Bone Research Articles

Effectiveness and biocompatibility evaluation of a novel absorbable bone wax used in bone tissue.

To determine the hemostatic effectivity and biocompatibility of a novel absorbable bone wax in comparison with a commercially available product. 18 small fat-tail sheep were used to simulate clinical surface bleeding of sternal injury. Hemostasis effectiveness, the degree of bone healing, Mirco-CT, histopathology were evaluated over a period after the application of the material to the surgically created wound. The absorbable bone wax used in the study stopped bleeding immediately and did not affect bone healing. The histopathological results also showed that there were no complications associated with the new material. The results showed that the new absorbable bone wax used in this study was effective and biocompatible.

Enhancing Bone Healing Through Localized Cold Therapy in a Murine Femoral Fracture Model.

Fracture healing, a critical and complex biological process, often presents challenges in clinical practice with the current standards failing to fully address the medical needs for rapid and effective recovery. In this work, a localized cold therapy is investigated as an alternative approach to expedite bone healing. We hypothesized that optimized cold application can enhance bone healing within a fracture model by inducing hypoxia, leading to accelerated angiogenesis along with improved osteogenesis. A short, localized cold exposure is directly applied to the fracture site over a 4-week period in a mouse fracture model, aiming to assess its impact on bone formation through mechanisms of angiogenesis and osteogenesis. Our results revealed a significantly greater volume of new bone tissue and enhanced vascularity at the fracture site in the cold-treated group compared with controls. Calcified tissue histology analysis showed that the accelerated callus maturation and development of the vascular network following cold exposure were associated with an activity increase of alkaline phosphatase and transient receptor potential vanilloid 1. These biological changes were accompanied by a hypoxic environment induced during cold therapy. The study provides compelling evidence supporting the efficacy of intermittent cold therapy in accelerating fracture healing. These promising results highlight the need for further research in larger-scale studies and diverse fracture models, underlining the potential of cold therapy as a novel, noninvasive treatment strategy in orthopedic care.

Prevention of chemotherapy-related bone loss with doxorubicin-loaded solid lipid nanoparticles.

Aim: Breast cancer and its metastases involve high mortality even with advances in chemotherapy. Solid lipid nanoparticles provide a platform for drug delivery, reducing side effects and treatment-induced bone loss. A solid nanoparticle containing doxorubicin was evaluated for its ability to prevent bone loss in a pre-clinical breast cancer model. Methods: We investigated the effects of SLNDox in an aggressive metastatic stage IV breast cancer model, which has some important features that are interesting for bone loss investigation. This study evaluates bone loss prevention potential from solid lipid nanoparticles containing doxorubicin breast cancer treatment, an evaluation of the attenuation of morphological changes in bone tissue caused by the treatment and the disease and an assessment of bone loss imaging using computed tomography and electron microscopy. Results: Chemotherapy-induced bone loss was also observed in tumor-free animals; a solid lipid nanoparticle containing doxorubicin prevented damage to the growth plate and to compact and cancellous bones in the femur of tumor-bearing and healthy animals. Conclusion: The association of solid lipid nanoparticles with chemotherapeutic drugs with proven efficacy promotes the prevention of serious consequences of chemotherapy, reducing tumor progression, increasing quality of life and improving prognosis and survival.

Recent advances of bone tissue engineering: carbohydrate and ceramic materials, fundamental properties and advanced biofabrication strategies ‒ a comprehensive review.

