Cortical Bone Research Articles

Doxycycline decelerates aging in progeria mice.

Beyond the antimicrobial activity, doxycycline (DOX) exhibits longevity-promoting effect in nematodes, while its effect on mammals is unclear. Here, we applied a mouse model of Hutchinson-Gilford progeria syndrome (HGPS), Zmpste24 knockout (KO) mice, and analyzed the antiaging effect of DOX. We found that the DOX treatment prolongs lifespan and ameliorates progeroid features of Zmpste24 KO mice, including the decline of body and tissue weight, exercise capacity and cortical bone density, and the shortened colon length. DOX treatment alleviates the abnormal nuclear envelope in multiple tissues, and attenuates cellular senescence and cell death of Zmpste24 KO and HGPS fibroblasts. DOX downregulates the level of proinflammatory IL6 in both serum and tissues. Moreover, the elevated α-tubulin (K40) acetylation mediated by NAT10 in progeria, is rescued by DOX treatment in the aorta tissues in Zmpste24 KO mice and fibroblasts. Collectively, our study uncovers that DOX can decelerate aging in progeria mice via counteracting IL6 expression and NAT10-mediated acetylation of α-tubulin.

Influence of a change in activity regime on femoral bone architecture and failure behaviour.

The incidence and morbidity of femoral fractures increases drastically with age. Femoral architecture and associated fracture risk are strongly influenced by loading during physical activities and it has been shown that the rate of loss of bone mineral density is significantly lower for active individuals than inactive. The objective of this work is to evaluate the impact of a cessation of some physical activities on elderly femoral structure and fracture behaviour. The authors previously established a biofidelic finite element model of the femur considered as a structure optimised to loading associated with daily activities. The same structural optimisation algorithm was used here to quantify the changes in bone architecture following cessation of stair climbing and sit-to-stand. Side fall fracture simulations were run on the adapted bone structures using a damage elasticity formulation. Total cortical and trabecular bone volume and failure load reduced in all cases of activity cessation. Bone loss distribution was strongly heterogeneous, with some locations even showing increased bone volume. This work suggests that maintaining the physical activities involved in the daily routine of a young healthy adult would help reduce the risk of femoral fracture in the elderly population by preventing bone loss.

Role of preservation methods using deep-freezing and liquid nitrogen in bone allograft characteristics: An in vitro study.

Bone grafting has emerged as a key solution in bone defect management such as allograft, graft of bone from another individual. However, bone allografts usually undergo rigorous preparation to eliminate immune-triggering elements. The deep-freezing methods may delay graft use, while cryopreservation using liquid nitrogen allows rapid freezing but may alter graft characteristics. The aim of this study was to investigate the post-preservation changes in bone allograft characteristics and to compare the effectiveness of deep-freezing and liquid nitrogen methods using animal model. An experimental study using a post-test only control group design was conducted. Fresh-frozen femoral cortical bone was obtained from male New Zealand white rabbits. Preservation by deep-freezing involved placing bone samples in a -80°C freezer for 30 days. For liquid nitrogen preservation, bone grafts were immersed in liquid nitrogen for 20 min, followed by a 15-min rest at room temperature and a final immersion in 0.9% sodium chloride at 30°C for 15 min. Bone samples then underwent evaluation of cell viability, compression, and bending tests. Cell viability test employed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and the compression and bending tests used the Universal Testing Machine (UTM). Independent Student t-test or Mann-Whitney U test were used to compare the methods as appropriate. Our study found that the use of deep-freezing and liquid nitrogen resulted in similar outcomes for cell viability, compression, and bending tests, with p-values of 0.302, 0.745, and 0.512, respectively. Further exploration with larger sample sizes may help to optimize the methods for specific applications.

Efficacy and safety of a new heterologous fibrin biopolymer on socket bone healing after tooth extraction: An experimental pre-clinical study.

