Human Cancellous Bone Research Articles

A New Anorganic Equine Bone Substitute for Oral Surgery: Structural Characterization and Regenerative Potential.

Different xenogeneic inorganic bone substitutes are currently used as bone grafting materials in oral and maxillo-facial surgery. The aim of the present study was to determine the physicochemical properties and the in vivo performance of an anorganic equine bone (AEB) substitute. AEB is manufactured by applying a process involving heating at >300 °C with the aim of removing all the antigens and the organic components. AEB was structurally characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray fluorescence (XRF), and Fourier-transformed infrared (FT-IR) spectroscopy and compared to the anorganic bovine bone (ABB). In order to provide a preliminary evaluation of the in vivo performance of AEB, 18 bone defects were prepared and grafted with AEB (nine sites), or ABB (nine sites) used as a control, in nine Yucatan Minipigs. De novo bone formation, residual bone substitute, as well as local inflammatory and tissue effects were histologically evaluated at 30 and 90 days after implantation. The structural characterization showed that the surface morphology, particle size, chemical composition, and crystalline structure of AEB were similar to cancellous human bone. The histological examination of AEB showed a comparable pattern of newly formed bone and residual biomaterial to that of ABB. Overall, the structural data and pre-clinical evidence reported in the present study suggests that AEB can be effectively used as bone grafting material in oral surgery procedures.

Scattering in Cancellous Bone.

Two theoretical models for ultrasonic scattering from cancellous bone have been extensively validated in human cancellous bone in vitro. Many metrics have been devised to assess scattering in vivo. In the diagnostic frequency range (<1MHz), multiple scattering is much weaker than single scattering. However, evidence for multiple scattering has been detected. At higher frequencies (>1MHz), the effects of multiple scattering are more pronounced. Clinical trials indicate that backscatter parameters provide useful diagnostic information regarding bone status in adults and neonates. This chapter will emphasize developments in scattering research in the last decade since the previous volume Bone QUS was published.

Pulsatile Lavage Systems with High Impact Pressure and High Flow Produce Cleaner Cancellous Bone Prior to Cementation in Cemented Arthroplasty.

In cemented joint arthroplasty, state-of-the-art cementing techniques include high-pressure pulsatile saline lavage prior to cementation. Even with its outstanding importance in cementation, there are surprisingly few studies regarding the physical parameters that define pulsatile lavage systems. To investigate the parameters of impact pressure, flow rate, frequency and the cleaning effect in cancellous bone, we established a standardized laboratory model. Standardized fat-filled carbon foam specimens representing human cancellous bone were cleaned with three different high-pressure pulsatile lavage systems. Via CT scans before and after cleaning, the cleaning effect was evaluated. All systems showed a cleaning depth of at least 3.0 mm and therefore can be generally recommended to clean cancellous bone in cemented joint arthroplasty. When comparing the three lavage systems, the study showed significant differences regarding cleaning depths and volume, with one system being superior to its peer systems. Regarding the physical parameters, high impact pressure in combination with high flow rate and longer distance to the flushed object seems to be the best combination to improve the cleaning of cancellous bone and therefore increase the chances of a deeper cement penetration that is required in cemented joint arthroplasty. In summary, this study provides the first standardized comparison of different lavage systems and thus gives initial guidance on how to optimally prepare cancellous bone for cemented joint arthroplasty.

3D gel-printing of porous MgFe2O4 magnetic scaffolds for bone tissue engineering

It is increasing evidence that the synergistic effects of magnetic scaffolds and magnetic fields can accelerate bone repairing and regeneration, and the bone tumor may be treated using magnetite nanoparticles (MNPs) with hyperthermia. In this study, in order to apply the magnetocaloric performance of MgFe2O4 to bone tissue engineering, porous MgFe2O4 magnetic scaffolds were successfully prepared by chemical coprecipitation method and 3D gel-printing (3DGP) technology. The printing slurry based on polyvinyl alcohol (PVA) system exhibited shear thinning properties, and its maximum solid loading was about 63 wt%. When the slurry was squeezed out of the needle, the slurry viscosity was 0.58 Pa·s at the shear rate of 316.3 s-1. The scaffolds sintered above 1100 °C were superparamagnetic and their compressive strength was within 1.8–12.51MPa, which is suitable for human cancellous bone. The highest saturation magnetization of porous MgFe2O4 scaffolds printed by 3DGP was 10.63 emu/g when they were sintered at 1200 °C. The weight loss rate of the scaffolds was 2.15% after degradation in simulated body fluid (SBF) for 5 weeks, pH value of SBF was between 6.78 and 7.4. Preliminary biological experiment shows that MC3T3-E1 cells had good adhesion and proliferation on MgFe2O4 scaffolds surface, and MgFe2O4 scaffolds can promote alkaline phosphatase (ALP) activation, which explain that porous MgFe2O4 magnetic scaffolds may be used for bone repairing.

