Multilayered Microneedles for Triphasic Controlled Delivery of Small Molecules and Proteins.

Transdermal delivery is an attractive delivery method that increases bioavailability, is suitable for a wide variety of therapeutics, and offers stable delivery outcomes. However, many therapeutics are unable to readily cross the stratum corneum. Microneedles mechanically disrupt the cutaneous barrier to deliver small molecules, proteins, and vaccines. To date, microneedles have not been used in conjunction with coacervate, a liquid-liquid phase separation that protects unstable proteins. A three-layer microneedle for the controlled release of three different molecules is designed. Through micromolding, microneedles are efficiently generated, which benefits product scalability. The microneedles have good mechanical integrity and effectively penetrate porcine skin ex vivo. The three layers, in the microneedles, release the cargo in a three-phase manner. The released protein maintains its structure well. Moreover, layer thickness can be controlled by varying fabrication parameters. The microneedles can incorporate both small molecule drugs and protein therapeutics, thus promising uses in multi-drug therapies through a single treatment.

Curcumin attenuates inflammation of Macrophage-derived foam cells treated with Poly-L-lactic acid degradation via PPARγ signaling pathway.

Poly-L-lactic acid (PLLA) is considered to be a promising candidate material for biodegradable vascular scaffolds (BVS) in percutaneous coronary intervention (PCI). But, PLLA-BVS also faces the challenge of thrombosis (ST) and in-stent restenosis (ISR) caused by in-stent neo-atherosclerosis (ISNA) associated with inflammatory reactions in macrophage-derived foam cells. Our previous studies have confirmed that curcumin alleviates PLLA-induced injury and inflammation in vascular endothelial cells, but it remains unclear whether curcumin can alleviate the effect of inflammatory reactions in macrophage-derived foam cells while treated with degraded product of PLLA. In this study, PLLA-BVS was implanted in the porcine coronary artery to examine increased macrophages and inflammatory cytokines such as NF-κb and TNF-α by histology and immunohistochemistry. In vitro, macrophage-derived foam cells were induced by Ox-LDL and observed by Oil Red Staining. Foam cells were treated with pre-degraded PLLA powder, curcumin and PPARγ inhibitor GW9662, and the expression of IL-6, IL-10, TNF-α, NF-κb, PLA2 and PPARγ were investigated by ELISA or RT-qPCR. This study demonstrated that the macrophages and inflammatory factors increased after PLLA-BVS implantation in vivo, and foam cells derived from macrophages promoted inflammation by products of PLLA degradation in vitro. This present study was found that the inflammation of foam cells at the microenvironment of PLLA degraded products were significantly increased, and curcumin can attenuate the inflammation caused by the PLLA degradation via PPARγ signal pathway. In addition, curcumin should be further studied experimentally in vivo experiments on animal models as a potential therapeutic to reduce ISNA of PLLA-BVS. Graphical abstract.

Novel Telephone-Based Interactive Voice Response System for Incident Reporting.

BACKGROUND: The voluntary reporting of medical errors and near misses is a well-established patient safety reporting mechanism. However, studies suggest that these incident reporting systems (IRSs) detect less than 10% of all adverse events. Improving the process of reporting can facilitate more informative and timely data capture while providing more opportunities to improve health care quality and safety. The purpose of this study was to understand the barriers to incident reporting via the existing Web-based IRS and develop solutions to increase the ease and efficiency of reporting. METHODS: A survey of staff in a diagnostic imaging department in St. Catharines, Ontario was performed to identify barriers to incident reporting. Based on the barriers identified, two methods of incident reporting were tested in successive phases: (1) a phone-based voice message mailbox, in the computed tomography suite; and (2) a phone-based structured interactive voice response system (IVRS), across the entire department. We measured the rate of incident reports/day and time required to complete reports. OUTCOMES: The three most common barriers to reporting identified were lack of time, complexity of reporting system, and lack of feedback. There was a significant difference in reports per day for the IVRS (mean [M] = 3.43, standard deviation [SD] = 2.71) compared to the IRS (M = 0.99, SD = 0.55); t(31) = 4.58, p ≤ 0.00001. There was also a significant difference in the average time to make a report for the IVRS (M = 97 seconds [s], SD = 30 s) compared to the IRS (M = 644 s, SD = 90 s); t(4) =13.55, p = 0.00025. CONCLUSION: IVRS is an innovative approach to incident reporting that may prove to be more efficient than Web-based approaches and encourage higher reporting rates.

