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Postmenopausal osteoporosis reduces circulating estrogen levels, which leads to osteoclast resorption, bone loss, and fracture. This review addresses emerging evidence that osteoporosis is not simply a disease of bone loss but that mechanosensitive osteocytes that regulate both osteoclasts and osteoblasts are also impacted by estrogen deficiency. At the onset of estrogen deficiency, the osteocyte mechanical environment is altered, which coincides with temporal changes in bone tissue composition. The osteocyte microenvironment is also altered, apoptosis is more prevalent, and hypermineralization occurs. The mechanobiological responses of osteocytes are impaired under estrogen deficiency, which exacerbates osteocyte paracrine regulation of osteoclasts. Recent research reveals changes in osteocytes during estrogen deficiency that may play a critical role in the etiology of the disease. A paradigm change for osteoporosis therapy requires an advanced understanding of such changes to establish the efficacy of osteocyte-targeted therapies to inhibit resorption and secondary mineralization.

International audience; Purpose of review: To describe the methods that can be used to obtain functional and mature osteoclasts from peripheral blood mononuclear cells (PBMCs) and report the data obtained with this model in two peculiar diseases, namely pediatric chronic kidney disease-associated mineral and bone disorders (CKD-MBD) and nephropathic cystinosis. To discuss future research possibilities in the field.Recent findings: Bone tissue undergoes continuous remodeling throughout life to maintain bone architecture; it involves two processes: bone formation and bone resorption with the coordinated activity of osteoblasts, osteoclasts, and osteocytes. Animal models fail to fully explain human bone pathophysiology during chronic kidney disease, mainly due to interspecies differences. The development of in vitro models has permitted to mimic human bone-related diseases as an alternative to in vivo models. Since 1997, osteoclasts have been generated in cell cultures, notably when culturing PBMCs with specific growth factors and cytokines (i.e., M-CSF and RANK-L), without the need for osteoblasts or stromal cells. These models may improve the global understanding of bone pathophysiology. They can be been used not only to evaluate the direct effects of cytokines, hormones, cells, or drugs on bone remodeling during CKD-MBD, but also in peculiar genetic renal diseases inducing specific bone impairment.

A bone scaffold added to the dental alveolus immediately after an extraction avoids bone atrophy and deformity at the tooth loss site, enabling rehabilitation with implants. Photobiomodulation accelerates bone healing by stimulating blood flow, activating osteoblasts, diminishing osteoclastic activity, and improving the integration of the biomaterial with the bone tissue. The aim of the present study was to evaluate the effect of photobiomodulation with LED at a wavelength of 850 nm on bone quality in Wistar rats submitted to molar extraction with and without a bone graft using hydroxyapatite biomaterial (Straumann® Cerabone®). Forty-eight rats were distributed among five groups (n = 12): basal (no interventions); control (extraction) (basal and control were the same animal, but at different sides); LED (extraction + LED λ = 850 nm); biomaterial (extraction + biomaterial), and biomaterial + LED (extraction + biomaterial + LED λ = 850 nm). Euthanasia occurred at 15 and 30 days after the induction of the extraction. The ALP analysis revealed an improvement in bone formation in the control and biomaterial + LED groups at 15 days (p = 0.0086 and p = 0.0379, Bonferroni). Moreover, the LED group had better bone formation compared to the other groups at 30 days (p = 0.0007, Bonferroni). In the analysis of AcP, all groups had less resorption compared to the basal group. Bone volume increased in the biomaterial, biomaterial + LED, and basal groups in comparison to the control group at 15 days (p

Globally, millions require bone replacements with the help of scaffolds to enable bone tissue regeneration. However, scaffold manufacturing techniques do not allow precise control over scaffold geometry and provide diagnostics on scaffold-cell status. Towards addressing these challenges, we studied the use of optimized 3D printing of bioresorbable scaffolds with fluorescent carbon quantum dots (CDs). These can overcome the challenges with toxic and invasive dyes used in clinical settings as probes, while promoting cellular adhesion, proliferation, and osteogenic differentiation. We developed a biodegradable polymer nanocomposite based on PLA with CDs to produce smart biomaterials. As a luminescent, biocompatible material with low toxicity, CDs allowed us to fabricate functionalized biochemical structures that were shown to enhance cell proliferation and promote cell-to-cell communication. The composites were tested in vitro in a cellular microenvironment with optimized 3D-printed scaffolds to demonstrate enhancements in cellular proliferation by 32%, bone mineralization by 8% and osteogenic differentiation by 8% with concomitant negligible cytotoxic effect.

BACKGROUND: Bone defect difficult to manage clinically and it is a big challenge to repair it. Secondary metabolites source from herb has shown potential for the treatment of bone defect. METHODS: Mesenchymal stem cells (MSCs) were isolated from mice and incubated with urolithin A (UA) (10, 25, and 50 µg/mL). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed to estimate apoptosis and mineralisation was evaluated by alkaline phosphatase assay and alizarin red S staining. A middle femoral defect was induced in mice and bone tissue was prepared for endochondral ossification by treating with UA. The effect of UA was estimated by determining markers of osteoblast proliferation in serum and micro-computed tomography to analyse bone defects. RESULTS: UA enhanced mineralisation of MSCs and osteogenic gene markers in MSCs in vitro. Also, the bone defect score and bone mineral density were improved by UA. Moreover, UA ameliorated the altered Wnt3a protein and histopathological changes in bone defect mice. CONCLUSION: Presented report conclude that UA enhances osteoblast proliferation in bone-defect mice by activating the Wnt pathway.

Hydroxyapatite has been extensively used in bone tissue regeneration but its application in skin tissue engineering and the underlying molecular mechanism remains unexplored. In the present study, we have developed a polymer hybrid scaffold functionalized with hydroxyapatite nanoparticles. Thiolated chitosan was combined with thiolated eudragit and polyethylene glycol to form the scaffold using the freeze–thawing technique. During the freeze–thawing process, the scaffolds were functionalized with hydroxyapatite nanoparticles. FTIR and XRD studies confirmed the polymeric interlinking in the scaffold during the freeze–thawing method. SEM and micro-CT analysis indicated the functionalization of the nanoparticle on the scaffold moiety and a spongy structure of the nanocomposite scaffold with controlled pore intensity. In silico study in corroboration with in vivo evaluation indicated that the component of the nanocomposite scaffold acts via controlling the actions of epidermal growth factor and glycogen synthase kinase and may prove to be a suitable material for tissue engineering.

