Mature Bone Research Articles

Static magnetic field enhances the bone remodelling capacity of human demineralized bone matrix in a rat animal model of cranial bone defects.

The regeneration of bone defects that exceed 2 cm is a challenge for the human body, necessitating interventional therapies. Demineralized bone matrices (DBM) derived from biological tissues have been employed for bone regeneration and possess notable osteoinductive and osteoconductive characteristics. Nevertheless, their efficiency in regenerating critically sized injuries is limited, and therefore additional signaling cues are required. Thanks to the piezoelectric properties of the bone, external physical stimulation is shown to accelerate tissue healing. We have implanted human DBM in critically sized cranial bone defects in rat animal models and exposed them to an external magnetic field (1 T) to enhance endogenous bone formation. Our in vitro experiments showed the superior cytocompatibility of DBM compared to cell culture plates. Furthermore, alkaline phosphatase activity after 14 days and Alizarin red staining at 28 days demonstrated differentiation of rat bone marrow mesenchymal stem cells into bone lineage on DBM. Computer tomography images together with histological analyses showed that implanting DBM in the injured rats significantly enhanced bone regeneration. Notably, combining DBM transplantation with a 2 h daily exposure to a 1 T magnetic field for 2 weeks (day 7 to 21 post-surgery) significantly improved bone regeneration compared to DBM transplantation alone. This research indicates that utilizing external magnetic stimulation significantly enhances the potential of bone allografts to regenerate critically sized bone defects.

Can silver nanoparticles stabilized by Fenugreek (Trigonella foenm -graecum) improve tibial bone defects repair in rabbits? A preliminary study

Background: A fracture is considered a medical emergency leading to considerable complications. Aim: This study aimed to describe the accelerating action of Ag-NPs-FG on fracture healing in rabbits. Methods: AgNPs were reduced with FG, loaded into a starch gel base, and investigated for their morphology, size, and charge. Four equal groups were randomly formed of 40 adult male rabbits. A 3.5 mm diameter bone defect was created at the proximal metaphysis the right tibia in each rabbit. Groups 1 to 4 were injected with placebo saline, AgNPs-FG, plain gel, and FG-gel at the bone defect zone, respectively. The healing was assessed for 8 weeks postoperatively based on the radiographic, bone turnover markers, and histopathological examinations. Results: The AgNPs-FG was obtained as a faint reddish color, spherical in shape, with an absorbance of 423 nm, a size of 118.0±1.7 nm, and a surface charge of -7.8±0.518 mV. The prepared AgNPs-FG hydrogel was clear, translucent, and homogenous. The pH values were 6.55-6.5±0.2, the viscosity of 4000 and 1875 cPs, and spreadability of 1.6±0.14 and 2.0±0.15 for both FG and AgNPs-FG hydrogel, respectively. Radiographic union scale was significantly (p<0.05) improved in group 2 with significant (P < 0.05) increase of bone turnover markers was found in comparison to other treated groups. Histopathological examination revealed the formation of mature bone on the 28th postoperative day in groups 2 and 4. Conclusion: Colloidal nano-formulation of AgNPs-FG loaded hydrogel could be a promising formulation to accelerate rabbits' tibial bone healing process.

Composite bone graft of CaO-MgO-SiO2 glass-ceramics and CaSO4 ceramics for boosting bone formation rate.

This study develops a composite bone graft of CaO-MgO-SiO2 glass-ceramic and CaSO4 [abbreviated as (CMS)3-x(CS)x] via the sponge replication technique with weight fractions of x = 0, 1, 1.5, 2, and 3. The (CMS)1.5(CS)1.5 composite displays a superior degradability and, a suitable compressive strength of ∼3 MPa, and excellent cell proliferation and differentiation. The in vivo rat femur test in the hybrid-pore (CMS)1.5(CS)1.5 composite granules achieves a higher rate of bone formation, which is ∼2.7 times better than that of the commercial HAP/β-TCP at 12 weeks. Improved expressions of osteocyte and mature osteocyte marker genes, namely (Spp1, Dmp1, and Fgf23), were observed in the (CMS)1.5(CS)1.5 group, indicating a faster differentiation into mature bone tissue. The ions release of (CMS)1.5(CS)1.5 through the ERK1/2 signaling pathway promotes osteogenic differentiation. The high bone generation rate can be attributed to faster active ions release and modified surface topography. This work highlights an excellent bone graft candidate for clinical applications in orthopedic surgery.