Risk Factors Associated With the Prescription of Opioids Among Service Members Following a First Mild Traumatic Brain Injury.

OBJECTIVE: To evaluate factors impacting opioid receipt among active-duty service members (SMs) following a first mild traumatic brain injury (mTBI). SETTING: Active-duty SMs receiving care within the Military Health System. PARTICIPANTS: In total, 14 757 SMs who have sustained an initial mTBI, as documented within electronic health records (EHRs), between 2016 and 2017. DESIGN: A retrospective analysis of EHR metadata. MAIN MEASURES: Multivariable logistic regression assessed factors impacting opioid receipt and initiation. Factors include demographics, military characteristics, and preexisting clinical conditions, including prior opioid prescription. RESULTS: Of the sample population, 33.4% (n = 4927) were prescribed opioids after their initial mTBI, of which, 60.6% (n = 2985) received opioids for the first time following injury. Significant risk factors associated with the increased probability of opioid receipt included age, gender, and preexisting behavioral health and musculoskeletal conditions. Military characteristics also exhibited changes in the probability of opioid receipt, both among initiation and new prescription. No changes were observed among race, nor among those with preexisting headaches or migraines. CONCLUSION: Despite concerns about the negative impact on recovery, the prescribing of opioids is common in this population of active-duty SMs first diagnosed with an mTBI. As several demographic and preexisting health conditions are factors in the receipt of opioids post-mTBI, the entire medical history of these patients should be considered prior to prescription. Understanding these factors may further inform policy for opioid use in the Military Health System.

Burden of Behavioral Health Comorbidities on Outpatient Health Care Utilization by Active Duty Service Members With a First Documented mTBI.

OBJECTIVE: More than 280,000 Active Duty Service Members (ADSMs) sustained a mild traumatic brain injury (mTBI) between 2000 and 2019 (Q3). Previous studies of veterans have shown higher utilization of outpatient health clinics by veterans diagnosed with mTBI. Additionally, veterans with mTBI and comorbid behavioral health (BH) conditions such as post-traumatic stress disorder, depression, and substance use disorders have significantly higher health care utilization than veterans diagnosed with mTBI alone. However, few studies of the relationship between mTBI, health care utilization, and BH conditions in the active duty military population currently exist. We examined the proportion of ADSMs with a BH diagnosis before and after a first documented mTBI and quantified outpatient utilization of the Military Health System in the year before and following injury. MATERIALS AND METHODS: Retrospective analysis of 4,901,840 outpatient encounters for 39,559 ADSMs with a first documented diagnosis of mTBI recorded in the Department of Defense electronic health record, subsets of who had a BH diagnosis. We examined median outpatient utilization 1 year before and 1 year after mTBI using Wilcoxon signed rank test, and the results are reported with an effect size r. Outpatient utilization is compared by BH subgroups. RESULTS: Approximately 60% of ADSMs experience a first mTBI with no associated BH condition, but 17% of men and women are newly diagnosed with a BH condition in the year following mTBI. ADSMs with a history of a BH condition before mTBI increased their median outpatient utilization from 23 to 35 visits for men and from 32 to 42 visits for women. In previously healthy ADSMs with a new BH condition following mTBI, men more than tripled median utilization from 7 to 24 outpatient visits, and women doubled utilization from 15 to 32 outpatient visits. CONCLUSIONS: Behavioral health comorbidities affect approximately one-third of ADSMs following a first mTBI, and approximately 17% of previously healthy active duty men and women will be diagnosed with a new BH condition in the year following a first mTBI. Post-mTBI outpatient health care utilization is highly dependent on the presence or absence of BH condition and is markedly higher is ADSMs with a BH diagnosis in the year after a first documented mTBI.