Synthetic polymeric materials have demonstrated great promise for bone tissue engineering based on their compatibility with a wide array of scaffold-manufacturing techniques, but are limited in terms of the bioactivity when compared to naturally occurring materials. To enhance the regenerative properties of these materials, they are commonly functionalised with bioactive factors to guide growth within the developing tissue. Extracellular matrix vesicles (EVs) play an important role in facilitating endochondral ossification during long bone development and have recently emerged as important mediators of cell-cell communication coordinating bone regeneration, and thus represent an ideal target to enhance the regenerative properties of synthetic scaffolds. Therefore, in this paper we developed tools and protocols to enable the attachment of MLO-Y4 osteocyte-derived EVs onto electrospun polycaprolactone (PCL) scaffolds for bone repair. Initially, we optimize a method for the functionalization of PCL materials with collagen type-1 and fibronectin, inspired by the behaviour of matrix vesicles during endochondral ossification, and demonstrate that this is an effective method for the adhesion of EVs to the material surface. We then used this functionalization process to attach osteogenic EVs, collected from mechanically stimulated MLO-Y4 osteocytes, to collagen-coated electrospun PCL scaffolds. The EV-functionalized scaffold promoted osteogenic differentiation (measured by increased ALP activity) and mineralization of the matrix. In particular, EV-functionalised scaffolds exhibited significant increases in matrix mineralization particularly at earlier time points compared to uncoated and collagen-coated controls. This approach to matrix-based adhesion of EVs provides a mechanism for incorporating vesicle signalling into polyester scaffolds and demonstrates the potential of osteocyte derived EVs to enhance the rate of bone tissue regeneration. Supplementary Information The online version of this article (10.1007/s10439-021-02872-2) contains supplementary material, which is available to authorized users.

This study investigated the efficacy of combined 3D printing and electrospinning to form hybrid 3D scaffolds to provide inductive cues for stems cells to differentiate into an osteogenic lineage. Hybrid scaffolds mimicking the three-dimensional architecture and bioactivity of the extracellular matrix were fabricated by co-electrospinning poly(lactic acid) (PLA) and hydroxyapatite (HA) in varying percentages onto 3D-printed PLA. The 3D-printed scaffold provided a porous structure with the requisite mechanical properties for a bone tissue scaffold. Coating the PLA scaffold with electrospun nanofibers provided bioactivity. The nano-topology of the scaffold surface promoted cell attachment, and that affinity was increased by incorporating HA. It was also found that the HA provided inductive cues to stem cells to differentiate into an osteogenic lineage. The scaffolds promoted the bone mesenchymal stem cell (BMSC) proliferation, induced cellular synthesis of extracellular matrix molecules as well as controlled the expression of osteogenic cell markers in BMSC.

In order to create a perfect bone scaffold, nanocomposites are the best options, as they can be engineered to have the composition, structure and properties of natural bone. In the present study, the layer-by-layer and hybrid nanofiber scaffold are fabricated by electrospinning method using a combination of PCL/PVP and PVA/β-TCP layers. We study and compare the morphological properties (scanning electron microscope (SEM), swelling ratio and porosity), mechanical properties (tensile strength, elongation at break and tensile modulus) and biodegradability of the scaffolds. The average fiber diameter measured for layer-by-layer and hybrid scaffolds is 446 ± 128 nm and 505 ± 261 nm, respectively. The tensile strength for the layer-by-layer and hybrid scaffolds is 7.40 ± 3.40 MPa and 6.57 ± 1.64 MPa, respectively, and the degradation rate for layer-by-layer and hybrid scaffolds is 26 ± 2% and 40 ± 5%, respectively. So the results show the desired mechanical properties and compatibility of scaffolds. The (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay shows cell viability above 80% and absence of cell cytotoxicity for layer-by-layer and hybrid scaffolds after 3, 5 and 7 days of rat marrow stromal cell (rMSC) culture. The morphology and proliferation of rMSC cells show the suitability of the scaffolds for tissue engineering application. Therefore, both types of scaffolds can be used in several tissue engineering applications, including improvement of bone tissue regeneration.

Hydroxyapatite (HA) is similar to the inorganic component of human bone and teeth. Because of its excellent biocompatibility, bioactivity, and osteoconductivity, HA is widely used as a biomedical material. However, its biodegradability is poor. Oyster shells are mainly composed of CaCO3 and other trace elements, such as Mg, Sr, K, and Na. As a raw material for synthesizing HA, oyster shells not only serve as biowaste for efficient utilization but also contain various trace elements that are beneficial to the growth of bone tissue; they can thus enhance the overall biological performance of the bioceramic. In this study, microrod HA bundles were successfully synthesized using microwave irradiation with the aid of ethylene diamine tetra-acetic acid disodium salt (Na2EDTA) as a chelating agent. The formation of microrod HA bundles was expected to promote the material’s biodegradability, and the bundles could have potential in the field of bone tissue repair. The optimal parameters for synthesis of microrod HA bundles were a Na2EDTA-to-oyster-shell-powder ratio of 2/2 and a microwave power of 700 W. The microrod HA bundles degraded more easily than did the irregular HA aggregates, indicating that the morphology of the microrod bundles resulted in a higher HA degradation rate. Bioactivity tests revealed that numerous spherical apatite particles formed on the surface of the microrod HA bundles, indicating that they had excellent bioactivity. Finally, the microrod HA bundles had high protein adsorption capability, which facilitates the control of cell attachment and proliferation and is thus beneficial to tissue regeneration.

Osteoporosis is a polygenic disease associated with low bone mineral density and deterioration of bone miniscule architecture and increased chance of bone fractures. However, several signaling pathways regulate bone mineral density including parathyroid hormone (PTH), Core-binding factor α-1 (CBFA1), Wnt/β-catenin, the receptor activator of the nuclear factor kappa-B (NF-κB) ligand (RANKL), myostatin, estrogen, and osteogenic exercise signaling pathways. These signaling pathways occur at protein level that depends not only on messenger RNA transcriptional regulation but also on a number of translational and posttranslational controls. Moreover, proteomic alterations in bone tissue due to a disease may occur in several ways that are unpredictable from either genome or transcriptome analysis. Decades of genome and transcriptome analyses have identified few causative genes; nonetheless, the majority of osteoporosis susceptibility genes remain unknown. It appears that a deeper view of bone proteome alterations will influence bone health and disease. This article highlights the efficacy of proteomics as an emerging tool for the discovery of bone mineral density molecular pathways.

During total hip replacement (THR), prosthesis material is stiffer than the bone tissue, decreasing load transmission to the host tissue around the prosthesis. After a THR, the aim is to achieve stress distribution along the femur close to normal physiological stress distribution for all loads transferred across the hip joint. In this study, we analyzed the advantages of using a collared stem over collarless one with the finite element method (FEM), strain gauges (SGs), and the digital image correlation (DIC) system. In the biomechanical tests, we implanted composite femurs and loaded them with the stance configuration in a universal testing machine (Instron). We compared the predicted strains with the strains recorded experimentally in the same regions of the femur. The results revealed that for collarless stems, a high level of stress concentration is observed in the distal region of the implant but not in the proximal region. The collared case presents a strain distribution closer to that of a healthy bone proximal zone that was almost two times better than in case of the collarless stem, whereas stresses in the distal part of the femur corresponded to a healthy state. Finally, the numerical results for the bone adaptation around the implant provided clear evidence that the collar design strongly influences the proximal resorption because of better load transmission. According to both the numerical and experimental results, a collar that connects to the bone cut may decrease the proximal stress shielding effect and distal cortical hypertrophy.

