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.

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.

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.

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.

Impairment in activities of daily living and cognitive decline mediate the association between depressive symptoms and incident hip fractures in Chinese older adults.

BACKGROUND: The presence of depressive symptoms is associated with increasing risks of hip fractures (HFs). However, few studies investigated the longitudinal relationship between depressive symptoms and incident HFs among Chinese older adults, and the underlying mechanisms remain unclear. OBJECTIVES: To investigate the association between depressive symptoms and incident HFs, and the mediating role of cognitive function and impairment in activities of daily living (ADL) in the association among the older adults in China. METHODS: This population-based cohort study included 6336 Chinese older adults (age range, 60-101 years) without the history of HFs at baseline and with complete data during the follow-up. Discrete-time Cox regression was used to evaluate the relationship between depressive symptoms and incident HFs, and bootstrapped multiple mediation analyses were conducted to examine the effects of cognitive function and ADL impairment on the association. RESULTS: Among 6336 participants (3172 women [50.1%]; mean [SD] age, 67.9 [6.6] years), 264 (4.2%) subjects had HFs onset. After adjusting for age, sex, education, marital status, current residence, smoking status, drinking status, body mass index, number of chronic conditions, and falls history, elevated depressive symptoms were independently associated with increasing risks of HFs (adjusted hazard ratio [aHR]: 1.42; 95% CI: 1.07 to 1.88). However, this association was no longer significant (aHR: 1.09; 95% CI: 0.78 to 1.53) after adjusting for cognitive function and ADL impairment. When mortality and incident HFs were modeled as a composite outcome, the association between depressive symptoms and combined outcomes also remained non-significant after adjusting for cognitive function and ADL impairment. Furthermore, the mediation model demonstrated that cognitive decline (indirect effect: ß = 0.002, 95% CI: 0.001 to 0.003) and ADL impairment (indirect effect: ß = 0.002, 95% CI: 0.000 to 0.003) fully mediated the association between depressive symptoms and incident HFs after adjusting for age, sex, falls history, and number of chronic conditions. CONCLUSIONS: The positive association between depressive symptoms and incident HFs was confirmed among Chinese older adults, which was fully mediated by cognitive decline and ADL impairment. This study shed new light on the potential role played by depressive symptoms in incident HFs.

Chylothorax following posterior low lumbar fusion surgery: A case report.

BACKGROUND: Postoperative chylothorax is usually regarded as a complication associated with cardiothoracic surgery; however, it is one of the rare complications in orthopedic surgery. This case report describes a female patient who developed chylothorax after a successful L4-S1 transforaminal lumbar interbody fusion surgery. The etiology, diagnosis, and treatment were analyzed and discussed. CASE SUMMARY: A 50-year-old woman was admitted with repeated back and leg pain. She was diagnosed with L4 degenerative spondylolisthesis, L4/L5 and L5/S1 intervertebral disc herniation and L5 instability, and underwent successful posterior L4-S1 instrumentation and fusion surgery. Unfortunately, thoracic effusion was identified 2 d after operation. The thoracic effusion was finally confirmed to be chylous based on twice positive chyle qualitative tests. The patient was discharged after 12-d persisting drainage, 3-d total parenteral nutrition and fasting, and other supportive treatments. No recurring symptoms were observed within 12 mo follow-up. CONCLUSION: Differential diagnosis is crucial for unusual thoracic effusion. Comprehensive diagnosis and treatment of chylothorax are necessary. Thorough intraoperative protection to relieve high thoracic pressure caused by the prone position is important.

Synergy between vitamin E and D-sorbitol in enhancing oxidation stability of highly crosslinked ultrahigh molecular weight polyethylene.

Oxidative stability of radiation crosslinked ultrahigh molecular weight polyethylene (UHMWPE) artificial joints is significantly improved by vitamin E (VE), but there is a dilemma that VE hinders crosslinking and thus jeopardizes the wear of UHMWPE. In this effort, we proposed an efficient strategy to stabilize UHMWPE under limited antioxidant contents, where VE and D-sorbitol (DS) were used as the primary antioxidant and the secondary antioxidant respectively. For non-irradiated blends with fixed antioxidant contents, oxidative stability accessed by oxidation induction time (OIT) of VE/DS/UHMWPE blends was superior to that of VE/UHMWPE blends, while DS/UHMWPE blends showed no increase in OIT. The cooperation between DS and VE exhibited a synergistic effect on enhancing the oxidative stability of UHMWPE. Interestingly, the irradiated VE/DS/UHMWPE blends showed comparable OIT but a significantly higher crosslink density than the irradiated VE/UHMWPE blends. The crystallinity, melting point, and in vitro biocompatibility of the blends were not affected by VE and DS. The quantitative relationships of mechanical properties, oxidation stability, crystallinity and crosslink density were established to unveil the correlation of these key factors. The overall properties of VE/UHMWPE and VE/DS/UHMWPE blends were compared to elucidate the superiority of the antioxidant compounding strategy. These findings provide a paradigm to break the trade-off between oxidative stability, crosslink density and mechanical properties, which is constructive to develop UHMWPE bearings with upgraded performance for total joint replacements. STATEMENT OF SIGNIFICANCE: VE-stabilized UHMWPE is the most commonly used material in total joint replacements at present. However, oxidation and wear resistance of VE/UHMWPE implants cannot be unified since VE reduces the efficiency of radiation crosslinking. It limits the use of VE. Herein, we proposed a compounding stabilization by the synergy between VE and DS. The antioxidation capability of VE was revived by DS, thus enhancing the oxidation stability of unirradiated UHMWPE. The irradiated VE/DS/UHMWPE exhibited similar oxidation stability but higher crosslink density than irradiated VE/UHMWPE, which is beneficial to combat wear of UHMWPE and to inhibit the occurrence of osteolysis. This synergistic antioxidation strategy endows the UHMWPE joint material with good overall performance, which is of clinical significance.

