3D Bone Research Articles

Metatarsal bone model production using 3D printing and comparison of material properties with results obtained from CT-based modeling and real bone.

Using a real bone is very important to find correct results for the biomechanical studies. However, it is very difficult to find the real bone and sometimes artificial bone models can be preferred instead of real bone. The aim of this study is to obtain an easy-to-manufacture, easy-to-customize and inexpensive method the artificial first metatarsal bone model that is similar material properties with the real bone. 3D printer technology was used to produce the artificial bone model. First metatarsal bone was modeled using MIMICS software to produce and determined the mechanical properties. The bone mechanical properties were calculated via MIMICS software using computer tomography images. 3D bone models were produced in different infill density and infill pattern to determine the real bone mechanical properties using 3D printer. The infill density of the bone model was adjusted as 20%, 40%, and 60%. Five different infill pattern types were used as grid, cubic, triangle, trihexagon, and gyroid. The produced models were subjected to torsional test and the elasticity modulus of all models were obtained. The results of the elasticity modulus of all produced (artificial) and modeled (calculated) bone were compared and the optimum bone model was obtained. The optimum infill density and infill pattern was determined as 40% and trihexagon, respectively.

A three-dimensional actively spreading bone repair material based on cell spheroids can facilitate the preservation of tooth extraction sockets.

Introduction: Achieving a successful reconstruction of alveolar bone morphology still remains a challenge because of the irregularity and complex microenvironment of tooth sockets. Biological materials including hydroxyapatite and collagen, are used for alveolar ridge preservation. However, the healing effect is often unsatisfactory. Methods: Inspired by superwetting biomimetic materials, we constructed a 3D actively-spreading bone repair material. It consisted of photocurable polyether F127 diacrylate hydrogel loaded with mixed spheroids of mesenchymal stem cells (MSCs) and vascular endothelial cells (ECs). Results: Biologically, cells in the spheroids were able to spread and migrate outwards, and possessed both osteogenic and angiogenic potential. Meanwhile, ECs also enhanced osteogenic differentiation of MSCs. Mechanically, the excellent physical properties of F127DA hydrogel ensured that it was able to be injected directly into the tooth socket and stabilized after light curing. In vivo experiments showed that MSC-EC-F127DA system promoted bone repair and preserved the shape of alveolar ridge within a short time duration. Discussion: In conclusion, the novel photocurable injectable MSC-EC-F127DA hydrogel system was able to achieve three-dimensional tissue infiltration, and exhibited much therapeutic potential for complex oral bone defects in the future.

Quantification of the methodological error in kinematic evaluation of the DRUJ using dynamic CT

Distal radio-ulnar joint (DRUJ) motion analysis using dynamic CT is gaining popularity. Following scanning and segmentation, 3D bone models are registered to (4D-)CT target frames. Imaging errors like low signal-to-noise ratio (SNR), limited Z-coverage and motion artefacts influence registration, causing misinterpretation of joint motion. This necessitates quantification of the methodological error. A cadaver arm and dynamic phantom were subjected to multiple 4D-CT scans, while varying tube charge-time product and phantom angular velocity, to evaluate the effects of SNR and motion artefacts on registration accuracy and precision. 4D-CT Z-coverage is limited by the scanner. To quantify the effects of different Z-coverages on registration accuracy and precision, 4D-CT was simulated by acquiring multiple spiral 3D-CT scans of the cadaver arm. Z-coverage was varied by clipping the 3D bone models prior to registration. The radius position relative to the ulna was obtained from the segmentation image. Apparent relative displacement seen in the target images is caused by registration errors. Worst-case translations were 0.45, 0.08 and 1.1 mm for SNR-, Z-coverage- and motion-related errors respectively. Worst-case rotations were 0.41, 0.13 and 6.0 degrees. This study showed that quantification of the methodological error enables composition of accurate and precise DRUJ motion scanning protocols.

