Streamlined Formation and Manipulation of Charged Polymersomes.

Charged polymersomes are attractive for advanced material applications due to their versatile encapsulation capabilities and charge-induced functionality. Although desirable, the pH-sensitivity of charged block copolymers adds complexity to its self-assembly process, making it challenging to produce charged polymersomes in a reliable manner. In this work, a flow approach to control and strike a delicate balance between solvent composition and pH for self-assembly is used. This allows for the identification of a phase window to reliably produce of charged polymersomes. The utility of this approach to streamline downstream processes, such as morphological transformation or in-line purification is further demonstrated. As proof-of-concept, it is shown that the processed polymersomes can be used for surface modifications facilitated by charge complexation.

Fibroblast growth factor receptor 1/Klothoß agonist BFKB8488A improves lipids and liver health markers in patients with diabetes or NAFLD: A phase 1b randomized trial.

BACKGROUND AND AIMS: BFKB8488A is a bispecific antibody targeting fibroblast growth factor receptor 1c and Klothoß. This phase 1b study assessed safety, tolerability, pharmacokinetics, immunogenicity, and pharmacodynamics of BFKB8488A in patients with type 2 diabetes mellitus (T2DM) or NAFLD. APPROACH AND RESULTS: Patients were randomized to receive multiple doses of BFKB8488A at various dose levels and dosing intervals (weekly, every 2 weeks, or every 4 weeks) or placebo for 12 weeks. The primary outcome was the safety of BFKB8488A. Overall, 153 patients (T2DM: 91; NAFLD: 62) were enrolled and received at least one dose of treatment. Of these, 102 patients (62.7%) reported at least one adverse event (BFKB8488A: 83 [68.6%]; placebo: 19 [59.4%]). BFKB8488A exhibited nonlinear pharmacokinetics, with greater than dose-proportional increases in exposure. The treatment-emergent antidrug antibody incidence was 22.7%. Overall, trends in exposure-dependent increases in high-density lipoprotein (HDL) and decreases in triglyceride levels were observed. Decreases in alanine aminotransferase and aspartate aminotransferase were 0.7% and 9.2% for medium exposure and 7.3% and 11.2% for high-exposure tertiles, compared with increases of 7.5% and 17% in the placebo group, respectively, at Day 85. In patients with NAFLD, the mean decrease from baseline liver fat was 13.0%, 34.5%, and 49.0% in the low-, medium-, and high-exposure tertiles, respectively, compared with 0.1% with placebo at Day 85. CONCLUSIONS: BFKB8488A was adequately tolerated in patients with T2DM or NAFLD, leading to triglyceride reduction, HDL improvements, and trends in improvement in markers of liver health for both populations and marked liver fat reduction in patients with NAFLD. ( ClinicalTrials.gov : NCT03060538).

Subclinical Upper Eyelid Ptosis in Asian Patients: The Role of Levator Advancement in Optimizing Outcomes in "Cosmetic" Upper Blepharoplasty.

BACKGROUND: Subclinical ptosis is prevalent in Asian patients presenting for aesthetic upper blepharoplasty. To achieve predictable and satisfactory results in these patients, addressing the ptosis component is critical. In this paper, we present a precision levator advancement technique that enabled us to predictably incorporate the levator advancement into our upper blepharoplasty to deliver more predictable results in these patients. MATERIALS AND METHODS: Asian patients with normal or near normal margin to reflex distance 1 (MRD 1 of ≥ 3.5 mm) and symptoms and signs of straining of the frontalis with eyelid opening were diagnosed with subclinical upper eyelid ptosis and included in this prospective study. The advancement required was estimated pre-operatively using a formula that we developed. Our surgical technique is presented in detail here, and our long-term results were analysed. RESULTS: From December 2019 to August 2022, 97 patients were included in this study. Sixty-five patients were primary cases and 32 were revision cases. The mean follow-up was 15 months. Of the 192 eyelids analysed, our formula was able to correctly identify the required fixation location in 69% of eyelids. In majority of the eyelids (94%), the correct location of fixation location within +/- 1 mm of the estimated location. All patients (100%) were satisfied with their long-term results. Our revision rate was 3%. CONCLUSIONS: Incorporating a precisely done levator advancement into the upper blepharoplasty in patients with subclinical ptosis is critical for optimizing the aesthetic and functional outcomes. This approach has enabled us to perform this procedure greater predictably in this group of patients. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Mixtures of Acid- and Base-Functionalized Microparticles for One-Pot Cascade Reaction.

