Human Bone Research Articles

Morphometric analysis of proximal femur in Indian population and its implications in Total Hip Arthroplasty

Geometric understanding of the proximal end of femur is significant for functional bipedal erect posture and in pre-operative planning of osteotomy as well as the design and development of implants for THA. Moreover, the anthropological parameters of any bone are determined by genetic and environmental factors such as age, race, gender and lifestyle and this leads to racial variations in the morphological parameters of proximal end of femur owing to lifestyle, physique, applied force and their distribution in India population.The current study was designed to study and compare the morphology of proximal end of femur in Indian population and was conducted on 94 dry human cadaveric bones of unknown age and sex to determine the morphology of the proximal end of femur. We observed the Femur Length as 426.6 ± 15.82 mm, Femur Neck Length as 3.455 ± 0.378 mm and Neck Shaft Angle as 125.27 ± 2.54° amongst other parameters.The findings also revealed significant variations in the morphological parameters among different populations, emphasizing the importance of considering racial diversity in the design and selection of implants for THA for improving the success and longevity of hip arthroplasty procedures.

A phase I/II clinical trial of ex-vivo expanded human bone marrow derived allogeneic mesenchymal stromal cells in adult patients with perianal fistulizing Crohn’s Disease

BackgroundPerianal fistulas (PF) affect one-third patients with Crohn’s disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population.MethodsAn open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn’s disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with < 2 cm perianal collection on MRI, and fistula response was decrease in drainage by ≥ 50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model.ResultsTen patients (male:8, mean age:27.4 ± 12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index (P = 0.008), Van Assche Index (P = 0.008) and improvement in quality-of-life (P = 0.001) were observed over time.ConclusionsAllogeneic BMSCs are safe and effective for the treatment of perianal fistulizing CD with significant improvement in clinical severity and radiological healing.Trial registrationThe study was prospectively registered on Clinical trials registry – India (CTRI), CTRI/2020/01/022743 on 14 January 2020, http://ctri.nic.in.

GAGE-seq concurrently profiles multiscale 3D genome organization and gene expression in single cells.

The organization of mammalian genomes features a complex, multiscale three-dimensional (3D) architecture, whose functional significance remains elusive because of limited single-cell technologies that can concurrently profile genome organization and transcriptional activities. Here, we introduce genome architecture and gene expression by sequencing (GAGE-seq), a scalable, robust single-cell co-assay measuring 3D genome structure and transcriptome simultaneously within the same cell. Applied to mouse brain cortex and human bone marrow CD34+ cells, GAGE-seq characterized the intricate relationships between 3D genome and gene expression, showing that multiscale 3D genome features inform cell-type-specific gene expression and link regulatory elements to target genes. Integration with spatial transcriptomic data revealed in situ 3D genome variations in mouse cortex. Observations in human hematopoiesis unveiled discordant changes between 3D genome organization and gene expression, underscoring a complex, temporal interplay at the single-cell level. GAGE-seq provides a powerful, cost-effective approach for exploring genome structure and gene expression relationships at the single-cell level across diverse biological contexts.

From Data to Design: Constructing Scapula and Hip Bone Through Online Datasets, Open-Source Software and 3D Printers.

Introduction Human skeletons and bones are essential for medical and allied sciences students. Nowadays, it is becoming challenging to procure bone legally, resulting in medical students' inadequacy of bone. Plaster-of-Paris or resin bone models sold on the market are less detailed than real bones. Aims and objectives This study aims to create a three-dimensional (3D)-printed human bone model with free, open-source software and fused deposition modelling (FDM) 3D printers, compare its accuracy with the original bones and validate it with a textbook description. Methods Scapula and hip bone models were produced using open-source software 3D Slicer from computed tomography (CT) data from the "New Mexico Decedent Image Database". After automated segmentation, bones were edited manually with tools in a 3D Slicer(https://www.slicer.org/) and Meshmixer software(Autodesk Inc., San Rafael, California, United States) and 3D bone models were printed using polylactic (PLA) filament. Results and discussions 3Ddigital models of both bones were successfully created with the maximum possible accuracy with an FDM 3D printer. A 3D digital replica of the scapula obtained after segmentation retained most anatomical features except for the glenoid cavity, as the head of the humerus obscured the glenoid cavity. The 3D digital skeleton of the hip bone retained all anatomical features except articulating surfaces, such as the acetabulum and auricular surface ilium, which were obscured by the head of the femur and sacrum. A few morphological features of both bones differed from the original dry bone, and a few finer details were unclear in the iliac fossa and ischium. After manual editing and post-processing, the final physical model obtained has all the features. Conclusions We conclude that it is possible to produce anatomically accurate models with the greatest possible resemblance and accuracy to the original bones using free and open-source data with an FDM 3D printer.