Development of an aviation-style computerized checklist displayed on a tablet computer for improving handoff communication in the post-anesthesia care unit.

Critical patient care information is often omitted or misunderstood during handoffs, which can lead to inefficiencies, delays, and sometimes patient harm. We implemented an aviation-style post-anesthesia care unit (PACU) handoff checklist displayed on a tablet computer to improve PACU handoff communication. We developed an aviation-style computerized checklist system for use in procedural rooms and adapted it for tablet computers to facilitate the performance of PACU handoffs. We then compared the proportion of PACU handoff items communicated before and after the implementation of the PACU handoff checklist on a tablet computer. A trained observer recorded the proportion of PACU handoff information items communicated, any resistance during the performance of the checklist, the type of provider participating in the handoff, and the time required to perform the handoff. We also obtained these patient outcomes: PACU length of stay, respiratory events, post-operative nausea and vomiting, and pain. A total of 209 PACU handoffs were observed before and 210 after the implementation of the tablet-based PACU handoff checklist. The average proportion of PACU handoff items communicated increased from 49.3% (95% CI 47.7-51.0%) before checklist implementation to 72.0% (95% CI 69.2-74.9%) after checklist implementation (p < 0.001). A tablet-based aviation-style handoff checklist resulted in an increase in PACU handoff items communicated, but did not have an effect on patient outcomes.

Evaluation of Machine Learning Techniques to Predict the Likelihood of Mental Health Conditions Following a First mTBI.

OBJECTIVE: Limited research has evaluated the utility of machine learning models and longitudinal data from electronic health records (EHR) to forecast mental health outcomes following a traumatic brain injury (TBI). The objective of this study is to assess various data science and machine learning techniques and determine their efficacy in forecasting mental health (MH) conditions among active duty Service Members (SMs) following a first diagnosis of mild traumatic brain injury (mTBI). MATERIALS AND METHODS: Patient demographics and encounter metadata of 35,451 active duty SMs who have sustained an initial mTBI, as documented within the EHR, were obtained. All encounter records from a year prior and post index mTBI date were collected. Patient demographics, ICD-9-CM and ICD-10 codes, enhanced diagnostic related groups, and other risk factors estimated from the year prior to index mTBI were utilized to develop a feature vector representative of each patient. To embed temporal information into the feature vector, various window configurations were devised. Finally, the presence or absence of mental health conditions post mTBI index date were used as the outcomes variable for the models. RESULTS: When evaluating the machine learning models, neural network techniques showed the best overall performance in identifying patients with new or persistent mental health conditions post mTBI. Various window configurations were tested and results show that dividing the observation window into three distinct date windows [-365:-30, -30:0, 0:14] provided the best performance. Overall, the models described in this paper identified the likelihood of developing MH conditions at [14:90] days post-mTBI with an accuracy of 88.2%, an AUC of 0.82, and AUC-PR of 0.66. DISCUSSION: Through the development and evaluation of different machine learning models we have validated the feasibility of designing algorithms to forecast the likelihood of developing mental health conditions after the first mTBI. Patient attributes including demographics, symptomatology, and other known risk factors proved to be effective features to employ when training ML models for mTBI patients. When patient attributes and features are estimated at different time window, the overall performance increase illustrating the importance of embedding temporal information into the models. The addition of temporal information not only improved model performance, but also increased interpretability and clinical utility. CONCLUSION: Predictive analytics can be a valuable tool for understanding the effects of mTBI, particularly when identifying those individuals at risk of negative outcomes. The translation of these models from retrospective study into real-world validation models is imperative in the mitigation of negative outcomes with appropriate and timely interventions.

Long-Term Arterial Remodeling After Bioresorbable Scaffold Implantation 4-Year Follow-up of Quantitative Coronary Angiography, Histology and Optical Coherence Tomography.