Highly disordered and resorbable lithiated nanoparticles with osteogenic and angiogenic properties.

In this study, we have developed unique bioresorbable lithiated nanoparticles (LiCP, d50 = 20 nm), demonstrating a versatile material for bone repair and regeneration applications. The LiCPs are biocompatible even at the highest concentration tested (1000 μg mL-1) where bone marrow derived mesenchymal stem cells (BM-MSCs) maintained over 90% viability compared to the control. Notably, LiCP significantly enhanced the expression of osteogenic and angiogenic markers in vitro; collagen I, Runx2, angiogenin, and EGF increased by 8-fold, 8-fold, 9-fold, and 7.5-fold, respectively. Additionally, LiCP facilitated a marked improvement in tubulogenesis in endothelial cells across all tested concentrations. Remarkably, in an ectopic mouse model, LiCP induced mature bone formation, outperforming both the control group and non-lithiated nanoparticles. These findings establish lithiated nanoparticles as a highly promising material for advancing bone repair and regeneration therapies, offering dual benefits in osteogenesis and angiogenesis. The results lay the groundwork for future studies and potential clinical applications, where precise modulation of lithium release could tailor therapeutic outcomes to meet specific patient needs in bone and vascular tissue engineering.

Clinical case of bilateral rapidly progressive osteoma of the choroid

Choroidal osteoma is a benign neoplasm characterized by the appearance of mature bone tissues at the level of the choroid and unilateral development. This study highlights a clinical case of bilateral rapidly progressing osteoma of the choroid in a child, which was complicated by tumor decalcification and choroidal neovascularization. A 14-year-old male teen has been under observation in the S. Fyodorov Eye Microsurgery Federal State Institution, Saint-Petersburg branch since 2019, for bilateral choroidal osteoma. At the initial visit, a yellow-orange lesion with clear boundaries was noted in the left eye, localized at the level of the choroid and parapapillary, and had a trabecular bone structure. Based on the clinical picture and data from instrumental studies (ultrasound and optical coherence tomography), he was diagnosed with choroidal osteoma. During observation, a similar lesion appeared in the right eye, and its relatively rapid growth was observed in both eyes. Owing to the absence of zones of decalcification and neovascularization, further follow-up was initiated. However, in the presence of zones of decalcification of the bone tissue and newly formed vessels of the choroid, a threefold intravitreal injection of an angiogenesis inhibitor was performed. Consequently, regression of choroidal neovascularization was observed. Speculatively, the main reason for the atypical disease course in this teenager is the specificity of bone tissue development in childhood and adolescence.

Hybrid implants based on calcium-magnesium silicate ceramic diopside as a carrier of recombinant BMP-2 and demineralized bone matrix as a scaffold: ectopic osteogenesis in intramuscular implantation in mice

High efficiency of hybrid implants based on calcium-magnesium silicate ceramic diopside as a carrier of recombinant BMP-2 and xenogenic demineralized bone matrix (DBM) as a scaffold for bone tissue regeneration was demonstrated previously on the model of critical size cranial defects in mice. In order to investigate the possibility of using these implants for growing autologous bone tissue using the in vivo bioreactor principle in the patient’s own body, the effectiveness of the ectopic osteogenesis induced by them in intramuscular implantation in mice was studied. At 7 µg dose of BMP-2 per implant, after 1 week we observed a dense agglomeration of cells, probably skeletal muscle satellite precursor cells, with areas of intense chondrogenesis, the initial stage of indirect osteogenesis, around the implants. After 12 weeks, a dense bone capsule of trabecular structure was formed, covered with periosteum, with mature bone marrow located in the spaces between the trabeculae. The capsule volume was about 8-10 times the volume of the original implant. There were practically no signs of inflammation and foreign body reaction. Microcomputer tomography data showed a significant increase of the relative bone volume, number of trabeculae and bone tissue density in the group with BMP-2 in comparison with the group without BMP-2. Considering that DBM can be obtained in practically unlimited quantities, of the required size and shape, and the BMP-2 used, which is obtained by synthesis in E. coli cells, is relatively inexpensive, further development of the in vivo bioreactor model based on hybrid implants from BMP-2, diopside and xenogenic DBM seems promising.

