Congenital epiblepharon in Chinese school-age children: a cross-sectional study.

PURPOSE: To investigate the prevalence and body mass index (BMI) associations of congenital lower epiblepharon in children in China and the difference in the refractive errors between children with and without epiblepharon. METHODS: Children 6-12 years of age in Beichen District of Tianjin were screened for congenital epiblepharon from September to October 2017. All children underwent slit-lamp examination, strabismus screening, visual acuity examination and refraction. Weight and height were also recorded. The prevalence of lower epiblepharon in school-age children was evaluated, and its association with age, sex, BMI, and refractive error was analyzed. RESULTS: A total of 28,225 children were examined; 564 had epiblepharon. The prevalence of epiblepharon was found to be, for 6-year-olds, 2.50%; for 7-year-olds, 2.13%; for 8-year-olds, 2.10%; for 9-year-olds, 1.97%; for 10-year-olds, 1.85%; for 11-year-olds, 1.67%; and for 12-year-olds, 1.19% (P < 0.05). The prevalence of overweight and obesity in children with epiblepharon was found to be 16.7% and 47.2%, respectively. The prevalence and degree of astigmatism was higher than in nonepiblepharon children. We found a possible association between severity of astigmatism and severity of epiblepharon. CONCLUSIONS: In our study, the prevalence of epiblepharon decreased with advancing age, and the majority of children with epiblepharon were found to be overweight or obese. Epiblepharon was associated with astigmatism.

MRI-based endplate bone quality score predicts cage subsidence following oblique lumbar interbody fusion.

BACKGROUND CONTEXT: Cage subsidence is a common complication after lumbar interbody fusion surgery, with low bone mineral density (BMD) being a significant risk factor. ໿Endplate bone quality (EBQ) obtained from clinical MRI scans has been deemed reliable in determining regional BMD. However, the association between EBQ score and cage subsidence following oblique lumbar interbody fusion (OLIF) has not been clearly established. PURPOSE: This study aims to assess the relationship between EBQ score and cage subsidence in patients who underwent single-level OLIF. STUDY DESIGN/SETTING: A retrospective study. PATIENT SAMPLE: The study included adults with degenerative spinal conditions who underwent single-level OLIF at our institution OUTCOME MEASURES: Cage subsidence, disc height, EBQ score, fusion rate. METHODS: This retrospective study analyzed data from patients who underwent single-level OLIF surgery at our institution between October 2017 and August 2022. Postoperative CT scans were used to measure cage subsidence, while the EBQ score was calculated using preoperative non-contrast T1-weighted MRI. To determine the predictive ability of the EBQ score, receiver operating characteristic (ROC) curve analysis was conducted. Additionally, univariable and multivariable logistic regression analyses were performed. RESULTS: In this study, a total of 88 patients were included and followed up for an average of 15.8 months. It was observed that 32.9% (n=29/88) of the patients experienced cage subsidence. The post-surgery disc height was significantly higher in patients who experienced subsidence compared to those who did not. The mean EBQ scores for patients with non-subsidence and subsidence were 2.31±0.6 and 3.48±1.2, respectively, and this difference was statistically significant. The ROC curve analysis showed that the AUC for the EBQ score was 0.811 (95% CI: 0.717-0.905). The most suitable threshold for the EBQ score was determined to be 2.318 (sensitivity: 93.1%, specificity: 55.9%). Additionally, the multivariate logistic regression analysis revealed a significant association between a higher EBQ score and an increased risk of subsidence (odds ratio [OR]=6.204, 95% CI=2.520-15.272, p<.001). CONSLUSIONS: Our findings indicate that higher preoperative EBQ scores are significantly linked to cage subsidence following single-level OLIF. Preoperative measurement of MRI can serve as a valuable tool in predicting cage subsidence.

A Biomimetic Fibrous Composite Scaffold with Nanotopography-Regulated Mineralization for Bone Defect Repair.

