Targeting adipocyte ESRRA promotes osteogenesis and vascular formation in adipocyte-rich bone marrow.

Excessive bone marrow adipocytes (BMAds) accumulation often occurs under diverse pathophysiological conditions associated with bone deterioration. Estrogen-related receptor α (ESRRA) is a key regulator responding to metabolic stress. Here, we show that adipocyte-specific ESRRA deficiency preserves osteogenesis and vascular formation in adipocyte-rich bone marrow upon estrogen deficiency or obesity. Mechanistically, adipocyte ESRRA interferes with E2/ESR1 signaling resulting in transcriptional repression of secreted phosphoprotein 1 (Spp1); yet positively modulates leptin expression by binding to its promoter. ESRRA abrogation results in enhanced SPP1 and decreased leptin secretion from both visceral adipocytes and BMAds, concertedly dictating bone marrow stromal stem cell fate commitment and restoring type H vessel formation, constituting a feed-forward loop for bone formation. Pharmacological inhibition of ESRRA protects obese mice against bone loss and high marrow adiposity. Thus, our findings highlight a therapeutic approach via targeting adipocyte ESRRA to preserve bone formation especially in detrimental adipocyte-rich bone milieu.

Bidirectional control of parathyroid hormone and bone mass by subfornical organ.

Parathyroid hormone (PTH) is one of the most important hormones for bone turnover and calcium homeostasis. It is unclear how the central nervous system regulates PTH. The subfornical organ (SFO) lies above the third ventricle and modulates body fluid homeostasis. Through retrograde tracing, electrophysiology, and in vivo calcium imaging, we identified the SFO as an important brain nucleus that responds to serum PTH changes in mice. Chemogenetic stimulation of GABAergic neurons in SFO induces decreased serum PTH followed by a decrease in trabecular bone mass. Conversely, stimulation of glutamatergic neurons in the SFO promoted serum PTH and bone mass. Moreover, we found that the blockage of different PTH receptors in the SFO affects peripheral PTH levels and the PTH's response to calcium stimulation. Furthermore, we identified a GABAergic projection from the SFO to the paraventricular nucleus, which modulates PTH and bone mass. These findings advance our understanding of the central neural regulation of PTH at cellular and circuit level.

A Unified Therapeutic-Prophylactic Tissue-Engineering Scaffold Demonstrated to Prevent Tumor Recurrence and Overcoming Infection toward Bone Remodeling.

Osteosarcoma occurs in children and adolescents frequently and leads to a high fatality rate. Although surgical resection is the most common methods in clinic, patients always suffer from tumor metastasis and recurrence and it is difficult for them to self-repair large bone defects. Furthermore, the postoperative infection from bacteria triggers an inflammatory response and hinders the bone-repair process. This work demonstrates a gadolinium (Gd)-complex and molybdenum sulfide (MoS2 ) co-doped N-acryloyl glycinamide (NAGA)/gelatin methacrylate (Gel-MA) multifunctional hydrogel (GMNG). The combination between NAGA and Gel-MA endows the GMNG with attractive mechanical properties and controllable degradation ability. The MoS2 improves the hydrogel system, which has excellent photothermal ability to kill tumor cells and inhibit bacterial infection both in vitro and in vivo. Based on the Gd-complex, the magnetic resonance imaging (MRI) effect can be used to monitor the position and degradation situation of the hydrogel. Notably, accompanied by the degradation of GMNG hydrogel, the gradually released Gd3+ from the hydrogel exhibits osteogenic property and could promote new bone formation efficiently in vivo. Therefore, this strategy supplies a method to prepare multifunctional bone-defect-repair materials and is expected to represent a significant guidance and reference to the development of biomaterials for bone tissue engineering.

Distribution of bone voids in the thoracolumbar spine in Chinese adults with and without osteoporosis: A cross-sectional multi-center study based on 464 vertebrae.

