Soluble polyvinylpyrrolidone-based microneedles loaded with Sanguis draconis and Salvia miltiorrhiza for treatment of diabetic wound healing.

BACKGROUND: Nowadays, diabetic wound healing remains a crucial challenge due to their protracted and uncertain healing process. Traditional Chinese medicine (TCM) has demonstrated the therapeutic value of Sanguis draconis (SD)-Salvia miltiorrhiza (SMR) Herb Pair in diabetic wound healing. However, new administration modes are urgently needed for their convenient and wide-ranging applications. OBJECTIVE: We propose a soluble polyvinylpyrrolidone-based microneedle patch containing the herbal extracts of SD and SMR (MN-SD@SMR) for diabetic wound healing. METHODS: The herbal extracts of SD and SMR are purification and concentration via traditional lyophilization. SD endowed MN-SD@SMR with functions to improve high glycemic blood environment and migration of keratinocyte and fibroblast cells. RESULTS: SMR in MN-SD@SMR could improve blood flow velocity and microcirculation in the wound area. The effectiveness of transdermal release and mechanical strengths of MN-SD@SMR were verified. CONCLUSION: Integrating the advantages of these purified herbal compositions, we demonstrated that MN-SD@SMR had a positive healing effect on the wounds in vitro and vivo. These results indicate that soluble polyvinylpyrrolidone-based microneedle patch containing the herbal extracts of SD and SMR has a promising application value due to their superior capability to promote diabetic wound healing.

Modelling of the in-stent thrombus formation by dissipative particle dynamics.

BACKGROUND: Stent implantation is a highly efficacious intervention for the treatment of coronary atherosclerosis. Nevertheless, stent thrombosis and other post-operative complications persist, and the underlying mechanism of adverse event remains elusive. METHODS: In the present study, a dissipative particle dynamics model was formulated to simulate the motion, adhesion, activation, and aggregation of platelets, with the aim of elucidating the mechanisms of in-stent thrombosis. FINDINGS: The findings suggest that stent thrombosis arises from a complex interplay of multiple factors, including endothelial injury resulting from stent implantation and alterations in the hemodynamic milieu. Furthermore, the results suggest a noteworthy association between in-stent thrombosis and both the length of the endothelial injured site and the degree of stent malposition. Specifically, the incidence of stent thrombosis appears to rise in tandem with the extent of the injured site, while moderate stent malposition is more likely to result in in-stent thrombosis compared to severe or minor malposition. INTERPRETATION: This study offers novel research avenues for investigating the plasticity mechanism of stent thrombosis, while also facilitating the clinical prediction of stent thrombosis formation and the development of more precise treatment strategies.

Investigating biomechanical alterations and emptying patterns after various gastrojejunostomy strategy.

Gastrojejunostomy is a prominent approach in managing distal gastric cancer that is unresectable due to gastric outlet obstruction (GOO). Research has demonstrated that stomach-partitioning gastrojejunostomy (SPGJ) exhibits superior clinical efficacy compared to conventional gastrojejunostomy (CGJ), however, the underlying mechanism of this phenomenon remains elusive. This study constructed 3D models of the SPGJ and CGJ based on the computed tomography (CT) images obtained from a patient diagnosed with distal gastric cancer. The biomechanical patterns of these procedures in the digestive system were subsequently compared through numerical simulations and in vitro experiments. The results of the numerical simulation demonstrated that the model following SPGJ promoted the discharge of food through the anastomotic orifice and into the lower jejunum. Furthermore, a decrease in passage size after partitioning, the low-level velocity of esophageal, and an increase in contents viscosity effectively inhibited the flow through the passage to the pylorus, ultimately reducing stimulation to tumor. The study also revealed that favorable gastric emptying is associated with a smaller passage and faster inlet velocity, and that lower contents viscosity. ​The experimental findings conducted in vitro demonstrated that SPGJ exhibited superior efficacy in obstructing the flow near the pylorus in comparison to CGJ. Moreover, a decrease in passage size correlates with a reduction in fluid flow towards the pylorus. These results provide the foundation of theory and practice for the surgical management of patients with GOO resulting from unresectable distal gastric cancer, and have potential implications for clinical interventions.

Gastric emptying performance of stomach-partitioning gastrojejunostomy versus conventional gastrojejunostomy for treating gastric outlet obstruction: A retrospective clinical and numerical simulation study.