Improving the Management of Patients with Osteoporosis Undergoing Spinal Fusion: The Need for a Bone Mineral Density-Matched Interbody Cage

With an increasingly aging population globally, a confluence has emerged between the rising prevalence of degenerative spinal disease and osteoporosis. Fusion of the anterior spinal column remains the mainstay surgical intervention for many spinal degenerative disorders. However, decreased vertebral bone mineral density (BMD), quantitatively measured by dual x-ray absorptiometry (DXA), complicates treatment with surgical interbody fusion as weak underlying bone stock increases the risk of post-operative implant-related adverse events, including cage subsidence. There is a necessity for developing cages with advanced structural designs that incorporate bioengineering and architectural principles to tailor the interbody fusion device directly to the patient’s BMD status. Specifically, lattice-designed cages that mimic the web-like structure of native cancellous bone have demonstrated excellent resistance to post-operative subsidence. This article provides an introductory profile of a spinal interbody implant designed intentionally to simulate the lattice structure of human cancellous bone, with a similar modulus of elasticity, and specialized to match a patient’s bone status across the BMD continuum. The implant incorporates an open pore design where the degree of pore compactness directly corresponds to the patient’s DXA-defined BMD status, including patients with osteoporosis.

Compressional wave propagation in saturated porous media and its numerical analysis using a space-time conservation element and solution element method.

Compressional waves in saturated porous media are relevant to many fields from oil exploration to diagnostic of human cancellous bone and can be used to interpret physical behaviors of materials. In this work, based on Biot's theory in the low frequency range, a key finding is that there exists a critical frequency of Biot's theory in the low frequency range, which determines the coincidence of the properties of Biot waves of the first and second kinds. Furthermore, we have investigated the dispersion and attenuation of the coalescence of the first and second compressional waves in the low frequency range. The coalescence of the first and second waves is strongly attenuated with a moderate phase velocity and shows the in-phase feature. In addition, acoustic wave propagation has been calculated numerically using the space-time conservation element and solution element (CESE) method. The CESE-simulated results are compared to the experimental data and to those of the classical transfer function approach. We show that the CESEscheme preserves the local and global flux conservations in the solution procedure of Biot's theory. It is found that the CESEmethod provides more accurate predictions of high dispersion and strong attenuation of compressional waves in the low frequency range and is well suitable for predicting compressional wave fields in saturated porous media.

Fabrication of porous TiO2 foams by powder metallurgy technique and study of bulk crushing strength for biomedical application.

Despite the importance of porous titanium oxide (PA-TiO2) in diverse functional applications, very little information is available on the compatible mechanical properties for potential biomedical applications. In this study, PA-TiO2 foam was synthesized using space-holding powder metallurgy and sintering methods to produce interconnected opened-cell structure with surface morphology of mountain-like features associated with the extensive rift valley system. Three different types of PA-TiO2 foams with porosities of 35-52% and mean pore diameter of 190-210μm were fabricated for evaluating the effect of porosity on mechanical properties of bulk PA-TiO2. The modulus of elasticity of PA-TiO2 foams exhibited in the range of 45-262MPa which was within the range of modulus of elasticity of human cancellous bone. Cytotoxicity test is performed in vitro analysis to observe the effect of cell toxicity to produce osteointegration when used as implantable materials. There was no cytotoxicity effect found and remarkable cell growth was observed for human cancerous (HeLa) cell line. However, there was no cytotoxicity effect found and cell growth was not observed for Vero cell line. This study suggested that PA-TiO2 facilitates cell growth without spreading toxicity and has mechanical properties of cancellous bone. Hence, it has potential application as implant and medical devices in biomedical applications.

Ultrasonic Bone Assessment: Ability of Apparent Backscatter Techniques to Detect Changes in the Microstructure of Human Cancellous Bone.