Background: Most materials used clinically for filling severe bone defects either cannot induce bone re-generation or exhibit low bone conversion, therefore, their therapeutic effects are limited. Human umbilical cord mesenchymal stem cells (hUC-MSCs) exhibit good osteoinduction. However, the mechanism by which combining a heterogeneous bone collagen matrix with hUC-MSCs to repair the bone defects of alveolar process clefts remains unclear.Methods: A rabbit alveolar process cleft model was established by removing the bone tissue from the left maxillary bone. 48 young Japanese white rabbits (JWRs) were divided into normal, control, material and MSCs groups. An equal volume of a bone collagen matrix alone or combined with hUC-MSCs was implanted in the defect. X-ray, micro-focus computed tomography (micro-CT), blood analysis, histochemical staining and TUNEL were used to detect the newly formed bone in the defect area at 3 and 6 months after the surgery. Results: The bone formation rate obtained from the skull tissue in MSCs group was significantly higher than that in control group at 3 months (PPPPConclusions: Combining bone collagen matrix with hUC-MSCs promoted the new bone regeneration in the rabbit alveolar process cleft model through promoting osteoblasts formations and chondrocyte growth, and inducing type 1 collagen formation and BMP-2 generation.

In regenerative medicine, the problem of growing mesenchymal stem cells from the bone marrow often arises. In such cases is important that the number of initial cells was large enough and their proliferative activity was high. We believe that this problem can be solved by short-term heating of local areas of the bone marrow in vivo with laser radiation. In this regard, it is of interest to study the optical and temperature fields induced inside the tubular bone under external laser irradiation. In this work, we obtained experimental data on the spatial distribution of temperature in the bone marrow of the rat femur in vitro under external exposure to laser radiation with wavelengths of 970 and 1940 nm. Radiation delivery was carried out using an optical fiber which tip contacted the surface of the femur bone. A thin thermocouple was used to measure the temperature in a local area of the bone marrow. By moving the optical fiber tip discretely along the longitudinal axis of the bone, and the thermocouple in the perpendicular direction, the spatial temperature distributions in dynamics were measured. Similarly, the spatial distributions of the laser radiation intensity were measured by replacing thermocouple with optical fiber probe. A thermal camera was used to control the temperature of the bone surface near the tip of the fiber. It was shown that the marrow could be heated from the outside by about 5–10 °C during 10 s without significant overheating of the bone tissue. The data obtained make it possible to estimate the volume of the bone marrow heated by the laser to a predetermined temperature and to make a reasonable choice of laser exposure modes to stimulate the proliferative activity of bone marrow mesenchymal stem cells in vivo.

The incorporation of osteoconductive hydroxyapatite (HA) into poly(Ɛ-polycaprolactone) (PCL) may enhance the material hydrophilicity, protein adsorption, roughness, and consequently, bone formation. In this work, PCL/HA composites with 5, 10, and 25 wt% of HA were prepared by melt compounding followed by hot compression, and their properties such as torque, molecular weight, mechanical resistance, and viscosity were compared to neat PCL to understand the influence of the filler on the polymer stability and printability. The addition of 5 and 10 wt% of HA leads to properties similar to the neat PCL; therefore, these compositions were chosen to produce scaffolds by 3D printing. The scaffolds presented excellent printability and homogenous dispersion of the HA. The compressive strength modulus of both compressed samples and scaffolds is around 30 MPa, similar to cancellous bone. The presence of increasing HA content combined with surface treatment using NaOH enhanced osteoblast proliferation.

Localization of PCNA, CD44, osteocalcin, Mdm2, p53, and caspase-3 on the surface of implant with calcium phosphate and hydroxyapatite coating was studied by immunocytochemical method in a model of femur fracture in rats. PCNA+, Ost+, CD44+, and Mdm2+ cells were found in the periosteum, in the layer of the outer surrounding plates, and in the connective tissue of the Haversian canals. Cell density increased on day 7 after fracture and then decreased by day 30. The number of p53+ and CASP3+ cells reached a maximum on day 14 (they were predominantly located in the periosteum and bone plates adjacent to it) and decreased by day 30. Calcium phosphate coating stimulated proliferative activity of cells at the early stages of the regeneration phase and apoptotic death at the later stages. Components of coating can be viewed as a positioning clue for differentiation of mesenchymal stromal cells. The effectiveness of reparative osteogenesis is determined by the balance of proliferative and destructive factors at the site of the fracture healing. This process can be optimized with various nanostructured materials with osteoinductive properties, in particular bioresorbable calcium phosphate coatings on titanium implants. However, the influence of these components on the state of cambial cells, their differentiation, and positioning in the repair zone is unknown.

In the present report it is described the design, the manufacturing and the successful surgical implant of one of the first 3D custom titanium vertebra realized with Additive Manufacturing technique and its use for the spinal reconstruction after en-bloc resection for primary osteogenic sarcoma. Clinical case presentation and the design of the 3D custom titanium vertebra was reported. It was also described the complex procedures adopted to evaluate the retrieved device from the histological point of view, as a tumor relapse hit the patient, one year after the reconstruction procedure. The histological evaluation confirmed that the resection technique exerts an important role in promoting bone formation: vertebral body osteotomies favored the reconstruction procedure and maximized the contact area between host bone/vertebral prosthesis thus favoring the bone tissue penetration and device colonization. The sharing of these results is very important as they represent the starting point for improving the knowledge starting from the evidence obtained in a challenging clinical condition and with post-operative treatments that could be never reproduced in preclinical model.

This article presents a thermal sintering method to fabricate porous bone tissue engineering scaffolds based on polycaprolactone (PCL), polylactic acid (PLA), and their composites. The mechanical properties, porous structure, biodegradability, and biocompatibility of sintered scaffolds were evaluated. The scaffolds showed a porosity in the range of 86–91% with a pore size of 75 m $$\mu$$ to 400 m $$\mu$$ . PCL/PLA composite scaffolds showed a Young’s modulus of around 49 MPa, which was between the modulus values of PCL (24 MPa) and PLA (63 MPa) scaffolds. Fibroblast cells (SNL) exhibited spreading and adhesion on the scaffolds, and scaffolds demonstrated a significant difference in the osteogenic differentiation of human mesenchymal stem cells (hMSCs) after 7 and 14 days of culture in comparison with the control (tissue culture polystyrene). Our results demonstrated that the thermally sintered PCL/PLA composite scaffold could be a promising candidate for bone tissue regeneration.

Purpose of the study: The purpose of the study was to examine on the basis of radiographic images of bone tissue, whether there are differences in the rate of bone remodelling using different shapes of implants in the mandible and maxilla. Moreover, the study also compares texture features obtained on the basis of these images for healthy bone tissue, bone directly after implantation and after a 12-month period of prosthetic loading. Materials and Methods: The subject of the analysis was radiovisiogram images obtained from the Medical University of Bialystok from the Department of Dental Surgery. They are radiovisiogram photographs of 146 people aged 18–74, treated implantally due to missing teeth. The whole group of patients received two types of implants (Active and Replace) of the same company, made of titanium, intraosseous, screw-in. Results: It has been shown that both in the upper jaw and the mandible, the values of texture parameters obtained for bone images made after one year of prosthetic loading are closer to healthy tissue than immediately after implantation. These values for the mandible were relatively closer to those obtained on the basis of healthy tissue than those for the upper jaw. The bone around the implant with a single threading achieved better results in the mandible than the one with a double threading. Conclusion: The type of bone tissue and the shape of the implant have an impact on the achieved osseointegration. With the passage of time and the process of bone remodelling, the damaged tissue returns to its normal structure.

