Osteoinductive Properties Research Articles

The osteoinductive potential of different root-end filling materials in a rat femur model

In pediatric dentistry, the enduring success of root-end filling materials employed for the establishment of apical plugs in immature teeth undergoing endodontic intervention is contingent upon their possessing a robust osteoinductive capacity. Hence, the primary objective of this study was to histologically assess the osteoinductive potential of four distinct dental materials, specifically recommended for retrograde filling applications, utilizing an animal hard tissue model. Within the designed experimental model, two bone defects measuring 2 mm in diameter and 2 mm in depth were created in both femurs of a cohort comprising 21 male Wistar albino rats. The first defect in the right femur was left blank as the control group, and Neo MTA Plus was placed in the second defect. The EndoSequence BCRRM Fast Set Putty was placed in the first of the defects on the left femur, and Endo Repair was placed in the second defect. Subjects were sacrificed after 7, 14, and 28 days of follow-up, and sections were examined to assess the degree of inflammation, connective tissue formation, and new bone formation. The data were statistically evaluated with Kruskal‒Wallis and post hoc Dunn's tests using SPSS 12 software. The bone healing levels of the Neo MTA Plus group were significantly higher than those of the other groups in all periods (p < 0.05). Bone organization in all groups decreased over time, and fibrous tissue was enriched. The results of this study demonstrate that NeoMta Plus has superior osteoinductive properties compared to other materials but that EndoSequence and Endo Repair have the potential to be developed.

Characterization of the osteogenic differentiation capacity of human bone cells on hybrid β-TCP/ZrO2 structures

This study deals with synthetic biomaterials that are biocompatible and mechanically stable to serve as a potential bone graft for improved mandibular reconstruction. To fabricate novel hybrid scaffolds containing beta-tricalcium phosphate (β-TCP) and zirconia (ZrO2), 3D printing was combined with Freeze Foaming to achieve a certain porosity, mimicking cancellous bone. The aim was to characterize the differentiation capacity of human pre-osteoblasts on the hybrid scaffolds. Although a good biocompatibility was demonstrated for the tested components of the hybrid scaffold, pure β-TCP foams showed the best results regarding osteogenic differentiation and pro-inflammatory processes. To enhance the osteoinductive properties of the β-TCP foam, the structures were also biofunctionalized with bone morphogenic protein 2 (BMP–2) and its effect was analyzed either on single cell cultures of pre-osteoblasts or pre-osteoblasts directly co-cultured with human peripheral blood mononuclear cells (PBMCs). The latter served to analyze the induction of bone remodelling processes. The immobilization of BMP-2 on scaffolds and its biological accessibility could be demonstrated, however, the biofunctionalization did not result in an enhanced differentiation capacity and bone remodeling processes of either pre-osteoblasts or directly co-cultured pre-osteoblasts and PBMCs.

Stimulation of Osteogenic Activity of Autologous Teeth Hard Tissues as Bone Augmentation Material.

The issue of bone volume loss is playing an increasing role in bone tissue engineering. Research has focused on studying the preparation and use of different types of human or xenogenic materials and their osteogenic properties. An alternative source for this purpose could be autologous extracted teeth. The simple preparation protocol, minimal immune response, and rapid organizing of the newly formed bone with optimal mechanical properties predispose autologous hard teeth tissues (HTTs) as a promising material suitable in the indication of augmentation of maxillary and mandible defects, comparable to other high-end augmentation materials. The aim of this study was to experimentally evaluate the osteogenic potential of ground native autologous HTTs prepared by different demineralization procedures, aimed at potentiating the osteoinductive and osteoconductive properties of their organic components. The results indicate that the most effective preparation process for HTT stimulation is the application of Cleanser for 10 min followed by exposure to 0.6 N HCl for 5 min with a wash in phosphate-buffered saline solution.