Bone void is a novel intuitive morphological indicator to assess bone quality but its use in vertebrae has not been described. This cross-sectional and multi-center study aimed to investigate the distribution of bone voids in the thoracolumbar spine in Chinese adults based on quantitative computed tomography (QCT). A bone void was defined as a trabecular net region with extremely low bone mineral density (BMD) (<40 mg/cm3), detected by an algorithm based on phantom-less technology. A total of 464 vertebrae from 152 patients (51.8 ± 13.4 years old) were included. The vertebral trabecular bone was divided into eight sections based on the middle sagittal, coronal, and horizontal planes. Bone void of the whole vertebra and each section were compared between healthy, osteopenia, and osteoporosis groups and between spine levels. Receiver operator characteristic (ROC) curves were plotted and optimum cutoff points of void volume between the groups were obtained. The total void volumes of the whole vertebra were 124.3 ± 221.5 mm3, 1256.7 ± 928.7 mm3, and 5624.6 ± 3217.7 mm3 in healthy, osteopenia, and osteoporosis groups, respectively. The detection rate of vertebrae with bone voids was higher and the normalized void volume was larger in the lumbar than in thoracic vertebrae. L3 presented the largest void (2165.0 ± 3396.0 mm3), while T12 had the smallest void (448.9 ± 699.4 mm3). The bone void was mainly located in the superior-posterior-right section (40.8 %). Additionally, bone void correlated positively with age and increased rapidly after 55 years. The most significant void volume increase was found in the inferior-anterior-right section whereas the least increase was found in the inferior-posterior-left section with aging. The cutoff points were 345.1 mm3 between healthy and osteopenia groups (sensitivity = 0.923, specificity = 0.932) and 1693.4 mm3 between osteopenia and osteoporosis groups (sensitivity = 1.000, specificity = 0.897). In conclusion, this study demonstrated the bone void distribution in vertebrae using clinical QCT data. The findings provide a new perspective for the description of bone quality and showed that bone void could guide clinical practice such as osteoporosis screening.

Infiltration from Suspension Systems Enables Effective Modulation of 3D Scaffold Properties in Suspension Bioprinting.

Bioprinting is a biofabrication technology which allows efficient and large-scale manufacture of 3D cell culture systems. However, the available biomaterials for bioinks used in bioprinting are limited by their printability and biological functionality. Fabricated constructs are often homogeneous and have limited complexity in terms of current 3D cell culture systems comprising multiple cell types. Inspired by the phenomenon that hydrogels can exchange liquids under the infiltration action, infiltration-induced suspension bioprinting (IISBP), a novel printing technique based on a hyaluronic acid (HA) suspension system to modulate the properties of the printed scaffolds by infiltration action, was described in this study. HA served as a suspension system due to its shear-thinning and self-healing rheological properties, simplicity of preparation, reusability, and ease of adjustment to osmotic pressure. Changes in osmotic pressure were able to direct the swelling or shrinkage of 3D printed gelatin methacryloyl (GelMA)-based bioinks, enabling the regulation of physical properties such as fiber diameter, micromorphology, mechanical strength, and water absorption of 3D printed scaffolds. Human umbilical vein endothelial cells (HUVEC) were applied as a cell culture model and printed within cell-laden scaffolds at high resolution and cell viability with the IISBP technique. Herein, the IISBP technique had been realized as a reliable hydrogel-based bioprinting technique, which enabled facile modulation of 3D printed hydrogel scaffolds properties, being expected to meet the scaffolds requirements of a wide range of cell culture conditions to be utilized in bioprinting applications.

Osteoarthritis Pain.

Joint pain is the hallmark symptom of osteoarthritis (OA) and the main reason for patients to seek medical assistance. OA pain greatly contributes to functional limitations of joints and reduced quality of life. Although several pain-relieving medications are available for OA treatment, the current intervention strategy for OA pain cannot provide satisfactory pain relief, and the chronic use of the drugs for pain management is often associated with significant side effects and toxicities. These observations suggest that the mechanisms of OA-related pain remain undefined. The current review mainly focuses on the characteristics and mechanisms of OA pain. We evaluate pathways associated with OA pain, such as nerve growth factor (NGF)/tropomyosin receptor kinase A (TrkA), calcitonin gene-related peptide (CGRP), C-C motif chemokine ligands 2 (CCL2)/chemokine receptor 2 (CCR2) and tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1ß), the NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, and the Wnt/ß-catenin signaling pathway. In addition, animal models currently used for OA pain studies and emerging preclinical studies are discussed. Understanding the multifactorial components contributing to OA pain could provide novel insights into the development of more specific and effective drugs for OA pain management.