Bone is a dynamic tissue that can always regenerate itself through remodelling to maintain biofunctionality. This tissue performs several vital physiological functions. However, bone scaffoldsarerequired for critical-sizes damages and fractures and these can be addressed bybone tissue engineering. Bone tissue engineering (BTE) has the potential to develop scaffolds forrepairingcritical-size damagedbone. BTE is a multidisciplinary engineered scaffold with the desired properties for repairing damaged bone tissue. Herein, we have provided an overview of the common carbohydrate polymers, fundamental structural, physicochemical and biological properties, and fabrication techniques for bone tissue engineering. We also discussed advanced biofabrication strategies and provided the limitations and prospects by highlighting significant issues in bone tissue engineering. There are several review articles available on bone tissue engineering but we have provided a state-of-the-art review article that discussed the recent progress and trends within 3-5 years by emphasizing challenges and future perspectives.
Bone is a dynamic tissue that can always regenerate itself through remodeling to maintain biofunctionality. This tissue performs several vital physiological functions. However, bone scaffolds are required for critical-size damages and fractures, and these can be addressed by bone tissue engineering. Bone tissue engineering (BTE) has the potential to develop scaffolds for repairing critical-size damaged bone. BTE is a multidisciplinary engineered scaffold with the desired properties for repairing damaged bone tissue. Herein, we have provided an overview of the common carbohydrate polymers, fundamental structural, physicochemical, and biological properties, and fabrication techniques for bone tissue engineering. We also discussed advanced biofabrication strategies and provided the limitations and prospects by highlighting significant issues in bone tissue engineering. There are several review articles available on bone tissue engineering. However, we have provided a state-of-the-art review article that discussed recent progress and trends within the last 3-5 years by emphasizing challenges and future perspectives.

A 3D micro-CT assessment of composition and structure of bone tissue after vertical and horizontal alveolar ridge augmentation using CAD/CAM-customized titanium mesh.

To date, no studies have exploited micro-CT in humans to evaluate bone morphology and structure after bone augmentation with CAD/CAM-customized titanium mesh, in mandible and maxilla. The aim of this study was to assess the composition and microstructure of bone biopsy through micro-CT analysis. Bone augmentation at both maxillary and mandible sites was performed on 30 patients randomly treated with customized mesh, either alone (M-) or covered with resorbable membrane (M+), in both cases filled 50:50 with autogenous bone and xenograft. After 6 months, biopsies were taken and micro-CT was performed on consecutive 1-mm-thick VOIs from coronal to apical side, measuring tissue volumes, trabecular thickness, spacing, and number. In both groups, irrespective of membrane use, bone tissue (M-: 29.76% vs. M+: 30.84%) and residual graft material (M-: 14.87% vs. M+: 13.11%) values were similar. Differences were site-related (maxillary vs. mandibular) with higher percentage of bone tissue and trabecular density of low-mineralized bone and overall bone in the mandible. The composition and structure of bone tissue, as assessed by micro-CT after alveolar ridge augmentation using CAD/CAM-customized titanium meshes, showed similar features regardless of whether a collagen membrane was applied.

The effect of initial temperature on the mechanical strength of tricalcium phosphate/Chitosan/Silica aerogels nanocomposites using molecular dynamics simulation

BackgroundChitosan is an organic polymer derived from chitin, showcasing commendable biocompatibility and biodegradability, while tricalcium phosphate emerges as an active ceramic with proven biocompatibility and superior compatibility with bone tissue. This composite material, endowed with a unique amalgamation of attributes including biocompatibility, porosity, and mechanical strength, proves highly applicable in diverse fields such as tissue engineering, drug delivery systems, wound repair, and as scaffolds for cell proliferation in regenerative medicine. MethodsThe focal point of this study is an exploration of the nuanced interplay between the mechanical properties of silica aerogel/chitosan tricalcium phosphate nanocomposites with increasing initial temperature. Employing molecular dynamics (MD) simulation, the research aims to unveil the temperature-induced variations in the critical properties. Significant FindingsThe results reveal that the ultimate strength and Young's modulus values are determined to converge to 772.28 MPa and 62.291 GPa, at 297 K. As the initial temperature escalates from 300 to 350 K, the US decreases from 72.28 to 714.47 MPa. The decrease in US could be due to higher temperatures, the increased thermal energy can lead to greater atomic vibrations within the material, which can promote easier dislocation movement and result in reduced resistance to deformation. The results reveal that as temperature increases to 320 K, YM increases to 67.134, and with further increase in temperature, YM decreases to 62.865 GPa

Customized Flexible Osteoid Electrode for Traumatic Brain Injury Induced Posttraumatic Epilepsy Monitoring