Dopamine-mediated copper-loaded ZnTiO3 antimicrobial coating with immunomodulatory properties effectively enhances vascularised osteogenesis on titanium implants

In this study, zinc (Zn) with osteogenic activity and copper (Cu) with angiogenic activity were simultaneously introduced into titanium dioxide nanotubes (TN) by means of anodic oxidation technique, hydrothermal reaction and dopamine (PDA) polymerisation effect (ZnTN-PDA-Cu). The ZnTN-PDA-Cu coating had favourable mechanical, hydrophilic, corrosion-resistant, and bioactive characteristics, according to the results. Zn2+ and Cu2+ could be continuously released from the coating and was pH-responsive. In addition, ZnTN-PDA-Cu showed good antibacterial properties against E. coli and S. aureus. Cellular assays revealed that RAW264.7 (immune), HUVEC (angiogenic) and MC3T3-E1 (osteogenic) exhibited good adhesion and proliferation activities on the ZnTN-PDA-Cu coated Ti. The expression of anti-inflammatory markers, angiogenic markers and osteogenic markers was significantly up-regulated in ZnTN-PDA-Cu coatings at both the gene level and protein level. ZnTN-PDA-Cu also demonstrated the capacity to stimulate RAW264.7 towards M2 polarisation and HUVEC tube formation. In addition, it demonstrated the capacity to stimulate MC3T3-E1 towards osteogenic differentiation. In summary, the ZnTN-PDA-Cu coating had better antibacterial, anti-inflammatory, angiogenic and osteoinductive properties. The multifunctional coatings prepared in this study provide a promising new strategy and experimental basis for the design of antibacterial titanium surfaces with immunomodulatory functions.

Silicon and gadolinium co-doped hydroxyapatite/PLGA scaffolds with osteoinductive and MRI dual functions.

Introduction: An ideal bone repair scaffold should have dual functions of osteoinductive ability and in vivo imaging. In this study, the simultaneous substitution of silicon (Si) and gadolinium (Gd) in hydroxyapatite (HA) as potential multifunctional bone graft materials has been successfully developed. Methods: A series of HA nanoparticles (HA NPs) doped with different proportions of Si and Gd were prepared. The chemical structure and phase composition of the materials were analyzed using Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD). The microstructure, magnetic properties, surface potential, and cytotoxicity of the materials were also analyzed. The magnetic resonance imaging (MRI) effect of Gd&Si-HA/poly(lactic-co-glycolic acid) (Gd&Si-HA/PLGA) composite materials was evaluated. Osteogenic-related gene expression, alkaline phosphatase (ALP) level, and mineralization capacity of MC3T3-E1 cultured on Gd&Si-HA/PLGA composite materials were also detected. Results and Discussion: The 1.5Gd&Si-HA@PLGA group showed good ability to promote osteogenic differentiation of cells. The MRI effect of the 1.5Gd&Si-HA@PLGA scaffold was observable. This HA material containing Si and Gd co-doping has a broad application prospect in the field of bone tissue engineering owing to its ability to enhance osteoinductive property and improve MRI effect.

Porous PLGA/MBG scaffold enhanced bone regeneration through osteoimmunomodulation

The role of osteoimmunomodulation in orthopedic biomaterials has been demonstrated to be crucial in the regulation of bone repair and regeneration. Macrophages, the primary effector cells in the immune response to biomaterials, are highly heterogeneous and plastic, making them a prime target for immunomodulation. Mesoporous bioactive glass (MBG) is widely recognized for its biocompatibility, osteoconductivity, osteoinductivity, and immunomodulatory properties. However, the impact of MBG content on macrophage response remains unclear. To fill this knowledge gap, we designed a series of hierarchical PLGA-based composite scaffolds with varying MBG contents (0%, 10%, 20% and 40%, named as P, P10M, P20M and P40M, respectively) to investigate the osteoimmunomodulatory effects of these scaffolds. Our findings indicated that the P10M scaffolds showed a faster immune response in the early stage and exhibited superior ability to shift the pro-inflammatory immune microenvironment towards an anti-inflammatory state in the later stage, thereby enhancing the angiogenic potential of HUVECs and the osteogenic capacity of BMSCs. Furthermore, the in vivo implantation demonstrated that the immune microenvironment induced by P10M scaffolds facilitated optimal neovascularization and ectopic bone formation. These findings establish a theoretical foundation for the development of bone immunoregulatory biomaterials doped with MBG, which can effectively promote bone repair and regeneration.

Injectable thermosensitive hydrogel loading erythropoietin and FK506 alleviates gingival inflammation and promotes periodontal tissue regeneration.