Ultrasonic backscatter techniques may offer a useful approach for detecting changes in bone caused by osteoporosis. The goal of this study was to investigate how bone mineral density (BMD) and the microstructure of human cancellous bone affect three ultrasonic backscatter parameters that have been identified as potentially useful for ultrasonic bone assessment purposes: the apparent integrated backscatter (AIB), the frequency slope of apparent backscatter (FSAB), and the frequency intercept of apparent backscatter (FIAB). Ultrasonic measurements were performed with a 3.5-MHz broadband transducer on 54 specimens of human cancellous bone prepared from the proximal femur. Microstructural parameters and BMD were measured using X-ray microcomputed tomography (micro-CT). Relationships between AIB, FSAB, FIAB, and the micro-CT parameters were investigated using univariate and multivariate statistical analysis techniques. Moderate-to-strong univariate correlations were observed between the backscatter parameters and microstructure and BMD in many cases. The partial correlation analysis indicated that the backscatter parameters are dependent on microstructure independently of BMD in some cases. Multiple stepwise linear regression analysis used to generate multivariate models found that microstructure was a significant predictor of the backscatter parameters in most cases.

Effect of physical and mechanical parameters on the reflected signal from the first interface of human cancellous bone—application of Biot's theory

In this work, a simulated study on the effects of physical and mechanical parameters describing human cancellous bone on reflected ultrasound waves is proposed. The visco-inertial exchanges between the structure and the saturating fluid are described by the Biot theory modified by the Johnson model. A simplified expression of the reflection coefficient at the first interface is obtained in the frequency domain. This expression depends on three physical parameters which are porosity, tortuosity, and viscous characteristic length as well as the mechanical parameters; Young's modulus and Poisson's ratio. The reflected signal is calculated in the frequency domain by the product of the spectrum of the incident signal with the reflection coefficient. In the time domain, the reflected wave is obtained by taking the inverse Fourier transform of the reflected frequency signal. The effect of each parameter on the reflected signal is studied. The results obtained are discussed and compared with those given in the literature.

Negative Poisson’s ratio lattice for designing vertebral biomaterials

This work designs and experimentally validates a novel bone-mimicking biomaterial for human cancellous bone vertebral implants. The lattice architecture here proposed consists of a 3D printed titanium auxetic meta-biomaterial, with a complex micro-structure resembling vertebral trabeculae, and exhibiting a negative Poisson’s ratio. Through finite element analysis, the work finds the optimal geometrical parameters of the unit cells of the lattice and performs the shape optimization of the trabeculae. This leads to a meta-biomaterial with a Poisson’s ratio up to −0.64, and a Young’s modulus of 128.3 MPa, close to that of human vertebral cancellous bones, as the experimental validation confirms. The work demonstrates the great potential of additively manufactured hybrid titanium auxetic metamaterials, which can be designed to obtain peculiar mechanical properties that improve bone tissue regeneration while prevent stress-shielding phenomena.

3D Printing of Tricalcium Phosphate/Poly Lactic-co-glycolic Acid Scaffolds Loaded with Carfilzomib for Treating Critical-sized Rabbit Radial Bone Defects.

The rapid development of scaffold-based bone tissue engineering strongly relies on the fabrication of advanced scaffolds and the use of newly discovered functional drugs. As the creation of new drugs and their clinical approval often cost a long time and billions of U.S. dollars, producing scaffolds loaded with repositioned conventional drugs whose biosafety has been verified clinically to treat critical-sized bone defect has gained increasing attention. Carfilzomib (CFZ), an approved clinical proteasome inhibitor with a much fewer side effects, is used to replace bortezomib to treat multiple myeloma. It is also reported that CFZ could enhance the activity of alkaline phosphatase and increase the expression of osteogenic transcription factors. With the above consideration, in this study, a porous CFZ/β-tricalcium phosphate/poly lactic-co-glycolic acid scaffold (designated as “cytidine triphosphate [CTP]”) was produced through cryogenic three-dimensional (3D) printing. The hierarchically porous CTP scaffolds were mechanically similar to human cancellous bone and can provide a sustained CFZ release. The implantation of CTP scaffolds into critical-sized rabbit radius bone defects improved the growth of new blood vessels and significantly promoted new bone formation. To the best of our knowledge, this is the first work that shows that CFZ-loaded scaffolds could treat nonunion of bone defect by promoting osteogenesis and angiogenesis while inhibiting osteoclastogenesis, through the activation of the Wnt/β-catenin signaling. Our results suggest that the loading of repositioned drugs with effective osteogenesis capability in advanced bone tissue engineering scaffold is a promising way to treat critical-sized defects of a long bone.