Bone defect management with tissue-engineered constructs based on deproteinized cancellous bone: an experimental study

Background Management of bone defects with autologous bone grafting has always been the "gold standard" but it is not always possible to use it for a number of reasons. Preprocessed materials of biological and non-biological origin were developed as an alternative. A new branch of these materials is tissue-engineered constructs that fully imitate autologous bone in required volume.Aim is to study in vivo the possibility of using deproteinized human cancellous bone tissue as a matrix for creating tissue-engineered constructs.Methods The study was carried out on 24 NZW line rabbits, since this line has a fully characterized stromal-vascular fraction formula (SVF). The study design included 3 groups. First group (control) had surgical modeling of bone defects in the diaphysis of the contralateral femur without reconstruction; Group 2 had bone defect reconstruction using fragments of a deproteinized cancellous bone graft; group 3 underwent bone defect reconstruction using fragments of deproteinized cancellous bone matrix along with the autologous adipose tissue SVF (obtained according to ACP SVF technology). Animals were sacrificed with ether anesthesia at 2, 4 and 6 weeks after the operation and subsequent histological study followed.Result During all periods of the study, the newly formed bone tissue volume density in the 3rd group (reconstruction with deproteinized human cancellous bone + stromal-vascular fraction) was 1.78 times higher (p < 0.001) than in the first group (bone defect without reconstruction), 1.21 times higher (p < 0.001) than in the 2nd group (reconstruction with deproteinized cancellous bone alone). The dynamics of changes in the mature bone tissue volume density was similar to those of the newly formed bone tissue.Discussion The comparative analysis of reparative processes using a tissue engeneered construst based on deproteinized cancellous human bone with adipose tissue stromal vascular fraction revealed that the use of these bone substitute materials contributes not only to the early activation of reparative regeneration of the main structural elements of bone tissue at the site of bone defect, but also their timely differentiation.Conclusion The use of deproteinized cancellous bone matrix combined with stromal-vascular fraction to create a tissue-engineered construct could unleash several regeneration mechanisms and accelerate the process of bone defect site repair, compared with 1st and 2nd group of study.

Enhanced osteogenicity of the demineralized bone-dermal matrix composite by the optimal partial demineralization for sustained release of bioactive molecules.

Allogenic demineralized bone matrix (DBM), processed to expose bioactive proteins imbedded by calcium salts, is widely used for bone repair and regeneration as an alternative to the autologous bone graft. However, demineralized bone matrices from tissue banks vary significantly in residual calcium content and osteogenicity for clinical bone regeneration. The present study produced DBM with various residual calcium contents by partial demineralization using ethylenediaminetetraacetic acid disodium (EDTA) and hydrochloric acid. Compositional analysis reveals that, as the percent weight loss of bone materials increases from 0% to 74.9% during demineralization, the residual calcium content of DBM decreases from 24.8% to 0.2% and collagen content increases from 29.7% to 92.6%. Calorimetrical analysis and Fourier transform infrared (FTIR) analysis demonstrated that demineralization to the residual calcium content of <4% enables the complete exposure and/or release of bone collagen fibers and other bioactive molecules. In order to evaluate the relationship between the extent of demineralization and the osteogenicity of DBM, DBM particles were fabricated with the aid of acellular dermal matrix (ADM) microfibers to form flexible foam-like DBM/ADM composites. Proteomic analysis identified various type collagens and bone formation-related bioactive molecules in both ADM and DBM. Using the rat bilateral Φ = 5 mm calvarium defect repair model, the study had shown that the DBM/ADM composite with ~20% DBM residual calcium (e.g., ~40% calcium being removed) maximized the osteogenicity for bone defect repair after 4 and 8 weeks. DBM with ~40% calcium removal had the maximal osteogenicity presumably through the sustained release of bioactive molecules during the process of bone regeneration.