This study reports on the synthesis of surface-protected acid and base microparticles via surfactant-free emulsion polymerization. The protective layer allows to form particle mixtures with both colloidal catalysts that show excellent performance in a well-established model cascade reaction involving an acid-catalyzed deacetalization and a subsequent base-catalyzed Knoevenagel condensation. Compared to nanoreactors that contain both catalysts, the colloidal mixture shows comparable reaction kinetics despite the local separation of both catalysts onto separate particles. Since the synthesis of individual microparticles requires less steps, is scalable, and more versatile in terms of catalyst variation, colloidal mixtures are certainly an alternative to multifunctional nanoreactors, making them attractive for practical applications.

Antibody-mediated activation of the FGFR1/Klothoß complex corrects metabolic dysfunction and alters food preference in obese humans.

Fibroblast growth factor 21 (FGF21) controls metabolic organ homeostasis and eating/drinking behavior via FGF receptor 1/Klothoß (FGFR1/KLB) complexes expressed in adipocytes, pancreatic acinar cells, and the nervous system in mice. Chronic administration of recombinant FGF21 or engineered variants improves metabolic health in rodents, nonhuman primates, and humans; however, the rapid turnover of these molecules limits therapeutic utility. Here we show that the bispecific anti-FGFR1/KLB agonist antibody BFKB8488A induced marked weight loss in obese cynomolgus monkeys while elevating serum adiponectin and the adipose expression of FGFR1 target genes, demonstrating its action as an FGF21 mimetic. In a randomized, placebo-controlled, single ascending-dose study in overweight/obese human participants, subcutaneous BFKB8488A injection caused transient body weight reduction, sustained improvement in cardiometabolic parameters, and a trend toward reduction in preference for sweet taste and carbohydrate intake. These data suggest that specific activation of the FGFR1/KLB complex in humans can be used as therapy for obesity-related metabolic defects.

Current Progress of Platelet-Rich Derivatives in Cartilage and Joint Repairs.

In recent years, several types of platelet concentrates have been investigated and applied in many fields, particularly in the musculoskeletal system. Platelet-rich fibrin (PRF) is an autologous biomaterial, a second-generation platelet concentrate containing platelets and growth factors in the form of fibrin membranes prepared from the blood of patients without additives. During tissue regeneration, platelet concentrates contain a higher percentage of leukocytes and a flexible fibrin net as a scaffold to improve cell migration in angiogenic, osteogenic, and antibacterial capacities during tissue regeneration. PRF enables the release of molecules over a longer period, which promotes tissue healing and regeneration. The potential of PRF to simulate the physiology and immunology of wound healing is also due to the high concentrations of released growth factors and anti-inflammatory cytokines that stimulate vessel formation, cell proliferation, and differentiation. These products have been used safely in clinical applications because of their autologous origin and minimally invasive nature. We focused on a narrative review of PRF therapy and its effects on musculoskeletal, oral, and maxillofacial surgeries and dermatology. We explored the components leading to the biological activity and the published preclinical and clinical research that supports its application in musculoskeletal therapy. The research generally supports the use of PRF as an adjuvant for various chronic muscle, cartilage, and tendon injuries. Further clinical trials are needed to prove the benefits of utilizing the potential of PRF.

Brow and Eyelid Rejuvenation: Trends from the 100 Most Cited Articles over 30 Years.