AbstractTraumatic brain injury (TBI)‐induced post‐traumatic epilepsy (PTE) is a serious brain disease that causes the loss of motor functions, cognitive impairments, and even death. Real‐time and long‐term electrophysiological signal monitoring has significant implication for the treatment of patient with TBI. Brain–computer interfaces (BCIs) utilizing flexible electrodes enable accurate epilepsy identification by electrocorticography (ECoG) signal monitoring. In this study, a customized flexible osteoid electrode is developed, which contributes to demands and personal differentiation among patients with TBI. The end product of osteoid electrode after full osseointegration will be a stable and firmly integrated structure within the bone tissue, providing a secure platform for continuous electrophysiological signal monitoring. The flexibility and conductivity of the osteoid electrode enables high‐quality and long‐term epilepsy monitoring. Biocompatibility of the osteoid electrode is also demonstrated by in vitro cell experiments. Simultaneously, the porous osteoid electrode also exhibits osseointegration ability based on potential long‐term ECoG signal monitoring, which suggests its potential for the comprehensive treatment of TBI patients. This work not only introduces a potential therapeutic scaffold for TBI‐related diseases, but also provides promising techniques for clinical ECoG monitoring in patients with TBI.

Assessment of MDM2 Gene Locus Amplification by Fluorescence In-Situ Hybridization in Juvenile Ossifying Fibroma.

With IRB approval, a search of the institutional files of the archives of the Oral Pathology and Surgical Pathology biopsy services at the University of Florida Health was performed. The cases were re-evaluated by an oral pathology resident, an oral and maxillofacial pathologist, and a bone and soft tissue pathologist. Cases with consensus in diagnosis were selected (n = 9) for MDM2 testing. Testing by FISH for MDM2 gene locus amplification was applied to all retrieved cases. The examined cases were all negative for MDM2 gene locus amplification via FISH testing. In our small series, JOF did not demonstrate MDM2 gene locus abnormality, a characteristic of LGIOS. This finding suggests that JOF has a distinct underlying pathogenesis. If confirmed in a larger series, these findings may be useful in distinguishing these two entities in cases with overlapping features or when minimal biopsy material is available.

Site-specific cancer mortality after low level exposure to ionizing radiation: Findings from an update of the International Nuclear Workers Study (INWORKS).

A major update to the International Nuclear Workers Study was undertaken that allows us to report updated estimates of associations between radiation and site-specific solid cancer mortality. A cohort of 309,932 nuclear workers employed in France, the United Kingdom, and United States were monitored for external radiation exposure and associations with cancer mortality were quantified as the excess relative rate (ERR) per gray (Gy) using a maximum likelihood and a Markov chain Monte Carlo method (to stabilize estimates via a hierarchical regression). The analysis included 28,089 deaths due to solid cancer, the most common being lung, prostate, and colon cancer. Using maximum likelihood, positive estimates of ERR per Gy were obtained for stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura/mesothelioma, bone and connective tissue, skin, prostate, testis, bladder, kidney, thyroid, and residual cancers; negative estimates of ERR per Gy were found cancers of oral cavity and pharynx, esophagus, and ovary. A hierarchical model stabilized site-specific estimates of association, including for lung (ERR per Gy=0.65; 95% credible interval [CrI]: 0.24, 1.07), prostate (ERR per Gy=0.44; 95% CrI: -0.06, 0.91), and colon cancer (ERR per Gy=0.53; 95% CrI: -0.07, 1.11). The results contribute evidence regarding associations between low dose radiation and cancer.

Structural and biological properties of hydroxyfluorapatite containing sodium and potassium and substituted with carbonates bioceramics for bone tissue engineering

Structural and biological properties of hydroxyfluorapatite containing sodium and potassium and substituted with carbonates bioceramics for bone tissue engineering

Nanographene Oxide Promotes Angiogenesis by Regulating Osteoclast Differentiation and Platelet-Derived Growth Factor Secretion.