PURPOSE: Our previous studies have confirmed the safety and efficacy of the novel fully bioresorbable PLLA scaffold (PowerScaffold®) at 12 months implantation. In the present study, the scaffold absorption and coronary vessel remodeling at 4 years were evaluated. METHODS: After PowerScaffold® were implanted into 13 coronary arteries of 6 miniature pigs, quantitative coronary angiography (QCA) was performed at 15 days and 4 years follow-up to measure the mean lumen diameter (MLD), late lumen loss (LLL), and % stenosis of the coronary arteries. Optical coherence tomography (OCT) was performed to obtain the strut footprints at 4 years before euthanization for histological analysis. In addition, 2 PowerScaffold® were implanted into 2 miniature pigs for 2 years as supplementary data. All stented arteries were dissected and stained with HE, Masson, EVG, and Alcian blue to observe struts, cells, fibrinoid, elastin, and proteoglycans, respectively. RESULTS: There were no significant differences in MLD, LLL and % stenosis in stented coronary arteries between 15 days and 4 years by QCA. At 4 years, most strut sites were indiscernible and replaced by extracellular matrix and connective tissue by histology. Both strut/vessel wall interaction and strut coverage were shown 100% by OCT. CONCLUSION: At 4 years, the scaffold struts were completely embedded into vessel wall and mostly replaced by regenerated tissue. There was no sign of in-stent stenosis in all stented arteries.

Structural optimization and finite element analysis of poly-l-lactide acid coronary stent with improved radial strength and acute recoil rate.

Current poly-l-lactide acid (PLLA) scaffolds have issues of inadequate mechanical strength leading to thrombosis formation. Designing a novel bioabsorbable PLLA stent with a novel structure and improved mechanical property is urgently needed. In this study, stent structure modification and optimization based on bioresorbable vascular scaffold Version 1.1 (BVS 1.1, Abbott Laboratories) were conducted. The mechanical property of the redesigned stent was studied using both computerized finite element analysis and experimental mechanical deformation testing, including radial strength (RS), acute recoil (AR), foreshortening (FS), and bending stiffness (BS). The simulated and experimental results showed that the mechanical properties of the modified structure were significantly improved (modified stent vs. BVS 1.1: RS: 2.25 vs. 1.29 N/mm; AR: 3.03 vs. 4.41%; FS: 1.13 vs. 6.89%; BS: 1.49 vs. 0.72 N mm2 ).

Long-term clinical safety and efficacy of drug-coated balloon in the treatment of in-stent restenosis: A meta-analysis and systematic review.

OBJECTIVES: The aim of this study was to evaluate the long-term clinical safety and efficacy of drug-coated balloon (DCB) in the treatment of in-stent restenosis (ISR). BACKGROUND: There is a long-term safety issue in peripheral arterial disease patients treated with paclitaxel-coated balloon, this has also raised concerns on DCB in coronary intervention. METHODS: Nine randomized controlled trials (RCTs) and nine observational studies (OSs) were included with a total of 3,782 patients (1,827 in the DCB group, 1,955 in the drug-eluting stent [DES] group) being analyzed. The primary outcome measure-major adverse cardiovascular events (MACEs), target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), cardiac death (CD), stent thrombosis (ST), all-cause death (AD), and coronary angiography outcomes included late lumen loss (LLL), minimum luminal diameter (MLD), diameter stenosis (DS) were analyzed. RESULTS: DCB treatment significantly reduced the LLL (MD: -0.13; [CI -0.23 to -0.03], p = .01). No difference was found for MLD (MD: -0.1; [CI -0.24 to 0.04], p = .17) and DS% (RR = 0.98 [CI 0.80-1.20], p = .86). There was no significant difference in TLR, TVR, MI, CD, ST, AD, and the overall incidence of MACEs between the two groups up to 3 years follow-up. Subgroup analysis for different type of ISR and DES showed no significant difference in the incidence of endpoints, and there is no difference when considering RCTs or OSs only. CONCLUSIONS: The safety and efficacy of the DCB and DES in the treatment of ISR is comparable at up to 3 years follow-up.

Inflammation and dysfunction in human aortic endothelial cells associated with poly-l-lactic acid degradation in vitro are alleviated by curcumin.