Cultural Validation of the Chinese Central Sensitization Inventory in Patients with Chronic Pain and its Predictive Ability of Comorbid Central Sensitivity Syndromes.

BACKGROUND: Central sensitization (CS) is frequently reported in chronic pain, and the central sensitization inventory (CSI) is popularly used to assess CS. However, a validated Chinese CSI is lacking and its predictive ability for the comorbidity of central sensitivity syndromes (CSSs) remains unclear. Hence, this study aimed to generate the Chinese CSI (CSI-C) with cultural adaptation and examine its psychometric properties. METHODS: The CSI-C was formulated through forward and backward translation, panel review and piloting and then validated among patients with chronic pain (n = 235). Its internal consistency, test-retest reliability, and concurrent validity were measured. An exploratory factor analysis (EFA) was performed for the construct validity. Receiver operating characteristic (ROC) analysis was employed to determine the discriminative ability in the presence of comorbidity of CSSs. RESULTS: About 70% of the participants in the study experienced at least mild CS symptoms. CSI-C demonstrates a high internal consistency (Cronbach's alpha = 0.896) and excellent test-retest reliability (ICC = 0.932). CSI-C scoring was significantly correlated with pain intensity (r = 0.188), EQ-5D index (r = -0.375), anxiety (r=0.525), and depression (r = 0.467). The EFA generated a 5-factor model, including physical symptoms, emotional distress, hypersensitivity syndromes and so on. An CSI cutoff of 42 had a sensitivity of 71.4% and a specificity of 70% for identifying chronic pain patients with ≥2 CSSs. CONCLUSION: The CS manifestations are prevalent in those with persistent pain. CSI-C is a reliable and valid instrument for measuring CS. A CSI score ≥42 may predict the comorbidity of 2 or above CSSs in patients with chronic pain.

3D-bioprinted BMSC-laden biomimetic multiphasic scaffolds for efficient repair of osteochondral defects in an osteoarthritic rat model.

Osteochondral defect repair in osteoarthritis (OA) remains an unsolved clinical problem due to the lack of enough seed cells in the defect and chronic inflammation in the joint. To address this clinical need, we designed a bone marrow-derived mesenchymal stem cell (BMSC)-laden 3D-bioprinted multilayer scaffold with methacrylated hyaluronic acid (MeHA)/polycaprolactone incorporating kartogenin and ß-TCP for osteochondral defect repair within each region. BMSC-laden MeHA was designed to actively introduce BMSCs in situ, and diclofenac sodium (DC)-incorporated matrix metalloproteinase-sensitive peptide-modified MeHA was induced on the BMSC-laden scaffold as an anti-inflammatory strategy. BMSCs in the scaffolds survived, proliferated, and produced large amounts of cartilage-specific extracellular matrix in vitro. The effect of BMSC-laden scaffolds on osteochondral defect repair was investigated in an animal model of medial meniscectomy-induced OA. BMSC-laden scaffolds facilitated chondrogenesis by promoting collagen II and suppressed interleukin 1ß in osteochondral defects of the femoral trochlea. Congruently, BMSC-laden scaffolds significantly improved joint function of the injured leg with respect to the ground support force, paw grip force, and walk gait parameters. Therefore, this research demonstrates the potential of 3D-bioprinted BMSC-laden scaffolds to simultaneously inhibit joint inflammation and promote cartilage defect repair in OA joints.

A biomechanical study on the effect of lengthening magnitude on spine off-loading in magnetically controlled growing rod surgery: Implications on lengthening frequency.