EFFECTS OF RECOMBINED HUMAN BONE MORPHOGENETIC PROTEIN-2 AS ALVEOLAR RIDGE PRESERVATION ON PAIN REDUCTION AND SOFT TISSUE HEALING PROCESS: A SPLIT MOUTH DESIGNED PILOT STUDY

Background: The alveolar ridge undergoes physiological bone resorption following tooth extraction. Several alveolar ridge preservation (ARP) techniques have been researched and developed in an effort to reduce this process and maintain a favorable volume and morphology of the alveolar ridge for appropriate implant placement. Bone morphogenetic proteins (BMPs) are proteins derived from a subgroup of the transforming growth factor  family that accelerates ossification by controlling essential factors of the bone induction cascade, resulting in the proliferation of osteoblasts from mesenchymal stem cells and the biosynthesis of bone matrices. One of these BMPs is recombinant human bone morphogenetic protein-2 (rhBMP-2) that has been authorized to be used for ARP. Objective: This study aims to evaluate the effect of rhBMP-2 on the healing process and the level of pain following dental extraction. Methods: In this split-mouth pilot study, 11 patients underwent extractions of a minimum of two teeth, and randomly, one of the alveolar sockets was filled with a hemostatic sponge while the other was filled with a hemostatic sponge embedded with rhBMP-2. Both sockets were sutured using the X technique. Wound healing measurements were done on days 3, 7, and 14, and each participant was requested to document his pain experience using the Numerical Rating Scale (NRS). Results: In accordance with clinical evidence, it was observed that the mean pain score was at its peak on day 0 and progressively diminished in the subsequent days. Notably, this decline was more pronounced in the rhBMP-2 group compared to the control group. Importantly, a statistically significant reduction in pain level was detected on day 3 within the rhBMP-2 group, in contrast to the control group (P-value &lt; 0.05). This indicated that the application of rhBMP-2 led to a noteworthy and meaningful alleviation of pain on the third day after treatment, surpassing the impact observed in the control group. For the wound healing changes, it uncovered statistically significant mean differences across various time intervals: day 0 and day 3, day 0 and day 7, day 0 and day 14, day 3 and day 7, and day 7 and day 14 (P-value &lt; 0.0001). These significant differences strongly suggest dynamic changes in wound closure rates over time. Furthermore, the observed differences were more pronounced in the rhBMP-2-treated group compared to the control group. This augmentation of differences indicates that the utilization of rhBMP-2 for ARP within a fresh socket site resulted in a heightened acceleration of the wound healing process. Conclusion: Our results suggest that rhBMP-2 can decrease post-operative pain after tooth extraction and accelerate the soft tissue healing process.

Análisis histológico e histomorfométrico de la reparación ósea de mandíbulas de ratas usando geles de alendronato y aloe vera

The maintenance of bone mass in the jaws is a concern for dental professionals. Objective: To study the effect of local administration of Alendronate (AL) and Aloe vera (AV) on the tissue regeneration of the post-exodontia alveolus in rats. Materials and methods: Absorbable gelatin hemostatic sponges were used; they were embedded with a solution of LA (0.5 mg/Kg) and 70% AV gel; control group (C) used saline. The effect was evaluated in male Wistar rats (n=64), divided into 4 groups: C, AL, AV and AL+AV. The first lower molars were extracted, the embedded hemostatic sponges were placed in the alveoli. The handling of the animals was carried out following the norms established by SECyT according to CICUAL. Determinations were made at 0, 7, 15, 30 days. The lower jaw was extracted, placed in a sterile jar and fixed in 10% formalin; the samples were decalcified and then embedded in paraffin. Histological sections were made and stained with Hematoxylin/Eosin. Histological and histomorphometric parameters were analyzed. An analysis of Variance (ANOVA) was performed for two classification criteria. Results: In the histomorphological analysis, at 15 days the AV group presented greater new formation of bone tissue. At 30 days, the presence of mature bone with the presence of Haversian systems was observed in the AV and AL+AV group. The histomorphometric study at 15 and 30 days showed significant differences in the number of osteoblasts per linear mm, between the AV and AL+AV group with respect to group C (p&lt;0.01). Whenmeasuring trabecular thickness, significant differences were observed at 30 days between the AV group and the C group (p&lt;0.01). Conclusions: The parameters studied demonstrated that Aloe vera administered locally favored bone repair in the post-exodontia alveoli