Posterior decompression and fusion versus laminoplasty for cervical ossification of posterior longitudinal ligament: a systematic review and meta-analysis.

Both posterior decompression and fusion (PDF) and laminoplasty (LAMP) have been used to treat cervical myelopathy due to multilevel ossification of posterior longitudinal ligament (OPLL). However, considerable controversy exists over the choice of the two surgical strategies. Thus, the aim of this study is to compare clinical outcomes of PDF and LAMP for treatment of cervical myelopathy due to multilevel OPLL. We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials database to identify relevant clinical studies compared with clinical outcomes of PDF and LAMP for cervical OPLL. The primary outcomes including Japanese Orthopaedic Association (JOA) score and recovery rate of JOA were evaluated, and the secondary outcomes involving visual analogue scale (VAS), cervical curvature, OPLL progression rate, complication rate, reoperation rate and surgical trauma were also evaluated using Stata software. A total of nine studies were included in the current study, involving 324 patients. The current study suggests that compared with LAMP, PDF achieves a lower OPLL progression rate, better postoperative cervical curvature and similar neurological improvement in the treatment of multilevel cervical OPLL. However, PDF has a higher complication rate, more surgical trauma and higher postoperative VAS than LAMP.

The integration of pore size and porosity distribution on Ti-6A1-4V scaffolds by 3D printing in the modulation of osteo-differentation.

PURPOSE: In this study, pore size and porosity distribution of porous Ti-6Al-4V scaffolds (pTi) were controlled by 3D printing. The effects of pore size distribution at a constant porosity, or porosity distribution at a constant pore size pertaining to functions of adhesion, proliferation, and differentiation of the mouse embryonic osteoblast precursor (MC3T3-E1) cells were researched separately. METHODS: 3D printing was used to design five groups of pTi, designated as PS300/HP, PS300/LP, PS500/HP, PS500/LP, and PS800/HP based on pore size and porosity distribution. MC3T3-E1 cells were cultured on pTi, and non-porous Ti-6Al-4V samples (npTi) were prepared as control. The pTi was characterized with the scanning electron microscopy (SEM). MC3T3-E1 cells were stained via AlamarBlue assay and viability and proliferation analyzed. The mRNA levels of alkaline phosphatase (ALP), osteocalcin (OCN), collagentype-1 (Col-1), and runt-related transcription factor 2 (Runx2) in MC3T3-E1 cells were analyzed by real-time PCR analysis. RESULTS: The average pore size and porosity of pTi were recorded as (301 ± 9 µm, 58.8 ± 1.8%), (300 ± 9 µm, 43.4 ± 1.3%), (501 ± 11 µm, 58.3 ± 1.2%), (499 ± 12 µm, 42.7 ± 1.1%), and (804 ± 10 µm, 58.9 ± 1.3%), respectively. SEM images confirmed active attachment of cells and oriented with the direction of metal rod after pTi/MC3T3-E1 co-culture for 3 and 7 days. In addition, MC3T3-E1 cells grown on the PS800/HP displayed significantly higher proliferation compared with each group after 3 days incubation (p < 0.05). Moreover, cells showed some degree of proliferation in all groups, with the highest value recorded for PS800/HP after culture for 7 days (p < 0.05). The gene expression pattern of ALP, OCN, Col-1, and Runx2 confirmed that these were down-regulated when pore size increased or porosity decreased of pTi (p < 0.05). CONCLUSION: The pTi facilitated the adhesion and differentiation of osteoblast when pore size decreased or porosity increased. The scaffold model resembles physical modification with porous structures, which has potential application in the surface modifications of Ti implant.

Insights into Oxidation of the Ultrahigh Molecular Weight Polyethylene Artificial Joint Related to Lipid Peroxidation.

Oxidative degradation of ultrahigh molecular weight polyethylene (UHMWPE) bearings is one of the main factors that deteriorates their mechanical properties and abrasive wear resistance, which further results in the failure of total joint replacements. Absorption and diffusion of synovial fluids have been considered as causes of the oxidation of UHMWPE bearings. However, the role of synovial fluids in oxidation of UHMWPE remains elusive. In this work, we aimed to reveal the oxidation mechanism of UHMWPE joints with respect to squalene (a representative component of the synovial fluid). The UHMWPE doped in squalene showed slight oxidation, while severe oxidation was observed when squalene doped UHMWPE was exposed to oxygen atmosphere. Squalene manifested lipid peroxidation with notable oxidation products and oxygen-derived free radicals during thermo-oxidative aging. Lipid peroxidation was deduced to follow two routes including autoxidation and thermal oxidation. The aggressive free radicals of squalene abstracted hydrogen atoms from the UHMWPE chains, initiating the oxidation of UHMWPE artificial joints. These findings not only provide evidence for comprehending the process of squalene-induced UHMWPE oxidation but also are instructive to develop highly oxidative-resistant UHMWPE.