Purpose: To assess whether the magnitude of lengthening in magnetically controlled growing rod (MCGR) surgeries has an immediate or delayed effect on spinal off-loading. Methods: 9 whole porcine spines were instrumented using two standard MCGRs from T9 to L5. Static compression testing using a mechanical testing system (MTS) was performed at three MCGR lengthening stages (0 mm, 2 mm, and 6 mm) in each spine. At each stage, five cycles of compression at 175N with 25 min of relaxation was carried out. Off-loading was derived by comparing the load sustained by the spine with force applied by the MTS to the spine. Micro-CT imaging was subsequently performed. Results: The mean load sustained by the vertebral body before lengthening was 39.69N, and immediately after lengthening was 25.12N and 19.91N at 2 mm and 6 mm lengthening, respectively; decreasing to 10.07N, 8.31N, and 8.17N after 25 minutes of relaxation, at 0 mm, 2 mm, and 6 mm lengthening stages, respectively. There was no significant difference in off-loading between 2 mm and 6 mm lengthening stages, either instantaneously (p = 0.395) or after viscoelastic relaxation (p = 0.958). CT images showed fractures/separations at the level of pedicle screws in six spines and in the vertebral body's growth zone in five spines after 6 mm MCGR lengthening. Conclusion: This study demonstrated MCGRs cause significant off-loading of the spine leading to stress shielding. 6 mm of lengthening caused tissue damage and microfractures in some spines. There was no significant difference in spine off-loading between 2 mm and 6 mm MCGR lengthening, either immediately after lengthening or after viscoelastic relaxation.

Types of vertebral fractures could influence the selection of clinical bone mineral measures to predict biomechanical properties.

Areal and volumetric BMD (aBMD and vBMD) measured by DXA and quantitative CT (QCT), respectively, are usually employed to predict vertebral fracture risks. In this study, we induced compression and wedge vertebral fractures to test if the types of fracture could influence the selection of bone mineral measures to predict biomechanical properties of vertebral bodies. DXA and QCT were employed to scan twenty-four male cadaveric vertebral bodies of humans for bone mineral content (BMC) and aBMD measures, and vBMD measures, respectively. We computed vBMD measures from three kinds of volumes of interest: intact structures (vertebral body, cortical compartment, and trabecular core), axially middle sections (1.250-1.875 cm height) of the intact structures, and clinically used elliptical regions of trabecular bone. We loaded vertebral bodies to failure for properties of strength (Pu), failure displacement (δu), and stiffness (K). Thirteen vertebral bodies sustained compression fractures and the remaining sustained wedge fractures. Linear and power regression models were used to test bone mineral predictions for Pu, δu, and K. We also did equality tests of correlation coefficients. Our results showed aBMD, BMC, and vBMD of the middle section of trabecular bone had the strongest correlations with Pu (R2 = 0.6420, p < 0.001), δu (R2 = 0.4619, p < 0.001), and K (R2 = 0.5992, p < 0.001) in power regression models, respectively when compression and wedge fractures were mixed. Considering compression fractures only, vBMD of the intact vertebral body displayed the strongest correlations with both Pu (R2 = 0.6529, p < 0.001) and K (R2 = 0.6354, p < 0.001) while BMC showed the strongest correlation with δu (R2 = 0.4376, p < 0.001) in linear regression models. When only wedge fractures were analyzed, vBMD of the elliptical regions of trabecular bone exhibited the strongest correlations with both Pu (R2 = 0.5845, p < 0.001) and K (R2 = 0.6420, p < 0.001) in power regression models, however, no bone mineral measure could significantly correlate with δu. These results may suggest the type of fracture could influence the determination of bone mineral measures to predict biomechanical properties of vertebral bodies.

Rapid external erosion of coral substrate in subtropical Hong Kong waters.

Erosion of coral substrate plays a crucial role in reef calcium carbonate budget, but little is known about erosion in subtropical corals. In a 2-year study of coral substrate erosion, we deployed Porites skeletal blocks at nine sites across subtropical Hong Kong waters. External erosion varied from 0.05 to 3.07 kg m-2 yr-1 and accounted for 23.4-99.2% of the total erosion. More than half of the study sites had substantial external erosion (> 1 kg m-2 yr-1), and the values were positively correlated with density of the sea urchin Diadema setosum. Excluding urchins from access to the skeletal blocks using cages reduced external erosion by more than 90%. Overall, our study revealed that external erosion caused by urchin grazing contributed predominantly to the total coral skeletal loss in Hong Kong waters. Control of sea urchin population is needed to reduce coral erosion in places with high urchin density. (149 words).