We studied immunolocalization of CD29, CD44, osteocalcin, and TGF-β1 in the bone tissue of the mandible of miniature pigs with extra-bone fixation of a free gingival graft. Three months after surgery, neoosteogenesis foci with high expression of the studied markers were found in the contact area of the free gingival graft with the alveolar bone. The markers were localized in the layer of external circumferential lamellae, on the surface of concentric lamellae of the growing osteons, and in the connective tissue of the Haversian canals. TGF-β1-immunopositive cells predominated in the connective tissue of the Haversian and Volkmann canals and in the adventitia and inner lining of the vascular wall. The established morphochemical patterns of osteogenous cells indicate significant reparative capabilities of a free gingival graft and allows considering it as an effective osteoinductive factor.

During the bone drilling process, in case of excessive force can cause breakage, crack initiation and severe damage to bone tissue. Additionally, if drilling temperature rises higher than the generally believed 47 °C, it can cause thermal necrosis phenomenon which leads cell death of the bone tissue. In this paper, using helix angle and point angle as most influential factors, the evolution of process force and temperature are studied at the same time. For this purpose, using a central composite experimental design and preparing the required drills, the experimental tests have been performed on fresh bovine bone. Also, the present study benefits from an adaptive neuro-fuzzy inference system (ANFIS) whose parameters are optimized using the particle swarm optimization (PSO) method in order to predict force and temperature. To model the process behavior, the results of performed experiments for training (based on 70% of the data) and testing (based on 30% of the data) of the system are utilized. The findings of this research show that the adaptive neuro-fuzzy inference system is capable of properly predicting the force and temperature. Overall, the average errors in estimating the values of force and temperature in the training and test sections are 1.249 and 3.818%, respectively. After modeling with ANFIS-PSO, the Sobol sensitivity analysis method is used to quantitatively measure the effect of each input parameter over the process temperature and force. The results of sensitivity analysis show that with increasing both helix and point angles, the temperature in bone drilling process is decreased while the force is increased. In addition, it is proved that the sensitivity of temperature and force values to changes in helix angle is slightly higher than changes in drill point angle.

Trauma, congenital abnormalities or cancer-induced bone defects can be treated with tissue engineering products. Graphene oxide-containing polymeric scaffolds are used as an artificial extracellular matrix, acting as an environment where cells can grow and turn into living tissues. In the presented study, primarily cytotoxicity of graphene oxide was determined depending on the concentration. According to the cytotoxicity results, two different scaffolds containing low and high concentrations of GO were prepared and usability in bone tissue engineering was examined. For this purpose, water uptake, in vitro degradation and mechanical properties of the scaffolds were determined. On the predetermined days, MC3T3 cells proliferation and ACTB, COL1A1, OCN, OPN, RUNX2 gene expression were determined. According to the results, MC3T3 cell proliferation was increased when the incubation time increased, and also, gene expression related to bone tissue formation was increased.

Utilization of bone graft substitutes have increased due to the rising number of accidents, trauma, and aging population. Autograft is still considered as a gold standard for treating bone defects. However, limitations such as insufficient donor sites and secondary surgery, leads to the development of alternative grafts. Hydroxyapatite (HA) from natural resources gained much attention in recent years as a bone graft substitute due to its biocompatibility, excellent osteointegration, osteoconductive, and osteoinductive properties. In the current review, we have presented the isolation procedures of HA from marine fishbone and cuttlefish bone. Further, composite preparation using marine derived HA with other polymeric and ceramic materials were discussed, and cell-materials interaction were reviewed in detail towards bone tissue construction. Composite biomaterials with HA showed better cell proliferation, cell adhesion, increased gene expression (collagen, osteocalcin, osteopontin, bone sialoprotein, BMP-2 etc.), and in vivo studies demonstrated significant bone formation with HA composite materials. Hence, composite biomaterials with hydroxyapatite will be potential candidates for artificial synthetic bone graft substitute.

A previous bone remodelling model was presented elsewhere [30], and in the present paper, the same model was tested with new conditions; an interaction between bone tissue, bone substitute material and a dental implant was considered. The bone substitute material was assumed to be dead tissue, which does not synthesizes neither absorbs bone tissue, and it was considered, as well, resolvable. A moving border between the bone substitute material and the bone tissue was studied. The border moved as the newly synthesised bone tissue took over the bone substitute material. After the numerical calculations of time-steps, the whole bone substitute material was replaced by normal bone tissue and the implant was fixed in place only by bone tissue. Dynamical studies of the interaction of bone tissue and implant are used to improved implant design considering different factors, in this case, the presence of bone substitute material helping to fix the implant.

Bone tissues, with their porous structure and the crucial role of producing and releasing blood elements into the bloodstream, can act as a suitable candidate for drug delivery stations in all parts of the body. Making an appropriate osteoconductive scaffold with drug delivery is the basis of this study for designing such materials. In this research, bone scaffolds containing drugs and magnetite nanoparticles were designed and produced for bone tissue approaches. As a new class of treatment for bone defects or deformity, calcium silicate ceramics (CSC) have been able to attract a lot of attention among researchers as a viable solution. With the incorporation of metal oxides (like Fe3O4: magnetite nanoparticles; MNPs) into the base binary xCaO-ySiO2-MgO as well as the substitution of calcium ions, CSCs can be fabricated. In the current work, the scanning electron microscope (SEM) and X-ray diffraction (XRD) technique were used to determine the phase and morphology of the porous scaffolds for dental fracture. The observation shows that the compressive strength and elastic modulus increase from 0.9 to 1.76 MPa and 59 to 81 MPa, respectively. The SEM images proved that the porosity dimensions were reduced from sample 0 wt% to sample 15 wt% (From 85 to 70%). Also, the absorbance test was found to be increased from 0 to 15 wt% sample in the PBS immersion solution. The obtained results indicated that the samples with a maximum of 10 wt% MNPs might release the drug more comfortably, which can be reported as a suitable candidate for bone tissue application.

Additive manufacturing is a rapidly expanding technology in many scientific fields like tissue engineering. One of the most essential duties of tissue engineering scaffolds is to provide sufficient mechanical strength for the injured bone tissue. Scaffold architecture plays a significant role in its mechanical properties. Here, six delicate different geometry computer-aided design models with identical porosity were designed. The sets of 0/90, 0/45/135/90, 0/60/120, and their shifted models as the most prevalent scaffold geometries were fabricated by fused deposition modeling printer through the optimized processing parameters and were investigated by the upset test. Their modified models according to printing procedure changes were redesigned, and finite element analysis (FEA) simulations were accomplished through a simplifying strategy. Mechanical performances of the designed scaffolds were evaluated, and a good agreement was observed between the FEA and experiments. The strongest patterns were derived via evaluation of three aspects of scaffold elastic modulus, scaffold yield strength, and a newly defined parameter named “scaffold geometry rupture resistance factor”. The large difference between Young's modulus of 0/90 (230.44 MPa) and 0/90 shifted (156.56 MPa) indicated the role of scaffold geometry in mechanical properties. The mechanical effect of layer pattern sequence change was also investigated.

