Nuclear RNA catabolism controls endogenous retroviruses, gene expression asymmetry, and dedifferentiation.

Endogenous retroviruses (ERVs) are remnants of ancient parasitic infections and comprise sizable portions of most genomes. Although epigenetic mechanisms silence most ERVs by generating a repressive environment that prevents their expression (heterochromatin), little is known about mechanisms silencing ERVs residing in open regions of the genome (euchromatin). This is particularly important during embryonic development, where induction and repression of distinct classes of ERVs occur in short temporal windows. Here, we demonstrate that transcription-associated RNA degradation by the nuclear RNA exosome and Integrator is a regulatory mechanism that controls the productive transcription of most genes and many ERVs involved in preimplantation development. Disrupting nuclear RNA catabolism promotes dedifferentiation to a totipotent-like state characterized by defects in RNAPII elongation and decreased expression of long genes (gene-length asymmetry). Our results indicate that RNA catabolism is a core regulatory module of gene networks that safeguards RNAPII activity, ERV expression, cell identity, and developmental potency.

Negative feedback control of neuronal activity by microglia.

Microglia, the brain's resident macrophages, help to regulate brain function by removing dying neurons, pruning non-functional synapses, and producing ligands that support neuronal survival1. Here we show that microglia are also critical modulators of neuronal activity and associated behavioural responses in mice. Microglia respond to neuronal activation by suppressing neuronal activity, and ablation of microglia amplifies and synchronizes the activity of neurons, leading to seizures. Suppression of neuronal activation by microglia occurs in a highly region-specific fashion and depends on the ability of microglia to sense and catabolize extracellular ATP, which is released upon neuronal activation by neurons and astrocytes. ATP triggers the recruitment of microglial protrusions and is converted by the microglial ATP/ADP hydrolysing ectoenzyme CD39 into AMP; AMP is then converted into adenosine by CD73, which is expressed on microglia as well as other brain cells. Microglial sensing of ATP, the ensuing microglia-dependent production of adenosine, and the adenosine-mediated suppression of neuronal responses via the adenosine receptor A1R are essential for the regulation of neuronal activity and animal behaviour. Our findings suggest that this microglia-driven negative feedback mechanism operates similarly to inhibitory neurons and is essential for protecting the brain from excessive activation in health and disease.

Four-Meter Gait Speed: Normative Values and Reliability Determined for Adults Participating in the NIH Toolbox Study.

OBJECTIVES: To establish reference values and determine test-retest reliability for usual and maximal 4-meter gait speed. DESIGN: Cross-sectional observational study. SETTING: Offices in 10 geographically dispersed cities in the United States. PARTICIPANTS: Men and women (N=1320), aged 18 to 85 years, enrolled in the National Institutes of Health Toolbox norming study. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Specifically used were data from men and women who were timed over 4 meters (after a static start) while walking at their usual and maximum speeds. Norms for usual and maximum gait speed were derived using data from 1320 participants. Test-retest reliability for 164 participants was described using paired t tests, intraclass correlation coefficients (ICCs), and minimal detectable changes (MDCs). RESULTS: Mean usual speed was 1.12 meters per second, whereas mean maximum speed was 1.61 meters per second. As a general linear model showed 4-meter gait speed to differ significantly according to gait condition (speed), sex, and age group; estimates of normal were calculated accordingly. The usual speed of 80- to 85-year-old women was lowest at 0.95 meters per second; the maximum speed of 18- to 29-year-old men was highest at 1.85 meters per second. Test-retest measures did not differ significantly, but the ICCs were only fair and the MDCs were high. CONCLUSIONS: Normative reference values provided herein may be helpful in interpreting measurements of 4-meter gait speed obtained from adult men and women. The limited reliability of the gait speed measurements, however, limits their usefulness in making judgments regarding change.

Between-side differences in hand-grip strength across the age span: Findings from 2011-2014 NHANES and 2011 NIH Toolbox studies.

This project was undertaken to describe percentage differences in the grip strength between the dominant and nondominant-sides of left- and right-handed males and females across the age span. Data used in the project were from population-based samples of participants: 13,653 from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) and 3,571 from the 2011 normative phase of the National Institutes of Health (NIH) Toolbox project. Depending on how percentage differences were calculated, the overall grip strength was a mean 5.0-5.6% greater on the dominant than nondominant side. The percentage differences were significantly greater for individuals who were right-hand dominant rather than left-hand dominant. The differences also varied according to gender. We present summary data for percentage differences stratified by study, handedness, and gender. The values can be used to determine whether grip strength on one side is limited relative to the other.