Purpose: This study evaluated the gastric emptying performance of stomach-partitioning gastrojejunostomy (SPGJ) versus conventional gastrojejunostomy (CGJ) for treating gastric outlet obstruction (GOO). Methods: First, 73 patients who underwent SPGJ (n = 48) or CGJ (n = 25) were involved. Surgical outcomes, postoperative recovery of gastrointestinal function, delayed gastric emptying, and nutritional status of both groups were compared. Second, a three-dimensional stomach model was constructed based on the gastric filling CT images from a GOO patient with a standard stature. The present study evaluated SPGJ numerically by comparing it with CGJ in terms of local flow parameters such as flow velocity, pressure, particle retention time, and particle retention velocity. Results: Clinical data found that SPGJ had significant advantages over CGJ in terms of time to pass gas (3 versus 4 days, p < 0.001), time to oral intake (3 versus 4 days, p = 0.001), postoperative hospitalization (7 versus 9 days, p < 0.001), the incidence of delay gastric emptying (DGE) (2.1% versus 36%, p < 0.001), DGE grading (p < 0.001), and complications (p < 0.001) for GOO patients. Moreover, numerical simulation revealed that the SPGJ model would induce contents in stomach discharge to the anastomosis at a higher speed, and only 5% of that flowed to the pylorus. SPGJ model also had a low-pressure drop as the flow from the lower esophagus to the jejunum, reducing the resistance to food discharge. Besides, the average retention time of particles in the CGJ model is 1.5 times longer than that in the SPGJ models, and the average instantaneous velocity in CGJ and SPGJ models are 22 mm/s and 29 mm/s, respectively. Conclusion: Compared with CGJ, patients after SPGJ had better gastric emptying performance and better postoperative clinical efficacy. Therefore, we think that SPGJ may be a better option for treating GOO.

Effect of exercise rehabilitation on hemodynamic performance after carotid artery stenting: a numerical study.

A high in-stent restenosis rate and thrombosis have compromised clinical benefits after vascular stent placement. Exercise rehabilitation after stenting emerges as a promising and practical therapeutic strategy to improve the clinical performance of this therapy, although it remains controversial. The present study aimed to explore the impact of exercise training on hemodynamic performance after vascular stent implantation. Different 3-dimensional computational models based on the patient-specific carotids were constructed to calculate hemodynamic parameters, including flow velocity, time-averaged wall shear (TAWSS), oscillatory shear index (OSI) and relative residence time (RRT). The results demonstrated that exercise training increased TAWSS but decreased OSI and RRT in some cases after the intervention, and high-intensity exercise further suppressed the adverse blood flow. However, exercise training remarkably reduced TAWSS and elevated OSI and RRT in patients with mild stenosis at upstream of stented segment. Additionally, we discovered that the hemodynamic environment change induced by exercise training was not significant compared to the stent position in some cases. Exercise had a less beneficial impact on the disturbed blood flow after the distal common carotid artery (CCA) stenting. These findings highlighted that exercise-induced hemodynamic changes differ under different conditions. The exercise training for the intervention patients should only be performed after a comprehensive vascular function assessment.

Hemodynamic impact of snoring on carotid artery after stent implantation: the role of oscillation.

Snoring is common in overweight and elderly patients treated by endovascular stenting. Studies have proved a correlation between snoring and carotid stenosis, thus, snoring after carotid artery stenting (CAS) might promote or worsen clinical performance. This study tested this hypothesis by constructing a patient-specific carotid bifurcation model and numerically analyzing hemodynamic changes of the carotid artery under different snoring conditions. These conditions included small and large amplitude, low and high frequency, and different age groups. The results found that high amplitude snoring suppressed the disturbed flow at the stented segment while the downstream region of ICA became more chaotic, accounting for in-stent intimal restenosis and thrombosis. Furthermore, local blood flow patterns of elder groups with snoring symptoms were more likely to be changed due to low-speed flow, increasing the possibility of vascular remodeling and thrombosis. Besides, increased snoring frequency hardly influenced the local disturbed flow. Therefore, older adults should receive medical treatment actively after stenting for high-amplitude snoring as soon as possible to avoid potential adverse events.

Effect of microtopography on osseointegration of implantable biomaterials and its modification strategies.

Orthopedic implants are widely used for the treatment of bone defects caused by injury, infection, tumor and congenital diseases. However, poor osseointegration and implant failures still occur frequently due to the lack of direct contact between the implant and the bone. In order to improve the biointegration of implants with the host bone, surface modification is of particular interest and requirement in the development of implant materials. Implant surfaces that mimic the inherent surface roughness and hydrophilicity of native bone have been shown to provide osteogenic cells with topographic cues to promote tissue regeneration and new bone formation. A growing number of studies have shown that cell attachment, proliferation and differentiation are sensitive to these implant surface microtopography. This review is to provide a summary of the latest science of surface modified bone implants, focusing on how surface microtopography modulates osteoblast differentiation in vitro and osseointegration in vivo, signaling pathways in the process and types of surface modifications. The aim is to systematically provide comprehensive reference information for better fabrication of orthopedic implants.