Purpose of Review Bone matrix exhibits great complexity in its composition, structure and mechanics. Here, we provide a review of recent research articles and appraise the evidence that bone matrix quality is clinically important and possibly targetable for fracture prevention. Recent Findings Deformation of mineralised collagen fibrils determines bone fracture mechanics. Slipping and separation at the mineral-fibril and fibril-fibril interfaces, respectively, are the structural mechanisms for plastic deformation and microcrack nucleation. Existing technologies for assessing bone tissue in vivo cannot measure matrix structure or fracture mechanics but have shown limited use in clinical settings for identifying fragility or following treatment outcomes based on composition. Summary Matrix is biomechanically and clinically important, but the knowledge has not translated into clinical practice. The structural mechanisms by which a load is transferred from mineralised collagen fibrils to the whole bone via microcracking have been proven too complex to measure in vivo. The mineral-fibril or fibril-fibril interfaces might be suitable targets for diagnosing fragility or delivering molecules that reduce fracture risk by strengthening the mineral bonds while maintaining flexibility in the fibrils.

The periosteal progenitor cell is suitable for bone tissue regeneration duo to its multipotent differentiation in osteogenesis and chondrogenesis. It was found that both physical and physiological stimuli can induce the differentiation of periosteal progenitor cells. However, the combined-effect of these two stimuli is not clear. The imitation of the nature movement—the cyclic tensile strain stimulation and the multiple growth factors producing cells—adipose-derived stem cells (ADSCs) were used as physical and physiological stimuli to investigate the differentiation of rabbit periosteal cells in this study. For this, a new membrane-type micro-system was invented to provide a simple examination platform for both factors in one single system. The specific rectangular culture chamber not only provided two different types of cells to grow separately but also delivered the single axial tensile strain generated in the micro-system to the cells. It was found that application of either physical or physiological stimuli alone was sufficient to induce the differentiation of periosteal cells. The low tensile strain (4, 5, 6 kPa) led to osteogenesis whereas high tensile strain (7 kPa) induced chondrogenesis. Even though the co-culture of ADSCs only induced osteogenic differentiation of periosteal cells, the co-culture of ADSCs to tensile strain treated periosteal cells further strengthened the osteogenic and chondrogenic differentiation potent in low and high tensile strain, respectively. This study provided the pre-clinical evidence of the stem cell therapy and continuous exercise in cell level bone tissue regeneration.

Bone whitlockite (WH) exists in the collagen matrix along with hydroxyapatite (HA) and plays a vital role during earlier stages of bone development. It is present in short-range order and is difficult to identify in the bone, as compared to HA mineral, that covers 80% of the bone inorganic phase. It has the same structural analogy with β-TCP, but detailed structural and crystallographic analyses of bone have shown that β-tricalcium phosphate (β-TCP) is merely a synthetic analog of bone whitlockite, having the same crystalline structure but different chemically. WH contains magnesium at Ca(IV), Ca(V) positions, and HPO42− on a threefold axis in a rhombohedral crystal lattice. Its biocompatibility, functionality, negative surface charge, mechanical strength, and stability in physiological solvents make it an ideal bone substitute as compared to hydroxyapatite (HA) and β-TCP. It has magnesium as a major component that has a strong affinity with integrin protein. Integrin protein plays a vital role in bone tissue integration. It is bioresorbable and biodegradable and the rate of degradation complements with regeneration. However, despite these excellent properties, this material has always been overshadowed by other calcium phosphates (CaPs), because it is difficult to synthesize. In this review article, we present a comprehensive study on the difference in the crystalline structure of bone whitlockite and β-TCP, its presence in the natural system, and conditions under which its nucleation occurs in native bone and at lab scale. Furthermore, the reaction conditions that favor homogenous precipitation of synthetic WH and the role of magnesium in the stabilization of different CaPs to obtain pure WH phase are also discussed. Finally, the applications of WH in biomedical and for heavy metal adsorption are summarized.

Designing of a suitable ‘cell-material’ construct has enabled the regeneration of bone. It was in accordance with the increasing demand for the repair of defective and/or diseased bone tissue. In this research, the relative behavior of the osteoblast-seeded materials was demonstrated. It enabled the selection of the cell-material system for rabbit bone bioengineering studies. Significant role of polypeptide-polymer-ceramic-cell material in bone tissue engineering was shown. The properties of natural polymer-based scaffold were attributed to their origin and chemical modifications. In this study, the lyophilized osteoblast-material conjugate was designed and characterized extensively. The same was done by physicochemical measurement, for surface and core morphology analysis. The atomic force microscopy (AFM) and transmission electron microscopy (TEM) data from these conjugates have shown surface parameters. The surface suitable for cell attachment and proliferation along with uniform interconnected porous morphology was selected. The calcium to phosphate proportion-based energy-dispersive X-ray was done. It defines the inorganic content in these composites. The crystal spots were found from the selected area electron diffraction pattern. It had supported the insights from the physicochemical measurements. AFM and TEM micrographs have shown surface and core morphology with median surface roughness of 14.96 nm and uniform porous architecture, respectively. Fourier transmission Infra-red spectroscopy and X-ray diffraction had confirmed the formation of mineral deposits within the scaffolds. The subsequent in vitro study has revealed that among the biomaterials, ‘gelatin in hydroxyapatite-coated chitosan matrix’ has prominence over ‘gelatin-hydroxyapatite.’ It was confirmed only after seeding them with the rabbit ‘iliac crest-derived’ osteoblast. Two types of rabbit osteoblast derivatives were used. They are the osteoblast from the bone tissue (rT) and osteoblast obtained after Mesenchymal stem cell (MSCs) differentiation. Bone marrow was the source of MSCs. This ‘rT-seeded’ biomaterial was found appropriate for bone bioengineering applications.

The incidence of osteoporosis is positively correlated with age. Berberine has been reported to treat osteoporosis due to its beneficial actions on bone formation. However, the direct effects of berberine on senile osteoporosis remain unclear. The present study investigated the protective effects of berberine on senile osteoporosis in mice and preliminarily evaluated its potential mechanism. 20-month-old male C57BL/6 J mice were used as senile osteoporosis mouse model and treated with strontium ranelate (SR) or berberine or solvent control by daily gavage for 2 months. Thereafter, bone mass and microstructure parameters were assessed. Histological staining was performed to identify the osteogenic, adipogenic and osteoclastic activity of bone tissue. Moreover, role of cAMP/PKA/CREB signaling pathway in berberine affecting bone marrow mesenchymal stem cells (BMSCs) differentiation was clarified by enzyme-linked immunosorbent assay and western blot analysis. The results showed that the SR-treated group displayed a high trabecular bone mass phenotype. For mice administrated with berberine, cancellous bone mass was upregulated in a dose-dependent manner, as indicated by gradually increased bone mass, trabecular bone volume fraction and trabecular number. Furthermore, berberine promotes osteogenic and inhibits adipogenic differentiation of BMSCs via cAMP/PKA/CREB signaling. Also, bone resorption effect becomes more obvious with increasing dose of berberine in vitro. The present results suggest that berberine exerts potent bone protective effects by promoting bone formation, inhibiting marrow fat accumulation and bone resorption. This effect may be achieved through cAMP/PKA/CREB signaling pathway.