Chondrosarcoma evaluation using hematein-based x-ray staining and high-resolution 3D micro-CT: a feasibility study

BackgroundChondrosarcomas are rare malignant bone tumors diagnosed by analyzing radiological images and histology of tissue biopsies and evaluating features such as matrix calcification, cortical destruction, trabecular penetration, and tumor cell entrapment.MethodsWe retrospectively analyzed 16 cartilaginous tumor tissue samples from three patients (51-, 54-, and 70-year-old) diagnosed with a dedifferentiated chondrosarcoma at the femur, a moderately differentiated chondrosarcoma in the pelvis, and a predominantly moderately differentiated chondrosarcoma at the scapula, respectively. We combined a hematein-based x-ray staining with high-resolution three-dimensional (3D) microscopic x-ray computed tomography (micro-CT) for nondestructive 3D tumor assessment and tumor margin evaluation.ResultsWe detected trabecular entrapment on 3D micro-CT images and followed bone destruction throughout the volume. In addition to staining cell nuclei, hematein-based staining also improved the visualization of the tumor matrix, allowing for the distinction between the tumor and the bone marrow cavity. The hematein-based staining did not interfere with further conventional histology. There was a 5.97 ± 7.17% difference between the relative tumor area measured using micro-CT and histopathology (p = 0.806) (Pearson correlation coefficient r = 0.92, p = 0.009). Signal intensity in the tumor matrix (4.85 ± 2.94) was significantly higher in the stained samples compared to the unstained counterparts (1.92 ± 0.11, p = 0.002).ConclusionsUsing nondestructive 3D micro-CT, the simultaneous visualization of radiological and histopathological features is feasible.Relevance statement3D micro-CT data supports modern radiological and histopathological investigations of human bone tumor specimens. It has the potential for being an integrative part of clinical preoperative diagnostics.Key points• Matrix calcifications are a relevant diagnostic feature of bone tumors.• Micro-CT detects all clinically diagnostic relevant features of x-ray-stained chondrosarcoma.• Micro-CT has the potential to be an integrative part of clinical diagnostics.Graphical

An Advanced Human Bone Tissue Culture Model for the Assessment of Implant Osteointegration In Vitro

An Advanced Human Bone Tissue Culture Model for the Assessment of Implant Osteointegration In Vitro

An Innovative Design to Enhance Osteoinductive Efficacy and Biomechanical Behavior of a Titanium Dental Implant

The present study investigated the in vivo bone-forming efficacy of an innovative titanium (Ti) dental implant combined with a collagen sponge containing recombinant human bone morphogenetic protein-2 (BMP-2) in a pig model. Two different concentrations of BMP-2 (20 and 40 µg/mL) were incorporated into collagen sponges and placed at the bottom of Ti dental implants. The investigated implants were inserted into the edentulous ridge at the canine–premolar regions of Lanyu small-ear pigs, which were then euthanized at weeks 1, 2, 4, 8, and 12 post-implantation. Specimens containing the implants and surrounding bone tissue were collected for histological evaluation of their bone-to-implant contact (BIC) ratios and calculation of maximum torques using removal torque measurement. Analytical results showed that the control and BMP-2-loaded implants presented good implant stability and bone healing for all testing durations. After 1 week of healing, the BMP-2-loaded implants with a concentration of 20 µg/mL exhibited the highest BIC ratios, ranging from 58% to 76%, among all groups (p = 0.034). Additionally, they also possessed the highest removal torque values (50.1 ± 1.3 N-cm) throughout the 8-week healing period. The BMP-2-loaded implants not only displayed excellent in vivo biocompatibility but also presented superior osteoinductive performance. Therefore, these findings demonstrate that BMP-2 delivered through a collagen sponge can potentially enhance the early-stage osseointegration of Ti dental implants.