Treatment of Critical-Size Femoral Bone Defects with Chitosan Scaffolds Produced by a Novel Process from Textile Engineering.

The purpose of this study was to investigate, in vitro and in vivo, the suitability of chitosan (CHS) scaffolds produced by the net-shape-nonwoven (NSN) technology, for use as bone graft substitutes in a critical-size femoral bone defect in rats. For in vitro investigations, scaffolds made of CHS, mineralized collagen (MCM), or human cancellous bone allograft (CBA) were seeded with human telomerase-immortalized mesenchymal stromal cells (hTERT-MSC), incubated for 14 days, and thereafter evaluated for proliferation and osteogenic differentiation. In vivo, CHS, MCM and CBA scaffolds were implanted into 5 mm critical-size femoral bone defects in rats. After 12 weeks, the volume of newly formed bone was determined by microcomputed tomography (µCT), while the degree of defect healing, as well as vascularization and the number of osteoblasts and osteoclasts, was evaluated histologically. In vitro, CHS scaffolds showed significantly higher osteogenic properties, whereas treatment with CHS, in vivo, led to a lower grade of bone-healing compared to CBA and MCM. While chitosan offers a completely new field of scaffold production by fibers, these scaffolds will have to be improved in the future, regarding mechanical stability and osteoconductivity.

Bioactivity and Bone Cell Formation with Poly-ε-Caprolactone/Bioceramic 3D Porous Scaffolds.

This study applied poly-ε-caprolactone (PCL), a biomedical ceramic powder as an additive (nano-hydroxyapatite (nHA) or β-tricalcium diphosphate (β-TCP)), and sodium chloride (NaCl) and ammonium bicarbonate ((NH4)HCO3) as porogens; these stuffs were used as scaffold materials. An improved solvent-casting/particulate-leaching method was utilized to fabricate 3D porous scaffolds. In this study we examined the physical properties (elastic modulus, porosity, and contact angle) and degradation properties (weight loss and pH value) of the 3D porous scaffolds. Both nHA and β-TCP improved the mechanical properties (elastic modulus) of the 3D porous scaffolds. The elastic modulus (0.15~1.865 GPa) of the various composite scaffolds matched that of human cancellous bone (0.1~4.5 GPa). Osteoblast-like (MG63) cells were cultured, a microculture tetrazolium test (MTT) was conducted and alkaline phosphatase (ALP) activity of the 3D porous scaffolds was determined. Experimental results indicated that both nHA and β-TCP powder improved the hydrophilic properties of the scaffolds. The degradation rate of the scaffolds was accelerated by adding nHA or β-TCP. The MTT and ALP activity tests indicated that the scaffolds with a high ratio of nHA or β-TCP had excellent properties of in vitro biocompatibility (cell attachment and proliferation).

Reamer-irrigator-aspirate versus bone marrow aspirate concentrate for osteoprogenitor cell retention and osteoinductive protein release on cancellous bone

Bone defects often require operative intervention with the use of bone graft. Two sources of autologous bone graft include reamer-irrigator-aspirate (RIA) and bone marrow aspirate concentrate (BMC). Osteoprogenitor cells and osteoconductive proteins have been identified in both sources. This study collected samples of these cells and proteins from a canine model and cultured them on human cancellous allograft bone blocks. Findings suggest that BMC may be preferred for indications that allow for delivery via injection, saturation of the patient's tissues, or an implanted scaffold, whereas RIA may be preferred when the biologic augment is delivered as a scaffold or graft.