Clay-based nanocomposite hydrogel with attractive mechanical properties and sustained bioactive ion release for bone defect repair.

Although clay-based nanocomposite hydrogels have been widely explored, their instability in hot water and saline solution inhibits their applications in biomedical engineering, and the exploration of clay-based nanocomposite hydrogels in bone defect repair is even less. In this work, we developed a stable clay-based nanocomposite hydrogel using 4-acryloylmorpholine as the monomer. After UV light illumination, the obtained poly(4-acryloylmorpholine) clay-based nanocomposite hydrogel (poly(4-acry)-clay nanocomposite hydrogel) exhibits excellent mechanical properties due to the hydrogen bond interactions between the poly(4-acryloylmorpholine) chains and the physical crosslinking effect of the nanoclay. Besides good biocompatibility, the sustainable release of intrinsic Mg2+ and Si4+ from the poly(4-acry)-clay nanocomposite hydrogel endows the system with excellent ability to promote the osteogenic differentiation of primary rat osteoblasts (ROBs) and can promote new bone formation effectively after implantation. We anticipate that these kinds of clay-based nanocomposite hydrogels with sustained release of bioactive ions will open a new avenue for the development of novel biomaterials for bone regeneration.

Metformin Hydrochloride Encapsulation by Alginate Strontium Hydrogel for Cartilage Regeneration by Reliving Cellular Senescence.

Cartilage lesion is a common tissue defect and is challenging in clinical practice. Trauma-induced cellular senescence could decrease the chondrocyte capability of maintaining cartilage tissue regeneration. A previous investigation showed that, by controlling the cellular senescence, the cartilage regeneration can be significantly accelerated. Based on this finding, we design a novel hydrogel, Alg/MH-Sr, that combines metformin, an established drug for inhibiting senescence, and strontium, an effective anti-inflammatory material for cartilage tissue engineering. A RT-PCR test suggests the significant inhibitory effect of the hydrogel on senescent, apoptotic, oxidative, and inflammatory genes' expression. Histological examinations demonstrate that the Alg/MH-Sr hydrogel accelerated cartilage repairment, and chondrocyte senescence was significantly inhibited. Our study demonstrates that the Alg/MH-Sr hydrogel is effective for cartilage defect treatment and provides a new clue in accelerating tissue repairment by inhibiting the senescence of cells and tissues.

Lingzhi and San-Miao-San with hyaluronic acid gel mitigate cartilage degeneration in anterior cruciate ligament transection induced osteoarthritis.

OBJECTIVE: To investigate the mitigate efficacy of Chinese medicine Lingzhi (LZ) and San-Miao-San (SMS) combined with hyaluronic acid (HA)-gel in attenuating cartilage degeneration in traumatic osteoarthritis (OA). METHODS: The standardized surgery of anterior cruciate ligament transection (ACLT) was made from the medial compartment of right hind limbs of 8-week-old female SD rats and resulted in a traumatic OA. Rats (n â€‹= â€‹5/group) were treated once intra-articular injection of 50 â€‹µl HA-gel, 50 â€‹µl HA-gel+50 â€‹µg LZ-SMS, 50 â€‹µl of saline+50 â€‹µg LZ-SMS and null (ACLT group) respectively, except sham group. Limbs were harvested for µCT scan and histopathological staining 3-month post-treatment. Inflammatory cytokines from plasma and synovial fluid were detected using Immunology Multiplex Assay kit. The putative targets of active compounds in LZ-SMS and known therapeutic targets for OA were combined to construct protein-protein interaction network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was adopted to predict the potential targets and signaling pathway of LZ-SMS in OA through the tool of DAVID Bioinformatics. RESULTS: In vivo, HA-gel â€‹+ â€‹LZ-SMS treatment resulted in a higher volume ratio of hyaline cartilage (HC)/calcified cartilage (CC) and HC/Sum (total volume of cartilage), compared to ACLT and HA-gel groups. In addition, histological results showed the elevated cartilage matrix, chondrogenic and osteoblastic signals in HA-gel â€‹+ â€‹LZ-SMS treatment. Treatment also significantly altered subchondral bone (SCB) structure including an increase in BV/TV, Tb.Th, BMD, Conn.Dn, Tb.N, and DA, as well as a significant decrease in Tb.Sp and Po(tot), which implied a protective effect on maintaining the stabilization of tibial SCB microstructure. Furthermore, there was also a down-regulated inflammatory cytokines and upregulated anti-inflammatory cytokine IL-10 in HA+LZ-SMS group. Finally, 64 shared targets from 37 active compounds in LZ-SMS related to the core genes for the development of OA. LZ-SMS has a putative role in regulating inflammatory circumstance through influencing the MAPK signaling pathway. CONCLUSION: Our study elucidated a protective effect of HA-gel â€‹+ â€‹LZ-SMS in mitigating cartilage degradation and putative interaction with targets and signaling pathway for the development of traumatic OA. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our results provide a biological rationale for the use of LZ-SMS as a potential candidate for OA treatment.