The differentiation of human induced pluripotent stem cells into hematopoietic stem cells on 3D bone scaffold in a dynamic culture system

Hematopoietic stem cell transplantation is used for cell-based therapy for many hematological disorders. However, difficulty in finding proper donors has limited this source of stem cells. For clinical application, the generation of these cells from induced pluripotent stem cells (iPSs) is a fascinating and endless source. One of the experimental methods to generate HSCs from iPSs is the mimicking of the hematopoietic niche. In the current study, as the first phase of differentiation, embryoid bodies were formed from iPSs. They were then cultured in different dynamic conditions in order to determine the appropriate settings for their differentiation into HSCs. The dynamic culture was composed of DBM Scaffold with or without growth factor. After ten days, the specific HSC markers (CD34, CD133, CD31 and CD45) were assessed using flow-cytometry. Our findings demonstrated that the dynamic conditions were significantly suitable than static ones. In addition, in 3D scaffold and dynamic system the expression of CXCR4, as a homing marker, was increased. These results suggest that the 3D culture bioreactor with DBM scaffold could provide a new approach for differentiation of iPSs into HSCs. Moreover, this system could provide maximum mimicry of bone marrow niche.

Comparison of 3D quantitative osteoarthritis imaging biomarkers from paired CT and MR images: data from the IMI-APPROACH study

IntroductionMRI bone surface area and femoral bone shape (B-score) measures have been employed as quantitative endpoints in DMOAD clinical trials. Computerized Tomography (CT) imaging is more commonly used for 3D visualization of bony anatomy due to its high bone-soft tissue contrast. We aimed to compare CT and MRI assessments of 3D imaging biomarkers.MethodsWe used baseline and 24-month image data from the IMI-APPROACH 2-year prospective cohort study. Femur and tibia were automatically segmented using active appearance models, a machine-learning method, to measure 3D bone shape, area and 3D joint space width (3DJSW). Linear regression was used to test for correlation between measures. Limits of agreement and bias were tested using Bland-Altman analysis.ResultsCT-MR pairs of the same knee were available from 434 participants (78% female). B-scores from CT and MR were strongly correlated (CCC = 0.967) with minimal bias of 0.1 (SDD = 0.227). Area measures were also correlated but showed a consistent bias (MR smaller). 3DJSW showed different biases (MR larger) in both lateral and medial compartments.DiscussionThe strong correlation and small B-score bias suggests that B-score may be measured reliably using either modality. It is likely that the bone surface identified using MR and CT will be at slightly different positions within the bone/cartilage boundary. The negative bone area bias suggests the MR bone boundary is inside the CT boundary producing smaller areas for MR, consistent with the positive 3DJSW bias. The lateral-medial 3DJSW difference is possibly due to a difference in knee pose during acquisition (extended for CT, flexed for MR).Trial registrationNCT03883568

Characterization and Applicability of a Bone Spheroid Model for the Evaluation of Cytocompatibility of Bone Substitutes

In vitro cell-based tests are an important preclinical step for the safety assessment of biomaterials and drugs. Three-dimensional cell culture models (3D) may improve the limitations of the usual 2D models, as they better simulate a physiological environment. This work describes the characterization of a 3D spheroid model of MC3T3-E1 murine preosteoblasts for the testing of bone-substitute materials and investigates its adequacy to some of the most employed cell viability tests. The spheroids presented structural stability for 28 days in culture, with a regular spheroidal aspect, compact surface, and dense inner structure, with high potential for mineralization, but a time-dependent reduction in size. The use of colorimetric tests (MTT, XTT, and NRU) did not achieve satisfactory optical densities and did not correlate with cell density in the 3D model, as the aggregates remain strongly stained even after dye extraction steps. On the other hand, the LDH test achieved appropriate optical density and a high correlation with cell density (r2 = 0.77) and identified a dose–response for a well-known cytotoxic polymer (latex), while no toxicity was identified for biocompatible PLA wires. These results indicate that material testing with 3D bone cell models requires a careful choice of test methods and parameters.

Construction of 3D bioprinting of HAP/collagen scaffold in gelation bath for bone tissue engineering.