Background: Periodontitis is a chronic multifactorial inflammatory disease associated with dysbiotic plaque biofilms and characterized by progressive destruction of the tooth-supporting apparatus. Therefore, there is significant potential in the discovery of drugs that inhibit periodontal inflammatory responses and promote periodontal regeneration. Methods: In this study, we generated a periodontitis rat model to detect the effects of chitosan/β-sodium glycerophosphate (β-GP)/glycolic acid (GA) hydrogel carried Erythropoietin and FK506 (EPO-FK506-CS/β-GP/GA). A total of forty-eight male Wistar rats were used to establish the periodontitis model. Drug injection was administered every 3days for a total of five times over a 2-week period. After a period of 2weeks following implantation, the rats underwent anesthesia, and a section of their maxillae encompassing the maxillary first and secondmolars, along with the alveolar bone, was obtained. micro-CT scanning, histopathology, immunohistochemistry and reverse transcription-quantitative PCR (RT-qPCR) assays were performed. Meanwhile, ELISA assay was performed to detect the levels of inflammatory mediators (TNF-α, IL-6 and IL-1β). Results: The synthesis and characterization of EPO-FK506-CS/β-GP/GA revealed that the hydrogel has stability and sustained release of drugs. The application of FK506+EPO was found to significantly enhance new bone formation in the defect area, as evidenced by the results of HE staining. Additionally, the use of FK506+EPO in the treated groups led to a notable increase in the density of alveolar bone, as observed through micro-CT analysis, when compared to the Model group. EPO-FK506-CS/β-GP/GA hydrogel exhibited notable efficacy in modulating inflammatory mediators (TNF-α, IL-6 and IL-1β). Furthermore, the osteoinductive properties of the EPO-FK506-CS/β-GP/GA hydrogel were extensive, as evidenced by a significant upregulation in the expression of key markers (Collagen I, Runx2, OPN, and OCN) associated with osteoblastic differentiation. Conclusion: Taken together, EPO-FK506-CS/β-GP/GA hydrogel alleviates gingival inflammation and promotes periodontal tissue regeneration in the periodontitis.

3D POROUS COMPOSITE SCAFFOLDS WITH HIGH CALCIUM PHOSPHATE CONTENT AND ADDITION OF INORGANIC IONS FOR BONE REGENERATION APPLICATIONS

Critical-sized bone defects remain challenging in the clinical setting. Autologous bone grafting remains preferred by clinicians. However, the use of autologous tissue is associated with donor-site morbidity and limited accessibility to the graft tissue. Advances in the development of synthetic bone substitutes focus on improving their osteoinductive properties. Whereas osteoinductivity has been demonstrated with ceramics, it is still a challenge in case of polymeric composites. One of the approaches to improve the regenerative properties of biomaterials, without changing their synthetic character, is the addition of inorganic ions with known osteogenic and angiogenic properties. We have previously reported that the use of a bioactive composite with high ceramic content composed of poly(ethyleneoxide terephthalate)/poly(butylene terephthalate) (1000PEOT70PBT30, PolyActive, PA) and 50% beta-tricalcium phosphate (β-TCP) with the addition of zinc in a form of a coating of the TCP particles can enhance the osteogenic differentiation of human mesenchymal stromal cells (hMSCs) (3). To further support the regenerative properties of these scaffolds, inorganic ions with known angiogenic properties, copper or cobalt, were added to the coating solution.β-TCP particles were immersed in a zinc and copper or zinc and cobalt solution with a concentration of 15 or 45 mM. 3D porous scaffolds composed of 1000PEOT70PBT30 and pure or coated β-TCP were additively manufactured by 3D fibre deposition. The osteogenic and angiogenic properties of the fabricated scaffolds were tested in vitro through culture with hMSCs and human umbilical vein endothelial cells, respectively. The materials were further evaluated through ectopic implantation in an in vivo mini-pig model. The early expression of relevant osteogenic gene markers (collagen-1, osteocalcin) of hMSCs was upregulated in the presence of lower concentration of inorganic ions. Further analysis will focus on the evaluation of ectopic bone formation and vascularisation of these scaffolds after implantation in a mini-pig ectopic intramuscular model.