Carbonated Hydroxyapatite-Based Honeycomb Scaffold Coatings on a Titanium Alloy for Bone Implant Application—Physicochemical and Mechanical Properties Analysis

In this work, carbonated hydroxyapatite (CHA) based on abalone mussel shells (Haliotis asinina) is synthesized using the co-precipitation method. The synthesized CHA was mixed with honeycomb (HCB) 40 wt.% for the scaffold fabrication process. CHA and scaffold CHA/HCB 40 wt.% were used for coating a Titanium (Ti) alloy using the electrophoretic deposition dip coating (EP2D) method with immersion times of 10, 20, and 30 min. The synthesized B-type CHA with a stirring time of 45 min could have lower transmittance values and smaller crystallite size. Energy dispersive X-ray spectroscopy (EDS) showed that the Ca/P molar ratio was 1.79. The scaffold CHA/HCB 40 wt.% had macropore size, micropore size, and porosity of 102.02 ± 9.88 μm, 1.08 ± 0.086 μm, and 66.36%, respectively, and therefore it can also be applied in the coating process for bone implant applications due to the potential scaffold for bone growth. Thus, it has the potential for coating on Ti alloy applications. In this study, the compressive strength for all immersion time variations was about 54–83 MPa. The average compression strengths of human cancellous bone were about 0.2–80 MPa. The thickness obtained was in accordance with the thickness parameters required for a coating of 50–200 μm.

Fracture behavior of cancellous bone and cancellous bone-PMMA bone cement interface: An experimental study using an integrated methodology (wedge splitting test and Heaviside-based digital image correlation)

Minimally invasive methods, such as balloon kyphoplasty (BKP) and percutaneous sacroplasty (PS), which are now widely used for the surgical treatment of compression fractures, involve injection of a bolus of poly (methyl methacrylate) bone cement (hereafter, “bone cement”) into the fractured tissue. Many of the common complications following these surgeries, such as cement leakage and adjacent-level fractures (in the case of BKP), have been postulated to be related to the quality of the cancellous bone–bone cement interface, which, in turn, is a function of its fracture resistance. It is common to use bovine cancellous bone or polyurethane foam (PF) as a substitute for human cancellous bone in biomechanical studies of these surgical methods. The literature is lacking in studies of determination of fracture properties of human cancellous bone–bone cement interface, bovine cancellous bone–bone cement interface, and PF–bone cement interface. In the present work, an integrated methodology (combination of wedge splitting test and Heaviside-based digital image correlation) was used to make these determinations as well as those for the bone cement, bones and the PF alone. The fracture properties determined were maximum fracture load (Fmax), fracture toughness (Kc), and specific fracture energy (Gf). For example, Gf values for human cancellous bone and human cancellous bone–bone interface were 0.48±0.14 N/mm and 0.38±0.05 N/mm, respectively, whereas in the case of bovine cancellous bone and bovine cancellous bone–bone cement interface, they were 1.08±0.11 N/mm and 0.22±0.05 N/mm, respectively, and for PF (Grades 12.5 and 15.0) and PF–bone cement interface, they were 0.81±0.12 and 0.55±0.06 N/mm, respectively. The same trends were seen in the Fmax and Kc results. These results suggest that it may not be justified to use either bovine cancellous bone or either of the PF grades as a substitute for human cadaveric cancellous bone in biomechanical studies of BKP, PS, and similar surgical methods.

Does Pressurized Carbon Dioxide Lavage Improve Bone Cleaning in Cemented Arthroplasty?

Cemented implant fixation in total joint arthroplasty has been proven to be safe and reliable with good long-term results. However, aseptic loosening is one of the main reasons for revision, potentially caused by poor cementation with low penetration depth in the cancellous bone. Aim of this prospective laboratory study was, to compare impact pressure and cleaning effects of pulsatile saline lavage to novel carbon dioxide lavage in a standardized carbon foam setup, to determine whether or not additional use of carbon dioxide lavage has any impact on cleaning volume or cleaning depth in cancellous bone. Carbon specimens simulating human cancellous bone were filled with industrial grease and then underwent a standardized cleaning procedure. Specimens underwent computed tomography pre- and post-cleaning. Regarding the impact pressure, isolated carbon dioxide lavage showed significant lower pressure compared to pulsatile saline lavage. Even though the combination of carbon dioxide lavage and pulsatile saline lavage had a positive cleaning effect compared to the isolated use of pulsatile saline lavage or carbon dioxide lavage, this was not significant in terms of cleaning volume or cleaning depth.