Vasoactive intestinal peptide exerts an osteoinductive effect in human mesenchymal stem cells.

Several neuropeptides present in bone tissues, produced by nerve fibers and bone cells, have been reported to play a role in regulating the fine-tuning of osteoblast and osteoclast functions to maintain bone homeostasis. This study aims to characterize the influence of the neuropeptide vasoactive intestinal peptide (VIP) on the differentiation process of human mesenchymal stem cells (MSCs) into osteoblasts and on their anabolic function. We describe the mRNA and protein expression profile of VIP and its receptors in MSCs as they differentiate into osteoblasts, suggesting the presence of an autocrine signaling pathway in these cells. Our findings reveal that VIP enhances the expression of early osteoblast markers in MSCs under osteogenic differentiation and favors both bone matrix formation and proper cytoskeletal reorganization. Finally, our data suggest that VIP could be exerting a direct modulatory role on the osteoblast to osteoclast signaling by downregulating the receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio. These results highlight the potential of VIP as an osteoinductive differentiation factor, emerging as a key molecule in the maintenance of human bone homeostasis.

Effect of plate orientation on apparent thickness of mineral plates by transmission electron microscopy.

Transmission electron microscopy (TEM) is widely used to study the ultrastructure of bone. The mineral of bone occurs as polycrystalline mineral plates about 3 to 6 nm in thickness. A problem in using TEM to make quantitative analyses of bone is that the orientation of the plates with respect to the plane of the section being imaged is expected to affect their apparent thickness. The purpose of this study was to test if this was true, if the apparent thickness of plates changed substantially as a result of tilt of the section. We prepared TEM sections of samples of cortical human bone by ion beam milling, orienting one section parallel to the collagen fibril axes and one perpendicular to them. We obtained TEM bright field and HAADF images of these sections, tilting the sections up to ± 20° at 2° intervals and measuring the apparent thickness of individual mineral platelets at each angle of tilt. Thickness appears to double as section is tilted ± 20°. True thickness of plates is determined by tilting the section along an axis parallel to the plate orientation and determining the minimum apparent thickness. However, as plates are tilted away from minimum-thickness orientation, they become less well-resolved, disappearing when tilted more than 20°. We therefore also measured apparent thickness of only the darkest (most electron scattering) plate images in an untilted section and obtained the same average thickness as that obtained by tilting. We conclude that tilting of the section is not necessary to obtain an accurate measurement of the thickness of mineral plates.

A new laboratory‐based method to experimentally induce diagenetic modifications in human bone tissue using archaeological gravesoils

AbstractThe conditions of the burial environment trigger microstructural modifications and physical‐chemical changes in the bone, such as chemical dissolution, increase of crystallinity, chemical exchanges, collagen degradation and changes in porosity, hence to reproduce these patterns is a challenging task. This work presents a new method to accelerate the diagenetic processes in the laboratory. Artificial aging is obtained by immersion at 80°C in “enriched” solutions derived from the leaching of gravesoils, maintaining the same pH, for 1 month, on modern bones collected from an autopsy. Two distinct solutions from two graves of the necropolis of Travo (IT) (7th–8th century AD) were adopted. The induced damage patterns, on the bone microstructure and the organo‐mineral fraction, have been compared with those observed on buried skeletal elements from the same graves, by providing a multi‐analytical approach (BSE‐SEM, EMPA, FT‐IR, MP‐AES). Bioapatite parameters, such as crystallinity index and Ca/P molar ratio, evolved similarly and, in some cases, reached the same values of buried bones. Conversely, in the absence of microbial activity, the organic fraction better survived the artificial aging. For the same reason, the porosity due to bioerosion was absent in the artificially aged samples, whereas the biological pores and the post‐mortem fractures exhibited the same histomorphology. It is believed that the opportunity of reproducing the diagenetic changes by replicating the chemical environment of the burial site at the laboratory scale is of great interest to forensic science and archaeology (e.g., to reconstruct the burial environment).