To assess the efficacy of heterologous fibrin biopolymer (HFB) in promoting alveolar bone healing after tooth extraction in rats. The upper right incisors of 48 Wistar rats were extracted. Toothless sockets were filled with HFB (HFBG, n = 24) or blood clot (BCG, n = 24). The tooth extraction sites were subjected to micro-computed tomography (micro-CT), histological, histomorphometric and immunohistochemical (for Runt-related transcription factor 2/Runx2 and tartrate-resistant acid phosphatase/TRAP) analyses on days 0, 7, 14 and 42 after extraction. Socket volume remained similar between days 0 and 14 (69 ± 5.4 mm3), except in the BCG on day 14, when it was 10% lower (p = .043). Although the number of Runx2+ osteoblasts was high and similar in both groups (34 × 102 cells/mm2), the HFBG showed lower inflammatory process and osteoclast activity than BCG at 7 days. On day 14, the number of Runx2+ osteoblasts remained high and similar to the previous period in both groups. However, osteoclast activity increased. This increase was 55% lower in the HFBG than BCG. In the BCG, the presence of an inflammatory process and larger and numerous osteoclasts on day 14 led to resorption of the alveolar bone ridge and newly formed bone. On day 42, numbers of Runx2+ osteoblast and TRAP+ osteoclasts decreased dramatically in both groups. Although the BCG exhibited a more mature cortical bone formation, it exhibited a higher socket reduction (28.3 ± 6.67%) and smaller bone volume (37 ± 5.8 mm3) compared with HFBG (socket reduction of 14.8 ± 7.14% and total bone volume of 46 ± 5.4 mm3). HFB effectively suppresses osteoclast activity and reduces alveolar bone resorption compared with blood clot, thus preventing three-dimensional bone loss, particularly during the early healing period. HFB emerges as a promising biopharmaceutical material for enhancing healing processes after tooth extraction.

Amyloid-β neuropathology induces bone loss in male mice by suppressing bone formation and enhancing bone resorption

Alzheimer's disease (AD) and osteoporosis often coexist in the elderly. Although observational studies suggest an association between these two diseases, the pathophysiologic link between AD and skeletal health has been poorly defined. We examined the skeletal phenotype of 5xFAD mice, an AD model with accelerated neuron-specific amyloid-β accumulation causing full-blown AD phenotype by the age of 8 months. Micro-computed tomography indicated significantly lower trabecular and cortical bone parameters in 8-month-old male, but not female, 5xFAD mice than sex-matched wild-type littermates. Dynamic histomorphometry revealed reduced bone formation and increased bone resorption, and quantitative RT-PCR showed elevated skeletal RANKL gene expression in 5xFAD males. These mice also had diminished body fat percentage with unaltered lean mass, as determined by dual-energy X-ray absorptiometry (DXA), and elevated Ucp1 mRNA levels in brown adipose tissue, consistent with increased sympathetic tone, which may contribute to the osteopenia observed in 5xFAD males. Nevertheless, no significant changes could be detected between male 5xFAD and wild-type littermates regarding the serum and skeletal concentrations of norepinephrine. Thus, brain-specific amyloid-β pathology is associated with osteopenia and appears to affect both bone formation and bone resorption. Our findings shed new light on the pathophysiologic link between Alzheimer's disease and osteoporosis.

Vertebral and Femoral Bone Mineral Density (BMD) Assessment with Dual-Energy CT versus DXA Scan in Postmenopausal Females.

This study aimed to demonstrate the potential role of dual-energy CT in assessing bone mineral density (BMD) using hydroxyapatite-fat material pairing in postmenopausal women. A retrospective study was conducted on 51 postmenopausal female patients who underwent DXA and DECT examinations for other clinical reasons. DECT images were acquired with spectral imaging using a 256-slice system. These images were processed and visualized using a HAP-fat material pair. Statistical analysis was performed using the Bland-Altman method to assess the agreement between DXA and DECT HAP-fat measurements. Mean BMD, vertebral, and femoral T-scores were obtained. For vertebral analysis, the Bland-Altman plot showed an inverse correlation (R2: -0.042; RMSE: 0.690) between T-scores and DECT HAP-fat values for measurements from L1 to L4, while a good linear correlation (R2: 0.341; RMSE: 0.589) was found for measurements at the femoral neck. In conclusion, we demonstrate the enhanced importance of BMD calculation through DECT, finding a statistically significant correlation only at the femoral neck where BMD results do not seem to be influenced by the overlap of the measurements on cortical and trabecular bone. This outcome could be beneficial in the future by reducing radiation exposure for patients already undergoing follow-up for chronic conditions.