Background and Objective: Various periorbital rejuvenation techniques have been introduced over the last 3 decades. This study highlights important milestones in the evolution of periorbital rejuvenation surgery by identifying the 100 most-cited articles in this field. Material and Methods: The Web of Science citation index was used to identify the 100 most-cited articles concerning periorbital rejuvenation. Articles published in English from January 1989-April 2020 describing periorbital rejuvenation-related surgical techniques, facial aging, and anatomy were included. The terms "lower blepharoplasty", "upper blepharoplasty", "browlift", "browplasty", "endobrow lift", "endoscopic brow", "Foreheadplasty", "lower eyelid anatomy", "upper eyelid anatomy", "forehead lift", "eyelid rejuvenation", "canthopexy", "canthoplasty", "eyelid fat pad", "orbital fat pad", "tear trough", and "eyelid bags" were entered into the citation search. Web of Science Core Collection was the database used for the search. A manual review of the initial 159 studies was performed. Articles describing reconstructive or non-invasive techniques, injectable fillers, lasers, and neurotoxins were excluded. Of the 100 most-cited articles, the publication year, specialty journal, the corresponding author's primary specialty, the focus of the article, the corresponding author's country of residence, the type of study, and the level of evidence were analyzed. Results: The mean number of citations per article was 75 ± 42. There were more articles published from 1989-1999 (n = 53) than later decades. Most articles originated from the USA (n = 82) and were published in plastic surgery journals (n = 81). Plastic surgery was the primary specialty of the corresponding authors (n = 71), followed by oculoplastic surgery (n = 22). Most articles (n = 69) reported on surgical techniques. Of the clinical studies (n = 69), 45 (79%) provided level IV evidence. Conclusions: Of the 100 most-cited studies on periorbital rejuvenation, studies focusing on periorbital anatomy, aging, and surgical techniques comprised the most-cited publications. An anatomically based approach accounting for age-related changes in the periorbital structures is paramount in the field of contemporary periorbital rejuvenation.

Radial T2* mapping reveals early meniscal abnormalities in patients with knee osteoarthritis.

OBJECTIVE: We aimed to validate a 2D radial T2* mapping method and its ability to reveal subtle alterations in the menisci of patients with knee osteoarthritis (OA). METHODS: Of 40 enrolled participants, 20 were diagnosed with OA, and 20 were age- and sex-matched asymptomatic controls. Data from the right knee of each participant were collected using a 1.5-T MRI equipped with a single-channel knee coil. T2* values were acquired using a conventional T2* mapping protocol and a radial T2* mapping method. Mean T2* values in the meniscal white zones, meniscal red zones, and total menisci were calculated. Numerical simulation was performed for validation. RESULTS: Both simulation and clinical data confirmed that 2D radial T2* mapping provided better discrimination than the conventional method. Compared to controls, the OA group showed significantly greater mean (standard deviation) T2* values in the white zones (9.33 [2.29] ms vs. 6.04 [1.05] ms), red zones (9.18 [2.03] ms vs. 6.81 [1.28] ms), and total menisci (9.26 [2.06] ms vs. 6.34 [1.14] ms). Correlations were found between the Lequesne index and the meniscal T2* values in all three regions (r = 0.528, p = 0.017; r = 0.635, p = 0.003; and r = 0.556, p = 0.011, respectively). CONCLUSION: These findings indicate that in early OA, radial T2* mapping is an alternative means of assessing meniscal degeneration and can be used to monitor its progression. KEY POINTS: • Radial T2* mapping outperforms Cartesian T2* mapping. • Radial T2* measurements are useful in assessing meniscal degeneration. • Meniscal T2* values correlate well with disease severity.

Variant Hepatocellular Carcinoma Subtypes According to the 2019 WHO Classification: An Imaging-Focused Review.