MiR-26b-5p/TET3 regulates the osteogenic differentiation of human bone mesenchymal stem cells and bone reconstruction in female rats with calvarial defects

MiR-26b-5p/TET3 regulates the osteogenic differentiation of human bone mesenchymal stem cells and bone reconstruction in female rats with calvarial defects

Life histories in Fiji as reconstructed from first millennium CE Sigatoka Sand Dune burials using isotopes

This paper aims to re-examine the dietary practices of individuals buried at Sigatoka Sand Dunes site (Fiji) in Burial Ground 1 excavated by Simon Best in 1987 and 1988 using two approaches and a reassessment of their archaeological, bioarchaeological and chronological frame. First, stable carbon and nitrogen isotope analysis was applied to document dietary changes between childhood and adulthood using an intra–individual approach on paired bone–tooth. Second, the potential adaptation of the individuals to their environment was evaluated through regional and temporal comparisons using inter–individual bone analysis. Ten AMS radiocarbon dates were measured directly on human bone collagen samples, placing the series in a range of approximately 600 years covering the middle of the first millennium CE (1,888 to 1,272 cal BP). δ13C and δ15N ratios were measured on bone and tooth collagen samples from 38 adult individuals. The results show that δ15N values from tooth are higher than those s from bone while bone and tooth δ13C values are similar, except for females. Fifteen individuals were included in an intra–individual analysis based on paired bone and tooth samples, which revealed six dietary patterns distinguished by a differential dietary intake of marine resources and resources at different trophic levels. These highlight sex–specific differences not related to mortuary practices but to daily life activities, supporting the hypothesis of a sexual division of labour. Compared to other Southwest Pacific series, Sigatoka diets show a specific trend towards marine food consumption that supports the hypothesis of a relative food self–sufficiency requiring no interactions with other groups.

Progress in the Optimization of Compositional Design and Thermomechanical Processing of Metastable β Ti Alloys for Biomedical Applications.

Over the past few years, significant research and development in the manufacturing industry related to the medical field has been done. The aim has been to improve existing biomaterials and bioimplants by exploring new methods and strategies. Beta titanium alloys, known for their exceptional strength-to-modulus ratio, corrosion resistance, biocompatibility, and ease of shaping, are expected to play a crucial role in manufacturing the next generation of biomedical equipment. To meet the specific requirements of human bone, researchers have employed key techniques like compositional design and thermomechanical processing routes to advance biomaterial development. These materials find extensive applications in orthopedic, orthodontic, and cardiovascular biomedical implants. Several studies have shown that precise material composition, with appropriate heat treatment and suitable mechanical approaches, can yield the desired mechanical properties for bone implants. In this review article, we explore the evolution of alloys at different stages, with a particular focus on their preparation for use in biomedical implants. The primary focus is on designing low-modulus β Ti alloy compositions and employing processing techniques to achieve high strength while maintaining a low young modulus suitable for biomedical applications.

The Species Effect: Differential Sphingosine-1-Phosphate Responses in the Bone in Human Versus Mouse

The deterioration of osteoblast-led bone formation and the upregulation of osteoclast-regulated bone resorption are the primary causes of bone diseases, including osteoporosis. Numerous circulating factors play a role in bone homeostasis by regulating osteoblast and osteoclast activity, including the sphingolipid—sphingosine-1-phosphate (S1P). However, to date no comprehensive studies have investigated the impact of S1P activity on human and murine osteoblasts and osteoclasts. We observed species-specific responses to S1P in both osteoblasts and osteoclasts, where S1P stimulated human osteoblast mineralisation and reduced human pre-osteoclast differentiation and mineral resorption, thereby favouring bone formation. The opposite was true for murine osteoblasts and osteoclasts, resulting in more mineral resorption and less mineral deposition. Species-specific differences in osteoblast responses to S1P were potentially explained by differential expression of S1P receptor 1. By contrast, human and murine osteoclasts expressed comparable levels of S1P receptors but showed differential expression patterns of the two sphingosine kinase enzymes responsible for S1P production. Ultimately, we reveal that murine models may not accurately represent how human bone cells will respond to S1P, and thus are not a suitable model for exploring S1P physiology or potential therapeutic agents.

