Development of a novel approach for restoration of the meniscus using silk-elastin in a rabbit meniscus injury model.

BACKGROUND: Limited healing potential of the meniscus remains a burden for the successful repair of meniscus injuries in the orthopaedic fields. Silk-elastin (SE) is a novel recombinant protein with favorable properties for wound healing. This proof-of-concept study aimed to investigate the therapeutic effect of silk-elastin in a rabbit meniscal defect model. METHODS: A migration assay using rabbit meniscus and synovial cells with various concentrations of SE in a culture medium was conducted to investigate the mechanism of meniscal healing by SE. Additionally, cylindrical defects with a 1.5 mm diameter were created at the anterior horn of the medial meniscus of rabbits. The animals were divided into three groups: 1) the Blank group; defect only, 2) the Col I group; implantation of type I atelocollagen sponge, and 3) the SE group; implantation of SE (150 mg/ml) sponge. Whole medial menisci were harvested at 4, 8, 12, and 24 weeks after surgery. Histological analyses including immunohistochemical staining were performed to assess meniscal healing. RESULTS: In vitro study, Migration assay demonstrated a significantly higher number of migrated cells only in synovial cells. Especially, the SE concentration of 10 µg/mL demonstrated the highest number of migrated cells compared with other concentrations. In vivo study, the SE group exhibited significantly higher Ishida scores than other groups at all time points. Furthermore, the SE group showed higher synovial coverage scores than the Col I group at 4 and 8 weeks. Immunohistochemical staining demonstrated higher type II collagen staining in the SE group compared to other groups at 12 weeks. Implanted SE was efficiently replaced by safranin-O staining positive tissue within 8 weeks. CONCLUSIONS: SE could effectively repair a meniscal defect by inducing coverage of synovial cells. SE has the potential to be a useful material for meniscal repair.

[Repair of Vaginal Cuff Dehiscence after Laparoscopic Radical Cystectomy with Gracilis Myocutaneous Flap].

Vaginal cuff dehiscence after total hysterectomy or total cystectomy had been increasing since laparoscopic or robotic surgery became a common surgery among gynecologists and urologists. A 52-yearold woman underwent laparoscopic radical total cystectomy for muscle invasive bladder carcinoma at Rakuwakai Otowa Hospital. She was emergently admitted with a fist-sized lump protruding from her vagina four months after surgery. Physical examination and her past history on admission disclosed vaginal cuff dehiscence after cystectomy. Computed tomographic scan and magnetic resonance imaging showed no bowel evisceration in the lump. We confirmed that the content of lump was peritoneal tissue and removed it by laparoscopic surgery. Simultaneously, we repaired the vaginal cuff dehiscence with a gracilis myocutaneous flap. There was no subsequent recurrence of vaginal dehiscence or bladder carcinoma in one-year follow-up.

The c.1617del variant of TMEM260 is identified as the most frequent single gene determinant for Japanese patients with a specific type of congenital heart disease.

Although the molecular mechanisms underlying congenital heart disease (CHD) remain poorly understood, recent advances in genetic analysis have facilitated the exploration of causative genes for CHD. We reported that the pathogenic variant c.1617del of TMEM260, which encodes a transmembrane protein, is highly associated with CHD, specifically persistent truncus arteriosus (PTA), the most severe cardiac outflow tract (OFT) defect. Using whole-exome sequencing, the c.1617del variant was identified in two siblings with PTA in a Japanese family and in three of the 26 DNAs obtained from Japanese individuals with PTA. The c.1617del of TMEM260 has been found only in East Asians, especially Japanese and Korean populations, and the frequency of this variant in PTA is estimated to be next to that of the 22q11.2 deletion, the most well-known genetic cause of PTA. Phenotype of patients with c.1617del appears to be predominantly in the heart, although TMEM260 is responsible for structural heart defects and renal anomalies syndrome (SHDRA). The mouse TMEM260 variant (p.W535Cfs*56), synonymous with the human variant (p.W539Cfs*9), exhibited truncation and downregulation by western blotting, and aggregation by immunocytochemistry. In situ hybridization demonstrated that Tmem260 is expressed ubiquitously during embryogenesis, including in the development of cardiac OFT implicated in PTA. This expression may be regulated by a ~ 0.8 kb genomic region in intron 3 of Tmem260 that includes multiple highly conserved binding sites for essential cardiac transcription factors, thus revealing that the c.1617del variant of TMEM260 is the major single-gene variant responsible for PTA in the Japanese population.