The 2019 5th edition of the WHO classification of digestive system tumors estimates that up to 35% of hepatocellular carcinomas (HCCs) can be classified as one of eight subtypes defined by molecular characteristics: steatohepatitic, clear cell, macrotrabecular-massive, scirrhous, chromophobe, fibrolamellar, neutrophil-rich, and lymphocyte-rich HCCs. Due to their distinct cellular and architectural characteristics, these subtypes may not display arterial phase hyperenhancement and washout appearance, which are the classic MRI features of HCC, creating challenges in noninvasively diagnosing such lesions as HCC. Moreover, certain subtypes with atypical imaging features have a worse prognosis than other HCCs. A range of distinguishing imaging features may help raise suspicion that a liver lesion represents one of these HCC subtypes. In this review, we describe the MRI features that have been reported in association with various HCC subtypes according to the 2019 WHO classification, with attention given to the current understanding of these subtypes' pathologic and molecular bases and relevance to clinical practice. Imaging findings that differentiate the subtypes from benign liver lesions and non-HCC malignancies are highlighted. Familiarity with these sub-types and their imaging features may allow the radiologist to suggest their presence, though histologic analysis remains needed to establish the diagnosis.

Comparison of two different types of hybrid Tibial fixations for anterior cruciate ligament reconstruction: a prospective comparative cohort study.

BACKGROUND: Previous studies have compared different kinds of fixations for anterior cruciate ligament reconstruction. Nevertheless, there is no optimal method to date. To the best of authors' knowledge, there is no article discussing the combination of adjustable suspensory device and interference screw for hybrid tibial fixation. METHODS: In total, 66 patients (n = 34, adjustable suspensory device and interference screw; n = 32, cortical screw and interference screw) were analyzed. Their International Knee Documentation Committee score and Tegner activity level scale were evaluated before and after a 2-year follow-up. The Single Assessment Numeric Evaluation score was evaluated after a 2-year follow-up. Physical exams such as range of motion, anterior knee pain (VAS > = 3) and Lachman test were assessed before and at least 12 months after surgery. To evaluate tunnel widening, anteroposterior and lateral view radiography was conducted 1 day and at least 12 months after surgery. A more than 10% change was considered tibial tunnel widening. Mann-Whitney U test, independent t test, paired t test, Fisher's exact test and chi-squared test were used to compare the variables. Linear and logistic regression models were applied to adjust for potential confounders. RESULTS: No variable except gender (P = 0.006) showed significant difference with regard to demographic data. After adjustment, there was no statistically significant difference between the groups regarding post-operative physical exams. Patients who used adjustable suspensory device and interference screw had lower post-operative Single Assessment Numeric Evaluation score (adjusted ß - 8.194; P = 0.017), Tegner activity level scale (adjusted ß - 1.295; P = 0.001) and pre-operative degrees of knee flexion (adjusted ß - 2.825; P = 0.026). Less percentage of tunnel widening in the lateral view of radiographs was seen in patients in group of adjustable suspensory device and interference screw (adjusted ß - 1.733; P = 0.038). No significant difference was observed in the anteroposterior view of radiographs (adjusted ß - 0.667; P = 0.26). CONCLUSION: In these 66 patients, we observed less tibial tunnel widening and lower post-operative functional scores in the group of adjustable suspensory device and interference screw. Both groups displayed similar outcomes of physical exams as well as improvement after operation. The proposed method may become an alternative option. Nonetheless, the quality of our study is still limited, and thus further studies are warranted to determine the efficacy and further application. TRIAL REGISTRATION: Joint Institutional Review Board of Taipei Medical University, Taipei, Taiwan (No: N201805094 ). STUDY DESIGN: Prospective comparative cohort study; Level of evidence, II.

Asian Upper Blepharoplasty with the Hinge Technique.