The effective regeneration of large bone defects via bone tissue engineering is challenging due to the difficulty in creating an osteogenic microenvironment. Inspired by the fibrillar architecture of the natural extracellular matrix, we developed a nanoscale bioengineering strategy to produce bone fibril-like composite scaffolds with enhanced osteogenic capability. To activate the surface for biofunctionalization, self-adaptive ridge-like nanolamellae were constructed on poly(ε-caprolactone) (PCL) electrospinning scaffolds via surface-directed epitaxial crystallization. This unique nanotopography with a markedly increased specific surface area offered abundant nucleation sites for Ca2+ recruitment, leading to a 5-fold greater deposition weight of hydroxyapatite than that of the pristine PCL scaffold under stimulated physiological conditions. Bone marrow mesenchymal stem cells (BMSCs) cultured on bone fibril-like scaffolds exhibited enhanced adhesion, proliferation, and osteogenic differentiation in vitro. In a rat calvarial defect model, the bone fibril-like scaffold significantly accelerated bone regeneration, as evidenced by micro-CT, histological histological and immunofluorescence staining. This work provides the way for recapitulating the osteogenic microenvironment in tissue-engineered scaffolds for bone repair.

Biomimetic Mineralized 3D-Printed Polycaprolactone Scaffold Induced by Self-Adaptive Nanotopology to Accelerate Bone Regeneration.

Three-dimensional (3D)-printed biodegradable polymer scaffolds are at the forefront of personalized constructs for bone tissue engineering. However, it remains challenging to create a biological microenvironment for bone growth. Herein, we developed a novel yet feasible approach to facilitate biomimetic mineralization via self-adaptive nanotopography, which overcomes difficulties in the surface biofunctionalization of 3D-printed polycaprolactone (PCL) scaffolds. The building blocks of self-adaptive nanotopography were PCL lamellae that formed on the 3D-printed PCL scaffold via surface-directed epitaxial crystallization and acted as a linker to nucleate and generate hydroxyapatite crystals. Accordingly, a uniform and robust mineralized layer was immobilized throughout the scaffolds, which strongly bound to the strands and had no effect on the mechanical properties of the scaffolds. In vitro cell culture experiments revealed that the resulting scaffold was biocompatible and enhanced the proliferation and osteogenic differentiation of mouse embryolous osteoblast cells. Furthermore, we demonstrated that the resulting scaffold showed a strong capability to accelerate in vivo bone regeneration using a rabbit bone defect model. This study provides valuable opportunities to enhance the application of 3D-printed scaffolds in bone repair, paving the way for translation to other orthopedic implants.

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Bacterial cellulose (BC) is a type of extracellular polymeric nanomaterial secreted by microorganisms over the course of their growth. It has gained significant attention in the field of bone tissue engineering due to its unique structure of three-dimensional fibrous network, excellent biocompatibility, biodegradability, and exceptional mechanical properties. Nevertheless, BC still has some weaknesses, including low osteogenic activity, a lack of antimicrobial properties, small pore size, issues with the degradation rate, and a mismatch in bone tissue regeneration, limiting its standalone use in the field of bone tissue engineering. Therefore, the modification of BC and the preparation of BC composite materials have become a recent research focus. Herein, we summarized the relationships between the production, modification, and bone repair applications of BC. We introduced the methods for the preparation and the modification of BC. Additionally, we elaborated on the new advances in the application of BC composite materials in the field of bone tissue engineering. We also highlighted the existing challenges and future prospects of BC composite materials.

ECM-inspired calcium/zinc laden cellulose scaffold for enhanced bone regeneration.

Cellulose-based polymer scaffolds are highly diverse for designing and fabricating artificial bone substitutes. However, realizing the multi-biological functions of cellulose-based scaffolds has long been challenging. In this work, inspired by the structure and function of the extracellular matrix (ECM) of bone, we developed a novel yet feasible strategy to prepare ECM-like scaffolds with hybrid calcium/zinc mineralization. The 3D porous structure was formed via selective oxidation and freeze drying of bacterial cellulose. Following the principle of electrostatic interaction, calcium/zinc hybrid hydroxyapatite nucleated, crystallized, and precipitated on the 3D scaffold in simulated physiological conditions, which was well confirmed by morphology and composition analysis. Compared with alternative scaffold cohorts, this hybrid ion-loaded cellulose scaffold exhibited a pronounced elevation in alkaline phosphatase (ALP) activity, osteogenic gene expression, and cranial defect regeneration. Notably, the hybrid ion-loaded cellulose scaffold effectively fostered an M2 macrophage milieu and had a strong immune effect in vivo. In summary, this study developed a hybrid multifunctional cellulose-based scaffold that appropriately simulates the ECM to regulate immunomodulatory and osteogenic differentiation, setting a measure for artificial bone substitutes.