Osteobiologics and Value-Based Care: Challenges and Opportunities.

Autologous bone grafts, sourced from the iliac crest, are the gold standard for bone substitution in spine surgery. However, harvesting autografts increases the risk of postoperative complications. Bone allografts are another popular source of graft material, but their use is rapidly surpassing their availability. There has been considerable interest in manufactured bone graft substitutes, commonly referred to as osteobiologics, which mimic the properties of autologous bone and may be osteoconductive, osteoinductive, osteogenic, or a combination. Osteobiologics have been developed to mimic the properties of autologous bone, but their high cost and variable effectiveness raise questions about their value. This article explores the challenges and opportunities associated with the use of osteobiologics used to aid in bone healing in spinal fusion surgery within a value-based care framework. Spinal fusion treatments such as bone morphogenetic proteins, platelet-rich plasma, autologous conditioned serum, demineralized bone matrix, biomaterial scaffolds, stem cells, and cellular bone matrices are compared. Bone morphogenetic proteins are highly effective but often associated with serious risks; platelet-rich plasma shows promising results but lacks standardization in research protocols. Autologous conditioned serum is inconclusive and cost-effective, while demineralized bone matrix has variable effectiveness and limited data to use in anterior spinal fusions. Biomaterial scaffolds have limited application in the anterior spine but demonstrate high efficacy when it comes to spinal fusion. Stem cells demonstrate improved postsurgical outcomes but have low yield from bone marrow and potential risks associated with genetic engineering and cell therapy. Cellular bone matrices show promising results and have high fusion rates, yet there is currently no US Food and Drug Adminstration requirement for preclinical or clinical data before commercial usage. Although osteobiologics have considerable potential, their high price and uncertain efficiency raise questions concerning their usefulness in spinal fusion surgery. To ensure better patient outcomes, extensive research is needed to explore their utilization within a value-based care framework.

Evaluation of osseous healing in induced mandibular defects grafted with biphasic calcium phosphate doped with silver and zirconium nanoparticles: An experimental study in dogs

ObjectiveEvaluation of the osteoconductive p otential of the nanocomposite tricalcium phosphate/hydroxyapatite (TCP/HA) bi-doped with zirconium (Zr) and silver (Ag) ions versus TCP/HA & 4AgTCP/HA in induced defects. MethodsFifteen dogs were divided into four groups in 12 weeks duration before euthanasia: 1-control, 2- TCP/HA, 3- TCP/HA doped with Ag and 4-TCP/HA bi-doped with Ag & Zr groups. Four surgically created defects were randomly allocated in each animal on the left and right mandibular sides, three defects were grafted with mentioned alloplasts and one empty control. Clinical, radiographic, and histological evaluations were performed for the newly formed bone. ResultsClinical results revealed no infection or inflammatory conditions. All graft groups revealed a significant increase (P<0.05) in mature bone mean density versus controls. TCP/HA bidoped with Ag and Zr group elucidated a highly significant increase (P <0.01) in mature bone density compared to other groups while the TCP/HA was statistically insignificant (P > 0.05) compared to the Ag-doped TCP/HA. The bactericidal action of both Zr and Ag nanoparticles was evident by antibacterial testing. ConclusionBi-doping of TCP/HA with Ag and Zr has a synergistic osteoconductive effect to enhance bone formation as an excellent modality for defective bone reconstruction. Histomorphometric investigation clarified that Ag and Zr doped TCP/HA stimulated osteogenesis and bone remodeling as compared to un-doped TCP/HA. Therefore, this nanocomposite has promising clinical significance in grafting maxillofacial bone defects for optimal healing compared to un-doped TCP/HA. Moreover, Zr and Ag nanoparticles are effective bactericidal materials with optimal biological safety on the animals.