Probing the influence of strontium doping and annealing temperature on the structure and biocompatibility of hydroxyapatite nanorods.

Among numerous biologically important metal cations, strontium (Sr2+) has received much attention in bone tissue regeneration because of its osteoinductive properties combined with its ability to inhibit osteoclast activity. In this study, strontium-doped hydroxyapatite (Sr-HAp) nanorods with varying molar ratios of Ca : Sr (10 : 0, 9 : 1, 5 : 5, 3 : 7 and 0 : 10) were synthesized using the chemical precipitation technique. The synthesized Sr-HAp nanostructures were characterized using powder X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy, energy dispersive X-ray spectroscopy, and Raman and Fourier transform infrared (FTIR) spectroscopies to understand their structural and morphological features, and composition. XRD results revealed the formation of HAp nanostructures, whose unit cell volume increased as a function of the dopant level. The reaction process investigation showed the formation of hydroxyapatite (HAp), strontium apatite (SAp) and various Sr-HAp phases. FESEM micrographs displayed the morphological transformation of Sr-HAp from nanorods to nanosheets upon increasing the dopant level. In the FTIR spectra, the bands of the PO43- group shifted towards a lower wavenumber upon increasing the dopant concentration in Sr-HAp that signifies the structural distortion due to the presence of a large amount of strontium ions. The peaks of PO43- and OH- vibrations in the Raman spectra were further analysed to corroborate the structural distortion of Sr-HAp. Selected area electron diffraction patterns obtained using TEM reveal the reduced crystallinity of Sr-HAp due to Sr-doping, which is in line with the XRD results. Finally, the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay showed that the synthesized Sr-HAp has no toxic effect on the survival and growth of mesenchymal stem cells. In summary, the synthesized novel Sr-HAp nanorods exhibit great promise for bone tissue engineering applications.

Alginate and Collagen Composite for Hard Tissue Generation: A Mini Review

The bone regeneration process involves the formation of the regenerative cells, the cell proliferation to produce new tissue and subsequently will repair the fractured area. During regeneration process, the osteoblast cells will secrete several proteins, organic and inorganic components as the base components to form the bone tissues or known as matrix. However, some conditions such as bone tumor removal, massive bone loss injury, extensive infections at the bone, minerals deficiency resulting the failure of bone regeneration and lead to prolonged bone fracture. To overcome this, bone scaffold is implanted or encapsulated bioactive cells are applied at the damaged area to support the bone regeneration. The materials should be osteogenic, osteoconductive and have osteoinductive properties. Natural polymer such as alginate and collagen are often used as biomaterials due to their high biocompatibility, degradability, low toxicity and easy to form a crosslinker with other materials through various method process. Therefore, this review will highlight the properties of alginate and collagen, the fabrication method to form composite and its application in biomedical area.

Effects of Aging on Osteosynthesis at Bone-Implant Interfaces.

Joint replacement is a common surgery and is predominantly utilized for treatment of osteoarthritis in the aging population. The longevity of many of these implants depends on bony ingrowth. Here, we provide an overview of current techniques in osteogenesis (inducing bone growth onto an implant), which is affected by aging and inflammation. In this review we cover the biologic underpinnings of these processes as well as the clinical applications. Overall, aging has a significant effect at the cellular and macroscopic level that impacts osteosynthesis at bone-metal interfaces after joint arthroplasty; potential solutions include targeting prolonged inflammation, preventing microbial adhesion, and enhancing osteoinductive and osteoconductive properties.

An Overview of Recent Advances in Anterior Cervical Decompression and Fusion Surgery.