Six months of voluntary alcohol consumption in male cynomolgus macaques reduces intracortical bone porosity without altering mineralization or mechanical properties

Chronic heavy alcohol consumption is a risk factor for low trauma bone fracture. Using a non-human primate model of voluntary alcohol consumption, we investigated the effects of 6 months of ethanol intake on cortical bone in cynomolgus macaques (Macaca fascicularis). Young adult (6.4 ± 0.1 years old, mean ± SE) male cynomolgus macaques (n = 17) were subjected to a 4-month graded ethanol induction period, followed by voluntary self-administration of water or ethanol (4 % w/v) for 22 h/d, 7 d/wk. for 6 months. Control animals (n = 6) consumed an isocaloric maltose-dextrin solution. Tibial response was evaluated using densitometry, microcomputed tomography, histomorphometry, biomechanical testing, and Raman spectroscopy. Global bone response was evaluated using biochemical markers of bone turnover. Monkeys in the ethanol group consumed an average of 2.3 ± 0.2 g/kg/d ethanol resulting in a blood ethanol concentration of 90 ± 12 mg/dl in longitudinal samples taken 7 h after the daily session began. Ethanol consumption had no effect on tibia length, mass, density, mechanical properties, or mineralization (p > 0.642). However, compared to controls, ethanol intake resulted in a dose-dependent reduction in intracortical bone porosity (Spearman rank correlation = −0.770; p < 0.0001) and compared to baseline, a strong tendency (p = 0.058) for lower plasma CTX, a biochemical marker of global bone resorption. These findings are important because suppressed cortical bone remodeling can result in a decrease in bone quality. In conclusion, intracortical bone porosity was reduced to subnormal values 6 months following initiation of voluntary ethanol consumption but other measures of tibia architecture, mineralization, or mechanics were not altered.

Histology and chronological magnetic resonance images of congenital spinal deformity: An experimental study in mice model

BackgroundThe natural history of the congenital spinal deformity and its clinical magnitude vary widely in human species. However, we previously reported that the spinal deformities of congenital scoliosis mice did not progress throughout our observational period according to soft X-ray and MRI data. In this study, congenital vertebral and intervertebral malformations in mice were assessed via magnetic resonance (MR) and histological images.MethodsCongenital spinal anomalies were chronologically assessed via soft X-ray and 7 T MR imaging. MR images were compared to the histological images to validate the findings around the malformations.ResultsSoft X-ray images showed the gross alignment of the spine and the contour of the malformed vertebrae, with the growth plate and cortical bone visible as higher density lines, but could not be used to distinguish the existence of intervertebral structures. In contrast, MR images could be used to distinguish each structure, including the cortical bone, growth plate, cartilaginous end plate, and nucleus pulposus, by combining the signal changes on T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI). The intervertebral structure adjacent to the malformed vertebrae also exhibited various abnormalities, such as growth plate and cartilaginous end plate irregularities, nucleus pulposus defects, and bone marrow formation. In the chronological observation, the thickness and shape of the malformed structures on T1WI did not change.ConclusionsSpinal malformations in mice were chronologically observed via 7 T MRI and histology. MR images could be used to distinguish the histological structures of normal and malformed mouse spines. Malformed vertebrae were accompanied by adjacent intervertebral structures that corresponded to the fully segmented structures observed in human congenital scoliosis, but the intervertebral conditions varied. This study suggested the importance of MRI and histological examinations of human congenital scoliosis patients with patterns other than nonsegmenting patterns, which may be used to predict the prognosis of patients with spinal deformities associated with malformed vertebrae.

