experimental design incorporating the use of Rattus norvegicus (Wistar strain) as subjects. Results: Data analysed by means of a Brown Forsythe test indicated differences between the increase in BMP-2 expression (p < 0.000) and Osx expression (p < 0.001) and between RANKL expression (p < 0.001, Tukey HSD) and OPG expression (p < 0.000, Games Howell). Conclusion: According to the findings of this research, hUCMSCs induction is successful in accelerating and enhancing osteogenic activity and implant osseointegration in peri-implantitis rat subjects.