Asian upper blepharoplasty is one of the most commonly requested procedures in Asian patients. Many incisional and suture methods have been described in the literature. While the suture method is advantageous for its simplicity and quick recovery, the incision method is more versatile and able to deliver predictable and reproducible results for Asian patients presenting with a diverse range of anatomy and requests. Accordingly, the incision method remains the preferred approach for many surgeons performing Asian upper blepharoplasty. In this paper, we detail our open incision hinge upper blepharoplasty technique to create dynamic upper eyelid creases in Asian patients. The surgical videos associated with this paper present our surgical technique in detail, highlighting technical refinements and surgical nuances to perform the surgery precisely and predictably. The conceptual core of our approach is the use of a vascularized orbital septum as a flap to create a fibrous extension from the levator aponeurosis to the dermis at the location of eyelid crease. This vascularized flap securely connects the posterior lamella with the anterior lamella to securely form the eyelid crease with eye opening. This most accurately recreates the anatomy that is present in attractive Asian patients with naturally occurring double eyelid and predictably creates a dynamic and crisp upper eyelid crease. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Prevalence and associations of axillary web syndrome in Asian women after breast cancer surgery undergoing a community-based cancer rehabilitation program.

BACKGROUND: Patients who have breast cancer surgery are at risk of axillary web syndrome (AWS), an under-recognized postsurgical complication which can result in shoulder morbidity and functional impairment. Emerging studies have indicated that AWS may persist beyond the first few months after surgery, although few studies have assessed the prevalence and association of AWS beyond a year after diagnosis. Therefore, the aim of this study was to investigate the prevalence and associations for AWS in post-operative breast cancer patients up to 3 years after surgery. METHODS: This cross sectional observational study was conducted at a community-based cancer rehabilitation center. Patients were evaluated for the presence of AWS via physical examination. Disease-related data was obtained from clinical review and medical records. Descriptive statistics were utilized to illustrate patient demographics and clinical characteristics. Logistic regression analyses were used to determine associations of AWS. RESULTS: There were 111 Asian women who were recruited, who had undergone breast surgery and were referred to a national outpatient rehabilitation center. The prevalence of AWS in this population was 28.9%. In the multivariate regression model, significant factors were age < 50 years (OR = 3.51; 95% CI = 1.12-11.0; p = 0.031) and ALND (OR = 6.54; 95% CI = 1.36-31.3; p = 0.019). There was reduced shoulder flexion ROM (p < 0.001) in patients with AWS compared to patients without AWS. CONCLUSIONS: A high prevalence of AWS was reported in breast cancer survivors even at 3 years after breast surgery. Our findings highlight the need to identify breast cancer survivors with AWS even in the survivorship phase, and develop strategies to raise awareness and minimize functional impairment in these patients.

Flavonoids from Woodfordia fruticosa as potential SmltD inhibitors in the alternative biosynthetic pathway of peptidoglycan.

SmltD is an ATP-dependent ligase that catalyzes the condensation of UDP-MurNAc-l-Ala and l-Glu to form UDP-MurNAc-l-Ala-l-Glu, in the newly discovered peptidoglycan biosynthesis pathway of a Gram-negative multiple-drug-resistant pathogen, Stenotrophomonas maltophilia. Phytochemical investigation of the 70% ethanol extract from Woodfordia fruticosa flowers collected in Myanmar led to the identification of anti-SmltD active flavonoids, kaempferol 3-O-(6''-galloyl)-ß-d-glucopyranoside (1), astragalin (2), and juglalin (3). Among them, 1 showed the most potent SmltD inhibitory activity. An enzyme steady-state kinetic study revealed that 1 exerted competitive inhibition with respect to ATP. The results of this study provided an attractive foundation for the further development of novel inhibitors of SmltD.

Prevalence and Risk Factors of Adhesive Capsulitis in Asian Breast Cancer Patients Undergoing an Outpatient Community Cancer Rehabilitation Program.