Optimizing the generation of mature bone marrow-derived dendritic cells in vitro: a factorial study design

BackgroundFactorial design is a simple, yet elegant method to investigate the effect of multiple factors and their interaction on a specific response simultaneously. Hence, this type of study design reaches the best optimization conditions of a process. Although the interaction between the variables is widely prevalent in cell culture procedures, factorial design per se is infrequently utilized in improving cell culture output. Therefore, we aim to optimize the experimental conditions for generating mature bone marrow-derived dendritic cells (BMDCs). Two different variables were investigated, including the concentrations of the inducing factors and the starting density of the bone marrow mononuclear cells. In the current study, we utilized the design of experiments (DoE), a statistical approach, to systematically assess the impact of factors with varying levels on cell culture outcomes. Herein, we apply a two-factor, two-level (22) factorial experiment resulting in four conditions that are run in triplicate. The two variables investigated here are cytokines combinations with two levels, granulocyte–macrophage colony-stimulating factor (GM-CSF) alone or with interleukin-4 (IL4). The other parameter is cell density with two different concentrations, 2 × 106 and 4 × 106 cells/mL. Then, we measured cell viability using the trypan blue exclusion method, and a flow cytometer was used to detect the BMDCs expressing the markers FITC-CD80, CD86, CD83, and CD14. BMDC marker expression levels were calculated using arbitrary units (AU) of the mean fluorescence intensity (MFI). ResultsThe current study showed that the highest total viable cells and cells yield obtained were in cell group seeded at 2 × 106 cells/mL and treated with GM-CSF and IL-4. Importantly, the expression of the co-stimulatory molecules CD83 and CD80/CD86 were statistically significant for cell density of 2 × 106 cells/mL (P < 0.01, two-way ANOVA). Bone marrow mononuclear cells seeded at 4 × 106 in the presence of the cytokine mix less efficiently differentiated and matured into BMDCs. Statistical analysis via two-way ANOVA revealed an interaction between cell density and cytokine combinations. ConclusionThe analysis of this study indicates a substantial interaction between cytokines combinations and cell densities on BMDC maturation. However, higher cell density is not associated with optimizing DC maturation. Notably, applying DoE in bioprocess designs increases experimental efficacy and reliability while minimizing experiments, time, and process costs.

Multipotent Mesenchymal Cells Homing and Differentiation on Poly(ε-caprolactone) Blended with 20% Tricalcium Phosphate and Polylactic Acid Incorporating 10% Hydroxyapatite 3D-Printed Scaffolds via a Commercial Fused Deposition Modeling 3D Device.

As highlighted by the 'Global Burden of Disease Study 2019' conducted by the World Health Organization, ensuring fair access to medical care through affordable and targeted treatments remains crucial for an ethical global healthcare system. Given the escalating demand for advanced and urgently needed solutions in regenerative bone procedures, the critical role of biopolymers emerges as a paramount necessity, offering a groundbreaking avenue to address pressing medical needs and revolutionize the landscape of bone regeneration therapies. Polymers emerge as excellent solutions due to their versatility, making them reliable materials for 3D printing. The development and widespread adoption of this technology would impact production costs and enhance access to related healthcare services. For instance, in dentistry, the use of commercial polymers blended with β-tricalcium phosphate (TCP) is driven by the need to print a standardized product with osteoconductive features. However, modernization is required to bridge the gap between biomaterial innovation and the ability to print them through commercial printing devices. Here we showed, for the first time, the metabolic behavior and the lineage commitment of bone marrow-derived multipotent mesenchymal cells (MSCs) on the 3D-printed substrates poly(e-caprolactone) combined with 20% tricalcium phosphate (PCL + 20% β-TCP) and L-polylactic acid (PLLA) combined with 10% hydroxyapatite (PLLA + 10% HA). Although there are limitations in printing additive-enriched polymers with a predictable and short half-life, the tested 3D-printed biomaterials were highly efficient in supporting osteoinductivity. Indeed, considering different temporal sequences, both 3D-printed biomaterials resulted as optimal scaffolds for MSCs' commitment toward mature bone cells. Of interest, PLLA + 10% HA substrates hold the confirmation as the finest material for osteoinduction of MSCs.