Anterior cervical diskectomy and fusion (ACDF) has evolved significantly in the last few years with the aim of enhancing effectiveness and safety while reducing hospitalization and healthcare-related costs. Transitioning from iliac crest autografts to allografts minimizes donor-site complications like pain, infections, and hematoma. Allograft options, such as polyetheretherketone (PEEK) and tantalum, vary in their osteoinductive properties and elastic modulus, influencing fusion rates, time, and the rate of subsidence. Recently introduced zero-profile cages offer bone fixation through screws, resulting in reduced blood loss, improved spinal alignment, and decreased complications like dysphagia and adjacent segment disease. Intraoperative neuromonitoring (IONM) has gained widespread use. The North American Spine Society (NASS) 2023 recommendations endorse IONM in cervical deformity corrections and myelopathy cases. Insufficient studies hinder clear radiculopathy recommendations, but emerging research supports IONM for patients at greater risk of C5 nerve root injury or positional injury. Advancements in hemostatic agents, such as gelatin sponges, oxidized cellulose, and fibrin sealants, contribute to safety by reducing postoperative hematoma rates and eliminating the need for drainage. Innovations like the exoscope, endoscope, and computed-tomography (CT) navigation have transformed surgical practices. Exoscopes are emerging as an alternative to microscopes, offering benefits like a smaller footprint, adjustable positioning, lower costs, and shared intraoperative views for educational purposes. The use of endoscope offers the possibility of performing a minimally invasive technique with improved results in terms of cosmesis and patient-perceived outcome. CT navigation can be useful in high-risk procedures, such as cervical plate placement for major instability. This paper provides an overview of cutting-edge technologies in ACDF surgery, emphasizing cage materials and designs, safety measures, and operating room advancements. It also highlights areas for future research, underlining the procedure's continuous evolution.

Tunable Release of Calcium from Chitosan-Coated Bioglass.

Bioglass presents a standard biomaterial for regeneration of hard tissues in orthopedics and dentistry. The notable osteo-inductive properties of bioglass are largely due to the release of calcium ions from it. However, this release is not easily controllable and can often be excessive, especially during the initial interaction of the biomaterial with the surrounding tissues. Consequently, this excessive release can deplete the calcium content of the bioglass, ultimately reducing its overall bioactivity. In this study, we have tested if applying biopolymer chitosan coatings of different thicknesses would be able to mitigate and regulate the calcium ion release from monodisperse bioglass nanoparticles. Calcium release was assessed for four different chitosan coating thicknesses at different time points over the period of 28 days using a fluorescence quencher. Expectedly, chitosan-coated particles released less calcium as the concentration of chitosan in the coating solution increased, presumably due to the increased thickness of the chitosan coating around the bioglass particles. The mechanism of release remained constant for each coating thickness, corresponding to anomalous, non-Fickian diffusion, but the degree of anomalousness increased with the deposition of chitosan. Zeta potential testing showed an expected increase in the positive double layer charge following the deposition of the chitosan coating due to the surface exposure of the amine groups of chitosan. Less intuitively, the zeta potential became less positive as thickness of the chitosan coating increased, attesting to the lower density of the surface charges within thicker coatings than within the thinner ones. Overall, the findings of this study demonstrate that chitosan coating efficiently prevents the early release of calcium from bioglass. This coating procedure also allows for the tuning of the calcium release kinetics by controlling the chitosan concentration in the parent solution.

Stability, biomechanics and biocompatibility analysis following different preparation strategies of hierarchical zeolite coatings on titanium alloy surfaces.

Traditional titanium alloy implant surfaces are inherently smooth and often lack effective osteoinductive properties. To overcome these limitations, coating technologies are frequently employed to enhance the efficiency of bone integration at the implant-host bone interface. Hierarchical zeolites, characterized by their chemical stability, can be applied to 3D-printed porous titanium alloy (pTi) surfaces as coating. The resulting novel implants with a "microporous-mesoporous-macroporous" spatial gradient structure can influence the behavior of adjacent cells; thereby, promoting the integration of bone at the implant interface. Consequently, a thorough exploration of various preparation methods is warranted for hierarchical zeolite coatings with respect to biocompatibility, coating stability, and osteogenesis. In this study, we employed three methods: in situ crystal growth, secondary growth, and layer-by-layer assembly, to construct hierarchical zeolite coatings on pTi, resulting in the development of a gradient structure. The findings of this investigation unequivocally demonstrated that the LBL-coating method consistently produced coatings characterized by superior uniformity, heightened surface roughness, and increased hydrophilicity, as well as increased biomechanical properties. These advantages considerably amplified cell adhesion, spreading, osteogenic differentiation, and mineralization of MC3T3-E1 cells, presenting superior biological functionality when compared to alternative coating methods. The outcomes of this research provide a solid theoretical basis for the clinical translation of hierarchical zeolite coatings in surface modifications for orthopedic implants.