Relationships among hip instability, iliofemoral ligament, and pain in patients with developmental dysplasia of the hip.

BACKGROUND: To evaluate the relationships among hip instability, pain, and morphology of the iliofemoral ligament (ILFL) in patients with developmental dysplasia of the hip (DDH) using ultrasonography (US). METHODS: We reviewed 86 patients (109 hips) with DDH (Group D), 40 patients (46 hips) with borderline hip dysplasia (BDDH) (Group B) and 20 patients (23 hips) without hip pain and bony abnormality (control group). Group D was classified into three subgroups-the severe (group SP), moderate (group MP), and none/mild (group NMP) hip pain groups-using the visual analogue scale (VAS). For evaluating hip instability and ILFL morphology, the distance between the anterior edge of the anterior inferior iliac spine (AIIS) and the horizontal line to the femoral head, and ILFL thickness were measured using US. The difference between the distance in the neutral position and Patrick position was calculated and defined as the femoral head translation distance (FTD). RESULTS: FTD and ILFL thickness in group D were significantly larger than those in the control group and group B (P < 0.05). There was a significant positive correlation between FTD and ILFL thickness in three groups (r = 0.57, P < 0.05; r = 0.55, P < 0.05; r = 0.62, P < 0.05, respectively). FTD and ILFL thickness in group SP were significantly larger than those in group NMP (P < 0.05). FTD and ILFL thickness in group D had significantly negative correlations with the lateral center edge (r = -0.54, P < 0.05; r = -0.40, P < 0.05, respectively) and vertical-center-anterior angle (r = -0.51, P < 0.05; r = -0.43, P < 0.05, respectively). CONCLUSIONS: Acetabular bony deficiency, especially in the anterior and lateral region can result in antero-posterior hip instability, leading to thickened ILFL and hip pain, even in patients with BDDH. These findings may facilitate our understanding and treatment of patients with DDH. When hip instability is suspected, hip US examination may help confirm the diagnosis and assist in providing objective clinical diagnostic evidence.

Clinical Characteristics of Coronary-to-Pulmonary Artery Fistula in Patients with Pulmonary Atresia and Ventricular Septal Defect.

The existence of a coronary-to-pulmonary artery fistula (CPF) in pulmonary atresia with ventricular septal defect (PAVSD) potentially affects treatment; however, its clinical features have not been comprehensively described due to the disease's rarity. We reviewed 69 cases from 42 studies to reveal the clinical overview of patients with CPF and PAVSD. Among the included patients, the male-to-female ratio was exactly 1:1, and only two patients (3%) exhibited the 22q11.2 microdeletion syndrome. Regarding anatomical features, CPFs originated from the left coronary artery in 65% of patients, and 62% had other major aortopulmonary collateral arteries. Thirty-nine percent of patients had a definitive CPF diagnosis at 0 years of age, whereas 10% were diagnosed in adulthood. Seventy percent underwent catheter angiography to obtain a definitive CPF diagnosis. Ninety-five percent of patients underwent cardiac surgery, and among them, 43% underwent palliative surgery, whereas 52% underwent one-stage repair. Four patients including three adult patients developed cardiac dysfunction due to myocardial ischemia, and three of them exhibited improved cardiac function after the intervention for CPF. Of all the patients, 88% survived and 12% died. The surgical strategy and prognosis were similar to those in PAVSD patients without CPF. This review provides detailed clinical phenotypes that are potentially useful in enhancing the management of patients with this rare disease.

Investigating the subchondral trabecular bone microstructure in patients with osteonecrosis of the femoral head using multi-detector row computed tomography.