Centrosome clustering control in osteoclasts through CCR5-mediated signaling

Osteoclasts uniquely resorb calcified bone matrices. To exert their function, mature osteoclasts maintain the cellular polarity and directional vesicle trafficking to and from the resorbing bone surface. However, the regulatory mechanisms and pathophysiological relevance of these processes remain largely unexplored. Bone histomorphometric analyses in Ccr5-deficient mice showed abnormalities in the morphology and functional phenotype of their osteoclasts, compared to wild type mice. We observed disorganized clustering of nuclei, as well as centrosomes that organize the microtubule network, which was concomitant with impaired cathepsin K secretion in cultured Ccr5-deficient osteoclasts. Intriguingly, forced expression of constitutively active Rho or Rac restored these cytoskeletal phenotypes with recovery of cathepsin K secretion. Furthermore, a gene-disease enrichment analysis identified that PLEKHM1, a responsible gene for osteopetrosis, which regulates lysosomal trafficking in osteoclasts, was regulated by CCR5. These experimental results highlighted that CCR5-mediated signaling served as an intracellular organizer for centrosome clustering in osteoclasts, which was involved in the pathophysiology of bone metabolism.

Local H2 release remodels senescence microenvironment for improved repair of injured bone

The senescence microenvironment, which causes persistent inflammation and loss of intrinsic regenerative abilities, is a main obstacle to effective tissue repair in elderly individuals. In this work, we find that local H2 supply can remodel the senescence microenvironment by anti-inflammation and anti-senescence effects in various senescent cells from skeletally mature bone. We construct a H2-releasing scaffold which can release high-dosage H2 (911 mL/g, up to 1 week) by electrospraying polyhydroxyalkanoate-encapsulated CaSi2 nanoparticles onto mesoporous bioactive glass. We demonstrate efficient remodeling of the microenvironment and enhanced repair of critical-size bone defects in an aged mouse model. Mechanistically, we reveal that local H2 release alters the microenvironment from pro-inflammation to anti-inflammation by senescent macrophages repolarization and secretome change. We also show that H2 alleviates the progression of aging/injury-superposed senescence, facilitates the recruitment of endogenous cells and the preservation of their regeneration capability, thereby creating a pro-regenerative microenvironment able to support bone defect regeneration.

Ossified intramuscular hematoma of the paraspinal muscles: a case report

BackgroundOssified intramuscular hematomas (OIH) are an exceptionally rare condition that may be mistaken for alternative calcified intramuscular pathologies, such as myositis ossificans. Exceedingly few cases of OIHs have been reported to date, with no cases yet to be reported in the paraspinal muscles.Case presentationHere, we report on a patient who presented with a chronic back pain and swelling in the setting of trauma 15 years prior. Radiographic workup revealed a calcified mass in the erector spinae muscles. The lesion was surgically excised, and histologic examination confirmed the presence of an OIH. The patient did well postoperatively.ConclusionAn OIH is a poorly understood pathology. Although benign, these lesions can cause significant morbidity, and surgical excision is a reasonable and safe treatment option. OIHs may be distinguished from related calcified intramuscular pathologies based on key clinical features and distinct histopathology. Clinically, they are characterized by a history of remote trauma and, on histopathology, by compact, mature bone in the setting of an old, organizing hematoma. Despite this, similarities with other calcified intramuscular pathologies persist, and further study is warranted to better understand and classify these lesions.

Active Osteoblasts or Quiescent Bone Lining Cells? Preosteoblasts Fate Orchestrated by Curvature and Stiffness of an In Vitro 2.5D Biomimetic Culture System.