Bioinspired Multichannel Nerve Guidance Conduit Based on Shape Memory Nanofibers for Potential Application in Peripheral Nerve Repair.

Repairing peripheral nerve injury, especially long-range defects of thick nerves, is a great challenge in the clinic due to their limited regeneration capability. Most FDA-approved nerve guidance conduits with large hollow lumen are only suitable for short lesions, and their effects are unsatisfactory in repairing long gaps of thick nerves. Multichannel nerve guidance conduits have been shown to offer better regeneration of long nerve defects. However, existing approaches of fabricating multichannel nerve conduits are usually complicated and time-consuming. Inspired by the intelligent responsive shaping process of shape memory polymers, in this study, a self-forming multichannel nerve guidance conduit with topographical cues was constructed based on a degradable shape memory PLATMC polymer. With an initial tubular shape obtained by a high-temperature molding process, the electrospun shape memory nanofibrous mat could be temporarily formed into a planar shape for cell loading to realize the uniform distribution of cells. Then triggered by a physical temperature around 37 °C, it could automatically restore its permanent tubular shape to form the multichannel conduit. This multichannel conduit exhibits better performance in terms of cell growth and the repair of rat sciatic nerve defects. These results reveal that self-forming nerve conduits can be realized based on shape memory polymers; thus, the fabricated bioinspired multichannel nerve guidance conduit has great potential in peripheral nerve regeneration.

Prevent action of magnoflorine with hyaluronic acid gel from cartilage degeneration in anterior cruciate ligament transection induced osteoarthritis.

According to the Chinese medicine, magnoflorine exerted significant anti-inflammatory effects and potentially promoted synthesis of proteoglycans in chondrocytes to reverse the progression of rheumatoid arthritis. However, the latent beneficial effect of magnoflorine for the treatment of traumatic osteoarthritis (OA) is still unknown. Therefore, we aim to demonstrate the efficacy of magnoflorine combined with HA-gel in attenuating cartilage degeneration in anterior cruciate ligament transection (ACLT) induced OA rat model. We found that the histological results showed the elevated cartilage matrix, chondrogenic signals and chondroprogenitor cells in HA-gel + magnoflorine treatment. HA-gel + magnoflorine treatment resulted in a decreased modified Mankin's score, and a higher volume ratio of hyaline cartilage (HC)/calcified cartilage (CC) and HC/Sum (whole cartilage), compared to ACLT and HA-gel groups. Furthermore, both the volume ratios of HC/Sum and HC/CC were negatively correlated with modified Mankin's scores. Finally, HA-gel + magnoflorine could significantly increase the BV/TV, Tb.Th, and decrease the Tb.Pf, Po(tot), Conn.Dn and Tb.Sp. In vitro, 50 µg/ml magnoflorine treatment could significantly increase the viability, S-phase, migration rate and chondrogenesis of chondroprogenitor cells. There were significant downregulations of MAPK/NF-κB signaling, and upregulations of chondrogenic signals in 50 µg/ml magnoflorine treatment. There were significant downregulations of proinflammatory cytokines and upregulation of IL-10 in HA-gel + magnoflorine treated group. Therefore, our study elucidated a protective effect of HA-gel + magnoflorine on attenuating cartilage degradation and maintaining SCB stabilization in ACLT induced OA.