Poly-l-lactic acid (PLLA) is widely used in clinic, for example, as biodegradable coronary artery stents. However, inflammatory responses in endothelial cells associated with PLLA degradation are relatively undefined. We previously reported inflammation in human aortic endothelial cells (HAEC) in vitro and in vivo. Here, we further assessed inflammatory injury, including cell migration, cell function, and inflammatory cytokines expressed in HAEC treated with PLLA and curcumin by CCK-8, wound healing assay, ELISA, and Western blot. Significant inhibition of cell migration, remarkable dysfunction, and inflammatory responses were found in HAEC treated with PLLA degradation extract, and these effects were alleviated by Cur treatment. These findings indicated that cautious evaluation of biodegradable polymers should be performed, and Cur represents a promising anti-inflammatory agent for alleviating endothelial dysfunction and inflammation caused by PLLA degradation. In addition, Cur should be further studied experimentally in in vivo experiments on animal models as a potential therapeutic to reduce thrombosis of biodegradable polymer stents.

Effect of inflammation on endothelial cells induced by poly-L-lactic acid degradation in vitro and in vivo.

As a promising candidate, biodegradable Poly-L-lactic Acid (PLLA) has been extensively used in coronary artery stents. In our previous reports, PLLA stents implanted in porcine coronary arteries showed safety without stent thrombosis. However, inflammatory responses were observed, which needed further study. In this study, human aortic endothelial cells (HAEC) were treated with different volume percentages of extract of pre-degraded PLLA (extract of PLLA) in vitro, and the cell growth curve and morphological changes were examined. The expression of inflammatory cytokines such as NF-κB, VEGF and VCAM-1 were also observed by ELISA. In addition, PLLA stent was implanted in porcine coronary artery to examine morphological changes, functional marker eNOS and inflammatory responses. The extract of PLLA caused significant growth inhibition and release of NF-κB, VEGF and VCAM-1 in HAEC with volume percentage-dependence. Although re-endothelialization and expression of eNOS was observed, expression of NF-κB and lymphocytes surrounding PLLA were also found after PLLA stents were implanted in the artery. This study demonstrated the effects of inflammation on endothelial cells induced by PLLA degradation in vitro and showed the inflammation in vivo, suggesting that anti-inflammatory strategy is necessary for PLLA stent implantation in the artery.

Six-month evaluation of novel bioabsorbable scaffolds composed of poly-L-lactic acid and amorphous calcium phosphate nanoparticles in porcine coronary arteries.

Objective Using coronary angiography and intravascular ultrasound methods to evaluate the performance of the novel fully bioabsorbable scaffold (NFBS) composed of poly-L-lactic acid/amorphous calcium phosphate (PLLA/ACP) at six-month follow-up by comparing with PLLA scaffolds Methods Twelve PLLA/ACP scaffolds and 12 PLLA scaffolds were implanted into the coronary arteries of 12 miniature pigs. Quantitative coronary angiography (QCA) was used to measure the reference vessel diameter (RVD), mean lumen diameter (MLD) and late lumen loss (LLL). According to IVUS images, we calculated the strut malapposition rate (SMR) at post implantation, strut overlap rate (SOR), reference vessel area (RVA), mean stent area (MSA), mean lumen area (MLA) and luminal patency rate (LPR) at six-month follow-up. The radial strength of the scaffold was evaluated using a catheter tensile testing machine. Results QCA results indicated that, at six month, MLD of PLLA/ACP scaffolds was greater than those of PLLA scaffolds (2.47 ± 0.22 mm vs. 2.08 ± 0.25 mm, P < 0.05); LLL of PLLA/ACP scaffolds was less than those of PLLA scaffolds (0.42 ± 0.20 mm vs. 0.75 ± 0.22 mm, P < 0.05). IVUS results showed the SMR and SOR were all significantly less with the PLLA/ACP scaffolds than the PLLA scaffolds (5.84% ± 3.56% vs. 17.72% ± 4.86%, P < 0.05) (6.17% ± 4.63% vs. 17.65% ± 4.29%, P < 0.05). MSA, MLA and LPR of the PLLA/ACP scaffolds were all greater than those of PLLA scaffolds (6.35 ± 0.45 mm2 vs. 5.35 ± 0.51 mm2, P < 0.05) (4.76 ± 0.46 mm2 vs. 3.77 ± 0.46 mm2, P < 0.05) (78.01% ± 12.29% vs. 61.69% ± 9.76%, P < 0.05). Radial strength of PLLA/ACP scaffold at six month was greater than that of PLLA scaffold (76.33 ± 3.14 N vs. 67.67 ± 3.63 N). Conclusion The NFBS had less stent recoil, better lumen patency rate and greater radial strength than PLLA scaffolds. The results suggest the NFBS scaffolds can maintain the structural strength and functional performance, which are effective for up to six months when implanted in porcine coronary arteries.