COMPLETE AND INCOMPLETE BONY BRIDGES NEAR FORAMEN OVALE WITH POTENTIAL SURGICAL AND CLINICAL IMPLICATIONS

Objectives: Pterygospinous or Pterygoalar ligaments may pose mandibular nerve compression by when present near foramen ovale. The presence of ossified pterygospinous or pterygoalar ligaments might cause trouble to surgeons in performing percutaneous rhizotomy for trigeminal neuralgia, electroencephalographic procedures, or taking biopsy from cavernous sinus tumors. The present study aims to find the incidence and specific morphological variations related to the ossification of pterygospinous and pterygoalar ligaments. Methods: The study was conducted on 200 dried adult human cadaveric skull of unknown age and sex in the department of Anatomy, Mahatma Gandhi Medical College and Hospital, Jaipur. Skulls were obtained from different medical colleges of the Rajasthan region. The study included fully dried, intact, adult human skull bones with no structural defects. Damaged, fractured, skull with the developmental anomaly, injured or pathologically malformed skull especially at or near the foramen ovale on either side were excluded from the study. Ossification of pterygospinous and pterygoalar bar was studied on both sides. Statistical analyses were performed using SPSS Version 26 software. Results: Ossified ligaments were studied in 400 sides of 200 skulls. The ossification of pterygospinous bar was observed in 53 cases (13.25%). The pterygospinous bar was complete in twelve (3%) cases and incomplete in 41 cases (10.25%). The ossified pterygoalar ligament was observed in 62 cases (15.5%). Ossification was complete in 15 cases (3.75%) and incomplete in 47 cases (11.75%). Conclusion: Ossification of pterygospinous and pterygoalar bars was observed in skulls obtained from medical colleges in the Rajasthan region. Knowledge of such morphological variations of the skull base will improve the therapeutic outcomes in the treatment of trigeminal neuralgia.

Microfluidic Platforms to Screen Granular Hydrogel Microenvironments for Tissue Regeneration

AbstractGranular hydrogels have emerged as a promising class of biomaterials in medical research, enabling independent control of matrix stiffness within a porous biomaterial. Such microgel packings comprise interconnected pores and high surface‐to‐volume ratios. These features facilitate cell viability and nutrient diffusion, which are critical in enabling tissue regeneration. Despite the current interest in granular hydrogels for tissue engineering applications, only a few in vitro platforms are used to investigate cell interactions, limiting their design, and translation. In this study, microfluidic platforms able to reproducibly confine and immobilize microgels without the need for secondary cross‐linking are developed. Protocols are established for the generation of human bone marrow‐derived mesenchymal stem/stromal cells (hBM‐MSC)‐infiltrated microporous substrates and early‐time responses of cells to their environment are studied. Further, a tissue invasion assay is established, where cells infiltrate granular materials at different rates depending on growth factor presence or material properties. This platform is compatible with a range of different granular materials, and it is envisioned to have significant utility as a pre‐clinical tool for the rational design of materials for tissue healing applications.

Correlation between positron annihilation lifetime and photoluminescence measurements for calcined Hydroxyapatite

Hydroxyapatite (HAp) Ca10(PO4)6(OH)2 is a compound that has stable chemical properties, composition, and an affinity for human bone. As a result, it can be used in odontology, cancer treatment, and orthopedic grafts to repair damaged bone. To produce calcined HAp at 600 °C with different pH values, a wet chemical precipitation method was employed. All synthesized HAp samples were characterized by X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), photoluminescence (PL), Zeta potential, and positron annihilation lifetime spectroscopy (PALS). The XRD results revealed that all calcined HAp samples were formed in a hexagonal structure with a preferred (002) orientation at different pH values. The crystal size of the samples was determined using the Scherrer equation, which ranged from 16 to 25 nm. The SEM and TEM results showed that the morphology of the samples varied from nanorods to nanospheres and rice-like structures depending on the pH value of the sample. The PL measurements indicated that the blue and green emission peaks of HAp were due to defects (bulk, surface, and interface) in the samples, which created additional energy levels within the band gap. According to Zeta potential measurements, the charge carrier changed from a positive to negative value, ranging from 3.94 mV to − 2.95 mV. PALS was used to understand the relationship between the defects and the photoluminescence (PL) properties of HAp. Our results suggest that HAp nanoparticles have excellent potential for developing non-toxic biomedical and optical devices for phototherapy.