An imbalanced system of angiogenesis-osteoblasts-osteoclasts is regarded as the main factor in bone remodeling dysfunction diseases or osseointegration loss. Osteoclast precursors are the key cells that accelerate bone-specific angiogenesis and maintain normal osteoblast and osteoclast function. Graphene oxide is an effective scaffold surface modification agent with broad application prospects in bone tissue engineering. However, the effect of graphene oxide on the interaction between osteoclasts and angiogenesis has not yet been elucidated. In this study, a rat calvarial defect model was established and treated with an electrochemically derived nanographene oxide (ENGO) hydrogel. Higher angiogenesis and platelet-derived growth factor (PDGF) B in preosteoclasts were observed in the ENGO group compared with that in the control group. Moreover, in vitro experiments demonstrate the efficacy of ENGO in substantially reducing the expression of the receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast-associated markers and inhibiting bone resorption activity. Additionally, ENGO enhances the secretion of the osteoclast-derived coupling factor PDGF-BB and promotes angiogenesis. Our investigation revealed the crucial role of isocitrate dehydrogenase 1 (IDH1) in the ENGO-mediated regulation of osteoclast differentiation and PDGF-BB secretion. The decreased expression of IDH1 reduces the level of histone lysine demethylase 7A (KDM7A) and subsequently increases the H3K9me2 level in the cathepsin K promoter region. In summary, we found that ENGO promotes angiogenesis by inhibiting the maturity of RANKL-induced osteoclasts and enhancing PDGF-BB secretion. These results indicate that ENGO holds promise for the application in fostering osteoclast-endothelial cell crosstalk, providing an effective strategy for treating bone resorption and osteoclast-related bone loss diseases.

Development of a Biodegradable PLGA Carrier to Provide Wnt Agonists and Antibiotics to Meet the Requirements for Patients with Bone Infections

Antibiotic beads can be used to treat surgical infections. In this study, polylactide–polyglycolide (PLGA) was mixed with vancomycin, the osteogenic enhancer lithium chloride (LiCl), and hot compression to form PLGA-vancomycin-LiCl delivery beads to treat bone infection. An elution method was used to characterize in vitro release characteristics of vancomycin and Li over a 42-day period. The release profiles lasted for more than 42 days for vancomycin and 28 days for Li. The concentration of vancomycin in each sample was well above the breakpoint sensitivity. Lithium cotreatment enhanced the bactericidal effect of vancomycin. Released Li and vancomycin increased the mRNA or protein expressions of osteogenic markers of mesenchymal stem cells (MSCs). In vivo, the PLGA delivery systems were implanted into the distal femoral cavities of rabbits, and the cavity fluid content was aspirated and analyzed at each time point. The released Li and vancomycin lasted more than 6 weeks, and the vancomycin concentrations were much greater than the breakpoint sensitivity. Four rabbits in each group were sacrificed at 8 weeks for histological observation. More mature bone tissue was observed in the Li treatment group. This study provides a PLGA drug delivery system to meet the requirements of patients with bone infections.

Complications of chest wall around malignant tumors: differences based on reconstruction strategy

BackgroundMalignant chest wall tumors need to be excised with wide resection to ensure tumor free margins, and the reconstruction method should be selected according to the depth and dimensions of the tumor. Vascularized tissue is needed to cover the superficial soft tissue defect or bone tissue defect. This study evaluated differences in complications according to reconstruction strategy.MethodsForty-five patients with 52 operations for resection of malignant tumors in the chest wall were retrospectively reviewed. Patients were categorized as having superficial tumors, comprising Group A with simple closure for small soft tissue defects and Group B with flap coverage for wide soft tissue defects, or deep tumors, comprising Group C with full-thickness resection with or without mesh reconstruction and Group D with full-thickness resection covered by flap with or without polymethyl methacrylate. Complications were evaluated for the 52 operations based on reconstruction strategy then risk factors for surgical and respiratory complications were elucidated.ResultsTotal local recurrence-free survival rates in 45 patients who received first operation were 83.9% at 5 years and 70.6% at 10 years. The surgical complication rate was 11.5% (6/52), occurring only in cases with deep tumors, predominantly from Group D. Operations needing chest wall reconstruction (p = 0.0016) and flap transfer (p = 0.0112) were significantly associated with the incidence of complications. Operations involving complications showed significantly larger tumors, wider areas of bony chest wall resection and greater volumes of bleeding (p < 0.005). Flap transfer was the only significant predictor identified from multivariate analysis (OR: 10.8, 95%CI: 1.05–111; p = 0.0456). The respiratory complication rate was 13.5% (7/52), occurring with superficial and deep tumors, particularly Groups B and D. Flap transfer was significantly associated with the incidence of respiratory complications (p < 0.0005). Cases in the group with respiratory complications were older, more frequently had a history of smoking, had lower FEV1.0% and had a wider area of skin resected compared to cases in the group without respiratory complications (p < 0.05). Preoperative FEV1.0% was the only significant predictor identified from multivariate analysis (OR: 0.814, 95%CI: 0.693–0.957; p = 0.0126).ConclusionsSurgical complications were more frequent in Group D and after operations involving flap transfer. Severe preoperative FEV1.0% was associated with respiratory complications even in cases of superficial tumors with flap transfer.