A finite element model to investigate the effect of ulnar variance on distal radioulnar joint mechanics.

Ulnocarpal impaction syndrome involves excessive loading of the ulnocarpal joint. Ulnar shortening osteotomies are an effective way to reduce ulnocarpal loading but alter contact mechanics at the distal radioulnar joint (DRUJ). This study used a computational model to investigate the relationship between ulnar length and DRUJ mechanics. Detailed, finite element models of the radius and ulna bones were constructed from magnetic resonance imaging data. The length of the ulna bone model was increased and decreased up to 5 mm in 1 mm increments. A computational model was used to predict joint contact at the DRUJ for each ulnar length. Lengthening the ulna caused a slight decrease in DRUJ contact pressure, with a more substantial decrease in contact area. Shortening the ulna caused a substantial increase in contact area, with a smaller increase in DRUJ contact pressure. The location of contact on the radial sigmoid notch changed with 2 mm lengthening and 3 mm shortening. The results of this study demonstrate the sensitivity of DRUJ contact to ulnar length changes, which may explain the DRUJ cartilage degeneration that often follows ulnar osteotomies. The joint contact model implemented in this study allowed the relationship between ulnar length and DRUJ contact to be examined systematically, in a way that is difficult to achieve through cadaveric experimentation. The results confirmed published experimental data showing an increased DRUJ contact pressure with ulnar shortening. It is important that clinicians consider the influence of ulnar osteotomies, not only on ulnocarpal loading but also on DRUJ mechanics. Copyright © 2016 John Wiley & Sons, Ltd.

12-Month Coronary Angiography, Intravascular Ultrasound and Histology Evaluation of a Novel Fully Bioabsorbable Poly-L-Lactic Acid/Amorphous Calcium Phosphate Scaffolds in Porcine Coronary Arteries.

Our previous studies have confirmed the superior biocompatibility of the poly-L-lactic acid/amorphous calcium phosphate (PLLA/ACP) scaffolds (PowerScaffold) compared to PLLA scaffolds and their similar 6-month radial strength compared with TAXUS stents. In order to conduct further dynamic observations on the performance of the PowerScaffold after 12-month implantation compared with the TAXUS stents. Twenty PowerScaffold and 20 TAXUS were implanted in porcine coronary arteries. At 12-month follow-up, Quantitative Coronary Angiography showed that the stent reference vessel diameter (3.19 ± 0.25 mm vs. 2.75 ± 0.22 mm, p < 0.05), the mean lumen diameter (3.07 ± 0.22 mm vs. 2.70 ± 0.17 mm, p < 0.05) and the late lumen gain (0.45 ± 0.07 mm vs. 0.06 ± 0.06 mm, p < 0.01) were all significantly greater with the PowerScaffold than the TAXUS. As well, Intravascular Ultrasound showed the stent reference vessel area (7.74 ± 0.48 mm2 vs. 6.96 ± 0.51 mm2, p < 0.05), the mean stent area (7.49 ± 0.46 mm2 vs. 6.53 ± 0.47 mm2, p < 0.05) and the mean lumen area (7.22 ± 0.50 mm2 vs. 6.00 ± 0.48 mm2, p < 0.01) were all significantly greater with the PowerScaffold than the TAXUS. The luminal patency rate of the PowerScaffold significantly increased from 72.45 ± 6.84% at 1 month to 93.54 ± 8.15% at 12 months (p < 0.01) while the TAXUS stents were associated with a non-significant decreasing trend (89.44 ± 8.44% vs. 86.53 ± 8.22%). Pathology indicated the average thickness of the struts degraded by 14.25 ± 3.04 µm at 1 month, 23.39 ± 2.45 µm at 6 months and 35.54 ± 2.20 µm at 12 months. Immunohistochemical examination showed that the expression of inflammatory factors NF-κB gradually decreased from 1-month to 12-month (36.79 ± 4.78 vs. 5.79 ± 2.85, P < 0.01). As the late lumen gain of arteries implanted with the PowerScaffold increases over time with the growth of vessels, it effectively reverse the late vascular negative remodeling observed with the TAXUS stents, providing a better option for lumen restoration treatment in clinical practice.