Reconstruction of bone defects remains a clinical challenge, and 3D bioprinting is a fabrication technology to treat it via tissue engineering. Collagen is currently the most popular cell scaffold for tissue engineering; however, a shortage of printability and low mechanical strength limited its application via 3D bioprinting. In the study, aiding with a gelatin support bath, a collagen-based scaffold was fabricated via 3D printing, where hydroxyapatite (HAP) and bone marrow mesenchymal stem cells (BMSCs) were added to mimic the composition of bone. The results showed that the blend of HAP and collagen showed suitable rheological performance for 3D extrusion printing and enhanced the composite scaffold's strength. The gelatin support bath could effectively support the HAP/collagen scaffold's dimension with designed patterns at room temperature. BMSCs in/on the scaffold kept living and proliferating, and there was a high alkaline phosphate expression. The printed collagen-based scaffold with biocompatibility, mechanical properties and bioactivity provides a new way for bone tissue engineering via 3D bioprinting.

Bioengineering Bone‐on‐a‐Chip Model Harnessing Osteoblastic and Osteoclastic Resolution

Organ‐on‐a‐chip (OoC) systems allow the generation of microphysiological tissue models that can recapitulate key biological processes in healthy and diseased states. OoC bone models provide valuable tools to study cross‐cellular interactions that take place in bone‐related processes. Although few bone‐on‐a‐chip models have been proposed, structural and biological hierarchy to establish a functional unit is often lacking. Herein, a functional OoC‐based 3D bone co‐culture model is reported. This model comprises a highly porous β‐tricalcium phosphate (TCP) based scaffold that is seeded with primary osteoblast and osteoclast precursors. This engineered construct is formed and cultured dynamically inside an OoC platform for up to 21 days and exhibits a dense extracellular matrix (ECM). Further, cultured constructs are ectopically implanted in C57BL/6 mice for 8 weeks, then histological and tartrate‐resistant acid phosphatase (TRAP) analyses are carried out. These results demonstrate that both bone deposition and resorption processes are present in the bioengineered model. This study also has implications for understanding complex cellular cross‐talks occurring in the bone remodeling process.

Size And Locomotor Ecology Have Differing Effects on the External and Internal Morphologies of Squirrel (Rodentia: Sciuridae) Limb Bones.

Mammals exhibit a diverse range of limb morphologies that are associated with different locomotor ecologies and structural mechanics. Much remains to be investigated, however, about the combined effects of locomotor modes and scaling on the external shape and structural properties of limb bones. Here, we used squirrels (Sciuridae) as a model clade to examine the effects of locomotor mode and scaling on the external shape and structure of the two major limb bones, the humerus and femur. We quantified humeral and femoral morphologies using 3D geometric morphometrics and bone structure analyses on a sample of 76 squirrel species across their four major ecotypes. We then used phylogenetic generalized linear models to test how locomotor ecology, size, and their interaction influenced morphological traits. We found that size and locomotor mode exhibit different relationships with the external shape and structure of the limb bones, and that these relationships differ between the humerus and femur. External shapes of the humerus and, to a lesser extent, the femur are best explained by locomotor ecology rather than by size, whereas structures of both bones are best explained by interactions between locomotor ecology and scaling. Interestingly, the statistical relationships between limb morphologies and ecotype were lost when accounting for phylogenetic relationships among species under Brownian motion. That assuming Brownian motion confounded these relationships is not surprising considering squirrel ecotypes are phylogenetically clustered; our results suggest that humeral and femoral variation partitioned early between clades and their ecomorphologies were maintained to the present. Overall, our results show how mechanical constraints, locomotor ecology, and evolutionary history may enact different pressures on the shape and structure of limb bones in mammals.