Sema3A secreted by sensory nerve induces bone formation under mechanical loads.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A (Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement (OTM) model. Firstly, bone formation was activated after the 3rd day of OTM, coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor (NGF), highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells (hPDLCs) within 24 hours. Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.

Health-related Quality of Life (HRQOL) Outcomes of Selective/Nonselective Thoracic Fusion for Lenke 1C Adolescent Idiopathic Scoliosis (AIS) Patients with a Minimum 4-year Follow-up.

OBJECTIVE: Both the selective thoracic fusion (STF) and nonselective thoracic fusion (NSTF) are treatments for Lenke 1C adolescent idiopathic scoliosis (AIS). To date, the impacts of the two surgical strategies on patients' long-term quality of life remain unclear. Therefore, the purpose of this study was to explore the long-term effects of STF/NSTF on the quality of life in Lenke 1C AIS patients through a 4-10-year follow-up. METHODS: From January 2011 to April 2018, according to the inclusion and exclusion criteria, a retrospective single-center study of 75 surgical patients with Lenke 1C curves was performed (n = 75). They all underwent posterior fusion, and patients were divided into the selective thoracic fusion (STF) group (n = 42) and the nonselective thoracic fusion (NSTF) group (n = 33) based on their surgical approach. All participants received the survey of the visual analogue scale (VAS), SRS30, SF12, and Oswestry disability index (ODI) scales. Patients' gender, age, body mass index (BMI), surgical approach (STF/NSTF), surgical segments (UIV and LIV), follow-up time, complications, preoperative, postoperative, and last follow-up Cobb angles, and health-related quality of life (HRQOL) outcomes were collected, and analyzed through the Shapiro-Wilks test, Wilcoxon rank-sum test, t-test, and χ2 test. RESULTS: The mean follow-up of the entire cohort was 73 ± 5.6 months. The lumbar Cobb angle in the STF group improved from 31.8 ± 6.5° to 11.5 ± 5.1° after the operation and 10.3 ± 6.9° at the last follow-up. The postoperative correction rate of the lumbar curve was 63.8%, which increased to 67.7% at the last follow-up. In the NSTF group, the lumbar Cobb angle improved from 34.3 ± 11.3° to 4.3 ± 3.7° after the operation, and was 5.1 ± 3.1° at the last follow-up. The postoperative correction rate of the lumbar curve was 87.4%, and 85.1% at the last follow-up. At the last follow-up, the STF group had higher overall HRQOL scores than the NSTF group, and there were statistically differences between the different groups (STF/NSTF) in SRS-30-Mental health (p = 0.03), SRS-30-Satisfaction with management (p = 0.02), SRS-30-Pain (p = 0.03), ODI (p = 0.01), SF-12 PCS (p = 0.03), VAS back pain (p = 0.005) and VAS leg pain (p = 0.001). No statistically differences were found in SF12 MCS, SRS-30-Self-image/Appearance and SRS-30 Function/activity. CONCLUSION: After 4-10 years of follow-up, we found that the STF group achieved satisfactory correction results, and compared with the NSTF group, their overall HRQOL scores were higher, especially in terms of pain and satisfaction, where the STF group shows a significant advantage.

Tetrahedral Framework Nuclear Acids Can Regulate Interleukin-17 Pathway to Alleviate Inflammation and Inhibit Heterotopic Ossification in Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease that leads to serious spinal deformity and ankylosis. Persistent inflammation and progressive ankylosis lead to loss of spinal flexibility in patients with AS. Tetrahedral framework nucleic acids (tFNAs) have emerged as a one kind of nanomaterial composed of four specially designed complementary DNA single strands with outstanding biological properties. Results from in vivo experiments demonstrated that tFNAs treatment could inhibit inflammatory responses and heterotopic ossification to halt disease progression. In vitro, tFNAs were proved to influence the biological behavior of AS primary chondrocytes and inhibit the secretion of pro-inflammatory cytokines through interleukin-17 pathway. The osteogenic process of chondrocytes was as well inhibited at the transcriptional level to regulate the expression of related proteins. Therefore, we believe tFNAs had a strong therapeutic effect and could serve as a nonsurgical remedy in the future to help patients suffering from AS.

The Influence of Screw Positioning on Cage Subsidence in Patients with Oblique Lumbar Interbody Fusion Combined with Anterolateral Fixation.