Examining the influence of distal radius orientation on distal radioulnar joint contact using a finite element model.

Distal radius malunion is a problem that is common to distal radius fractures and can affect the contact mechanics of the distal radioulnar joint (DRUJ). The goal of this study was to use a computational model of the DRUJ to investigate the influence distal radius orientation has on its contact mechanics. Detailed, finite element models of the radius and ulna bones were constructed from magnetic resonance imaging data. The orientation of the distal radius was rotated in 2° increments about three orthogonal axes representing dorsal-palmar rotation, radial-ulnar rotation and anteversion-retroversion. A computational model was used to predict joint contact at the DRUJ in each condition. Joint contact was found to be most sensitive to dorsal rotation of the distal radius, while radial and ulnar rotation did not substantially affect joint contact pressure. Slight retroversion was found to lower joint contact pressure. In most cases, more than 6° rotation in a given direction resulted in dislocation of the DRUJ, so that adaptation at the joint would be required to maintain articular contact. The joint contact model implemented in this study allowed the relationship between distal radius orientation and DRUJ contact to be examined systematically, in a way that is difficult to achieve using a cadaver-based approach. The results demonstrated the distal radius displacements most critical for maintaining healthy joint mechanics at the DRUJ. It is important that clinicians consider the influence of distal radius malunion and its treatment on DRUJ mechanics, in addition to its consequences for wrist function and forearm rotation. Copyright © 2016 John Wiley & Sons, Ltd.

6-Month Follow-Up of a Novel Biodegradable Drug-Eluting Stent Composed of Poly-L-Lactic Acid and Amorphous Calcium Phosphate Nanoparticles in Porcine Coronary Artery.

RATIONALE: We reported previously, in porcine coronary arteries, that the novel biodegradable PowerStent Absorb paclitaxel-eluting stent had improved and sustained structural strength and functional performance at one month post-implantation. OBJECTIVE: To report the stent performance at 6-month follow-up. METHODS AND RESULTS: Six PowerStent Absorb and six TAXUS stents were randomly implanted in the left anterior descending and right coronary arteries of six Tibet miniature pigs. Quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) images were obtained at the time of implantation (T0) and at 6 months (T6). Two animals were sacrificed at T6 for histopathological evaluation. At T6, QCA showed that the mean luminal vascular diameter (mLD) between the PowerStent and the TAXUS stents were similar (2.36 ± 0.38 vs. 2.61 ± 0.31, respectively). Based on the IVUS analysis, the mLD and the mean lumen cross-sectional area (mCSA) in the PowerStent-treated arteries were similar between T0 and T6 (mLD: 2.74 ± 0.13 vs. 2.70 ± 0.20 and mCSA: 6.81 ± 0.62 mm2 vs. 6.68 ± 0.94 mm2). Histopathology showed that the PowerStent stents were well apposed to the vessel wall with no recoil, strut fracture and thrombus formation. The stents were fully covered with a layer of endothelial cells. CONCLUSIONS: At six-month post-implantation, the PowerStent Absorb stents maintained their structural strength and functional performance. The development of restenosis was controlled, no stent thrombosis was observed and the stents were fully re-endothelialized. These results suggest the PowerStent Absorb stent is safe and effective for up to 6 months when implanted in porcine coronary arteries.