Summary of grip strength measurements obtained in the 2011-2012 and 2013-2014 National Health and Nutrition Examination Surveys.

STUDY DESIGN: Cross-sectional and descriptive study. INTRODUCTION: Supported by the Centers for Disease Control and Prevention, the National Health and Nutrition Examination Survey (NHANES) began collecting grip strength data from nationally representative samples in 2011. PURPOSE OF THE STUDY: To examine the stability of the grip strength values across 2 data release cycles and provide updated US population-based grip strength values for 6 to 80 year olds. METHODS: Handgrip data from 13,676 participants aged 6-80 years were extracted from the NHANES 2011-2014 database. The muscle strength/grip test component measured the isometric grip strength using a Takei digital handgrip dynamometer (Takei Scientific Instruments, Shinagawa-Ku, Tokyo). Grip strength values (best of 3 trials for each hand) were summarized by gender, dominant side, and age group. Grip data from 2 data release cycles (2011-2012 vs 2013-2014) were compared. RESULTS: Differences between 2 data release cycles were negligible. Hence, we summarize grip strength values across the entire 2011-2014 period. The mean grip strength ranged from 50.3 kg for the dominant hand of 30- to 34-year-old men to 10.0 kg for the nondominant hand of 6-year-old girls. DISCUSSION: The summary data we present provide relatively current reference values to which tested individuals can be compared. However, clinicians and/or researchers should be aware that the instrumentation and procedures may influence the values. CONCLUSIONS: Results supported the stability of the NHANES grip strength values across data release cycles.

Handgrip Strength: A Comparison of Values Obtained From the NHANES and NIH Toolbox Studies.

IMPORTANCE: Handgrip dynamometry is probably the most commonly used method to characterize overall human muscle strength. OBJECTIVE: To compare and summarize grip strength measurements obtained from two population-based studies. DESIGN: Secondary data analysis. SETTING AND PARTICIPANTS: Data from (1) the 2011-2014 National Health and Nutrition Examination Survey (NHANES) with 13,918 participants and (2) the 2011 normative phase of the National Institutes of Health (NIH) Toolbox project with 3,594 participants. OUTCOMES AND MEASURES: The NHANES values used were the mean and best of three trials; the NIH Toolbox value used was the one maximum trial after a practice trial. RESULTS: General linear model analysis revealed that values obtained from the NIH Toolbox differed from NHANES best values but not from NHANES mean values. The analysis also indicated, regardless of the values used, that grip strength differed significantly between dominant and nondominant sides, males and females, and age groups. We provide updated reference values for handgrip strength. CONCLUSIONS AND RELEVANCE: On the basis of these analyses, we summarize grip strength measures obtained from the NHANES and NIH Toolbox for side, gender, and age group strata. Reference values are essential to assist in the interpretation of testing results and clinical decision making.

Relationships between grip strength, dexterity, and fine hand use are attenuated by age in children 3 to 13†years-of-age.

[Purpose] The purpose of this secondary analysis of data from the validation phase of National Institutes of Health Toolbox study was to describe the relationship between grip strength, dexterity, fine hand use, and age. [Participants and Methods] Children 3 to 13 years (n=132) contributed data. Grip strength was measured bilaterally with a Jamar dynamometer. Dexterity was measured bilaterally with the Nine-hole Peg Test. Fine hand use was characterized using 5 items of the Bruininks Oseretsky Test of Motor Proficiency. [Results] All grip strength and dexterity and fine hand use measures were correlated moderately to highly with one another and with age. The Cronbach's alpha for all measures was 0.88. Factor analysis suggested that all measures loaded strongly on a single component with the first factor explaining 75.6% of the total variance. Nevertheless, correlations between grip strength and dexterity and fine hand use measures were mostly negligible after controlling for age. [Conclusion] As moderate to strong relationships between grip strength and dexterity and fine hand use are attenuated by age in children of 3 to 13 years, we cannot recommend the use of any one measure over others to characterize motor function of the hand.

A new two square agility test for workplace health-reliability, validity and minimal detectable change.