OBJECTIVES: To analyse the microstructural changes of subchondral trabecular bone in patients with osteonecrosis of the femoral head (ONFH) using multi-detector row computed tomography (MDCT). METHODS: We retrospectively investigated 76 hips in 50 patients diagnosed with ONFH between 2017 and 2021. Groups 1, 2, 3, and 4 comprised hips without ONFH, ONFH without femoral head collapse (FHC), ONFH with mild collapse (<2 mm), and ONFH with severe collapse (>2 mm), respectively. All patients underwent MDCT, and the subchondral trabecular bone microstructure was assessed. Regions of interests were set at the lateral boundary of the femoral head necrotic lesion and centre of the acetabular weight-bearing portion. RESULTS: In both the femoral head and the acetabular regions, there were significant differences in Groups 2 and 3 compared to Group 1, with increased volumetric bone mineral density and apparent bone volume fraction, and more plate-like with increased connectivity, indicating that osteosclerotic changes were occurring. CONCLUSIONS: In both the femoral head and the acetabular regions, osteosclerotic changes of subchondral trabecular bone microstructure were present before FHC.

Evaluation of antero-posterior instability of the hip using modified Lequesne's false profile view.

BACKGROUND: Accurate evaluation of hip instability is critical for the diagnosis and successful treatment of developmental dysplasia of the hip (DDH). However, dynamic evaluation of hip instability is not well established. This study aimed to use the lateral view from a radiograph to evaluate dynamic antero-posterior hip instability in patients with DDH. METHODS: Seventy-four patients (92 hips) with DDH (DDH group) and 46 patients (59 hips) without hip pain and DDH (Control group) were examined. A false profile view (FPV) according to Lequesne was taken at standard and 90° flexion with the hip of interest defined as functional FPV; the translation of the center of the femoral head (CFH) obtained from the functional FPV was measured. As a validation test, we measured the anterior translation of the CFH using ultrasonography (US). RESULTS: There was a significant difference between the two groups in the translation of the CFH (p < 0.01). The degree of CFH translation depended on the severity of DDH (lateral center edge angle, r = -0.56, p < 0.01; vertical center anterior margin angle, r = -0.57, p<0.01) and lateralization of the femoral head (head lateralization index, r = 0.54, p < 0.01). There was a significant correlation between functional FPV and US measurements (r = 0.71, p < 0.01). CONCLUSION: The present study confirmed that antero-posterior hip instability in DDH patients can be detected using functional FPV. Our novel measurement, as a new method for assessing hip instability, may be useful for evaluating hip dynamic instability in diagnosing the etiology, and determining and evaluating the treatment for DDH at lower cost and improved accessibility.

Coordination polymer-forming liquid Cu(2-isopropylimidazolate).

The structure of the melt state of one-dimensional (1D) coordination polymer crystal Cu(isopropylimidazolate) (melting temperature T m = 143 °C) was characterized by DSC, variable temperature PXRD, solid-state NMR (SSNMR), viscoelastic measurements, XAS, and DFT-AIMD calculations. These analyses suggested "coordination polymer-forming liquid" formation with preserved coordination bonds above T m. Variable chain configurations and moderate cohesive interaction in adjacent chains are the keys to the rarely observed polymer-forming liquid. The melt structure is reminiscent of the common 1D organic polymer melts such as entanglement or random coil structures.

The impact of increasing femoral offset and stem anteversion on postoperative dislocation in bipolar hemiarthroplasty.