Hemodynamic impact of proximal anterior cerebral artery aneurysm: Mind the posteriorly projecting ones!

Intracranial aneurysm projected posteriorly is associated with high risk of aneurysm rupture. In order to investigate the biomechanical mechanisms for the adverse event, three-dimension intracranial cerebral aneurysms were constructed based on clinical data, and we numerically compared effect of location, position, size, and shape of aneurysm on hemodynamic conditions including velocity, pressure, and wall shear stress (WSS). The numerical results showed that the aneurysm projected posteriorly even at small sizes led to abnormal hemodynamic environment, which was featured by a local high pressure and stress concentration near aneurysm neck area. Moreover, the one located at the proximal A1 segment and ellipsoidal aneurysm would further worse local hemodynamic environment, causing high local stresses. These findings indicated the potential mechanical mechanism for high rupture rate of the aneurysms projected posteriorly, underscoring importance of early and accurate diagnosis and promptly treatment for improved the clinical outcome, even if these aneurysms are of small sizes.

Hemodynamic Impact of Stenting on Carotid Bifurcation: A Potential Role of the Stented Segment and External Carotid Artery.

Carotid stenting near the bifurcation carina is associated with adverse events, especially in-stent restenosis, thrombosis, and side branch occlusion in clinical data. This study is aimed at determining the potential biomechanical mechanisms for these adverse events after carotid stenting. The patient-specific carotid models were constructed with different stenting scenarios to study the flow distribution and hemodynamic parameters, such as wall shear stress (WSS), flow velocity, relative residence time (RRT), and oscillating shear index (OSI) in the carotid bifurcation. The results suggested that the existing stents surely reduced blood flow to the external carotid artery (ECA) but enhanced local flow disturbance both in ECA and stented internal carotid artery (ICA), and the inner posterior wall of the stented ICA and the outer posterior wall of ECA might endure a relatively low level of WSS and remarkably elevated OSI and RRT. In addition, the implanted stent leads to more ECA adverse flow than ICA after stenting. While disturbed flow near the strut increased as stent length increased, blood flow and areas of local flow disturbance in ECA slightly decreased as stent length increased. In conclusion, the results revealed that ECA might be in relatively high levels of abnormal local hemodynamics after stenting, followed by stented ICA, leading to potential adverse events after intervention.

Transfer of Low-Density Lipoproteins in Coronary Artery Bifurcation Lesions with Stenosed Side Branch: Numerical Study.

Evidence from clinical data suggests that the stenotic side branch (SB) is one of the key predictors for SB occlusion-based adverse events. In this study, we hypothesized that coronary bifurcations with stenotic SB might lead to severe concentration polarization of atherogenic lipids, such as the low-density lipoproteins (LDL), motivating the adverse events in the clinic. To confirm this hypothesis, this work numerically investigated the transport of LDL in different bifurcation lesions based on the Medina classification with various location and stenosis severities. The results showed that the coronary bifurcations with stenotic SB might be suffering more serious concentration polarization of LDL on the luminal surface of the SB due to higher level of LDL concentrations. Moreover, compared to the other bifurcation lesion types, the type (1,0,1) had the highest luminal surface LDL concentration along the SB and the highest degree of risk to enhance the process of atherosclerosis. In addition, this study also showed that the luminal surface LDL concentration increased with elevated stenosis severity. The type (1,0,1) with the severe stenosis (75% diameter reduction) had the highest concentration at the SB. In conclusion, these results suggested that both location of lesions and stenosis severities had great influence on the distribution of LDL on the luminal surface of the SB. Therefore, the estimation of disease severity and the interventional therapy should be carried out not only according to the stenosis severities in clinic. Moreover, compared to the other bifurcation lesion types, the type (1,0,1), rather than the type (1,1,1) as usually considered, had the highest luminal surface LDL concentration along the SB and the highest degree of risk to enhance the process of atherosclerosis.

Study of Infrared Laser Parameters on Surface Morphology and Hydrophobic Properties.

Many studies have shown that super hydrophobic surfaces have been applied to micro-nano structures and low surface energy materials. In the present study, infrared laser scanning and simple salinization modification were used to improve the hydrophobicity of a surface. When the scanning speed was 100 mm/s, the laser power was 30 W and the scanning interval was 200 µm, the apparent contact angle of surface was up to 157°. The assessment of surface characteristics revealed that decreasing scanning speed or increasing laser power were able to improve the hydrophobicity of the surface. After aging treatment, the superhydrophobic surface prepared by this method still had good durability.