Penicillin concentrations in bone and subcutaneous tissue: A porcine microdialysis study comparing oral and intravenous treatment.

Penicillin is available in both an oral (penicillin V) and intravenous formulation (penicillin G), theoretically allowing for a safe transition between the two. However, the use of oral penicillin remains a topic of debate due to low and variable bioavailability. This study aimed to assess the time for which the free penicillin concentration exceeded targeted minimum inhibitory concentrations for Staphylococcus aureus and Streptococcus species (0.125, 0.25, and 0.5 mg/L) in cancellous bone and subcutaneous tissue after intravenous penicillin and oral penicillin administration. 12 female pigs (68-75 kg) were assigned, according to local standard clinical regimes, to either intravenous penicillin (1.2 g) or oral penicillin (0.8 g) treatment every 6 h over an 18 h period. Microdialysis catheters were placed for sampling in tibial cancellous bone and adjacent subcutaneous tissue. Data was dynamic/continually collected in the first dosing interval (0-6 h), simulating a prophylactic situation, and the third dosing interval (12-18 h), simulating a therapeutic setting. Plasma samples were collected for reference. For all investigated targets, intravenous treatment resulted in a longer mean time above relevant minimum inhibitory concentrations in cancellous bone during the first dosing interval, and in both cancellous bone and subcutaneous tissue during the third dosing interval compared to oral treatment. With clinically relevant dosing, intravenous penicillin provides superior exposure compared to oral penicillin in both a prophylactic and therapeutic setting.

3D Printed PLA Porous Scaffolds with Engineered Cell Size and Porosity Promote the Effectiveness of the Kelvin Model for Bone Tissue Engineering

AbstractIn this study, the aim is to investigate the effect of engineering the cell size and porosity of 3D‐printed poly lactic acid (PLA) porous scaffolds from the Kelvin model for bone tissue engineering applications. The Kelvin model is used as a bone tissue scaffold with different cell sizes and porosities. PLA, as a biodegradable and biocompatible polymer, is used to fabricate these scaffolds using the FDM technique. A compression test is used to evaluate the mechanical properties of scaffolds. The MTT assay has been used to investigate cell viability. For osteogenic differentiation studies, ALP activity and ARS assays are used. Increasing the porosity reduces the mechanical properties of the scaffold. While increasing the cell size at constant porosity increases the Young's modulus and yield stress in the samples, it is also observed that, in high porosities, the increase in cell size weakens the mechanical properties. Also, Kelvin model scaffolds help the proliferation and osteogenic differentiation of cells and have no toxic effect. It is demonstrated that this approach promotes the effectiveness of the Kelvin architecture for bone tissue engineering. As a result, designing the most suitable model based on cell size and porosity for the treatment process in the targeted area could be promising.

Chronic osteoarthritis caused by Propionibacterium australiense infection in a captive sand gazelle.

Osteoarthritis is a common cause of morbidity and mortality in geriatric gazelles. Propionibacterium australiense has been reported as a cause of systemic granulomas in cattle, but there are no descriptions of this bacteria infecting other species nor causing osteoarthritis, to our knowledge. An 8-y-old, castrated male, sand gazelle (Gazella leptoceros leptoceros) was managed for chronic, intermittent, progressive osteoarthritis of the right tarsus. Serial biopsies revealed pyogranulomatous dermatitis with intralesional bacteria. Serial diagnostic imaging identified osseous and soft tissue proliferation with draining tracts. Treatments over 1 y included broad-spectrum antibiotics, anti-inflammatories, joint debridement, and infusion with platelet-rich plasma and stem cells. Despite therapy, lameness persisted, azotemia developed, and subsequently, the animal was euthanized. On postmortem examination, the periarticular tissue of the right tarsus was markedly expanded by pyogranulomas and fibrosis. Histologically, the synovium, joint capsule, and overlying soft tissues were markedly expanded by pyogranulomas and numerous gram-positive and acid-fast-negative filamentous bacteria surrounded by Splendore-Hoeppli material. Within the joint, there was regionally extensive cartilage ulceration, osteonecrosis, osteolysis, and pannus formation. PCR assay of affected formalin-fixed, paraffin-embedded tissue amplified segments of 16S rRNA and β subunit of bacterial RNA polymerase (rpoB) genes with 99.7% and 95.6% identity to P. australiense. This bacterium should be considered a differential for chronic pyogranulomatous osteoarthritis in gazelles.