On modelling large deformations of heterogeneous biological tissues using a mixed finite element formulation.

This study addresses the issue of modelling material heterogeneity of incompressible bodies. It is seen that when using a mixed (displacement-pressure) finite element formulation, the basis functions used for pressure field may not be able to capture the nonlinearity of material parameters, resulting in pseudo-residual stresses. This problem can be resolved by modifying the constitutive relation using Flory's decomposition of the deformation gradient. A two-parameter Mooney-Rivlin constitutive relation is used to demonstrate the methodology. It is shown that for incompressible materials, the modification does not alter the mechanical behaviour described by the original constitutive model. In fact, the modified constitutive equation shows a better predictability when compared against analytical solutions. Two strategies of describing the material variation (i.e. linear and step change) are explained, and their solutions are evaluated for an ideal two-material interfacing problem. When compared with the standard tied coupling approach, the step change method exhibited a much better agreement because of its ability to capture abrupt changes of the material properties. The modified equation in conjunction with integration point-based material heterogeneity is then used to simulate the deformations of heterogeneous biological structures to illustrate its applications.

Novel biodegradable drug-eluting stent composed of poly-L-lactic acid and amorphous calcium phosphate nanoparticles demonstrates improved structural and functional performance for coronary artery disease.

Bioabsorbable drug-eluting stents (BDES) offer multiple advantages over a permanent bare metal stent (BMS) for coronary artery disease (CAD). However, current BDES remains two major issues: inferior radial strength and biocompatibility. PowerStent Absorb BDES, fabricated by co-formulating amorphous calcium phosphate (ACP) nanoparticles with poly-L-lactic acid (PLLA/ACP, 98/2, w/w) and 2% Paclitaxel (PAX, w/w) was designed to address these issues. Two cohorts of 6 miniature pigs were each implanted with PLLA/PAX (control, 2% PAX, w/w) or PowerStent Absorb BDES. After 1 month in-vivo study, histological analyses showed significantly reduced restenosis in the PowerStent Absorb BDES cohort relative to the control cohort (44.49 +/- 410.49% vs. 64.47 +/- 16.2%, p < 0.05). Stent recoil (21.57 +/- 5.36% vs. 33.81 +/- 11.49, P < 0.05) and inflammation (3.01 +/- 0.62 vs. 4.07 +/- 0.86, P < 0.01) were also obviously decreased. From in-vitro studies, PLLA/ACP/PAX stent tube maintained significantly greater radial strength than control group during 6 months in-vitro degradation (PLLA/ACP/PAX vs. PLLA/PAX: before hydrolysis: 82.4 +/- 1.9 N vs.74.8 +/- 3.8 N; 6 weeks: 73.9 +/- 1.8 N vs. 68.0 +/- 5.3 N; 3 months: 73.5 +/- 3.4 N vs.67.2 +/- 3.8 N; 6 months: 56.3 +/- 8.1 N vs. 57.5 +/- 4.9 N). Moreover, ACP facilitated the hydrolytic degradation of PLLA compared with control one (62.6% vs. 49.8%), meanwhile, it also increased the crystallinity of PLLA (58.4% vs. 50.7%) at 6 months. From SEM observations, ACP created nanometer pores that enlarge gradually to a micrometer scale as degradation proceeds. The changes of the porosity may result in greatly promoting re-endothelialization.

Emulating facial biomechanics using multivariate partial least squares surrogate models.

A detailed biomechanical model of the human face driven by a network of muscles is a useful tool in relating the muscle activities to facial deformations. However, lengthy computational times often hinder its applications in practical settings. The objective of this study is to replace precise but computationally demanding biomechanical model by a much faster multivariate meta-model (surrogate model), such that a significant speedup (to real-time interactive speed) can be achieved. Using a multilevel fractional factorial design, the parameter space of the biomechanical system was probed from a set of sample points chosen to satisfy maximal rank optimality and volume filling. The input-output relationship at these sampled points was then statistically emulated using linear and nonlinear, cross-validated, partial least squares regression models. It was demonstrated that these surrogate models can mimic facial biomechanics efficiently and reliably in real-time.