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Biological cells in vivo typically reside in a dynamic flowing microenvironment with extensive biomechanical and biochemical cues varying in time and space. These dynamic biomechanical and biochemical signals together act to regulate cellular behaviors and functions. Microfluidic technology is an important experimental platform for mimicking extracellular flowing microenvironment in vitro. However, most existing microfluidic chips for generating dynamic shear stress and biochemical signals require expensive, large peripheral pumps and external control systems, unsuitable for being placed inside cell incubators to conduct cell biology experiments. This study has developed a microfluidic generator of dynamic shear stress and biochemical signals based on autonomously oscillatory flow. Further, based on the lumped-parameter and distributed-parameter models of multiscale fluid dynamics, the oscillatory flow field and the concentration field of biochemical factors has been simulated at the cell culture region within the designed microfluidic chip. Using the constructed experimental system, the feasibility of the designed microfluidic chip has been validated by simulating biochemical factors with red dye. The simulation results demonstrate that dynamic shear stress and biochemical signals with adjustable period and amplitude can be generated at the cell culture chamber within the microfluidic chip. The amplitudes of dynamic shear stress and biochemical signals is proportional to the pressure difference and inversely proportional to the flow resistance, while their periods are correlated positively with the flow capacity and the flow resistance. The experimental results reveal the feasibility of the designed microfluidic chip. Conclusively, the proposed microfluidic generator based on autonomously oscillatory flow can generate dynamic shear stress and biochemical signals without peripheral pumps and external control systems. In addition to reducing the experimental cost, due to the tiny volume, it is beneficial to be integrated into cell incubators for cell biology experiments. Thus, the proposed microfluidic chip provides a novel experimental platform for cell biology investigations.

Designing a reasonable electrode size and obtaining precise contact resistance parameters are always crucial in the field of chip manufacturing, especially in the cases of tiny chips with very low contact resistance. In this work, an improved analytical model featuring an electrode-pair (EP) layout design is proposed to accurately extract the electrical parameters of the planar Ohmic contact. The key feature of the proposed model layout is the adoption of a series of EPs with a fixed interval distance but varied electrode widths which is just opposite to the conventional transmission line model (TLM). Then, the effective electrode width depending on the conduction current requirement and practical Ohmic contact technology level in production can hence be derived to assist the engineers for a better design in chip layout. Furthermore, the model is analyzed and demonstrated by performing both technology computer-aided design (TCAD) simulations and experimental measurements. The results verify the ability to achieve more precise contact resistance parameters and distinguish the variance of the sheet resistance underneath the contact after annealing treatment by the proposed EP model (EPM). This work provides a distinct perspective to understand and quantify the electrical characteristics in a greater variety of Ohmic contacts.

Background. Cardiovascular disease (CVD) is closely related to arterial elasticity and hemodynamics. Exercises have been reported to immediately decrease arterial apparent elasticity and regulate hemodynamic variables. However, the relationship between them and exercise intensity remains elusive. The purpose of this study was to determine the acute effects of different intensities of acute cycling exercise on carotid arterial apparent elasticity and hemodynamics. Methods. 32 healthy men (age: 19.4 ± 0.6 years) attended the laboratory on five occasions and completed cycling acute exercise for 20 minutes at five intensities (40%, 50%, 60%, 70%, and 80% heart rate reserve (HRR)). At the right carotid artery, center-line velocity and arterial inner diameter waveforms were examined before and immediately after exercise. Based upon the measured data, the classical hemodynamic theory was used to calculate the apparent elasticity and the local hemodynamic variables. Results. The arterial apparent stiffness and the apparent elastic modulus following acute cycling exercise at 60% to 80% HRR were significantly higher than baseline. The mean center-line velocity accelerated from 50% to 80% HRR, but no intensity of intervention altered mean blood flow. Immediately after intervention, the mean wall shear stress and oscillatory shear index increased. Conclusions. Aerobic cycling intervention, with intensity from 40% to 80% HRR, did not change the brain blood supply. A bout of cycling intervention decreased apparent elasticity, and there was an intensity-dependent effect on apparent elasticity and hemodynamic variables. This study would provide referable data for the further study on the effects of aerobic exercise on arterial hemodynamics and elasticity and underlying physiological mechanisms.