[Purpose] One promising strategy for workplace wellness programs is to emphasize functional mobility screening and coaching to promote suitable physical activity and reduce musculoskeletal risks. This study examined intra-rater reliability, test-retest reliability, concurrent validity, known-groups validity and minimal detectable change for a new Two Square Agility Test (TSAT) designed as a functional mobility measure to promote workplace health. [Participants and Methods] Two hundred forty eight non-disabled participants (ages 18-69) were measured for body size, physical activity and 3 trials of the Two Square Agility Test. 78 participants were tested a week later on the Two Square Agility Test and other functional mobility tests. [Results] Intra-rater reliability was excellent (ICC=0.94) and test-retest reliability was good (ICC=0.87). Two Square Agility Test correlated moderately with Timed Up and Go (r=0.63), Five Times Sit to Stand (r=0.62), and Maximum Step Length (r= -0.54), supporting its concurrent validity. Performances for Two Square Agility Test were better in males, younger age, higher physical activity, and non-obese groups. The minimal detectable change at a 95% confidence level (MDC95) was 1.37 s. [Conclusion] Preliminary results supported reliability and validity of Two Square Agility Test as a functional mobility measure to promote workplace health.

Assessing manual dexterity: Comparing the WorkAbility Rate of Manipulation Test with the Minnesota Manual Dexterity Test.

STUDY DESIGN: Cross-sectional study. INTRODUCTION: The WorkAbility Rate of Manipulation Test (WRMT), an adaptation of the Minnesota Manual Dexterity Test (MMDT), contains a revised board and protocols to improve its utility for therapy or fitness assessment. PURPOSE OF THE STUDY: To describe the development and preliminary psychometric properties of WRMT. METHODS: Sixty-six healthy participants completed MMDT and WRMT in a random order followed by a user experience survey. We compared tests using repeated-measures analysis of variance, test-retest reliability, and examined agreement between tests. RESULTS: Despite the similarities of these 2 instruments, the different administration protocols resulted in statistically different score distributions (P < .001). Results supported good test-retest reliability of WRMT (placing test ICC = 0.88-0.90 and turning test ICC = 0.68-0.82). The WRMT correlated moderately with MMDT (r = 0.81 in placing test and r = 0.44-0.57 in turning test). Bland-Altman plot showed that the differences in completion time were 3.8 seconds between placing tests and 19.6 (both hands), 0.3 (right hand), and 3.9 (left hand) seconds between turning tests. Overall, participants felt that the instruction of WRMT was easier to follow (44%) and preferred its setup, color, and depth of the test board (49%). Time required to complete 1 panel of 20 disks correlated highly with the time needed to finish a complete trial of 60 disks in both MMDT (r = 0.91-0.97) and WRMT (r = 0.88-0.95). CONCLUSIONS: Caution is warranted in comparing scores from these 2 test variants. LEVEL OF EVIDENCE: 3b.

Normative Two-Minute Walk Test Distances for Boys and Girls 3 to 17 Years of Age.

AIMS: To provide normative reference values for the 2-minute walk test (2MWT) for children and adolescents. METHODS: A population-based sample of 2,631 boys and girls (3-17 years) contributed data to this 2011 study which was part of the NIH Toolbox for the Assessment of Neurological and Behavioral Function Norming Project. The 2MWT was performed over a 50 foot (15.2 meter) out-and-back course. RESULTS: Overall, the mean (standard deviation) distance walked by the participants was 186.2 (33.9) meters. As a general linear model demonstrated that gender (F = 11.0, p =.001) and age (F = 127.6, p <.001) affected 2MWT distance, separate norms are provided for each gender and age stratum (e.g., 3-year-old boys,16-year-old girls). Based on these findings and correlational and regression analysis, separate explanatory equations for 2MWT distance for boys and girls are provided. The separate equations for boys and girls include age, age squared, height, and body mass as variables that explain around 40% of the variance in 2MWT distance. CONCLUSIONS: The study presents norms for the 2MWT performed by American boys and girls. The norms can be used to determine the presence of limitations in walking endurance in this population.

Handgrip Strength: A Population-Based Study of Norms and Age Trajectories for 3- to 17-Year-Olds.