A cross-sectional study of the anatomy of the jaws of a central-European caucasian population using cone beam computer tomography as a prerequisite for designing pre-formed calcium phosphate cement scaffolds

PurposeThis study aims to measure the cortical and cancellous bone thickness in the upper and lower jaws, serving as a data template for developing pre-defined calcium phosphate cement primary implant forms. These measurements are crucial for creating a biphasic scaffold. MethodsForty complete jaws were assessed for cortical bone shape and thickness using statistical analysis and specific software tools. Sex and age were considered, and four groups were created. ResultsThe cumulative thickness of the cortical layer varied from region to region. In both the upper and lower jaws, the cortical layer in the molar region was significantly thicker than in the frontal region. Within the alveolar process, cortical thickness increases with distance from the alveolar crest on both sides. The oral side of the lower jaw is significantly thicker than the vestibular side. For the upper jaw, no significant differences between the oral and vestibular sides were found in this study. Additionally, it is noteworthy that men have a significantly thicker cortical layer than women. Regarding age, no significant overall differences were found. ConclusionMathematical analysis of anatomical forms using polynomial functions improves understanding of jaw anatomy. This approach facilitates the design of patient-specific scaffold structures, minimizing the need for costly and time-consuming planning and enabling more efficient implementation of optimal therapy.

Construction of multileveled and oriented micro/nano channels in Mg doped hydroxyapitite bioceramics and their effect on mimicking mechanical property of cortical bone and biological performance of cancellous bone

Drawing on the structure and components of natural bone, this study developed Mg-doped hydroxyapatite (Mg-HA) bioceramics, characterized by multileveled and oriented micro/nano channels. These channels play a critical role in ensuring both mechanical and biological properties, making bioceramics suitable for various bone defects, particularly those bearing loads. Bioceramics feature uniformly distributed nanogrooves along the microchannels. The compressive strength or fracture toughness of the Mg-HA bioceramics with micro/nano channels formed by single carbon nanotube/carbon fiber (CNT/CF) (Mg-HA(05-CNT/CF)) are comparable to those of cortical bone, attributed to a combination of strengthened compact walls and microchannels, along with a toughening mechanism involving crack pinning and deflection at nanogroove intersections. The introduction of uniform nanogrooves also enhanced the porosity by 35.4 %, while maintaining high permeability owing to the capillary action in the oriented channels. This leads to superior degradation properties, protein adsorption, and in vivo osteogenesis compared with bioceramics with only microchannels. Mg-HA(05-CNT/CF) exhibited not only high strength and toughness comparable to cortical bone, but also permeability similar to cancellous bone, enhanced cell activity, and excellent osteogenic properties. This study presents a novel approach to address the global challenge of applying HA-based bioceramics to load-bearing bone defects, potentially revolutionizing their application in tissue engineering.

TBS correlates with bone density and microstructure at trabecular and cortical bone evaluated by HR-pQCT.

Trabecular bone score (TBS) estimates bone microstructure, which is directly measured by high-resolution peripheral quantitative computed tomography (HRpQCT). We evaluated the correlation between these methods and TBS influence on fracture risk assessed by FRAX. We evaluated 129 individuals (82 women, 43 postmenopausal) 20 to 82.3 years without prevalent clinical or non-clinical morphometric vertebral fractures, using DXA (spine and hip), HR-pQCT at distal radius (R) and tibia (T) and TBS which classifies bone microarchitecture as normal (TBS ≥ 1.350), partially degraded (1.200 < TBS < 1.350), or degraded (TBS ≤ 1.200). Spine and hip BMD and HR-pQCT parameters at cortical bone: area (T), density (R,T) thickness (T) and trabecular bone: density (R,T), number (T) and thickness (R) were significantly better in the 78 individuals with normal TBS (group 1) versus the 51 classified as partially degraded (n = 42) or degraded microarchitecture (n = 9) altogether (group 2). TBS values correlated with age (r = -0.55), positively with spine and hip BMD and all cortical and trabecular bone density and microstructure parameters evaluated, p < 0.05 all tests. Binary logistic regression defined age (p = 0.008) and cortical thickness (p = 0.018) as main influences on TBS, while ANCOVA demonstrated that HR-pQCT data corrected for age were not different between TBS groups 1 and 2. TBS adjustment increased FRAX risk for major osteoporotic fractures and hip fractures. We describe significant association between TBS and both trabecular and cortical bone parameters measured by HR-pQCT, consistent with TBS influence on fracture risk estimation by FRAX, including hip fractures, where cortical bone predominates.

Comparison of different bone substitutes in the repair of rat calvaria critical size defects: questioning the need for alveolar ridge presentation.