BACKGROUND: Femoral offset and anteversion have been reported to affect the incidence of dislocation following bipolar hemiarthroplasty, although the magnitudes of contributions of the femoral offset and stem anteversion on dislocation, both singly and in combination is not fully understood. METHODS: Using the CT data of 61 patients (61 hips), including 30 male and 31 female who underwent bipolar hemiarthroplasty, three-dimensional dynamic motion analysis was performed using a modular implant that enabled adjustment of femoral offset and stem anteversion independently. The pattern of impingement and relationship between femoral offset/stem anteversion and range of motion were evaluated using the software. FINDINGS: We found that a higher femoral offset and stem anteversion correlate with a greater range of motion of flexion and internal rotation. Furthermore, an increased femoral offset has a great effect on increasing range of motion of flexion than stem anteversion, and increased both femoral offset and stem anteversion have fewer effect on the flexion, whereas increasing stem anteversion has a great impact on internal rotation than offset, especially in the case with lower femoral anteversion. However, a higher stem anteversion decrease the range of motion of external rotation, whereas a higher femoral offset leads to an increased range of motion of external rotation. INTERPRETATION: We demonstrated that both a higher femoral offset and stem anteversion substantially affected the range of motion in flexion, internal rotation and external rotation. However, these are not independent, but rather mutually confounding, the surgeons should consider retaining femoral/anterior offset in bipolar hemiarthroplasty.

Multi-energy dissipation mechanisms in supramolecular hydrogels with fast and slow relaxation modes.

Reversible cross-links by non-covalent bonds have been widely used to produce supramolecular hydrogels that are both tough and functional. While various supramolecular hydrogels with several kinds of reversible cross-links have been designed for many years, a universal design that would allow control of mechanical and functional properties remains unavailable. The physical properties of reversible cross-links are usually quantified by thermodynamics, dynamics, and bond energies. Herein, we investigated the relationship between the molecular mobility and mechanical toughness of supramolecular hydrogels consisting of two kinetically distinct reversible cross-links via host-guest interactions. The molecular mobility was quantified as the second-order average relaxation time (〈τ〉w) of the reversible cross-links. We discovered that hydrogels combining fast (〈τ〉w = 1.8 or 18 s) and slowly (〈τ〉w = 6.6 × 103 or 9.5 × 103 s) reversible cross-links showed increased toughness compared to hydrogels with only one type of cross-link because relaxation processes in the former occurred with wide timescales.

Associations between implant alignment or position and patient-reported outcomes after total hip arthroplasty.

BACKGROUND: We aimed to evaluate the associations between implant alignment/position and patient-reported outcomes following total hip arthroplasty using CT-based simulation software. METHODS: We reviewed hips of 137 patients (27 males, 110 females, mean age: 67.3 years old) who underwent total hip arthroplasty. Radiographic evaluations were based on the software for evaluation of the parameters related to implant alignment/position and femoral/3-dimensional offset using post-operative CT data. Pre-operative and one-year post-operative patient-reported outcomes using Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire scores were evaluated. FINDINGS: The total and movement scores of normal combined anteversion and stem anteversion angle groups were significantly higher than those of lower and higher groups. The pain and movement scores of decreased femoral offset group were significantly lower than those of restored and increased femoral offset group. There were no significant differences in all scores in cup inclination and anteversion angle, stem coronal alignment, and 3-dimensional femoral offset among groups. Moreover, investigation of the associations between combined anteversion angle/stem anteversion/femoral offset and movement scores revealed that combined anteversion angle and stem anteversion were significantly associated with the movement that needs deep hip flexion and occasionally deep abduction, and high femoral offset was also associated with the movement that needs deep hip flexion. INTERPRETATION: Surgeons should consider the stem anteversion, stem sagittal alignment, and combined anteversion, in addition to the femoral offset to achieve patient's post-operative satisfaction, although the surgeon may have a relatively larger choice for the implant positioning, especially on the cup side.

Preoperative T2 mapping MRI of articular cartilage values predicts postoperative osteoarthritis progression following rotational acetabular osteotomy.