OBJECTIVES: Cage subsidence (CS) has been reported to be one of the most common complications following oblique lumbar interbody fusion (OLIF). To reduce the incidence of CS and improve intervertebral fusion rates, anterolateral fixation (AF) has been gradually proposed. However, the incidence of CS in patients with oblique lumbar interbody fusion combined with anterolateral fixation (OLIF-AF) is still controversial. Additionally, there is a lack of consensus regarding the optimal placement of screws for OLIF-AF, and the impact of screw placement on the incidence of CS has yet to be thoroughly investigated and validated. The objective of this investigation was to examine the correlation between screw placements and CS and to establish an optimized approach for implantation in OLIF-AF. METHODS: A retrospective cohort study was undertaken. From October 2017 to December 2020, a total of 103 patients who received L4/5 OLIF-AF for lumbar spinal stenosis or spondylolisthesis or degenerative instability in our department were followed up for more than 12 months. Demographic and radiographic data of these patients were collected. Additionally, screw placement related parameters, including trajectory and position, were measured by anterior-posterior X-ray and axial CT. Analysis was done by chi-square, independent t-test, univariable and multivariable binary logistic regression to explore the correlation between screw placements and CS. Finally, the receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of screw placement-related parameters. RESULTS: A total of 103 patients were included, and CS was found in 28 (27.18%) patients. Univariable analysis was firstly performed for each parameter. Next, variables with p-value of <0.05, including bone mineral density (BMD), concave morphology, and screw placement-related parameters were included in the multivariate logistic regression analysis. Significant predictor factors for subsidence were coronal plane angle (CPA) (OR 0.580 ± 0.208, 95% CI 1.187-2.684), implantation point (IP) (L4) (OR 5.732 ± 2.737, 95% CI 1.445-12.166), and IP (L5) (OR 7.160 ± 3.480, 95% CI 1.405-28.683). Furthermore, ROC curves showed that the predictive accuracy of CS was 88.1% for CPA, 77.6% for IP (L4) and 80.9% for IP (L5). CONCLUSIONS: We demonstrate that the trajectory of vertebral screws, including angle and position, was closely related to CS. Inserting screws parallel to each other and as close to the endplate as possible while keeping the cage inside the range of the superior and inferior screws are an optimal implantation strategy for OLIF-AF.

Tetrahedral Framework Nucleic Acids Inhibit Muscular Mitochondria-Mediated Apoptosis and Ameliorate Muscle Atrophy in Sarcopenia.

Sarcopenia is known as age-related muscle atrophy, which influences over a quarter of the elderly population worldwide. It is characterized by a progressive decline in muscle mass, strength, and performance. To date, clinical treatments in sarcopenia are limited to rehabilitative interventions and dietary supplements. Tetrahedral framework nucleic acids (tFNAs) represent a novel kind of DNA-based nanomaterial with superior antiapoptosis capacity in cells, tissues, organs, and systems. In our study, the therapeutic effect of tFNAs treatment on sarcopenia was evaluated both in vivo and in vitro. Results from muscular biophysiological characteristics demonstrated significant improvement in muscle function and endurance in the aged mouse model, and histologic examinations also showed beneficial morphological changes in muscle fibers. In vitro, DEX-induced sarcopenic myotube atrophy was also ameliorated through the inhibition of mitochondria-mediated cell apoptosis. Collectively, tFNAs treatment might serve as an alternative option to deal with sarcopenia in the near future.

The interplay between the nerves and skeleton: a 30-year bibliometric analysis.