Morphological, mechanical and biological assessment of PCL/pristine graphene scaffolds for bone regeneration

Scaffolds are physical substrates for cell attachment, proliferation, and differentiation, ultimately leading to the regeneration of tissues. They must be designed according to specific biomechanical requirements such as mechanical properties, surface characteristics, biodegradability, biocompatibility, and porosity. The optimal design of a scaffold for a specific tissue strongly depends on both materials and manufacturing processes. Polymeric scaffolds reinforced with electro-active particles could play a key role in tissue engineering by modulating cell proliferation and differentiation. This paper investigates the use of an extrusion additive manufacturing system to produce PCL/pristine graphene scaffolds for bone tissue applications. PCL/pristine graphene blends were prepared using a melt blending process. Scaffolds with regular and reproducible architecture were produced with different concentrations of pristine graphene. Scaffolds were evaluated from morphological, mechanical, and biological view. The results suggest that the addition of pristine graphene improves the mechanical performance of the scaffolds, reduces the hydrophobicity, and improves cell viability and proliferation.

Preventing bacterial adhesion on scaffolds for bone tissue engineering

Bone implant infection constitutes a major sanitary concern which is associated to high morbidity and health costs. This manuscript focused on overviewing the main research efforts committed up to date to develop innovative alternatives to conventional treatments, such as those with antibiotics. These strategies mainly rely on chemical modifications of the surface of biomaterials, such as providing it of zwitterionic nature, and tailoring the nanostructure surface of metal implants. These surface modifications have successfully allowed inhibition of bacterial adhesion, which is the first step to implant infection, and preventing long-term biofilm formation compared to pristine materials. These strategies could be easily applied to provide three-dimensional (3D) scaffolds based on bioceramics and metals, of which its manufacture using rapid prototyping techniques was reviewed. This opens the gates for the design and development of advanced 3D scaffolds for bone tissue engineering to prevent bone implant infections.

Freezing does not influence the microarchitectural parameters of the microstructure of the freshly harvested femoral head bone.

The femoral head is one of the most commonly used bones for allografts and biomechanical studies. However, there are few reports on the trabecular bone microarchitectural parameters of freshly harvested trabecular bones. To our knowledge, this is the first study to characterize the microstructure of femoral heads tested immediately after surgery and compare it with the microstructure obtained with conventional freezing. This study aims to investigate whether freezing at -80°C for 6weeks affects the trabecular microstructure of freshly harvested bone tissue. This study was divided into two groups: one with freshly harvested human femoral heads and the other withthe same human femoral heads frozen at -80°C for 6weeks. Each femoral head was scanned using an X-ray microcomputed tomography scanner (µCT) to obtain the microarchitectural parameters, including the bone volume fraction (BV/TV), the mean trabecular thickness (Tb.th), the trabecular separation (Tb.sp), the degree of anisotropy (DA), and the connectivity density (Conn.D). There was no statistically significant difference between the fresh and the frozen groups for any of the parameters measured. This study shows that freezing at -80°C for 6weeks does not alter bone microstructure compared with freshly harvested femoral heads tested immediately after surgery.

Recent development of chitosan-based biomaterials for treatment of osteomyelitis

Abstract Osteomyelitis is a complex infectious disease caused by bacterial infection, which has always been a difficult problem for clinical orthopedic surgeons. Although the traditional methods are effective in treating osteomyelitis, the heavy use of antibiotics and surgical treatment cause serious side effects and lead to bone loss and healing difficulties after surgery. Chitosan (CS), a natural polymer material, is a deacetylated derivative of chitin, which has good biodegradability, antibacterial, and osteogenic properties, and has been widely used in the treatment of osteomyelitis. In this review, the recent research progress in the application of CS based composites such as micro-nano drug delivery carriers, hydrogels, coating materials, and bone tissue engineering scaffolds for the treatment of osteomyelitis is summarized, in order to provide certain experimental and theoretical support for the development of CS based composites.