Level of Activity Changes Increases the Fatigue Life of the Porous Magnesium Scaffold, as Observed in Dynamic Immersion Tests, over Time

In the present study, the effects of human physiological activity levels on the fatigue life of a porous magnesium scaffold have been investigated. First, the dynamic immersion and biomechanical testing are carried out on a porous magnesium scaffold to simulate the physiological conditions. Then, a numerical data analysis and computer simulations predict the implant failure values. A 3D CAD bone scaffold model was used to predict the implant fatigue, based on the micro-tomographic images. This study uses a simulation of solid mechanics and fatigue, based on daily physiological activities, which include walking, running, and climbing stairs, with strains reaching 1000–3500 µm/mm. The porous magnesium scaffold with a porosity of 41% was put through immersion tests for 24, 48, and 72 h in a typical simulated body fluid. Longer immersion times resulted in increased fatigue, with cycles of failure (Nf) observed to decrease from 4.508 × 1022 to 2.286 × 1011 (1.9 × 1011 fold decrease) after 72 hours of immersion with a loading rate of 1000 µm/mm. Activities played an essential role in the rate of implant fatigue, such as demonstrated by the 1.1 × 105 fold increase in the Nf of walking versus stair climbing at 7.603 × 1011 versus 6.858 × 105, respectively. The dynamic immersion tests could establish data on activity levels when an implant fails over time. This information could provide a basis for more robust future implant designs.

ASD with high pelvic retroversion develop changes in their acetabular orientation during walking

IntroductionIt was hypothesized that pelvic retroversion in Adult Spinal Deformity (ASD) can be related to an increased hip loading explaining the occurrence of hip-spine syndrome. Research questionHow pelvic retroversion can modify acetabular orientation in ASD during walking? Methods89 primary ASD and 37 controls underwent 3D gait analysis and full-body biplanar X-rays. Classic spinopelvic parameters were calculated from 3D skeletal reconstructions in addition to acetabular anteversion, abduction, tilt, and coverage. Then, 3D bones were registered on each gait frame to compute the dynamic value of the radiographic parameters during walking. ASD patients having a high PT were grouped as ASD-highPT, otherwise as ASD-normPT. Control group was divided in: C-aged and C-young, age matched to ASD-hightPT and ASD-normPT respectively. Results25/89 patients were classified as ASD-highPT having a radiographic PT of 31° (vs 12° in other groups, p ​< ​0.001). On static radiograph, ASD-highPT showed more severe postural malalignment than the other groups: ODHA ​= ​5°, L1L5 ​= ​17°, SVA ​= ​57.4 ​mm (vs 2°, 48° and 5 ​mm resp. in other groups,all p ​< ​0.001). During gait, ASD-highPT presented a higher dynamic pelvic retroversion of 30° (vs 15° in C-aged), along with a higher acetabular anteversion of 24° (vs 20°), external coverage of 38° (vs 29°) and a lower anterior coverage of 52° (vs 58°,all p ​< ​0.05). ConclusionASD patients with severe pelvic retroversion showed an increased acetabular anteversion, external coverage and lower anterior coverage during gait. These changes in acetabular orientation, computed during walking, were shown to be related to hip osteoarthritis.

Personalized 3D printed bone scaffolds: A review.

3D printed bone scaffolds have the potential to replace autografts and allografts because of advantages such as unlimited supply and the ability to tailor the scaffolds' biochemical, biological and biophysical properties. Significant progress has been made over the past decade in additive manufacturing techniques to 3D print bone grafts, but challenges remain in the lack of manufacturing techniques that can recapitulate both mechanical and biological functions of native bones. The purpose of this review is to outline the recent progress and challenges of engineering an ideal synthetic bone scaffold and to provide suggestions for overcoming these challenges through bioinspiration, high-resolution 3D printing, and advanced modeling techniques. The article provides a short overview of the progress in developing the 3D printed scaffolds for the repair and regeneration of critical size bone defects. STATEMENT OF SIGNIFICANCE: Treatment of critical size bone defects is still a tremendous clinical challenge. To address this challenge, diverse sets of advanced manufacturing approaches and materials have been developed for bone tissue scaffolds. 3D printing has sparked much interest because it provides a close control over the scaffold's internal architecture and in turn its mechanical and biological properties. This article provides a critical overview of the relationships between material compositions, printing techniques, and properties of the scaffolds and discusses the current technical challenges facing their successful translation to the clinic. Bioinspiration, high-resolution printing, and advanced modeling techniques are discussed as future directions to address the current challenges.