Effect of longitudinal anatomical mismatch of stenting on the mechanical environment in human carotid artery with atherosclerotic plaques.

Longitudinal anatomic mismatch (LAM) of stenting (i.e., a stenotic artery segment is not fully covered by a deployed stent) worsens the mechanical environment in the treated artery, which most likely is the cause for the associated high risks of restenosis, myocardial infarction and stent thrombosis. To probe the possibility, we constructed a patient-specific carotid model with two components of plaques (lipid and calcified plaque) based on MRI images; we numerically compared three different stenting scenarios in terms of von Mises stress (VMS) distribution in the treated arteries, namely, the short stenting (LAM), the medium stenting and the long stenting. The results showed that the short stenting led to more areas with abnormally high VMS along the inner surface of the treated artery with a much higher surface-averaged VMS at the distal end of the stent than both the medium and long stenting. While the VMS distribution in the calcified plaques was similar for the three stenting models, it was quite different in the lipid plaques among the three stenting models. The lipid plaque of the short-stent model showed more volume of the lipid plaque subjected to high VMS than those of the other two models. Based on the obtained results, we may infer that the short stenting (i.e., LAM) may aggravate vascular injury due to high VMS on the artery-stent interaction surface and within the lipid plaque. Therefore, to obtain a better outcome, a longer stent, rather than a short one, might be needed for arterial stenting.

Influence of proximal drug eluting stent (DES) on distal bare metal stent (BMS) in multi-stent implantation strategies in coronary arteries.

The aim of this study was to investigate the drug distribution in arteries treated with DES-BMS stenting strategy and to analyze the influence of proximal DES on distal segments of BMS. A straight artery model (Straight Model) and a branching artery model (Branching Model) were constructed in this study. In each model, the DES was implanted at the proximal position and the BMS was implanted distally. Hemodynamic environments, drug delivery and distribution features were simulated and analyzed in each model. The results showed that blood flow would contribute to non-uniform drug distribution in arteries. In the Straight Model the proximal DES would cause drug concentration in BMS segments. While in the Branching Model the DES in the main artery has slight influence on the BMS segments in the branch artery. In conclusion, due to the blood flow washing effect the uniformly released drug from DES would distribute focally and distally. The proximal DES would have greater influence on the distal BMS in straight artery than that in branching artery. This preliminary study would provide good reference for atherosclerosis treatment, especially for some complex cases, like coronary branching stenting.

The accelerated atherogenesis of venous grafts might be attributed to aggravated concentration polarization of low density lipoproteins: a numerical study.

We hypothesize that after implantation the much elevated water filtration rate of venous grafts may cause aggravated concentration polarization of low density lipoproteins (LDLs), in turn lead to the accelerated atherogenesis of the grafts. To verify the hypothesis, we numerically simulated the transport of LDLs in various models of arterial bypasses with different grafts (veins or arteries) and geometrical configurations. The results showed that the venous grafts might endure abnormally high lipid infiltration/accumulation within the vessel wall due to severely elevated luminal surface LDL concentration. When compared to the conventional bypass models, the S-type bypass had the lowest luminal surface LDL concentration along its host artery floor, but the highest degree of risk to develop atherosclerotic lesions in its venous graft. Among the three conventional bypass models, the one with 30° anastomosis had the lowest risk to develop atherosclerosis in the venous graft. In conclusion, when compared with the bypass models with arterial grafts, the venous bypass models had rather high levels of LDL concentration polarization (cw) in the vein grafts, especially at the early stages of implantation. This might result in high infiltration/accumulation of LDLs within the walls of the venous grafts, leading to a fast genesis/development of atherosclerosis there.

Analysis of strain transfer of six-layer surface-bonded fiber Bragg gratings.

A theoretical analysis of strain transfer of six-layer surface-bonded fiber Bragg gratings (FBGs) subjected to uniform axial stress is presented. The proposed six-layer structure consists of optical fiber, protective coating, adhesive layer, substrate layer, outer adhesive layer, and host material, which is different from the four-layer case of common acknowledgement. A theoretical formula of strain transfer rate from host material to optical fiber is established to provide an accurate theoretical prediction. On the basis of the theoretical analysis, influence parameters of the middle layers that affect the average strain transfer rate of the six-layer surface-bonded FBG are discussed. After the parametric study, a selection scheme of sensor parameters for numerical validation, which makes the average strain transfer rate approach unity, is determined. Good agreement is observed between numerical results and theoretical predictions. In the end, the six-layer model is extended to the general situation of multiple substrate layers, which lays a theoretical groundwork for the research and design of surface-bonded FBGs with substrate layers in the future.