We performed a morphological study of the bone tissue after implantation of a cryogenically structured albumin sponge containing a bioregulator isolated from blood serum into an extensive experimental defect of the femur. By day 90, no complete reparation of the bone tissue was achieved in the control group (without implantation of 3D carrier), a loose spongy bone is formed at the site of the defect. After implantation of the 3D carrier without serum bioregulator, the defect was closed, but the formed bone was loose and contained no inflammation foci. After the defect was filed with the albumin sponge with the bioregulator, the repair pattern corresponded to the processes of epimorphic tissue regeneration. The results suggest that cryogenically structured protein material in combination with a serum bioregulator ensured complete restoration of the bone tissue.

The study aimed to improve the mechanical properties of a sol-gel-derived bioactive glass (BG) foam scaffold by poly-lactic co-glycolic acid (PLGA) coating as a potential scaffold for bone tissue regeneration. Polyurethane (PU) foam as the initial frame was submerged into a sol-gel-derived BG solution. The heat treatment process was carried out at 450°C to remove the PU foam and 860°C to consolidate the glass and remove the nitrate groups. The prepared BG scaffolds then were submerged into 10 and 15 wt% of PLGA solution. The uncoated BG scaffold was characterized by DTA/TGA, XRD, SEM, and TEM. The PLGA-coated scaffolds were characterized using SEM, and the mean compressive strength of the samples was measured. The DTA/TGA and XRD pattern indicated the removal of all nitrate groups at the temperatures above 700°C and also crystallization of BG after 800°C. The mean compressive strength of 10% and 15% PLGA-coated scaffolds were obtained 1.36±0.39 and 1.95±0.70 MPa, respectively, while the uncoated samples were crushed before the test. The SEM images exhibited that in the coated samples, the BG struts were covered with a PLGA layer and the coated layer was thicker in 15% PLGA samples. The SEM images also revealed that the PLGA coating maintained the structure of the broken struts and prevented them from coming apart. Thus, based on the obtained results, the PLGA coating was successfully toughened the BG scaffold and improved its elasticity. The study aimed to improve the mechanical properties of a sol-gel derived bioactive glass (BG) foam scaffold by Poly-lactic co-glycolic acid (PLGA) coating as a potential scaffold for bone tissue regeneration. Based on the results of this study, the PLGA coating can improve the elasticity and relieve the brittleness of sol-gel derived BG scaffold by supporting the fractured struts and prevent the scaffold from coming apart during a compressive strength test. Consequently, based on the obtained results a 15% PLGA-coated sol-gel derived BG scaffold can be considered as a potential scaffold for bone tissue regeneration.

Bone tissue exhibits piezoelectric properties and thus is capable of transforming mechanical stress into electrical potential. Piezoelectricity has been shown to play a vital role in bone adaptation and remodelling processes. Therefore, to better understand the interplay between mechanical and electrical stimulation during these processes, strain-adaptive bone remodelling models without and with considering the piezoelectric effect were simulated using the Python-based open-source software framework. To discretise numerical attributes, the finite element method (FEM) was used for the spatial variables and an explicit Euler scheme for the temporal derivatives. The predicted bone apparent density distributions were qualitatively and quantitatively evaluated against the radiographic scan of a human proximal femur and the bone apparent density calculated using a bone mineral density (BMD) calibration phantom, respectively. Additionally, the effect of the initial bone density on the resulting predicted density distribution was investigated globally and locally. The simulation results showed that the electrically stimulated bone surface enhanced bone deposition and these are in good agreement with previous findings from the literature. Moreover, mechanical stimuli due to daily physical activities could be supported by therapeutic electrical stimulation to reduce bone loss in case of physical impairment or osteoporosis. The bone remodelling algorithm implemented using an open-source software framework facilitates easy accessibility and reproducibility of finite element analysis made.

Bone metabolism imbalances cause bone metabolism diseases, like osteoporosis, through aging. Although some chemokines are known to be involved in bone mass regulation, many have not been investigated. Thus, the present study aimed to investigate the role of chemokine ligand 28 (CCL28) on bone metabolism. To investigate the role of CCL28 on bone metabolism, 10-week-old male wild-type and Ccl28 knockout (Ccl28 KO) mice were analyzed. Microcomputed tomography analysis and bone tissue morphometry were used to investigate the effect of Ccl28 deficiency on the bone. CCL28 localization in bone tissue was assumed by immunohistochemistry. Osteoblast and osteoclast markers were evaluated by enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction. Finally, in vitro experiments using MC3T3-E1 and bone marrow macrophages revealed the direct effect of CCL28 on osteoblast and osteoclast. This study showed that Ccl28 deficiency significantly increased bone mass and the number of mature osteoblasts. Immunoreactivity for CCL28 was observed in osteoblasts and osteoclasts on bone tissue. Additionally, Ccl28 deficiency promoted osteoblast and osteoclast maturation. Moreover, CCL28 treatment decreased osteoblast and osteoclast activities but did not affect differentiation. In summary, this study indicated that CCL28 is one of the negative regulators of bone mass by suppressing osteoblast and osteoclast activities. These results provide important insights into bone immunology and the selection of new osteoporosis treatments.

Osteoderms of Hoplophorus euphractus are historically mistaken by other glyptodonts osteoderms, such as Glyptodon, Glyptotherium and Neosclerocalyptus, which has created confusion regarding the proper identification of the remains. Recent revisions have granted a better taxonomic understanding of these taxa. In this work, we present a morphological description of a carapace fragment with four articulated osteoderms and other post-cranium bones. Morphological and histological information of an isolated osteoderm and a limb bone from Hoplophorus euphractus was combined, allowing some perception into their paleobiology. The combined paleohistological analysis of two bone elements, osteoderm and humerus, corroborates with the idea of how the pattern of bone microstructure is useful for making inferences about the functional morphology of extinct species. In the humerus, it is identifiable a bone tissue derived from dynamic osteogenesis, with elongated osteocytes lacunae and collagen fibre with a preferably transverse orientation (perpendicular to the long axis). In the superficial and deep layers of the osteoderm, a bone tissue derived from a combination of dynamic and static osteogenesis is seen. In the trabeculae of the osteoderm, a lamellar bone tissue is present, more organized than the ones present in the other regions of the bone. Both histological and morphological features of the osteoderm and humerus can be interpreted as a representation of a mature ontogenetic stage. The preferentially transversely fibre alignment found in H. euphractus bone could be indicative of good resistance of compressive forces, but a more extensive research with a broader sample is necessary for more definitive conclusions.

Muscle paralysis induced with botulinum toxin (Botox) injection increases vascular porosity and reduces osteocyte lacunar density in the tibial cortical bone of skeletally mature rats. These morphological changes potentially affect interstitial fluid flow in the lacunar–canalicular porosity, which is thought to play a role in osteocyte mechanotransduction. The aim of this study was to investigate the effects of disuse-induced morphological changes on interstitial fluid velocity around osteocytes in the bone cortex. Micro-CT images from a previous study that quantified the effects of Botox-induced muscle paralysis on bone microarchitecture in skeletally mature rats were used to create high-resolution, animal-specific finite element models that included the vascular pores and osteocyte lacunae within the tibial metaphysis of Botox-injected (BTX, n = 8) and saline-injected control (CTRL, n = 8) groups. To quantify fluid flow, lacunar and canalicular porosities were modeled as fluid-saturated poroelastic materials, and boundary conditions were applied to simulate physiological loading. This modeling approach allowed a detailed quantification of the fluid flow velocities around osteocytes in a relatively large volume of bone tissue. The analysis demonstrated that interstitial fluid velocity at the vascular pore surfaces was significantly lower in BTX compared to CTRL because of the decreased vascular canal separation. No significant differences in average fluid velocity were observed at the osteocyte lacunae and no correlation was found between the fluid velocity and the lacunar density, which was significantly lower in BTX. Instead, the lacunar fluid velocity was dependent on the osteocyte’s specific position in the bone cortex and its proximity to a vascular pore.