The use of solvent-preserved human and bovine cancellous bone blocks for lateral defect augmentation - an experimental controlled study in vivo

BackgroundThe aim of this study was to compare new bone formation, resorbed bone matrix, and fibrous enclosed residual bone substitute material in laterally augmented alveolar bone defects using allogeneic, pre-treated and cleaned human bone blocks (tested in dogs, therefore considered to be xenogeneic), and pre-treated and cleaned bovine cancellous bone blocks, both with and without a collagen membrane in order to evaluate their augmentative potential.MethodsThirty-two critical size horizontal defects were prepared in the mandible of 4 adult foxhound dogs (8 per dog, 4 on each side). After 3 months of healing, the defects were laterally augmented in a split-mouth-design with either human (HXB) or bovine solvent-preserved bone blocks (BXB). Afterwards, defects were randomly covered with a bovine collagenous membrane (HXB + M, BXB + M). After a healing interval of 6 months, percentages of new bone formation, resorbed bone matrix, and fibrous enclosed residual bone substitute material were compared.ResultsResults showed little new bone formation of up to 3.7 % in human bone blocks (HXB 3.7 % ± 10.2, HXB + M 0.3 %± 0.4, BXB, 0.1 % ± 0.8, BXB + M 2.6 % ± 3.2, p = > 0.05). Percentages of fibrous encapsulation were higher in human bone blocks than in bovine bone blocks (HXB 71.2 % ± 8.6, HXB + M 73.71 % ± 10.6, BXB, 60.5 % ± 27.4, BXB + M 52.5 % ± 28.4, p = > 0.05). Resorption rates differed from 44.8 % in bovine bone blocks covered with a membrane to 17.4 % in human bone blocks (HXB 17.4 % ± 7.4, HXB + M 25.9 % ± 10.7, BXB, 38.4 % ± 27.2, BXB + M 44.8 % ± 29.6, p = > 0.05). The use of additional membranes did not significantly affect results.ConclusionsWithin its limitations, results of this study suggest that solvent-preserved xenogenic human and bovine bone blocks are not suitable for lateral bone augmentation in dogs. Furthermore, defect coverage with a membrane does not positively affect the outcome.

Improved osteogenesis in rat femur segmental defects treated with human allograft and zinc adjuvants.

Bone allograft is widely used to treat large bone defects or complex fractures. However, processing methods can significantly compromise allograft osteogenic activity. Adjuvants that can restore the osteogenic activity of processed allograft should improve clinical outcomes. In this study, zinc was tested as an adjuvant to increase the osteogenic activity of human allograft in a Rag2 null rat femoral defect model. Femoral defects were treated with human demineralized bone matrix (DBM) mixed with carboxy methyl cellulose containing ZnCl2 (0, 75, 150, 300 µg) or Zn stearate (347 µg). Rat femur defects treated with DBM-ZnCl2 (75 µg) and DBM-Zn stearate (347 µg) showed increased calcified tissue in the defect site compared to DBM alone. Radiograph scoring and µCT (microcomputed tomography) analysis showed an increased amount of bone formation at the defects treated with DBM-Zn stearate. Use of zinc as an adjuvant was also tested using human cancellous bone chips. The bone chips were soaked in ZnCl2 solutions before being added to defect sites. Zn adsorbed onto the chips in a time- and concentration-dependent manner. Rat femur defects treated with Zn-bound bone chips had more new bone in the defects based on µCT and histomorphometric analyses. The results indicate that zinc supplementation of human bone allograft improves allograft osteogenic activity in the rat femur defect model.

Honeycomb structure is promising for the repair of human bone defects

In this paper, the results of the study on the performance of four groups of different honeycomb structures show that the application of honeycomb structure in the design of biomimetic bone scaffold is feasible and promising. In terms of static properties, the elastic modulus (1.6–3 GPa) of the four scaffolds matched the elastic modulus of human cancellous bone (0.1–4.5 GPa), and the yield strength (88–146 MPa) was much higher than that of the femoral neck (0.56–3.71 MPa). In terms of permeability, except for the excessive permeability of SU scaffold, the permeability of the other three groups of scaffolds (1.5*10−8–4.8*10−8 m2) are all in the range of cancellous bone permeability (0.5*10−8–5.0*10−8 m2). In terms of the distribution of wall shear stress, the wall shear stress of the four groups of scaffolds ranged from 2.8 to 42.8 MPa, which could stimulate cells to deposit mineralized extracellular matrix (0.55–30 MPa) in the 3D scaffold, which was conducive to bone tissue regeneration.