AIMS: Rotational acetabular osteotomy (RAO) has been reported to be effective in improving symptoms and preventing osteoarthritis (OA) progression in patients with mild to severe develomental dysplasia of the hip (DDH). However, some patients develop secondary OA even when the preoperative joint space is normal; determining who will progress to OA is difficult. We evaluated whether the preoperative cartilage condition may predict OA progression following surgery using T2 mapping MRI. METHODS: We reviewed 61 hips with early-stage OA in 61 patients who underwent RAO for DDH. They underwent preoperative and five-year postoperative radiological analysis of the hip. Those with a joint space narrowing of more than 1 mm were considered to have 'OA progression'. Preoperative assessment of articular cartilage was also performed using 3T MRI with the T2 mapping technique. The region of interest was defined as the weightbearing portion of the acetabulum and femoral head. RESULTS: There were 16 patients with postoperative OA progression. The T2 values of the centre to the anterolateral region of the acetabulum and femoral head in the OA progression cases were significantly higher than those in patients without OA progression. The preoperative T2 values in those regions were positively correlated with the narrowed joint space width. The receiver operating characteristic analysis revealed that the T2 value of the central portion in the acetabulum provided excellent discrimination, with OA progression patients having an area under the curve of 0.858. Furthermore, logistic regression analysis showed T2 values of the centre to the acetabulum's anterolateral portion as independent predictors of subsequent OA progression (p < 0.001). CONCLUSION: This was the first study to evaluate the relationship between intra-articular degeneration using T2 mapping MRI and postoperative OA progression. Our findings suggest that preoperative T2 values of the hip can be better prognostic factors for OA progression than radiological measures following RAO. Cite this article: Bone Joint J 2021;103-B(9):1472-1478.

Viscoelastic Relaxation of Polymerized Ionic Liquid and Lithium Salt Mixtures: Effect of Salt Concentration.

Polymerized ionic liquids (PILs) doped with lithium salts have recently attracted research interests as the polymer component in lithium-ion batteries because of their high ionic mobilities and lithium-ion transference numbers. To date, although the ion transport mechanism in lithium-doped PILs has been considerably studied, the role of lithium salts on the dynamics of PIL chains remains poorly understood. Herein, we examine the thermal and rheological behaviors of the mixture of poly(1-butyl-3-vinylimidazolium bis(trifluoromethanesulfonyl)imide (PC4-TFSI)/lithium TFSI (LiTFSI) in order to clarify the effect of the addition of LiTFSI. We show that the glass transition temperature Tg and the entanglement density decrease with the increase in LiTFSI concentration wLiTFSI. These results indicate that LiTFSI acts as a plasticizer for PC4-TFSI. Comparison of the frequency dependence of the complex modulus under the iso-frictional condition reveals that the addition of LiTFSI does not modify the stress relaxation mechanism of PC4-TFSI, including its characteristic time scale. This suggests that the doped LiTFSI, component that can be carrier ions, is not so firmly bound to the polymer chain as it modifies the chain dynamics. In addition, a broadening of the loss modulus spectrum in the glass region occurs at high wLiTFSI. This change in the spectrum can be caused by the responses of free TFSI and/or coordination complexes of Li and TFSI. Our detailed rheological analysis can extract the information of the dynamical features for PIL/salt mixtures and may provide helpful knowledge for the control of mechanical properties and ion mobilities in PILs.

Phase equilibrium and dielectric relaxation in mixture of 5CB with dilute dimethyl phthalate: effect of coupling between orientation and composition fluctuations on molecular dynamics in isotropic one-phase state.