Background: The mechanisms and effects of the interplay between the nerves and skeleton remain a popular research topic. This study aimed to analyze and evaluate publications on nerve-bone interactions using bibliometrics and to identify the state of the art of current research, hotspots, and future directions. Methods: This study included 1989 articles and reviews from the Web of Science Core Collection (WoSCC) published from January 1, 1991, to June 22, 2022. The Bibliometrix package of R 4.2.0 (The R Foundation for Statistical Computing, Vienna, Austria) was used to analyze basic information about the publications, including the annual number of publications, institution analysis, author influence analysis, journal analysis, and the national cooperation network. We also used CiteSpace 5.8.R3 for bibliometric analysis, including co-occurrence, co-citation, and cluster analysis. Results: We discovered a significant increase in the number of articles on nerve-bone interactions published over the last 10 years. The most active country and institution were the United States and the University of Minnesota, respectively. In terms of journals and cocited journals, Bone was ranked highest with respect to the number of publications, while Journal of Bone and Mineral Research was ranked highest among cited journals. Wang Lei was the author with the most publications, and Bjurholm A was the most cited author. The analysis of references and keywords revealed that the impact of nerve- and neuromodulation-related factors on stem cell differentiation was a persistently hot topic. Osteoarthritis, neuropeptide Y, and osteoclastogenic process are likely to be the next era of research hotspots. The neurovascular crosstalk within bone has received great attention, especially in skeletal diseases, which may provide potential targets for future treatments. Conclusions: We used a bibliometric method to provide an efficient, objective, and comprehensive assessment of existing research about the interplay between the skeletal and nervous systems and to accurately identify hotspots and research frontiers, providing valuable information for future research.

Injectable sodium alginate hydrogel loaded with plant polyphenol-functionalized silver nanoparticles for bacteria-infected wound healing.

A novel injectable hydrogel dressing (GA@AgNPs-SA) with long-term antimicrobial effect is developed that can accelerate the closure of bacteria-infected wounds. The hydrogel dressing was prepared by cross-linking sodium alginate molecular chains and gallic acid functionalized silver nanoparticles (GA@AgNPs) via calcium ions to form a three-dimensional network. The hydrogel dressing demonstrates excellent biocompatibility and can achieve a sustainable release of silver ions, ensuring a long-term antibacterial activity and inhibiting biofilm formation. Moreover, an in vivo study demonstrates that the GA@AgNPs-SA hydrogel can effectively decrease the expression of IL-6 and TNF-α to alleviate the inflammatory response, and promote angiogenesis by upregulating CD31, α-SMA and VEGF expression, thus significantly accelerating the repair of infected wounds. Given these interesting properties, this antibacterial hydrogel has great potential for application in the clinical care of bacteria-infected wounds.

Oblique lumbar interbody fusion combined with stress end plate augmentation and anterolateral screw fixation for degenerative lumbar spinal stenosis with osteoporosis: a matched-pair case-controlled study.

BACKGROUND CONTEXT: Oblique lumbar interbody fusion (OLIF) has been proven to be effective in treating degenerative lumbar spinal stenosis (DLSS). Whether OLIF is suitable for treating patients with DLSS with osteoporosis (OP) is still controversial. Bone cement augmentation is widely used to enhance the internal fixation strength of osteoporotic spines. However, the effectiveness of OLIF combined with bone cement stress end plate augmentation (SEA) and anterolateral screw fixation (AF) for DLSS with OP have not confirmed yet. PURPOSE: To evaluate the clinical, radiological, and functional outcomes of OLIF-AF versus OLIF-AF-SEA in the treatment of DLSS with OP. STUDY DESIGN: Retrospective case-control study. PATIENT SAMPLE: A total of 60 patients with OP managed for DLSS at L4-L5. OUTCOME MEASURES: Visual analog scale (VAS) score of the lower back and leg, Oswestry Disability Index (ODI), disk height (DH), lumbar lordosis (LL), segmental lordosis (SL), cage subsidence and fusion rate. METHODS: The study was performed as a retrospective matched-pair case‒controlled study. Patients with OP managed for DLSS at L4-L5 between October 2017 and June 2020 and completed at least 2 years of follow-up were included, which were 30 patients treated by OLIF-AF and 30 patients undergoing OLIF-AF-SEA. The demographics and radiographic data, fusion status and functional outcomes were therefore compared to evaluate the efficacy of the two approaches. RESULTS: Pain and disability improved similarly in both groups at the 24-month follow-up. However, the SEA group had lower pain and functional disability at 3 months postoperatively (p<.05). The mean postoperative disc height decrease (△DH) was significantly lower in the SEA group than in the control group (1.17±0.81 mm vs 2.89±2.03 mm; p<.001). There was no significant difference in lumbar lordosis (LL) or segmental lordosis (SL) between the groups preoperatively and 1 day postoperatively. However, a statistically significant difference was observed in SL and LL between the groups at 24 months postoperatively (p<.05). CS was observed in 4 cases (13.33%) in the SEA group and 17 cases (56.67%) in the control group (p<.001). A nonsignificant difference was observed in the fusion rate between the SEA and control groups (p=.347) at 24 months postoperatively. CONCLUSIONS: This study revealed that OLIF-AF-SEA was safe and effective in the treatment of DLSS with OP. Compared with OLIF-AF, OLIF-AF-SEA results in a minor postoperative disc height decrease, a lower rate of CS, better sagittal balance, and no adverse effect on interbody fusion.