Evaluation of the osteogenic potential of demineralized and decellularized bovine bone granules following implantation in rat calvaria critical-size defect model.

The aim of this study was to compare the ability of demineralized (DMB) and decellularized (DCC) bovine bone granules to support bone regeneration in rat calvaria critical-size defects. DMB and DCC were prepared using a previously published method. The granule size used ranged between 500 and 750 μm. A total of forty-eight Sprague-Dawley rats were divided into two groups (n = 24). A pair of 5 mm diameter defects were created on the calvaria of the rats in the right and left parietal bone in both groups. Group A animals received DMB granules and Group B received DCC granules in the right parietal defect side while the left parietal untreated defect acted as sham surgery for both groups. Four animals per group were euthanized in a CO2 chamber at day 7, 14 and 21 post-surgery and the calvaria implantation site biopsy harvested was subjected to osteogenic gene expression analysis. Another four animals per group were euthanized at days 15, 30 and 60 post surgery and the calvaria implantation site biopsy harvested was subjected to histological, immunohistochemistry, RAMAN spectroscopy and Micro-CT analysis at the mentioned time points. Statistical analysis was conducted using t-tests and ANOVA. Histomorphometry showed significantly higher new bone formation in the DCC sites (p<0.05) compared to DMB. Both DMB and DCC implantation sites showed distinct staining for osteocalcin and osteopontin proteins compared to their respective sham sites. By day 21 after implantation, DCC sites demonstrated significantly elevated mRNA levels of osteonectin (p<0.001), osteopontin (p<0.001), osteocalcin (p<0.0001), ALP (p<0.01), and BMP-2 (p<0.001) compared to DMB. However, VEGF expression showed no significant differences at this time point between the two groups. Micro-CT analysis also showed enhanced defect closure and higher bone density in DCC implanted sites while RAMAN spectra demonstrated increased abundance of collagen and bone minerals, especially, PO43- ions than DMB. In conclusion, both DMB and DCC granules demonstrated favorable osteogenic potential in critical-sized defects, with DCC exhibited superior osteoconductive, osteoinductive and osteogenesis properties.

Biomimetic thymoquinone incorporated nanofibrous matrix as periosteum substitute to promote bone healing

The resemblance of nanofibers to the extracellular matrix (ECM) makes it suitable for various tissue engineering application. In this study, electro-spun polycaprolactone (PCL)-gelatin nanofibers had been fabricated with the incorporation thymoquinone (TQ) biomolecule as a periosteum substitute to promote regeneration of bone. The fabricated nanofibrous matrix possess osteo-conductive and osteo-inductive property. It is biocompatible and also acts as an excellent drug delivery vehicle. The significant expression of the bone matrix proteins, alkaline phosphatase secretion and calcium deposition studied in the MG-63 osteoblast like cells seeded on the nanofibrous matrix proves that it makes a suitable periosteum-substitute by enhancing bone mineralization.

Antibacterial and osteoinductive properties of wollastonite scaffolds impregnated with propolis produced by additive manufacturing

Biocompatible ceramic scaffolds offer a promising approach to address the challenges in bone reconstruction. Wollastonite, well-known for its exceptional biocompatibility, has attracted significant attention in orthopedics and craniofacial fields. However, the antimicrobial properties of wollastonite have contradictory findings, necessitating further research to enhance its antibacterial characteristics. This study aimed to explore a new approach to improve in vitro biological response in terms of antimicrobial activity and cell proliferation by taking advantage of additive manufacturing for the development of scaffolds with complex geometries by 3D printing using propolis-modified wollastonite. The scaffolds were designed with a TPMS (Triply Periodic Minimal Surface) gyroid geometric shape and 3D printed prior to impregnation with propolis extract. The paste formulation was characterized by rheometric measurements, and the presence of propolis was confirmed by FTIR spectroscopy. The scaffolds were comprehensively assessed for their mechanical strength. The biological characterization involved evaluating the antimicrobial effects against Staphylococcus aureus and Staphylococcus epidermidis, employing Minimum Inhibitory Concentration (MIC), Zone of Inhibition (ZOI), and biofilm formation assays. Additionally, SaOs-2 cultures were used to study cell proliferation (Alamar blue assay), and potential osteogenic was tested (von Kossa, Alizarin Red, and ALP stainings) at different time points. Propolis impregnation did not compromise the mechanical properties of the scaffolds, which exhibited values comparable to human trabecular bone. Propolis incorporation conferred antibacterial activity against both Staphylococcus aureus and Staphylococcus epidermidis. The implementation of TPMS gyroid geometry in the scaffold design demonstrated favorable cell proliferation with increased metabolic activity and osteogenic potential after 21 days of cell cultures.