Phase equilibrium and dielectric relaxation were examined for mixtures of liquid-crystalline (LC)-forming 4-cyano-4'-pentylbiphenyl (5CB) with dilute dimethyl phthalate (DMP). The mixtures were in an isotropic one-phase state at high temperatures T but were separated into nematic and isotropic phases at low T < TIN (isotropic-to-nematic transition temperature), and the isotropic phase disappeared and a nematic one-phase state was realized on a further decrease of T below another transition temperature . These TIN and data (phase diagram) were described considerably well by a simple model of free energy contributed from a Flory-Huggins type mixing entropy (no enthalpic contribution) and a Landau-de Gennes type nematic interaction. This success of the model, not expected for ordinary (not LC-forming) components exhibiting enthalpically-driven phase separation, suggested that the phase separation in the DMP/5CB mixtures was triggered by the nematic transition of 5CB (possibly governed by the packing entropy) and thus the orientation fluctuation of 5CB molecules was coupled with the composition fluctuation. This coupling was expected to affect the dielectric relaxation detecting the rotational dynamics of 5CB molecules, the major component in the mixtures. This expectation was examined for a representative mixture having the DMP content of wDMP = 3.1 wt% and TIN ≅ 27.0 °C. In a high-T asymptote (T > TIN + 10 °C), the dielectric relaxation of this mixture was close to that of pure 5CB, which suggested no significant effect of the above coupling on 5CB dynamics in the mixture at such high T. Nevertheless, in a significantly wide range of T between TIN and TIN + 10 °C, the dielectric relaxation time τε of the isotropic one-phase mixture increased on cooling much more significantly compared to τε in that high-T asymptote. The kinematic viscosity ν of the mixture exhibited a qualitatively similar increase in the same range of T, but this increase was weaker than that of τε. This difference between the dielectric τε and the rheological ν was attributed to coupling of the orientation and the composition fluctuations mentioned above. Namely, the composition fluctuation enhances the orientation fluctuation in the mixture thereby providing τε (reflecting the orientation fluctuation) with an extra increase. Pure 5CB exhibited similar increases of τε and ν (stronger for the former) but only in a close vicinity of (within 2-3 °C), because the orientation fluctuation in pure 5CB is coupled with the density fluctuation, not with the composition fluctuation being absent in the pure 5CB system. This behavior of pure 5CB in turn suggests an importance of the coupling of orientation and composition fluctuations in the mixture.

Three-dimensional analysis of the cortical contact state of short and conventional stems in different stem positions in total hip arthroplasty.

BACKGROUND: Despite the increasing use of short cementless stems in total hip arthroplasty, their potential benefits have yet to be confirmed. We evaluated the cortical contact state of short and conventional stems in different femoral canal types and stem positions using a CT-based 3-dimensional templating software. METHODS: We reviewed 153 hips in 153 patients, grouped according to femoral canal type-normal (68), champagne-flute (41), and stove-pipe canal (44). We investigated the influence of stem position on the contact state by evaluating three situations of stem anteversion (original anteversion, +5°anteverted, and +5°retroverted), three stem positions, neutral +2°extended, and +2°flexed positions using Taperloc Complete MicroplastyⓇ stem. FINDINGS: The contact values of all zones between both stems in all canal types exhibited no significant differences. The values in zones 1, 2, 6, and 7 of both stems in 5° retroverted and anteverted, 2° extended and flexed positions were not significantly different compared to those of the neutral position. However, the values in zones 3, 4, and 5 of both stems were significantly greater compared to those of the neutral position in 2° extended and flexed positions; these values were also significantly larger in all canal types for the conventional stem. INTERPRETATION: We demonstrated that the short and conventional stems can achieve the same proximal cortical contact in any femoral canal, regardless of the stem position. However, extended and flexed stem positions increase the distal contact, especially in conventional stems. Furthermore, the distal contact increases for the retroverted stem insertions.

Intracardiac Echocardiography as a Guide for Transcatheter Closure of Patent Ductus Arteriosus.

BACKGROUND: Transcatheter closure of patent ductus arteriosus (TC-PDA), conventionally guided by aortography, has become the standard treatment of this disease. The purposes of this study were to evaluate whether intracardiac echocardiography (ICE) may be used for measuring PDA size and be used as a guide for TC-PDA. METHODS: This study had 2 phases. In phase 1, we compared the measurements of PDA size: pulmonary artery side diameter (PA-D), length, and aortic side diameter (Ao-D) of PDA, as measured by ICE with those measured by aortography or cardiac computed tomography (AoG/CCT) in 23 patients who underwent TC-PDA. In phase 2, we compared the demographics, fluoroscopic time, contrast volume, and complications of the TC-PDAs between 10 adult patients with ICE guidance and 16 without it. RESULTS: In phase 1, we found great correlation and agreement between ICE and AoG/CCT in PA-D (r = 0.985, bias -0.077 to 0.224), but moderate to poor correlation and agreement in length (r = 0.653, bias -0.491 to 3.065) and Ao-D (r = 0.704, bias 0.738 to 4.732), respectively. Nevertheless, all patients underwent successful TC-PDA with ICE guidance that allowed us to continuously monitor the whole process. In phase 2, TC-PDA required a significantly lower contrast volume with ICE guidance than without it, and there was no significant difference in the remaining variables between the 2 groups. CONCLUSION: ICE is comparable to AoG/CCT in providing accurate PA-D of the PDA and may be a safe alternative to guide TC-PDA as compared to conventional aortography.