Revealing the mechanisms underlying the intracellular calcium responses in vascular endothelial cells (VECs) induced by mechanical stimuli contributes to a better understanding for vascular diseases, including hypertension, atherosclerosis, and aneurysm. Combining with experimental measurement and Computational Fluid Dynamics simulation, we developed a mechanobiological model to investigate the intracellular [Ca2+] response in a single VEC being squeezed through narrow microfluidic channel. The time-dependent cellular surface tension dynamics was quantified throughout the squeezing process. In our model, the various Ca2+ signaling pathways activated by mechanical stimulation is fully considered. The simulation results of our model exhibited well agreement with our experimental results. By using the model, we theoretically explored the mechanism of the two-peak intracellular [Ca2+] response in single VEC being squeezed through narrow channel and made some testable predictions for guiding experiment in the future.

Objective Allogeneic cartilage transplantation is used to treat severe osteochondral defects or cartilaginous injury. However, acute immune rejection has been a key problem interfering with graft healing. Methods Full-thickness osteochondral defects were performed in Sprague Dawley rats. The allograft implants were set into the defect region. Blood and spleen samples from Postoperative Day 3 onward were collected for inflammatory cell analysis, including analysis of monocytes, natural killer cells, CD4+CD25+Foxp3+ regulatory T cells, CD4+ T cells, and CD8+ T cells. Gross observation and histologic staining (hematoxylin and eosin, toluidine blue) were carried out at the same time point to assess the repair effect of the cartilage graft and the degree of immune rejection. Results Treatment with basic fibroblast growth factor, agarose gel, and allogeneic cartilage was similar to that of the autologous group. The percentage of monocytes in allografts was at a higher level in the spleen and blood; the frequency of CD4+ T cells in the allogeneic group was higher than in the autologous group and the other agarose groups at 6 weeks after transplantation. The number of regulatory T cells in the autograft was increased from Postoperative Week 1; similar results were observed in groups containing basic fibroblast growth factor beginning at Postoperative Week 3. Conclusions Allogeneic cartilage transplantation induces acute immune rejection, which compromises the validity of the implant. The combination of basic fibroblast growth factor and agarose gel facilitates the goal of immune privilege and promotes the success of the allograft tissues. The translational potential of this article This study investigated the combination of basic fibroblast growth factor (bFGF) and agarose gel facilitates promotes the success of the allograft tissues transplantation. This work may help clinicians find a new way to repair articular cartilage damage. This will affect the treatment of articular cartilage movement injuries and arthritis.

Generating precise in vivo arterial endothelial hemodynamic microenvironments using microfluidics is essential for exploring endothelial mechanobiology. However, a hemodynamic principle guiding the fabrication of microfluidic systems is still lacking. We propose a hemodynamic similarity principle for quickly obtaining the input impedance of the microfluidic system in vitro derived from that of the arterial system in vivo to precisely generate the desired endothelial hemodynamic microenvironments. First, based on the equivalent of blood pressure (BP) and wall shear stress (WSS) waveforms, we establish a hemodynamic similarity principle to efficiently map the input impedance in vivo to that in vitro, after which the multi-component microfluidic system is designed and fabricated using a lumped parameter hemodynamic model. Second, numerical simulation and experimental studies are carried out to validate the performance of the designed microfluidic system. Finally, the intracellular Ca

Focusing of biological particles has important applications in the fields of biology, medicine, chemistry and environment. The emergence of microfluidic technology has brought new opportunities for the manipulation of biological particles. However, existing methods generally produce a relatively large shear stress or thermal effect on biological particles, which may cause negative biological effects during manipulation, especially for sensitive bioparticles. Herein, we propose a novel strategy for microfluidic focusing of microparticles based on negative magnetophoresis and oscillatory flow. A simple and efficient simulation model is first developed to calculate the motion of particles under magnetic field and fluid field. The non-monotonic size dependence of particle focusing is then revealed and elaborately analyzed. Furthermore, the effects of oscillatory flow field and magnetic field on particle focusing are quantitatively investigated and the particle size range for effective focusing in our proposed chip is provided. The proposed strategy of microfluidic focusing can guide the real applications such as enrichment and separation of sensitive biological particles.