PURPOSE: To provide normative values and equations for grip strength obtained from a population-based sample of individuals 3 to 17 years of age. METHODS: This cross-sectional study used grip strength data from 2706 participants (49.2% males, 91% right-hand dominant) in the normative phase of the National Institutes of Health Toolbox project. RESULTS: Analyses showed greater strength in the dominant hand in boys and with each yearly increase in age. Normative data are presented separately for each side, sex, and age. Separate regression equations using age and weight as explanatory variables of grip strength are provided for each side by sex. CONCLUSIONS: The normative data can serve as a guide for interpreting grip strength measurements. The trajectories can be used to investigate the effect of various pathologies and conditions on grip strength during physical maturation.

Integrating 400 million variants from 80,000 human samples with extensive annotations: towards a knowledge base to analyze disease cohorts.

BACKGROUND: Data from a plethora of high-throughput sequencing studies is readily available to researchers, providing genetic variants detected in a variety of healthy and disease populations. While each individual cohort helps gain insights into polymorphic and disease-associated variants, a joint perspective can be more powerful in identifying polymorphisms, rare variants, disease-associations, genetic burden, somatic variants, and disease mechanisms. DESCRIPTION: We have set up a Reference Variant Store (RVS) containing variants observed in a number of large-scale sequencing efforts, such as 1000 Genomes, ExAC, Scripps Wellderly, UK10K; various genotyping studies; and disease association databases. RVS holds extensive annotations pertaining to affected genes, functional impacts, disease associations, and population frequencies. RVS currently stores 400 million distinct variants observed in more than 80,000 human samples. CONCLUSIONS: RVS facilitates cross-study analysis to discover novel genetic risk factors, gene-disease associations, potential disease mechanisms, and actionable variants. Due to its large reference populations, RVS can also be employed for variant filtration and gene prioritization. AVAILABILITY: A web interface to public datasets and annotations in RVS is available at https://rvs.u.hpc.mssm.edu/.

Two-minute walk test performance by adults 18 to 85 years: normative values, reliability, and responsiveness.

OBJECTIVES: To provide (1) normative reference values for the 2-minute walk test (2MWT), (2) reference equations for the 2MWT, and (3) information on the reliability and responsiveness of the 2MWT across the adult lifespan. DESIGN: Cross-sectional study. SETTING: General community settings. PARTICIPANTS: A population-based sample of adult participants (N=1137) contributed data to this study, which was part of the National Institutes of Health (NIH) Toolbox for the Assessment of Neurological and Behavioral Function Norming Project. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: 2MWT. RESULTS: Overall, the distance participants walked ranged from 64.6 to 300.8m (mean, 180.9m). Men walked farther than did women (189.4m vs 176.0m; t=6.8; df=1,135; P<.001). Significant correlations were observed between the 2MWT and age (r=-.41), height (r=.29), weight (r=-.16), and body mass index (r=-.32). Age and body mass index were used in the linear regression modeling to predict the 2MWT distance (R(2)=.55-.56). Test-retest reliability of the 2MWT as characterized by the intraclass correlation coefficient was .82 (95% confidence interval, .76-.87). Based on a standard error of measurement of 15.3m, the minimum detectable change for the 2MWT was 42.5m. CONCLUSIONS: The study presents norms of the 2MWT established by the NIH Toolbox. The norms can be used to determine the presence of limitations in walking endurance across the lifespan.

Alteration of ankle kinematics and muscle activity during heel contact when walking with external loading.

PURPOSE: The risk of recurrent ankle sprains could be reduced if the ankle joint is positioned in a more closed pack position (eversion and dorsiflexion) with enhanced co-activation of Tibialis Anterior (TA) and Peroneus Longus (PL) around heel contact in walking. We examined whether such alteration can be induced by augmenting ankle position error in the inversion and plantarflexion directions. METHODS: Fifteen young, healthy subjects participated in this study. They walked on a treadmill while a light weight was affixed to the dorsal-lateral side of the test foot to create afferent error signals in the inversion and plantarflexion directions. We recorded and analyzed subjects' ankle kinematics and electromyographic (EMG) activity of TA and PL before (baseline), during (adaptation), and after (post adaptation) walking with the weight. Our analyses focused on 30 ms before and after heel contact where ankle sprains are most likely to occur. RESULTS: Subjects increased ankle eversion before and after heel contact during the adaptation period. This increase carried over to the post adaptation period following removal of the weight. The weight also induced an increase in the TA activity before heel contact during late adaptation, although this increase did not carry over to the post adaptation period. No significant changes were observed in ankle dorsiflexion, PL activity, and muscle co-activation. CONCLUSION: Our error-driven approach is feasible to reduce ankle inversion around heel contact in walking, and may have clinical implication on intervention of recurrent ankle sprains.