This study aimed to evaluate the effectiveness of biomaterials in bone healing of critical bone defects created by piezoelectric surgery in rat calvaria. Histomorphologic analysis was performed to assess bone regeneration and tissue response. Fifty animals were randomized into five groups with one of the following treatments: Control group (n = 10), spontaneous blood clot formation with no bone fill; BO group (Bio-Oss, Geistlich Pharma; n = 10), defects were filled with bovine medullary bone substitute; BF group (Bonefill, Bionnovation; n = 10), defects were filled with bovine cortical bone substitute; hydroxyapatite group (n = 10), defects were filled with hydroxyapatite; calcium sulfate group (n = 10), defects were filled with calcium sulfate. Five animals from each group were euthanized at 30 and 45 days. The histomorphometry calculated the percentage of the new bone formation in the bone defect. All data obtained were evaluated statistically considering P < .05 as statistically significant. The results demonstrated the potential of all biomaterials for enhancing bone regeneration. The findings showed no statistical differences between all the biomaterials at 30 and 45 days including the control group without bone grafting. In conclusion, the tested biomaterials presented an estimated capacity of osteoconduction, statistically nonsignificant between them. In addition, the selection of biomaterial should consider the specific clinical aspect, resorption rates, size of the particle, and desired bone healing responses. It is important to emphasize that in some cases, using no bone filler might provide comparable results with reduced cost and possible complications questioning the very frequent use of ridge presentation procedures.

A deep learning-based pipeline for developing multi-rib shape generative model with populational percentiles or anthropometrics as predictors

Rib cross-sectional shapes (characterized by the outer contour and cortical bone thickness) affect the rib mechanical response under impact loading, thereby influence the rib injury pattern and risk. A statistical description of the rib shapes or their correlations to anthropometrics is a prerequisite to the development of numerical human body models representing target demographics. Variational autoencoders (VAE) as anatomical shape generators remain to be explored in terms of utilizing the latent vectors to control or interpret the representativeness of the generated results. In this paper, we propose a pipeline for developing a multi-rib cross-sectional shape generative model from CT images, which consists of the achievement of rib cross-sectional shape data from CT images using an anatomical indexing system and regular grids, and a unified framework to fit shape distributions and associate shapes to anthropometrics for different rib categories. Specifically, we collected CT images including 3193 ribs, surface regular grid is generated for each rib based on anatomical coordinates, the rib cross-sectional shapes are characterized by nodal coordinates and cortical bone thickness. The tensor structure of shape data based on regular grids enable the implementation of CNNs in the conditional variational autoencoder (CVAE). The CVAE is trained against an auxiliary classifier to decouple the low-dimensional representations of the inter- and intra- variations and fit each intra-variation by a Gaussian distribution simultaneously. Random tree regressors are further leveraged to associate each continuous intra-class space with the corresponding anthropometrics of the subjects, i.e., age, height and weight. As a result, with the rib class labels and the latent vectors sampled from Gaussian distributions or predicted from anthropometrics as the inputs, the decoder can generate valid rib cross-sectional shapes of given class labels (male/female, 2nd to 11th ribs) for arbitrary populational percentiles or specific age, height and weight, which paves the road for future biomedical and biomechanical studies considering the diversity of rib shapes across the population.

Effect of angled abutments in the posterior maxillary region on tilted implants: a 3D finite element analysis.

The aim of this study was to evaluate the bone tissue effects under dynamic loading using finite element analysis (FEA) for four angled abutments with different deviated palatal lateral tilt angles. A three-dimensional model of the posterior maxillary region and an implant crown model were reconstructed and assembled with a three-dimensional model of the implant, angled abutment, and central screw to create a total of 10 three-dimensional finite element models tilted at , , , and in three groups, and the dynamic loads simulating oral mastication were loaded on the implant crown to analyze the equivalent stresses and strains in the peri-implant bone tissues. Under the dynamic loading, the cortical bone on the buccal side of the implant neck showed different degrees of stress concentration, and the cortical bone stress was much higher than the cancellous bone, and the strain concentration area of each model was located in the bone tissue around the implant neck and base. For the use of angular abutment, under the premise that the cortical bone stresses and strains of the 10 models meet the requirements for use, the peak stresses of 2.907 MPa, 3.018 MPa, and 2.164 MPa were achieved by using the angular abutment to achieve the tilt angles of , , and implantation, which is more advantageous compared with other models.