Fractal Analysis of Trabecular Alveolar Bone with Intrabony and Furcation Defects Using Periapical Dental Radiographs

Objective: Fractal analysis (FA) is a non-invasive method that quantitatively measures complex patterned geometric structures present throughout the image. Trabecular morphology of the alveolar bone and the changes occurring in the trabeculae in case of periodontitis can be detected with this method. To examine the periodontal defects in human skull bones using the FA, to compare them with healthy alveolar bone regions. Methods: Furcation and intrabony defects were artificially created in the mandible alveolar bones (n:24). Periapical X-ray images of alveolar bone regions containing teeth with defects were taken using the parallel technique. Fractal analysis was performed by box-counting method using Image J software on images from areas containing healthy and defective trabecular bone. Results: No statistically significant difference was found between the fractal values of healthy tissue and bifurcation defetcs and between the healthy tissue and intrabony defects (p&gt;0.05). Conclusion: Many factors may have affected the outcomes; patient selection, imaging methods, sample size, Region of interest (ROI) selection-location and size, individual and anatomical variations. These variables need to be standardized as much as possible and the limitations of the method need to be improved.

Friction and Wear Behavior of Selective Laser Melted Ti6Al4V-Equine Bone Nanocomposites

Ti6Al4V is commonly used in implants because of its excellent mechanical properties, corrosion resistance, and biocompatibility. While Hydroxyapatite (HAp) is typically used for strong biological bonding between Ti6Al4V implants and bone tissue, this study takes a different approach by incorporating Equine Bone (EB), which has a chemical structure similar to human bone tissue, as a substitute for HAp. In this study, to develop implant materials with a low elastic modulus, high strength, and excellent wear resistance, Ti6Al4V used in biomedical applications was combined with natural EB. Subsequently, a Ti6Al4V-0.05EB composite was fabricated using ball milling followed by Selective Laser Melting (SLM). SLM can reproduce even the interior of a 3D structure, so various studies are being conducted to apply it as a biomaterial. However, Ti6Al4V alloys produced by SLM are known to have low ductility due to localized heat gradients, rapid solidification, and cooling rates. This reduced ductility can result in decreased formability of biomaterials, and the high elastic modulus may lead to stress shielding phenomena, potentially reducing the lifespan of the biomaterial. To minimize this, a post-heat treatment was applied to the Ti6Al4V-0.05EB composite material manufactured by SLM. Afterwards, the microstructure, mechanical properties, and wear resistance, which are important in biomaterials, were evaluated.

Establishment of human hematopoietic organoids for evaluation of hematopoietic injury and regeneration effect

BackgroundHuman hematopoietic organoids have a wide application value for modeling human bone marrow diseases, such as acute hematopoietic radiation injury. However, the manufacturing of human hematopoietic organoids is an unaddressed challenge because of the complexity of hematopoietic tissues.MethodsTo manufacture hematopoietic organoids, we obtained CD34+ hematopoietic stem and progenitor cells (HSPCs) from human embryonic stem cells (hESCs) using stepwise induction and immunomagnetic bead-sorting. We then mixed these CD34+ HSPCs with niche-related cells in Gelatin-methacryloyl (GelMA) to form a three-dimensional (3D) hematopoietic organoid. Additionally, we investigated the effects of radiation damage and response to granulocyte colony-stimulating factor (G-CSF) in hematopoietic organoids.ResultsThe GelMA hydrogel maintained the undifferentiated state of hESCs-derived HSPCs by reducing intracellular reactive oxygen species (ROS) levels. The established hematopoietic organoids in GelMA with niche-related cells were composed of HSPCs and multilineage blood cells and demonstrated the adherence of hematopoietic cells to niche cells. Notably, these hematopoietic organoids exhibited radiation-induced hematopoietic cell injury effect, including increased intracellular ROS levels, γ-H2AX positive cell percentages, and hematopoietic cell apoptosis percentages. Moreover, G-CSF supplementation in the culture medium significantly improved the survival of HSPCs and enhanced myeloid cell regeneration in these hematopoietic organoids after radiation.ConclusionsThese findings substantiate the successful manufacture of a preliminary 3D hematopoietic organoid from hESCs-derived HSPCs, which was utilized for modeling hematopoietic radiation injury and assessing the radiation-mitigating effects of G-CSF in vitro. Our study provides opportunities to further aid in the standard and scalable production of hematopoietic organoids for disease modeling and drug testing.