Biomimetic cell culture systems are required to provide more physiologically relevant microenvironments for bone cells. Here, a simple 2.5D culture platform is proposed, combining adjustable stiffness and surface features that mimic bone topography by using sandpaper grits as master molds with two stiffness formulations of polydimethylsiloxane (PDMS). The subsequent replicas perfectly conform the grits and reproduce the corresponding negative relief with cavities separated by convex edges. Biomimicry is also provided by an extracellular matrix (ECM)-like thin film coating, using the layer-by-layer (LbL) method. The topographical features, alternating concave, and convex structures drive preosteoblasts organization and morphology. Strikingly, curvature orchestrates the commitment of preosteoblasts, with i) maturation to active osteoblasts able to produce a dense collagenous matrix that ultimately mineralizes in the cavities, and ii) edges hosting quiescent cells that synthetize a very thin immature collagen layer with no mineralization. In summary, the present in vitro culture system model offers a cell-instructive 2.5D microenvironment that controls preosteoblasts fate, leading to two coexisting subpopulations: mature osteoblasts and bone lining cells (BLC). This promising culture system opens new avenues to advanced tissue-engineered modeling and can be applied to precellularized bone biomaterials.

Gel Based on Hydroxyethyl Starch with Immobilized Amikacin for Coating of Bone Matrices in Experimental Osteomyelitis Treatment

Gel Based on Hydroxyethyl Starch with Immobilized Amikacin for Coating of Bone Matrices in Experimental Osteomyelitis Treatment

Injectable platelet rich fibrin versus hyaluronic acid with bovine derived xenograft for alveolar ridge preservation. A randomized controlled clinical trial with histomorphometric analysis.

Alveolar ridge preservation (ARP) is a technique that aims to maintain bone volume and minimize resorption after tooth extraction. This study aimed to compare the effectiveness of injectable platelet-rich fibrin (I-PRF) versus hyaluronic acid (HA) in combination with xenografts for ARP. This randomized controlled trial included 36 patients (20 females and 16 males) who required implant placement in the upper arch. The patients were randomly allocated to one of three groups (n = 12 each): I-PRF with xenografts, HA with xenografts, or xenografts alone. All patients underwent ARP, and the extraction sockets were sealed with a free gingival graft harvested from the palate, a total of 36 implants were inserted. Cone-beam CT scans were performed before and 4 months postoperatively to measure radiographic bone gain as the primary outcome. Clinical parameters, including soft tissue thickness and clinical bone width, were evaluated preoperatively, and at 4 months and 1 year postoperatively. Additionally, histological assessment of core bone biopsies was performed 4 months postoperatively using histomorphometric analysis to determine the percentages of newly formed bone, mature bone, and residual grafts. Regarding the radiographic bone gain 4 months postoperative the HA group exhibited the highest value (9.78 ± 0.87), which was significantly greater than the values observed in the I-PRF and control groups (8.60 ± 1.27 and 7.99 ± 0.89, respectively) (one-way ANOVA, p = 0.007). Crestal bone loss was significantly higher in the control group (-0.98 ± 0.18) than in the I-PRF group (-0.53 ± 0.11) and HA group (-0.33 ± 0.15) groups (one-way ANOVA, p < 0.001). In the histomorphometric analysis, the mean area fraction of newly formed bone trabeculae was significantly higher in the HA group (56.66 ± 7.35) than in the I-PRF group (28.74 ± 5.15) and the control group (24.05 ± 3.64) (repeated measures ANOVA, p < 0.001). Additionally, the mean area fraction of residual graft material was higher in the I-PRF group (6.76 ± 2.59), followed by the control group (2.71 ± 1.24), while the HA group had the lowest value (2.63 ± 1.27) (Repeated measures ANOVA, p < 0.001). The combination of HA with xenografts yielded better radiographic and histological outcomes in terms of new bone formation and degree of bone maturation than the I-PRF and control groups. Furthermore, I-PRF improved soft tissue thickness. Please note that clinical trial registration was not completed prior to participant recruitment and randomization. The registration link for this trial is https://clinicaltrials.gov/ct2/show/NCT05781529.