Reinforcement of antitumor effect of micelles containing anticancer drugs by binding of an anti-tissue factor antibody without direct cytocidal effects.

It has been preclinically and clinically proven that anticancer agent-incorporating (ACA-incorporating) polymeric micelles selectively accumulate in tumor via the enhanced permeability and retention (EPR) effect, yielding a wider therapeutic window and greater safety than conventional low-molecular weight ACAs. To increase the antitumor effect of these safer micelle formulations, epirubicin-incorporating polymer micelles (NC-6300) conjugated with monoclonal antibodies (mAbs) have been prepared. In this study, we used two types of mAb: an anti-tissue factor (TF) mAb that does not exert a direct cytocidal effect, and an anti-HER2 mAb that has a direct cytocidal effect. We compared the antitumor effects and pharmacological properties of the two types of antibody conjugated to NC-6300. Immunomicelles conjugated to anti-TF mAb exerted greater antitumor activity toward TF-positive stomach cancer than the combination of anti-TF mAb and NC-6300, and were distributed more uniformly throughout TF-positive tumor tissue than NC-6300. On the other hand, immunomicelles conjugated to anti-HER2 mAb did not exert significant antitumor activity toward HER2-positive stomach cancer relative to the combined use of anti-HER2 mAb and NC-6300. Thus, this immunomicelle-based strategy may be useful for antibodies that target cancer as pilot molecules even when the antibodies themselves do not have an antitumor effect.

Viscoelastic Relaxation of Cellulose Nanocrystals in Fluids: Contributions of Microscopic Internal Motions to Flexibility.

We report the viscoelastic relaxation mechanisms of cellulose nanocrystals (CNCs) dispersed individually in fluids. Linear viscoelasticity and flow birefringence of softwood and tunicate CNC/glycerol dispersions in the dilute regime were measured. The obtained results were then compared with molecular theories for the linear viscoelasticity of rigid rods and semiflexible rods at infinite dilution by taking length distributions of CNCs into account. Although CNCs are traditionally regarded as rigid Brownian rods, the viscoelastic relaxation was not explained solely by the rotational motions of rods. Alternatively, molecular theories for semiflexible rods well-described the viscoelastic behavior; the CNCs showed additional relaxation modes derived from microscopic internal motions including "tension" and "curvature", which originated from the finite flexural rigidity. Birefringence relaxation of the CNCs was dominated by the rotational motions of rods. Length distribution functions of the CNCs were thus calculated from the birefringence relaxation and agreed well with their microscopy-determined histograms.

Anti-VEGFR2 Antibody-modified Micelle for Triggered Drug Delivery and Effective Therapy of Choroidal Neovascularization.

OBJECTIVE: This study aimed to examine whether DC101 (anti-VEGFR2 antibody)- modified micelles have applications as novel drug delivery devices, which allow small molecule antiangiogenic agents to deliver to angiogenic sites on a murine laser-induced choroidal neovascularization (CNV) model. MATERIALS AND METHODS: CNV was induced by photocoagulation on the unilateral eye of each mouse under anesthesia. Immediately after laser coagulation, E7974-loaded DC101-modified micelles and motesanib-loaded DC101-modified micelles were intravitreally administrated. Two weeks after photocoagulation, CNV was visualized using fluorescein-conjugated dextran (MW=2,000 kDa), and the CNV area was measured in retinal pigment epithelium (RPE)-choroidal flat mounts. RESULTS: Intravitreal administration of both DC101-modified micelles loaded with E7974 at 2 µM and motesanib at 2 µM significantly reduced CNV area in the murine laser-induced CNV model at a clearly lower concentration than the effective dose of each agent. CONCLUSION: These results suggest that DC101-modified micelle might be effective drug carrier system for treating CNV and other ocular angiogenic diseases.