Determinants of Hip Displacement in Children With Cerebral Palsy.

BACKGROUND: Coxa valga and femoral anteversion often are seen in patients with spastic hip displacement and osteotomy is recommended. However, the relationship between femoral deformities and hip displacement has not been clearly defined and other factors, such as joint motion and posture, should be considered before recommending treatment. QUESTIONS: For children with cerebral palsy with Gross Motor Function Classification System Level IV or V, we questioned (1) whether hip abduction range correlates with hip displacement, (2) what the relationships are between proximal femoral deformities and hip displacement, and (3) whether the patient with a windblown posture has greater degrees of femoral anteversion? METHODS: We retrospectively studied 31 consecutive children with cerebral palsy with Level IV or V gross motor function who underwent three-dimensional CT for preoperative assessment of hip displacement between January 2010 and December 2013. Among the children, 23 had a windblown posture and eight had symmetric hip motion. Femoral anteversion and true neck-shaft angle were measured from the three-dimensional CT images. Migration percentage was the dependent variable we chose to study in relation to femoral anteversion, neck-shaft angle, maximal hip abduction, and hip flexion contracture, using correlations and multiple linear regressions. Using ANOVA and Scheffé's post hoc tests, we analyzed and compared the data of 23 abducted hips and 23 adducted hips in the 23 children with windblown posture and in 16 displaced hips in the eight children with symmetric hip abduction. RESULTS: Greater migration percentage was associated with less hip abduction range (r = -0.86; p < 0.001). Femoral anteversion had a weak correlation (r = 0.28; p < 0.05) to migration percentage, and the association became insignificant after considering hip abduction motion. Adducted windblown hips had greater femoral anteversion than the symmetric displaced hips and abducted windblown hips (46° vs 36° and 38°, respectively; p < 0.05). CONCLUSIONS: Our study results did not support a relationship between femoral deformities and hip displacement after considering gross motor function and hip abduction motion. Greater femoral anteversion was noted in the adducted hips of patients with windblown posture, and derotation osteotomy is especially recommended. LEVEL OF EVIDENCE: Level III, diagnostic study.

Motor unit number index examination in dominant and non-dominant hand muscles.

This study investigated the effect of handedness on motor unit number index (MUNIX). Maximal hand strength, compound muscle action potential (CMAP) and voluntary surface electromyography (EMG) signals were measured bilaterally for the first dorsal interosseous (FDI) and thenar muscles in 24 right-handed and 2 left-handed healthy subjects. Mean (±standard error) grip and pinch forces in the dominant hand were 43.99 ± 2.36 kg and 9.36 ± 0.52 kg respectively, significantly larger than those in the non-dominant hand (grip: 41.37 ± 2.29 kg, p < .001; pinch: 8.79 ± 0.46 kg, p < .01). Examination of myoelectric parameters did not show a significant difference among the CMAP area, the MUNIX or motor unit size index (MUSIX) between the two sides in the FDI and thenar muscles. In addition, there was a lack of correlation between the strength and myoelectric parameters in regression analysis. However, strong correlations were observed between dominant and non-dominant hand muscles in both strength and myoelectric measures. Our results indicate that the population of motor units or spinal motor neurons as estimated from MUNIX may not be associated with handedness. Such findings help understand and interpret the MUNIX during its application for clinical or laboratory investigations.

Six-Minute Walk Test Vs. Three-Minute Step Test for Measuring Functional Endurance.

The purpose of this study was to compare 2 practical measures of functional endurance. Specifically, the six-minute walk test (SMWT) and three-minute step test (TMST) were compared to determine their appropriateness for use as field tests and inclusion in the NIH Toolbox for the assessment of neurological and behavioral function. Individuals between 14 and 85 years performed both the SMWT and TMST in random order. We documented completion rates, criterion performance, heart rate responses, and subjective exertion associated with the 2 tests. All 189 participants completed the SMWT, but only 73.0% completed the TMST. Those completing the TMST were more likely to be male, report better health, and have a younger age and lower body mass index. The SMWT distance was greater for those who did vs. those who did not complete the TMST. For those completing both tests, the average distance walked in 6 minutes was 595.9 m; the average cumulative heart beats during the minute after the TMST was 107.4. Distance walked and cumulative heart beats correlated weakly. Average heart rate and perceived exertion were significantly higher after the TMST than the SMWT. Posttest heart rate and perceived exertion for the 2 tests correlated significantly but not strongly. We conclude that the SMWT is more likely to be completed and is usually less stressful physiologically than the TMST and therefore may be a better option for field testing functional endurance and inclusion in the NIH Toolbox.