Long-duration leptin transgene expression in dorsal vagal complex does not alter bone parameters in female Sprague Dawley rats

The hypothalamus and dorsal vagal complex (DVC) are both important for integration of signals that regulate energy balance. Increased leptin transgene expression in either the hypothalamus or DVC of female rats was shown to decrease white adipose tissue and circulating levels of leptin and adiponectin. However, in contrast to hypothalamus, leptin transgene expression in the DVC had no effect on food intake, circulating insulin, ghrelin and glucose, nor on thermogenic energy expenditure. These findings imply different roles for hypothalamus and DVC in leptin signaling. Leptin signaling is required for normal bone accrual and turnover. Leptin transgene expression in the hypothalamus normalized the skeletal phenotype of leptin-deficient ob/ob mice but had no long-duration (≥10 weeks) effects on the skeleton of leptin-replete rats. The goal of this investigation was to determine the long-duration effects of leptin transgene expression in the DVC on the skeleton of leptin-replete rats. To accomplish this goal, we analyzed bone from three-month-old female rats that were microinjected with recombinant adeno-associated virus encoding either rat leptin (rAAV-Leptin, n = 6) or green fluorescent protein (rAAV-GFP, control, n = 5) gene. Representative bones from the appendicular (femur) and axial (3rd lumbar vertebra) skeleton were evaluated following 10 weeks of treatment. Selectively increasing leptin transgene expression in the DVC had no effect on femur cortical or cancellous bone microarchitecture. Additionally, increasing leptin transgene expression had no effect on vertebral osteoblast-lined or osteoclast-lined bone perimeter or marrow adiposity. Taken together, the findings suggest that activation of leptin receptors in the DVC has minimal specific effects on the skeleton of leptin-replete female rats.

Diagnostic Anatomic Imaging for Neuroendocrine Neoplasms: Maximizing Strengths and Mitigating Weaknesses.

Neuroendocrine neoplasms are a heterogeneous group of gastrointestinal and lung tumors. Their diverse clinical manifestations, variable locations, and heterogeneity present notable diagnostic challenges. This article delves into the imaging modalities vital for their detection and characterization. Computed tomography is essential for initial assessment and staging. At the same time, magnetic resonance imaging (MRI) is particularly adept for liver, pancreatic, osseous, and rectal imaging, offering superior soft tissue contrast. The article also highlights the limitations of these imaging techniques, such as MRI's inability to effectively evaluate the cortical bone and the questioned cost-effectiveness of computed tomography and MRI for detecting specific gastric lesions. By emphasizing the strengths and weaknesses of these imaging techniques, the review offers insights into optimizing their utilization for improved diagnosis, staging, and therapeutic management of neuroendocrine neoplasms.

An Approach to Microscopic Cortical Bone Fracture Simulation: Enhancing Clinical Replication

The acquisition of bone models to perform simulations is a complex and expensive process. The hierarchical structure of bones is very complex, so that studies are mainly focused on the larger scales of bones. The objective of this work is to perform a fracture simulation at the microscale level. For this purpose, the first part of the process focuses on segmenting a bone model and selecting an area of it to generate a representation of the microstructures that make up the bone tissue from a microscopic point of view. The second part is dedicated to carry out a fracture simulation in the microscopic bone model. The developed algorithm follows a statistical approach and solves the main problems of the traditional approach (FEM) to perform a bone fracture simulation. The method returns the path that a fracture follows and demonstrates how bone structures affect fracture growth. The parameters used are configurable and can be adapted for specific cases. In addition, users can reproduce as many clinical cases as desired within seconds without have to manually segment images obtained from a microscope. The data obtained may be exported to obtain synthetic images that could be used to generate datasets for machine learning tasks or other purposes.

Reconstruction of Segmental Bone Defect in Canine Tibia Model Utilizing Bi-Phasic Scaffold: Pilot Study.