The design of scaffolds that could adjust and adapt greatly to bone defects is a significant challenge to bone tissue engineering. Recently, 3D printing technology emerged as a process that could precisely control the architecture and design an exact geometry of the scaffold to the site or defect where it will be implanted. Thus, this research aimed to design and synthesize individualized constructs of polylactic acid (PLA) by 3D printing using microtomographic images to fit the edge of Wistar rat calvaria's critical size defects. The 3D-printed construct using the DICOM data of microtomographic images process to STL manipulated and designed by various software showed an excellent geometry. The in vitro biocompatibility assay of the 3D printing scaffold was evaluated by WST-1, showing an excellent biological response. Moreover, the in vivo evaluation of the bone regeneration process onto the rat calvaria defect model measured by the bone mineral density (BMD) at 8, 30, 60, and 90 days via micro-CT showed that at the end of the evaluation period, the 3D construct was integrated into the edges of the bone tissue, and new tissue deposited was in the process of mineralization. These findings suggest that the 3D construct matches the calvaria defect, allowing the novo mineral tissue to form. These individualized printed scaffolds may be a promising candidate in bone tissue engineering for future regeneration strategies.

Objective Implantology represents the gold standard for oral rehabilitation, unfortunately, often, despite there are no local contraindications to this type of rehabilitation, there are uncertainties regarding the general health of our patients. Many patients nowadays take bisphosphonate drugs, often without first seeking advice from an oral surgeon or a dentist. The purpose of this review is precisely to highlight any contraindications to this type of treatment reported in the literature, in patients who take or have taken bisphosphonate drugs. Methods For this study the scientific information sources were consulted using as search terms “(“bisphosphonate AND “dental implant”)”, obtaining 312 results, these were subsequently skimmed according to the inclusion and exclusion criteria, and further evaluated their relevance to the study and the presence of requested outcomes. Results Only 9 manuscripts (RCTs, Multicentric studies and Clinical Trials) were included in this review, as they respected the parameters of this review, they were analyzed and it was possible to draw important results from them. Surely from this study it is understood that the use of bisphosphonate drugs does not represent an absolute contraindication to implant therapy, it is evident how adequate pharmacological prophylaxis, and an adequate protocol reduce the risks regarding implant failures. Furthermore, the values of marginal bone loss over time seem, even if not statistically significant, to be better in implant rehabilitation with bisphosphonate drugs association. Only a few molecules like risedronate, or corticosteroids, or some conditions like smoking or diabetes have shown a high risk of surgical failure. Conclusion Although this study considered different studies for a total of 378 patients and at least 1687 different dental implants, showing better results in some cases for dental implant therapy in cases of bisphosphonate intake, further clinical, randomized and multicentric studies are needed, with longer follow-ups, to fully clarify this situation which often negatively affects the quality of life of our patients and places clinicians in the face of doubts.

Mesenchymal stem cells (MSCs) were considered the promising source in the regeneration of bone tissue. These cells have been known to have the ability to differentiate into the osteogenic lineage. The identification of the new approaches improved the efficiency of these cells in bone tissue engineering. In the present study, we investigated the combinational effect of epigallocatechin gallate (EGCG) and hypoxia-inducible factor-1 (HIF-1) on the osteogenic differentiation ability of human bone marrow-mesenchymal stem cells (BM-MSCs). Ten differently treated groups of BM-MSCs were evaluated by expression analysis of osteogenic and angiogenic markers including Runx2, COL1A1, SPARC, VEGF, and ALP as well as RANKL/RANK/OPG pathway genes. They included the experimental (cells treated with the culture medium containing 5, 10, and 20 μM EGCG with 15, 30, and 45 ng/ml HIF-1 or without HIF-1) and the control groups (untreated cells). The obtained results indicated that the co-treating with 5 μM EGCG+ 30 ng/ml HIF-1 increased the osteogenic ability of BM-MSCs as compared with the other experimental groups and the control cells. Furthermore, treatment with EGCG and HIF-1 showed to be associated with the RANKL upregulation as well as OPG downregulation. These observations suggested that HIF-1 improved the EGCG efficiency in the MSC differentiation into the osteogenic lineage. The administration of mesenchymal stem cells (MSCs) has been suggested to be a potential therapy tool in the repair of bone tissue. The identification of novel approaches could play an important role in the improvement of bone tissue engineering. In the present study, we investigated the effect of co-treating the human MSCs with epigallocatechin gallate (EGCG) and hypoxia-inducible factor-1 (HIF-1). The obtained results provided the better understanding about the effect of EGCG and HIF-1 on expression level of Runx2, COL1A1, SPARC, VEGF, ALP, OPG, and RANKL genes in the treated cells.

To evaluate the effect of repeated administration of zoledronic acid (ZA) on the development and severity of osteonecrosis of the jaws. In the experiment, 36 rats were used, which were divided into 4 groups: group 1 was injected with saline for 6 weeks, group 2 was injected with ZA once, group 3 was injected zoledronic acid for 3 weeks once a week, group 4 was injected with ZA for 6 weeks once a week. While taking medications, the tooth was removed. The volumetric blood flow rate was studied using laser and high-frequency ultrasound Doppler in the area of the periodontium of an extracted tooth in rats with the application of acetylcholine. Bone tissue was examined out using CBCT. In group 2, there was a violation of blood flow in the mucous membrane, bone microcirculation, but no reliable data was obtained in the bone defect in comparison with group 1. In groups 3 and 4, there was significantly disrupted blood flow. This led to an increase of the osteonecrosis (maximum at the 4th group), which was confirmed by data obtained using CBCT. An inverse relationship was observed between the blood flow of bone tissue and the size of the defect after tooth extraction. The introduction of ZA in a dose-dependent fashion resulted in impaired endothelial vasodilation and impaired blood flow to extraction sockets. These findings might explain the development of osteonecrosis of the mandible following removal of a first molar.

The structure and geometry of bone depend on many biological and environmental factors. These factors affect the bone tissue's microstructure differently, and their interaction has not yet been fully elucidated. Our research investigated the effect of body mass on the macro- and microstructure of the compact bone. Therefore we analyzed the humerus and femur bones from females of 11 cows and 11 sheep at the age of 4–10 years. Both species have very similar dietary and locomotion patterns, but their body size and weight are very different. Within macroscopical analyzes of bones were observed ascending order of robustness index and bone diaphysis index. In both animals, plexiform and irregular Haversian bone tissues were identified in humerus and femur. Conversely, the dense Haversian tissue present only in cow above all in the femur. The most considerable interspecific osteonal difference between sheep and cow was in the osteon density, whose average value is 37% higher in the cow. The osteons of sheep humerus are almost circular, and osteons of cow femur are more elliptical. Within both species, the femoral osteons are elliptical than those of humerus. Despite the cow weighing more than 10 times the sheep, the measurements of osteons and Haversian canals, are very similar (the values of the ratio cow/sheep for these types are comprised from 1.04 to 1.86). Our findings indicate that the body mass does not affect the size of bone microstructure, probably more sensitive to other factors as a lifestyle and locomotor ability.