Modification of hydroxyapatite (HA) powder by carboxymethyl chitosan (CMCS) for 3D printing bioceramic bone scaffolds

The poor mechanical properties of 3D printed HA bone scaffold is always a challenge in tissue engineering, to address this issue, carboxymethyl chitosan (CMCS) was proposed to modify HA bone scaffolds by a physical blending method in this research. A series of HA and HA/CMCS composite ceramic scaffolds were printed by using piezoelectric inkjet 3D printing technology, and their properties were investigated in terms of forming quality, structural morphology, mechanical properties, degradability, cytotoxicity, and cell adhesion growth. The results of forming quality and structural morphology show that with the increase of CMCS content, the forming quality of the samples deteriorated, the pore size and porosity increased. However, when the content of CMCS reached 5 wt%, obvious cracks appeared on the surface of the sample, and the forming quality was relatively poor. The mechanical testing results indicated the toughness of composites could be enhanced by incorporating CMCS into HA, which was attributed to the higher strength connections of the CMCS polymer network between HA particles and the stronger interaction between HA and CMCS molecules. FTIR spectra further revealed the strong hydrogen bonding interaction between CMCS and HA. Moreover, the degradation rate and mineralization ability of the sample increased with the content of CMCS, but the compressive strength during degradation increased with the CMCS content, indicating that incorporating CMCS into HA cannot only improve the mechanical property and biological activity of the scaffold but also makes up the defect of slow degradation of pure HA scaffold. Finally, the cytotoxicity, cell adhesion, and cell proliferation tests show that HA and HA/CMCS composite samples had good cytocompatibility, HA/CMCS sample with 3 wt% CMCS possessed the best bioactivity. In summary, HA/CMCS composite powder with 3 wt% CMCS content is the optimal matrix material for 3D printing bone scaffolds.

In vitro evaluation of granules obtained from 3D sphene scaffolds and bovine bone grafts: chemical and biological assays.

Sphene is an innovative bone graft material. The aim of this study was to investigate and compare the physicochemical and biological properties of Bio-Oss® (BO) and in-lab synthesized and processed sphene granules. BO granules of 1000-2000 μm (BO-L), 250-1000 μm (BO-S) and 100-200 μm (BO-p) for derived granules, and corresponding groups of sphene granules obtained from 3D printed blocks (SB-L, SB-S, SB-p) and foams (SF-L, SF-S and SF-p) were investigated. The following analyses were conducted: morphological analysis, specific surface area and porosity, inductively coupled plasma mass spectrometry (ICP-MS), cytotoxicity assay, Alizarin staining, bone-related gene expression, osteoblast migration and proliferation assays. All pulverized granules exhibited a similar morphology and SF-S resembled natural bone. Sphene-derived granules showed absence of micro- and mesopores and a low specific surface area. ICP-MS revealed a tendency for absorption of Ca and P for all BO samples, while sphene granules demonstrated a release of Ca. No cellular cytotoxicity was detected and osteoblastic phenotype in primary cells was observed, with significantly increased values for SF-L, SF-S, BO-L and BO-p. Further investigations are needed before clinical use can be considered.

Impacted bone allograft personalised by a novel 3D printed customization kit produces high surgical accuracy in medial opening wedge high tibial osteotomy: a pilot study

PurposeContemporary medial opening wedge high tibial osteotomy (MOWHTO) still seems to struggle with inconsistent accuracy outcomes. Our objective was to assess surgical accuracy and short-term clinical outcomes when using 3D planning and a patient-specific instrumentation (PSI) kit to prepare customized bone allografts.MethodsThirty subjects (age 48y ± 13) were included in a double-center prospective case series. A low-dose CT-scan was performed to generate 3D bone models, a MOWHTO was simulated, and PSI was designed and 3D printed based on the complementary negative of the planned osteotomy gap. Clinical outcome was assessed at two, four, 12 weeks and one year using NRS, KOOS, UCLA activity score, EQ-5D and anchor questions. A linear-mixed model approach was implemented for data analysis.ResultsPreoperative 3D values were 175.0° ± 2.2 mechanical tibiofemoral angle (mTFA), 85.0° ± 3.0 medial proximal tibial angle (MPTA), and 94.1° ± 3.4 medial posterior tibial slope (MPTS). Target planning ranged from slight varus to the lateral tibial spine (slight valgus). Postoperative 3D analysis showed an accuracy of 1.1° ± 0.7 ΔMPTA (p = 0.04) and 1.2° ± 1.2 ΔMPTS (p = 0.11). NRS decreased from baseline 6.1 ± 1.9 to 2.7 ± 1.9 at four weeks (p < 0.001) and 1.7 ± 1.9 at one year (p < 0.001). KOOS increased from 31.4 ± 17.6 to 50.6 ± 20.6 at 12 weeks (p < 0.001) and to 71.8 ± 15.6 at one year (p < 0.001).ConclusionThe study suggests that 3D printed instrumentation to personalize structural bone allograft is a viable alternative method in MOWHTO that has the benefit of optimizing surgical accuracy while providing early and consistent pain relief after surgery.