The reunion and restoration of large segmental bone defects pose significant clinical challenges. Conventional strategies primarily involve the combination of bone scaffolds with seeded cells and/or growth factors to regulate osteogenesis and angiogenesis. However, these therapies face inherent issues related to immunogenicity, tumorigenesis, bioactivity, and off-the-shelf transplantation. The biogenic micro-environment created by implanted bone grafts plays a crucial role in initiating the bone regeneration cascade. To address this, a highly porous bi-phasic ceramic synthetic bone graft, composed of hydroxyapatite (HA) and alumina (Al), was developed. This graft was employed to repair critical segmental defects, involving the creation of a 2 cm segmental defect in a canine tibia. The assessment of bone regeneration within the synthetic bone graft post-healing was conducted using scintigraphy, micro-CT, histology, and dynamic histomorphometry. The technique yielded pore sizes in the range of 230-430 μm as primary pores, 40-70 μm as secondary inner microchannels, and 200-400 nm as tertiary submicron surface holes. These three components are designed to mimic trabecular bone networks and to provide body fluid adsorption, diffusion, a nutritional supply, communication around the cells, and cell anchorage. The overall porosity was measured at 82.61 ± 1.28%. Both micro-CT imaging and histological analysis provided substantial evidence of robust bone formation and the successful reunion of the critical defect. Furthermore, an histology revealed the presence of vascularization within the newly formed bone area, clearly demonstrating trabecular and cortical bone formation at the 8-week mark post-implantation.

Exploring the efficacy of photodynamic antimicrobial chemotherapy on diabetic foot ulcers in rats.

We investigate the efficacy of photodynamic antimicrobial chemotherapy (PACT) and its combination with an antibiotic in the treatment of diabetic foot ulcers (DFUs) in rats using a novel cationic amino acid porphyrin-based photosensitizer. The research findings demonstrate that the combination of novel cationic photosensitizer-mediated PACT and an antibiotic exhibits significant therapeutic efficacy in treating deep ulcers in a rat model of DFUs. Moreover, the PACT + Antibiotic group displays enhanced angiogenesis, improved tissue maturation, and superior wound healing effect. Micro-computed tomography examination showed that the periosteal reaction was most obvious in the PACT + Antibiotic group. The cortical bone volume ratio (BV/TV), the bone mineral density, and trabecular thickness were significantly higher in the PACT + Antibiotic group than in the model group (p < 0.05). The combination of PACT and antibiotic plays a sensitizing therapeutic role, which provides a new idea for the clinical treatment of DFUs.

Magnetic resonance-guided focused ultrasound thalamotomy for essential tremor patients with low skull density ratio: a case-matched analysis.

Skull density ratio (SDR) is the ratio between the mean Hounsfield units of marrow and cortical bone, impacting energy transmission through the skull. Low SDR has been used as an exclusion criterion in major trials of magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for medication-refractory essential tremor (ET). However, some studies have suggested that patients with low SDR can safely undergo MRgFUS with favorable outcomes. In this case-matched study, we aim to compare the characteristics, sonication parameters, lesion sizes, and clinical outcomes of patients with low SDR vs. patients with high SDR who underwent unilateral MRgFUS thalamotomy for medication-refractory ET. Between March 2016 and April 2023, all patients (n = 270) who underwent unilateral MRgFUS thalamotomy for medication-refractory ET at a single institution were classified as low SDR (<0.40) and high SDR (≥0.40). All clinical and radiological data was prospectively collected and retrospectively analyzed using non-case-matched and 1:1 case-matched methodology. Thirty-one patients had low SDR, and 239 patients had high SDR. Fifty-six patients (28 in each cohort) were included in 1:1 case-matched analysis. There were no significant differences in baseline characteristics between the two groups in both non-case-matched and 1:1 case-matched analyses. In both analyses, compared to patients with high SDR, patients with low SDR required a significantly higher maximum sonication power, energy, and duration, and reached a lower maximum temperature with smaller lesion volumes. In the non-case-matched and case-matched analyses, low SDR patients did not have significantly less tremor control at any postoperative timepoints. However, there was a higher chance of procedure failure in the low SDR group with three patients not obtaining an appropriately sized lesion. In both analyses, imbalance was observed more often in high SDR patients on postoperative day 1 and month 3. ET patients with SDR <0.40 can be safely and effectively treated with MRgFUS, though there may be higher rates of treatment failure and intraoperative discomfort.