Failure mechanisms of pedicle screws and cortical screws fixation under large displacement: A biomechanical and microstructural study based on a clinical case scenario.

STUDY DESIGN: Cadaveric biomechanical with imaging analysis. OBJECTIVE: This study aims to compare the fixation failure between pedicel screws (PS) and cortical screws (CS), thus to investigate their failure mechanisms under vertical migration. SUMMARY OF BACKGROUND DATA: Due to their minimal invasive nature, CS are gaining popularity. However, contradictions exist in the literature regarding whether CS may have superior fixation failure resistance compared to PS under vertical migration. METHODS: Human vertebral specimens were examined under Dual-energy X-ray. For each specimen, PS were inserted on the left and CS on the right with rods secured. Vertical force-displacement tests were applied to rods. MicroCT images were taken pre and post-MTS® for microstructural analysis. RESULTS: The average T-scores of the specimens were -4±0.25. Three phases of force-displacement behaviour featuring different PS and CS failure-resistance were discovered. For phase I, the force required to migrate PS tended to be slightly higher than CS. However, during phase II, a fixation instability occurred for PS and the CS fixation strength was superior. For phase III under large displacement, CS did not require increased force to displace, whereas PS re-stabilised and revealed improved displacement resistance. Both force analysis and microstructural analysis indicated that PS migrated along the direction of the vertical loading, whereas CS had a force component in the longitudinal axis of the screw. CONCLUSIONS: Different failure mechanisms underlay PS and CS under large vertical displacement. PS fail with trabecular bone compaction possibly altering the initial material property surround the screw. CS fail with screw cut-out due to the force component along the screw axis.

A novel mechanical parameter to quantify the microarchitecture effect on apparent modulus of trabecular bone: A computational analysis of ineffective bone mass.

BACKGROUND: One of the characteristics of osteoporotic bone is the deterioration of trabecular microarchitecture. Previous studies have shown microarchitecture alone can vary the apparent modulus of trabecular bone significantly independent of bone volume fraction (BV/TV) from morphological and topological perspectives. However, modulus is a mechanical quantity and there is a lack of mechanical explanatory parameters. This study aims to propose a novel mechanical parameter to quantify the microarchitecture effect on the apparent modulus of trabecular bone. MATERIALS AND METHODS: Fourteen human female cadaveric vertebrae were scanned with a dual-energy X-ray (DXA) equipment followed by a micro-CT (µCT) system at 18 µm isotropic resolution. Four trabecular bone specimens (3.46 × 3.46 × 3.46 mm) were obtained from each vertebral body and converted to voxel-based micro finite element (µFE) models. The apparent modulus (E) of the µFE model was computed using a linear micro finite element analysis (µFEA). The normalized apparent modulus (E*) was computed as E divided by BV/TV. The relationship between E and BV/TV was analyzed by linear, power-law and exponential regressions. Linear regression was performed between E* and BV/TV. Ineffective bone mass (InBM) was defined as the bone mass with a negligible contribution to the load-resistance and represented by elements with von Mises stress less than a certain stress threshold. InBM was quantified as the low von Mises stress ratio (LSVMR), which is the ratio of the number of InBM elements to the total number of elements in the µFE model. An incremental search technique with coarse and fine search intervals of 10 and 1 MPa, respectively, was adopted to determine the stress threshold for calculating LSVMR of the µFE model. Correlation between E* and LSVMR was analyzed using linear and power-law models for each stress threshold. The threshold producing the highest coefficient of determination (R2) in the correlation between E* and LSVMR was taken as the optimal stress threshold for calculating LSVMR. Linear regression was performed between E and LSVMR. Multiple linear regression of E against both BV/TV and LSVMR was further analyzed. RESULTS: E significantly (p < .001) correlates to BV/TV whereas E* has no significant (p = .75) correlation with BV/TV. Incremental search suggests 59 MPa to be the optimal stress threshold for calculating LSVMR. BV/TV alone can explain 59% of the variation in E using power-law regression model (E = 2254.64BV/TV1.04, R2 = 0.59, p < .001). LSVMR alone can explain 48% of the variation in E using linear regression model (E = 1696.4-1647.1LSVMR, R2 = 0.48, p < .001). With these two predictors taken into consideration, 95% of the variation in E can be explained in a multiple linear regression model (E = 1364.89 + 2184.37BV/TV - 1605.38LSVMR, adjusted R2 = 0.95, p < .001). CONCLUSION: LSVMR can be adopted as the mechanical parameter to quantify the microarchitecture effect on the apparent modulus of trabecular bone.