BACKGROUND Osteonecrosis of the femoral head (ONFH) often affects young, active patients, and the femoral head's preservation is the primary goal of treatment for this disease. Vascularized iliac crest bone grafting is one of the many vascularized procedures used in treating ONHF. In some cases, we selectively performed this procedure using the musculoperiosteal iliac flap with the ascending branch of the lateral femoral circumflex artery for ONFH treatment. METHODS Twelve patients (12 hips) with nontraumatic femoral head necrosis underwent musculoperiosteal iliac flap transfer with the ascending branch of the lateral femoral circumflex artery. The Harris Hip Score (HHS), visual analog scale score, and double-hip X-ray findings were used to analyze hip function changes within 10 days preoperatively and 6 and 12 months postoperatively. RESULTS The mean HHS increased from 52.33 ± 3.34 preoperatively to 65.92 ± 5.04 6 months postoperatively and 79.75 ± 3.84 12 months postoperatively, and the data showed a statistical significance difference between preoperative and postoperative (F = 131.90, P < 0.01). The HHS at 6 and 12 months after surgery were significantly different (P < 0.01). The visual analog scale score showed the same trend. The x-ray of hip joints at 6 and 12 months after surgery showed that the femoral heads' shape and contour were good, femoral heads did not collapse, and the transferred bone flaps healed well. CONCLUSIONS Musculoperiosteal iliac flap transfer with the ascending branch of the lateral femoral circumflex artery may be an effective method with a high clinical success rate for treating young patients with early to midstage ONFH.

Rotary left ventricular assist devices (LVAD) have emerged as a long-term treatment option for patients with advanced heart failure. LVADs need to maintain sufficient physiological perfusion while avoiding left ventricular myocardial damage due to suction at the LVAD inlet. To achieve these objectives, a control algorithm that utilizes a calculated suction index from measured pump flow (SIMPF) is proposed. This algorithm maintained a reference, user-defined SIMPF value, and was evaluated using an in silico model of the human circulatory system coupled to an axial or mixed flow LVAD with 5–10% uniformly distributed measurement noise added to flow sensors. Efficacy of the SIMPF algorithm was compared to a constant pump speed control strategy currently used clinically, and control algorithms proposed in the literature including differential pump speed control, left ventricular end-diastolic pressure control, mean aortic pressure control, and differential pressure control during (1) rest and exercise states, (2) rapid, eight-fold augmentation of pulmonary vascular resistance for (1), and (3) rapid change in physiologic states between rest and exercise. Maintaining SIMPF simultaneously provided sufficient physiological perfusion and avoided ventricular suction. Performance of the SIMPF algorithm was superior to the compared control strategies for both types of LVAD, demonstrating pump independence of the SIMPF algorithm.

The generation of dynamic biochemical signals in a microfluidic control system is of importance for the study of the interaction between biological cells and their niches. However, most of microfluidic control systems are not able to provide dynamic biochemical signals with high precision and stability due to inherent mechanical vibrations caused by the actuators of the programmable pumps. In this paper, we propose a novel microfluidic feedback control system integrating an external feedback control system with a Y-shaped microfluidic chip with a "Christmas tree" inlet. The Proportional Integral Derivative (PID) controller is implemented to reduce the influence of vibrations. In order to regulate the control parameters efficiently, a mathematical model is built to describe the actuator of the programmable pump, in which a fractional-order model is utilized. Both simulation and experimental studies are carried out, confirming that the microfluidic feedback control system can precisely and stably generate desired dynamic biochemical signals.

Background Osteonecrosis of the femoral head (ONFH) often affects young, active adults and leads to the destruction of the hip joint and disabling arthritis. Several procedures have been developed to prevent conversion to total hip arthroplasty (THA), especially in young patients who have a high rate of hip revision surgery. The aim of this long-term follow-up is to analyze the results of vascularized iliac bone flap transfer for ONFH treatment. Methods We retrospectively reviewed 856 patients (1006 hips) who accepted hip-preserving surgery with vascularized iliac bone grafting due to ONFH (Ficat and Arlet stages II-IV) from January 1985 to December 2012 at our hospital. Radiographic assessment was performed with the Ficat and Arlet system, clinical assessment was performed with the Harris Hip Score system, and quality of life was evaluated with the 36-Item Short Form Survey. The hips included 575 stage II hips, 382 stage III hips, and 49 stage IV hips. We defined clinical failure as conversion to THA or any other hip-preserving surgery because of hip symptoms. Results A total of 856 patients (1006 hips) were eventually followed up with an average time of 15 years (range 5-25). In total, 75 patients were lost to follow-up, and 105 hips were converted to THA. The average Harris Hip Score was 87.43 ± 6.42 points at the last follow-up, representing a great improvement compared to the 66.42 ± 6.52 points obtained preoperatively. The Kaplan-Meier survival analysis showed no difference in the 15-year survival rate between patients with stages II and III disease (using THA as an end point). However, the survival rate was lower for patients with stage IV disease than that for patients with stages II and III disease. The survival rate for patients in the glucocorticoid group was lower than that for patients in the idiopathic, alcoholic, and trauma groups. The Physical Component Summary scores ranged from 78 ± 10 to 85 ± 14 postoperatively compared to 30 ± 14 to 55 ± 15 preoperatively, and the postoperative Mental Component Summary scores (range from 34 ± 11 to 59 ± 12) were significantly higher than the preoperative scores (range from 72 ± 11 to 90 ± 10), representing great improvement in patient quality of life. Postoperative complications occurred in 86 patients (4.5%) during the follow-up, including 23 patients with deep venous thrombosis, 16 patients with meralgia paresthetica (which resolved), and 47 patients with secondary wound healing. Conclusion The vascularized iliac bone flap grafting technique yields significant improvement (particularly in the precollapse disease stages in young patients) for restoration of the biomechanical support of the collapsed femoral head and reconstruction of the blood supply to the osteonecrotic area. This procedure allows these patients to avoid or delay the need for THA surgery.