The effect of a bionic bone ionic environment on osteogenesis, osteoimmunology, and in situ bone tissue engineering

Bone, a mineralized tissue, continuously undergoes remodeling. It is a process that engages the mineralization and demineralization of the bone matrix, orchestrated by the interactions among cells and cell-secreted biomolecules under the bone ionic microenvironment (BIE). The osteoinductive properties of the demineralized organic bone matrix and many biological factors have been well-investigated. However, the impact of the bone ionic environment on cell differentiation and osteogenesis remains largely unknown. In this study, we extracted and isolated inorganic bone components (bone-derived monetite, BM) using a low-temperature method and, for the first time, investigated whether the BIE could actively affect cell differentiation and regulate osteoimmune reactions. It was evidenced that the BIE could foster the osteogenesis of human bone marrow stromal cells (hBMSCs) and promote hBMSCs mineralization without using osteogenic inductive agents. Interestingly, it was noted that BIE resulted in intracellular mineralization, evidenced by intracellular accumulation of carbonate hydroxyapatite similar to that oberved in osteoblasts cultured in osteoinductive media.Additionally, BIE was found to enhance osteogenesis by generating a favorable osteoimmune environment. In a rat calvarial bone defect model, the osteogenic capacity of BIE was evaluated using a collagen type I-impregnated BM (Col-BM) composite. It showed that Col-BM significantly promoted new bone formation in the critical-size bone defect areas. Taken together, this is the first study that investigated the influence of the BIE on osteogenesis, osteoimmunology, and in situ bone tissue engineering. The innate osteoinductive potential of inorganic bone components, both in vitro and in vivo, not only expands the understanding of the BIE on osteogenesis but also benefits future biomaterials engineering for bone tissue regeneration.

Osteoimmunology: Interactions With the Immune System in Spinal Fusion.

Spinal fusion is important for the clinical success of patients undergoing surgery, and the immune system plays an increasingly recognized role. Osteoimmunology is the study of the interactions between the immune system and bone. Inflammation impacts the osteogenic, osteoconductive, and osteoinductive properties of bone grafts and substitutes and ultimately influences the success of spinal fusion. Macrophages have emerged as important cells for coordinating the immune response following spinal fusion surgery, and macrophage-derived cytokines impact each phase of bone graft healing. This review explores the cellular and molecular immune processes that regulate bone homeostasis and healing during spinal fusion.

Development and Preclinical Trials of Castomized Porous Titanium Implants with Bioactive Coatings in Model Systems

This paper presents a technology for creating customized porous titanium implants with bioactive coatings, manufactured using additive technologies. The stages of creating an implant include obtaining primary data from the bone defect area using computed tomography; 3D modeling of the defect area and the corresponding implant; production of a customized implant from titanium alloys using selective laser fusion technology; application of bioactive coatings. The as-created customized implant can have several functional structures. Samples of titanium implants with bioactive coatings were subjected to extensive testing. Mathematical modeling and experiments were used to verify the correspondence of the mechanical properties of the developed structures to natural bone tissue. In vitro tests of the studied samples showed the absence of acute toxicity along with high levels of biocompatibility. In vivo tests of the studied samples on Soviet chinchilla rabbits and Anubis baboon monkeys approved by local ethical committees showed their adequate biomechanical and high osteoinductive properties. The successful results of preclinical studies, as well as toxicological and technical tests in certified laboratories, made it possible to create a registration dossier for state registration of customized porous titanium implants with bioactive coatings, manufactured using additive technologies.