Different Surgical Techniques in the All-on-4 Treatment Concept: Evaluation of the Stress Distribution Created in Implant and Peripheral Bone with Finite Element Analysis.

To examine the stresses caused by different All-on-4 surgical techniques-conventional, a combination of monocortical and bicortical, bicortical, and nasal floor elevation-on the implant and the surrounding bone using 3D finite element analysis (FEA). A 3D bone model of the atrophic maxilla was created based on CT imaging of the fully edentulous adult patient. All implants used in the models were 4 mm in diameter, and the length was 13 mm in the anterior and 15 mm in the posterior. Implants were applied to four different atrophic maxillary models with the All-on-4 technique: anterior and posterior monocortical implants in the first model, anterior monocortical and posterior bicortical in the second model, anterior and posterior bicortical in the third model, and anterior and posterior bicortical with nasal floor elevation in the fourth model. Eight linear analyses were performed by applying force from both vertical and 45-degree oblique directions to the four models prepared in our study. When the cortical and cancellous bone around the anterior implants was examined, it was observed that the oblique and vertical loading conditions and the stresses around the implant were similar in all models. When the posterior implants were examined, model 1 (ie, anterior and posterior monocortical implants) showed the greatest oblique compression, vertical compression, and vertical tension forces. According to the Von Mises stress (VMS) analysis results for anterior and posterior implants, higher values were observed in model 1 compared to models 3 and 4 under oblique and vertical forces. It was observed that bicortical placement of the implants reduced the stresses on the bone and implant-abutment system but had no significant effect on the stress on the bar. According to the results of our study, in the All-on-4 technique, bicortical placement of the implants reduced the stresses on the bone and implant when the anatomical limitations allowed. In addition, nasal floor elevation can be applied in the atrophic maxilla in appropriate indications.

Influence of typographic biocomposite scaffold in facilitating biomineralization to progress complex hard tissue repair

Biomaterial modifications and scaffold fabrication methods in hard tissue engineering applications have seen enormous growth. However, clinical demand in treating and regenerating large bone defects is intricate, as current methods fail to meet requirements such as regenerating bone with optimal physical and mechanical properties in complex bone repair due to poor scaffold design and less bioactivity. To meet such clinical expectations, biomaterials are combined to create a 3D bone composite scaffold to improve the quality of the regenerated bone by improving bioactivity through biomineralization. To advance this process, accelerated and homogenous biomineralization is facilitated by the scaffold with increased surface area and active molecules to progress the repair of large bone defect. This facilitation of biomineralization leads to minerals deposition as a layer on the substrate when 3D-printed porous scaffolds made of biocomposite are exposed to body fluid at the repair site where the substrate degrades and releases active biomolecules. These released molecules crystallized evenly to form an apatite layer on the scaffold surface, where bone-forming cells attach, grow, and regenerate bone. Additionally, the formation of the apatite layer through biomineralization to repair lost structure is also governed by the following factors, which include macromolecules and an active site present between collagen molecules in the bone. In this review, we explore the advantages of biocomposite materials and 3D-printed scaffold design in accelerating biomineralization at the bone defect area to facilitate the formation of an apatite layer to progress complex hard tissue regeneration with optimal properties (1).