Osteonecrosis of the femoral head (ONFH) results in collapse of the femoral head and rapid destruction of the hip joint. The repair of post-collapse articular cartilage and subchondral bone is challenging. We interrupted the blood supply to the femoral head and established a full-thickness articular defect animal model after ONFH was determined via X-ray. Porous tantalum and a Bio-Gide collagen membrane, co-cultured with bone marrow mesenchymal stem cells (BMSCs) in vitro, were implanted into the defect zone to repair the full-thickness articular defect. Hyaline cartilage was detected on top of the tantalum near the edge of the defect 12 weeks post-operatively. Porous tantalum and a Bio-Gide collagen membrane with BMSCs may repair full-thickness articular defects if the blood supply can be reconstructed in the post-collapse stage of ONFH.

The enhanced delivery of nanoparticle (NP) drugs in the human system is a revolutionary approach for various diseases, e.g., cancer therapy, in which nanoparticle diffusion is one of the main routes of transport. The diffusive transport of nanoparticles in complex tumor microenvironments is intriguing, while its complete understanding is still nascent. Herein, we experimentally report a systematic study of nanoparticle diffusion in model porous media, i.e., agarose (AG) hydrogels. By examining both the time-averaged and ensemble-averaged mean square displacements (MSDs), the heterogeneous and spatially dependent mobility, as well as the significant hydrodynamic damping effect, are identified. The concept of ergodicity breaking (EB) is employed and correlated with the measured non-Gaussian displacement probability distributions (DPDs). The non-Gaussian profile is clarified to be attributed to the superposition of the coexisted Gaussian and non-Gaussian motions of the individual nanoparticles. Furthermore, the interstitial viscosity is found to only affect the probed heterogeneity temporarily but never modify the intrinsic non-ergodicity of the porous media. Our results give a comprehensive understanding of anomalous diffusion in spatially heterogeneous porous media and could provide the imperative knowledge to improve drug delivery in physiological media.

Ginkgo biloba L. extract (EGb) is one of the world's most extensively used herbal medicines. Due to the diverse pharmacological properties of EGb, it has been used in the treatment of neurological illnesses, as well as cardiovascular and cerebrovascular ailments. However, the effect and pharmacological mechanism of EGb on steroid-induced necrosis of the femoral head (SINFH) are still unclear.SINFH remains a challenging problem in orthopedics. Previous investigations have shown that EGb has the potential to reduce the occurrence of SINFH. The goal was to determine the effect and mechanism of EGb in preventing SINFH by inhibiting apoptosis and improving vascular endothelial cells (VECs) functions.CCK-8, nitric oxide (NO) production and flow cytometry were used to determine the cell apoptosis and function. The scratch and angiogenesis tests assessed migration and tube formation. Western blot analysis detected the expressions of apoptosis-related proteins and PI3K/AKT/eNOS pathway-related proteins. Apoptosis and angiogenesis were also detected treated with the inhibitors. A mouse model of SINFH was established. Paraffin section was used to determine the necrotic pathology and apoptosis. Vessels in the femoral heads were assessed by immunofluorescence staining.When stimulated by methylprednisolone (MPS), cell viability, NO generation and tube formation were decreased, the apoptotic rate increased. Simultaneously, MPS decreased the expression levels of p-PI3K, p-AKT, and p-eNOS. EGb increased the expression levels of these proteins, restrained apoptosis, and restored cell functions. The addition of the inhibitors decreased anti-apoptotic effect and angiogenesis. In addition, when compared to the model mice, there were fewer empty lacunae and normal trabecular arrangement after taking different doses of EGb. The protective effect was also confirmed by the vascular quantitative analysis in vivo.This study established that EGb increased endothelial cell activity and inhibited apoptosis and function loss induced by MPS, elucidating the effect and molecular mechanism of EGb on early SINFH.