Multifunctional fibrous scaffolds for bone regeneration with enhanced vascularization.

Due to the structural similarity to the extracellular matrix of human tissue and the ultra-high surface area-to-volume ratio, three dimensional electrospun fibrous structures have been increasingly used as tissue engineering scaffolds. Given that successful bone regeneration requires both good osteogenesis and vascularization, producing scaffolds that have both osteogenic and angiogenic potential is highly desirable. In this investigation, tricomponent fibrous scaffolds simultaneously incorporated with recombinant human vein endothelial growth factor (rhVEGF), recombinant human bone morphogenetic protein-2 (rhBMP-2) and bioactive calcium phosphate (Ca-P) nanoparticles are produced through a novel multi-source multi-power electrospinning method, and sequential growth factor release with a quick rhVEGF release and a steady rhBMP-2 release is achieved. The enhanced human umbilical vein endothelial cell (HUVEC) migration and tube formation, and up-regulated human bone marrow derived mesenchymal stem cell (hBMSC) osteogenic differentiation and mineralization demonstrate that tricomponent scaffolds have balanced angiogenic-osteogenic properties in vitro. 8 weeks after the scaffold implantation into the cranial defects of mice, obvious new bone regeneration and newly formed capillaries are observed in tricomponent scaffolds, suggesting that the tricomponent scaffolds enhance osteogenesis in vivo with required vascularization, which shows the great potential of the tricomponent scaffolds in bone tissue regeneration.

The measured mechanical properties of osteoporotic trabecular bone decline with the increment of deformation volume during micro-indentation.

PURPOSE: Osteoporosis is a critical global health issue. However, the biomechanical properties of osteoporotic trabecular bone have not been well understood due to its hierarchically complex structure mingled with accumulated microcracks. Previous studies indicated the mechanical behaviors of trabecular bone may differ with varying amounts of deformation. Therefore, this study aims to further reveal the relationship between the measured mechanical properties of osteoporotic trabecular bone and various amounts of deformation volume during micro-indentation. METHODS: Two trabecular specimens were dissected transversally and frontally from an osteoporotic lumbar vertebral (L5) cadaver and embedded into Methyl methacrylate. On each specimen, two orthogonal cuts were performed to make a right-angle, followed by five parallel slicing. On each slice, the region of interest was gridded into 16 (4 × 4) sub-regions with the size equal to the microscope field. Within each sub-region, indentations were made on a single trabecula with five different indentation depths (3, 4, 5, 6, 7 µm) to induce different deformation volume. Both the indentation hardness and modulus were computed from the indenting curve for each measurement. The results of the five slices are pooled together to represent the longitudinal and circumferential mechanical characteristics, respectively. Linear regression was performed to investigate the relationship between the measured mechanical properties and various deformation volumes. RESULTS: A total of 1055 indents were made. After eliminating outliers, 840 indents were left for data analysis with 490 indents from transversal slices and 350 indents from frontal slices. Both the hardness and modulus decreased with the increasement of indentation depths. The hardness decreased by slopes of -0.65 (R2 = 0.72, p = 0.044) and -0.869 (R2 = 0.95, p = 0.003) longitudinally and circumferentially while the modulus decreased by slopes of -0.39 (R2 = 0.82, p = 0.02) and -0.348 (R2 = 0.94, p = 0.004) longitudinally and circumferentially. CONCLUSIONS: Mechanical properties of trabecular bone measured by micro-indentation can alter with the variation of deformation volume, which reflects the nonlinear behavior of vertebra from the material perspective.