Synthesis and Characterization of Bromelain Enzyme/Poly (Vinyl Alcohol) as Potential Bone Scaffold

3D bone scaffold is the temporary constructs substrates that enable and activate the bonding and reproduction of osteoinductive cells that lead to the creation of new usable tissues. The objectives of this research study are to synthesize and fabricate bromelain/poly (vinyl alcohol) (PVA) porous substrates by using a lyophilization technique and study the properties of the scaffold subsequently. In this study, bromelain (1, 2 and 3 wt.%) and PVA (15 wt.%) solutions were prepared, then mixed overnight to get homogeneous solution. The solutions were frozen for 24 hours before being freeze-dried under vacuum for 7 days at -80 °C. Thereafter, the porous substrates were crosslinked by using glutaraldehyde and characterized using X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR). According to the XRD findings, PVA/bromelain scaffolds exhibits great degree of crystallinity at 21.11° and 41.05°. The FTIR results shows no significant effect on the absorption peak at varied concentration of bromelain in bromelain/PVA substrates. For the DSC result, the glass transition temperature was found in the range of 65 to 75 °C. For TGA curve, it was obvious that the temperatures of the weight loss regions gradually increased with the bromelain content, indicating that bromelain improves the stability of the bromelain/PVA membranes at high temperatures. Bromelain/PVA showed high porosity (&gt;75%), and water-swelling ratio within 50 to 150 percent after 24, 48, and 72 hours immersion period. This newly developed scaffold composition may serve as a foundation for the growth of bone tissue.

A Human Bone Marrow 3D Model to Investigate the Dynamics and Interactions Between Resident Cells in Physiological or Tumoral Contexts.

The medullary niche is a complex ecosystem that is essential to maintain homeostasis for resident cells. Indeed, the bone marrow, which includes a complex extracellular matrix and various cell types, such as mesenchymal stem cells, osteoblasts, and endothelial cells, is deeply involved in hematopoietic stem cell regulation through direct cell-cell interactions, as well as cytokine production. To closely mimic this in vivo structure and conduct experiments reflecting the responses of the human bone marrow, several 3D models have been created based on biomaterials, relying primarily on primary stromal cells. Here, a protocol is described to obtain a minimal and standardized system that is easy to set up and provides features of bone marrow-like structure, which combines different cell populations including endothelial cells, and reflects the heterogeneity of in vivo bone marrow tissue. This 3D bone marrow-like structure-assembled using calcium phosphate-based particles and human cell lines, representative of the bone marrow microenvironment-allows the monitoring of a wide variety of biological processes by combining or replacing different primary cell populations within the system. The final 3D structures can then either be harvested for image analysis after fixation, paraffin-embedding, and histological/immunohistochemical staining for cell localization within the system, or dissociated to collect each cellular component for molecular or functional characterization.

Maqui Berry and Ginseng Extracts Reduce Cigarette Smoke-Induced Cell Injury in a 3D Bone Co-Culture Model.

Cigarette smoking-induced oxidative stress has harmful effects on bone metabolism. Maqui berry extract (MBE) and ginseng extract (GE) are two naturally occurring antioxidants that have been shown to reduce oxidative stress. By using an osteoblast and osteoclast three-dimensional co-culture system, we investigated the effects of MBE and GE on bone cells exposed to cigarette smoke extract (CSE). The cell viability and function of the co-culture system were measured on day 14. Markers of bone cell differentiation and oxidative stress were evaluated at gene and protein levels on day 7. The results showed that exposure to CSE induced osteoporotic-like alterations in the co-culture system, while 1.5 µg/mL MBE and 50 µg/mL GE improved CSE-impaired osteoblast function and decreased CSE-induced osteoclast function. The molecular mechanism of MBE and GE in preventing CSE-induced bone cell damage is linked with the inhibition of the NF-κB signaling pathway and the activation of the Nrf2 signaling pathway. Therefore, MBE and GE can reduce CSE-induced detrimental effects on bone cells and, thus, prevent smoking-induced alterations in bone cell homeostasis. These two antioxidants are thus suitable supplements to support bone regeneration in smokers.