Microgravity negatively affects the bone tissue which manifested in a decrease in mineral density of the bones during long-term space flights. Impairments of bone homeostasis are determined among other things by changes in secretory activity of heterogeneous populations of low-committed precursors, such as mesenchymal stromal cells (MSC) and osteoblasts. We studied the effect of microgravity modeling during 10 days on paracrine activity of osteogenically committed and intact MSC. Cell response to simulated microgravity depended on the degree of commitment. The response of osteogenically committed MSC was less pronounced and manifested in increased production of sclerostin. In intact MSC, an increase in IL-8 and VEGF secretion and a decrease in osteoprotegerin level were detected. These changes can underlie the shift of bone homeostasis towards bone resorption.

Currently, biomimetic scaffold is one of the most promising strategies in the field of bone tissue engineering. Zirconia (ZrO2), as a kind of bioceramic material, has attracted much attention in biomimetic scaffolds due to its excellent biocompatibility, high mechanical strength and great chemical stability. A lot of work has been carried out to investigate the characteristics and applications of the zirconia-based biomimetic scaffolds. However, there is few work which can provide a systematic comparison and overview on the research progress of zirconia-based biomimetic scaffolds. This review focuses on the properties and preparations of ZrO2 and its composite materials. In addition, the roles of ZrO2 along with other materials as scaffolds for bone tissue repair applications are highlighted. Simultaneously, the limitations of materials and technology are discussed.

In bone tissue engineering research, nanohydroxyapatite (n-HAp) has been recently gaining a lot of interest because of its excellent functional properties such as improvement in the formation of neo-tissue. In this study, the composite nanoscaffolds of n-HAp (0.1–0.5%)-doped polycaprolactone (PCL) (10%) were engineered by electrospinning as a drug delivery system and bone tissue growth. The cell proliferation activities of the prepared composite nanoscaffolds were examined in vitro using osteoblast cells like (MG-63) (Passage 10) cell line. The electrospun PCL/n-HAp nanoscaffolds were subjected to the drug delivery studies using a bone infection antibiotic cephalexin drug and the antibacterial study of the composite was carried out using Escherichia coli bacteria. These results revealed that the mechanical strength (13.25 ± 0.3536) increased and the fiber diameter decreased (100 nm) at the optimized n-HAp (0.4%) concentration, the maximum drug (68%) loading capacity of the electrospun nanofiber PCL/n-HAp takes place at 48 h and the maximum drug release was found to be 78% at 48 h. These novel nanohydroxyapatite-doped polycaprolactone (PCL/n-HAp) scaffolds show promising applications as a drug delivery system using cephalexin and this would also be a potential biomaterial for enhancing bone tissue growth.

Osteoporosis is a metabolic disease that affects bone tissue and is highly associated with bone fractures. Due to the low bioavailability of conventional treatments for this disease, an alternative has been developed to project systems for the local release of therapeutic agents, such as bioactive glass (BG) containing therapeutic ions and molecules that are released during dissolution. In this study, submicron BG spheres derived from the sol–gel process containing Sr, a potential ion to prevent bone loss and increase bone formation, were evaluated. For the first time, the effect of these particles was investigated on the reduced osteogenic potential of bone marrow mesenchymal stem cells (BMMSCs) obtained from osteoporotic rats. The obtained submicron and spherical Sr-containing BG particles showed controlled ion release capacity, and osteogenic differentiation assays showed that these materials could stimulate the reduced differentiation potential of BMMSCs from osteoporotic rats due to Sr release.

Cellular biomaterials with highly controlled microstructures are auspicious materials for medical orthopedics applications either as scaffold or implants due to their capability of encouraging better osseointegration and cell proliferation. This work focuses on the design and optimization of the hip implant by introducing a cellular structure into a solid implant to allow bone tissue ingrowth and reduce stress shielding. The cellular hip implant is incorporated with vintiles lattice topologies having different strut thickness and unit cell sizes to achieve the requirements of bone ingrowth and biomechanical mimic strength. All four optimized cellular hip implants with different unit cell size and porosity were manufactured via selective laser melting (SLM) using the Ti6Al4V material. To predict the mechanical property of hip cellular implant, finite element analysis (FEA) was employed and optimization methods were used for improving the mechanical performance of the hip cellular implant. To evaluate the reduction in stiffness of hip cellular implants, experimental tests were performed based on ISO 7206-4(2010) under static loading conditions. The experimental and simulation force-displacement results show that the optimized cellular hip implant has 62% lower stiffness than its solid counterpart. Moreover, the cellular hip implant was 50% lower in weight than the solid implant. Finally, the result of this study shows that the cellular implants with porosity of 56% and 58% have the potential to be used in orthopedic and prosthetic applications to improve osseointegration.

Due to the osteoconductive role of bioceramics, use of these bioactive nanocomposite scaffolds that can maintain their structural integrity during bone tissue repair is one of the major goals of tissue engineering. Herein, a nanofibrous poly-L-lactic acid (PLLA) scaffold was fabricated by electrospinning and then gelatin and hydroxyapatite nanoparticles (nHA) were coated over the surface of the scaffold. Osteoconductivity of the fabricated nano-composite scaffolds was then studied while grafted on the rat calvarial defects. Our results indicated that the coating of PLLA scaffold with nHA and gelatin increased the adhesion and growth of the human bone marrow derived mesenchymal stem cells (BM-MSCs) and also significantly increased the level of mineralization over a week culture period. The results of radiographic and histological studies showed that the newly created bone tissue at the defect site was significantly higher in animals treated with nanocomposite scaffolds than the empty scaffolds and control groups. This increase in the defect reconstruction was significantly increased after culturing BM-MSCs on the scaffolds, especially nanocomposite scaffolds. It can be concluded that the combination of nanocomposite scaffolds and BM-MSCs could be a very good candidate for treatment of bone lesions and could be considered as a bony bioimplant.

A biologically active complex of polypeptides was obtained from fetal bone to stimulate chondrogenesis. Its effectiveness was studied on the model of cartilage defect healing in rats. The biologically active complex was isolated from the intercellular matrix of long tubular bones of dog fetuses (57 – 63 d of fetal development). The resulting complex (0.1 mLvolume) was introduced into a cartilage defect in 10 rats (experimental group). Normal saline (0.1 mL) was injected into the defect in 10 animals of the control group. It was found that the sizes of the defects in experimental animals on the 30th day of the experiment were statistically significantly less than in the control group. The defect region was completely filled in animals of both groups on the 180th day of the experiment. However, the cartilage flexibility was statistically significantly lower in the control than in the experimental group. It is believed that the intercellular substance of fetal bone tissue can be a source of biologically active components that can stimulate reparative chondrogenesis (growth factors, procollagen and/or its derivatives).