The role of multi-modal intra-operative neurophysiological monitoring in corrective surgeries for thoracic tuberculosis with kyphosis.

OBJECTIVE: The aim of this study was to assess the performance and utility of motor evoked potentials (MEP) and somatosensory evoked potentials (SSEP) during corrective surgery for thoracic tuberculosis with kyphosis (TTK). METHODS: 68 patients (mean age 31.7 ± 20.3 years) who underwent corrective surgery for TTK from 2012 to 2019 were included in this retrospective study. Patients were neurologicaly evaluated before and after surgery with systematic neurologic examinations. Intraoperative neurophysiological monitoring (IONM) with SSEP and MEP was carried out. A receiver operating characteristic (ROC) curve and area under ROC curve (AUC) were used to identify the diagnostic accuracy of potential recovery. RESULTS: IONM alerting occurred in 12 surgeries (12/68, 17.6%), of which 6 were SSEP alerting, 2 MEP alerting, and 4 combinations of both SSEP and MEP. Among the 12 cases where there was IONM alerting, 3 (25%) had postoperative neurological deficits(PND), whereas one patient had PND without IONM alerting. IONM sensitivity and specificity were 0.75 (95% CI 0.22-0.99) and 0.86 (95% CI 0.74-0.93) respectively. Positive predictive value (PPV) and negative predictive value (NPV) were 0.25 and 0.98 respectively. The AUC of evoked potential recovery in diagnosing PND was 0.884. CONCLUSION: Our study showed that multi-modal IONM with SSEP and MEP can effectively indicate a potential neural injury and predict PND during TTK corrective surgery. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.

Senescent cells: A therapeutic target for osteoporosis.

BACKGROUND: Osteoporosis (OP) is a prevalent disorder characterized by the loss of bone mass and the deterioration of bone microarchitecture. OP is attributed to various factors, including menopause (primary), ageing (primary) and the adverse effects of medications (secondary). Recently, cellular senescence has been shown to have a crucial role in the maintenance of cellular homeostasis and organ function. The purpose of this review is to summarize recent findings regarding the roles of bone cellular senescence and senescence-associated secretory phenotype (SASP) in OP. METHODS: A comprehensive search of the PubMed database from inception to July 2022 was performed regarding the molecular mechanism of bone cell senescence in OP progression. RESULTS: We describe the pathophysiology of senescent bone cells and SASP, and how each contributes to OP. We also provide new options for treating OP by targeting cellular senescence pathways. CONCLUSION: Cellular senescence plays an important role in bone homeostasis, with variations based on the different types of OP. These variations are associated with pathogenic factors, bone turnover rate and systemic metabolism. Understanding the molecular relationship between bone cells and senescence provides for the possible targeting of senescence as a means by which to treat OP.

A sustained release of BMP2 in urine-derived stem cells enhances the osteogenic differentiation and the potential of bone regeneration.

Cell-based tissue engineering is one of the optimistic approaches to replace current treatments for bone defects. Urine-derived stem cells (USCs) are obtained non-invasively and become one of the promising seed cells for bone regeneration. An injectable BMP2-releasing chitosan microspheres/type I collagen hydrogel (BMP2-CSM/Col I hydrogel) was fabricated. USCs proliferated in a time-dependent fashion, spread with good extension and interconnected with each other in different hydrogels both for 2D and 3D models. BMP2 was released in a sustained mode for more than 28 days. Sustained-released BMP2 increased the ALP activities and mineral depositions of USCs in 2D culture, and enhanced the expression of osteogenic genes and proteins in 3D culture. In vivo, the mixture of USCs and BMP2-CSM/Col I hydrogels effectively enhanced bone regeneration, and the ratio of new bone volume to total bone volume was 38% after 8 weeks of implantation. Our results suggested that BMP2-CSM/Col I hydrogels promoted osteogenic differentiation of USCs in 2D and 3D culture in vitro and USCs provided a promising cell source for bone tissue engineering in vivo. As such, USCs-seeded hydrogel scaffolds are regarded as an alternative approach in the repair of bone defects.