Dexterity as measured with the 9-Hole Peg Test (9-HPT) across the age span.

STUDY DESIGN: Cross-sectional observational, clinical measurement. INTRODUCTION: Manual dexterity is an important aspect of motor function across the age span. PURPOSE OF THE STUDY: To present the norms for the 9-Hole Peg Test (9-HPT) across the age span (3-85 years) and compare the 9-HPT performance by age group, gender, dominance, handedness, ethnicity, race, and language preference. METHODS: A population-based sample of 4319 subjects contributed data to this study which was part of the NIH Toolbox Norming Project. RESULTS: The 16-39 age groups demonstrated the shortest completion time (dominant hand, males completed a trial in 19-20 s, and females 18-19 s), and the youngest children 3-5 age groups showed the longest completion time with largest variation (males 32-51 s and females 32-45 s). Across all age groups, females performed slightly better as compared to males (22.5 versus 24.2 s). Dominant hands completed the test more quickly than the non-dominant hands (23.3 versus 25.4 s). Individuals who are not Hispanic or Latino performed slightly better than individuals who are Hispanic or Latino (22.2 versus 25.6 s). The completion time for English speakers was shorter than Spanish speakers (22.3 versus 27.8 s). There were no statistical differences by handedness (P = 0.6) or race (White versus Black or African American, P = 0.4). CONCLUSIONS: We present norms of the 9-HPT established by the NIH Toolbox. The norms can be used to determine the presence of impairments in dexterity across the age span. LEVEL OF EVIDENCE: NA.

The strain index and TLV for HAL: risk of lateral epicondylitis in a prospective cohort.

BACKGROUND: This study's objective was to quantify exposure-response relationships between job physical exposure (JPE) and incidence of lateral epicondylitis (LE). METHODS: A cohort of 536 workers was enrolled from 10 manufacturing facilities and followed monthly for 6 years to ascertain changes in JPE and health status. JPE was individually measured and quantified using the Strain Index (SI) and TLV for HAL. Worker demographics, medical history, psychosocial factors, and current musculoskeletal disorders were obtained. RESULTS: Fifty-six workers developed LE. In multivariate models JPE, age, family problems, and swimming were associated with increased risk of LE. SI showed an exposure-response relationship with maximum hazard ratio (HR) of 4.5(P = 0.04). TLV for HAL showed a non-statistically significant trend for increased risk of LE (P = 0.19). CONCLUSION: JPE is associated with increased risk of LE. The SI and TLV for HAL are useful metrics for estimating JPE.

Biomimetic vascularized adipose-derived mesenchymal stem cells bone-periosteum graft enhances angiogenesis and osteogenesis in a male rabbit spine fusion model.

Aims: Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration. Methods: A total of 24 male New Zealand white rabbits were divided into four groups according to the experimental materials. Allogenic adipose-derived mesenchymal stem cells (AMSCs) were cultured and seeded evenly in the collagen/chitosan sheet to form cell sheet as periosteum. Simultaneously, allogenic AMSCs were seeded onto alginate beads and were cultured to differentiate to endothelial-like cells to form vascularized bone construct (VBC). The cell sheet was wrapped onto VBC to create a vascularized bone-periosteum construct (VBPC). Four different experimental materials - acellular construct, VBC, non-vascularized bone-periosteum construct, and VBPC - were then implanted in bilateral L4-L5 intertransverse space. At 12 weeks post-surgery, the bone-forming capacities were determined by CT, biomechanical testing, histology, and immunohistochemistry staining analyses. Results: At 12 weeks, the VBPC group significantly increased new bone formation volume compared with the other groups. Biomechanical testing demonstrated higher torque strength in the VBPC group. Notably, the haematoxylin and eosin, Masson's trichrome, and immunohistochemistry-stained histological results revealed that VBPC promoted neovascularization and new bone formation in the spine fusion areas. Conclusion: The tissue-engineered VBPC showed great capability in promoting angiogenesis and osteogenesis in vivo. It may provide a novel approach to create a superior blood supply and nutritional environment to overcome the deficits of current artificial bone graft substitutes.