OBJECTIVES: To investigate the prevalence and risk factors for adhesive capsulitis in postoperative breast cancer patients up to 5 years after surgery who were attending an outpatient community cancer rehabilitation program, and to determine whether any significant relationship exists between arm lymphedema and adhesive capsulitis. DESIGN: Cross-sectional observational study. SETTING: National cancer rehabilitation center. PARTICIPANTS: Asian women (N=135) who underwent breast surgery and were referred for an outpatient community cancer rehabilitation program. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Presence of adhesive capsulitis, lymphedema. RESULTS: The prevalence of adhesive capsulitis and lymphedema in this population was 22.2% and 33.3%, respectively. A history of mastectomy (odds ratio [OR], 3.93; 95% confidence interval [CI], 1.23-12.63; P=.021), mastectomy with reconstruction (OR, 2.72; 95% CI, 1.27-30.54; P=.024), and lymphedema (OR, 7.92; 95% CI, 2.73-22.95; P<.001) were found to be significantly associated with adhesive capsulitis on multivariate analysis. CONCLUSIONS: Adhesive capsulitis and lymphedema are common in breast cancer survivors. The design of cancer rehabilitation programs for breast cancer survivors should include surveillance and management of adhesive capsulitis, especially in the presence of lymphedema.

A Comprehensive Approach to Asian Upper Eyelid Ptosis Correction: The Levator Musculo-Aponeurotic Junction Formula.

BACKGROUND: The unique anatomy of the Asian upper eyelid requires specific adaptation to the levator advancement technique for ptosis correction to achieve predictable and reproducible outcomes. OBJECTIVES: The levator musculo-aponeurotic junction was employed as they key landmark. With a formula developed by the authors, the location of fixation relative to this landmark can be predicted preoperatively. The authors' clinical experience and outcomes with this technique are presented. METHODS: Inclusion criteria were Asian patients with mild to severe ptosis with at least fair levator function. Patients with acquired or congenital ptosis and primary and revisional cases were all included. The location for placement of the advancement sutures was measured from the musculo-aponeurotic junction of the upper eyelid levator. This distance was determined by a formula that considers (1) the amount of elevation of the upper eyelid margin needed, (2) the degree of compensatory brow elevation present, and (3) eye dominance. RESULTS: A total 156 Asian patients were included in this prospective study. Of these, 148 were bilateral and 8 were unilateral corrections. The technique was predictable with resolution of symptoms of eyelid ptosis post-surgery and good long-term symmetry of the palpebral aperture and crisp upper eyelid creases. The formula for estimating the fixation point on the levator was accurate to within ±1 mm in the majority of patients. The aperture revision rate was 2%. CONCLUSIONS: This novel technique provides a predictable and reliable approach for upper eyelid ptosis correction in Asian patients.

Scalable and Recyclable All-Organic Colloidal Cascade Catalysts.

We report on the synthesis of core-shell microparticles (CSMs) with an acid catalyst in the core and a base catalyst in the shell by surfactant-free emulsion polymerization (SFEP). The organocatalytic monomers were separately copolymerized in three synthetic steps allowing the spatial separation of incompatible acid and base catalysts within the CSMs. Importantly, a protected and thermo-decomposable sulfonate monomer was used as acid source to circumvent the neutralization of the base catalyst during shell formation, which was key to obtain stable, catalytically active CSMs. The catalysts showed excellent performance in an established one-pot model cascade reaction in various solvents (including water), which involved an acid-catalyzed deacetalization followed by a base-catalyzed Knoevenagel condensation. The CSMs are easily recycled, modified, and their synthesis is scalable, making them promising candidates for organocatalytic applications.

Size-Controlled Formation of Polymer Janus Discs.

A straightforward method is presented for the preparation of nano- to micrometer-sized Janus discs with controlled shape, size, and aspect ratio. The method relies on cross-linkable ABC triblock terpolymers and involves first the preparation of prolate ellipsoidal microparticles by combining Shirasu porous glass (SPG) membrane emulsification with evaporation-induced confinement assembly (EICA). By varying the pore diameter of the SPG membrane, we produce Janus discs with controlled size distributions centered around hundreds of nanometers to several microns. We further transferred the discs to water by mild sulfonation of PS to polystyrene sulfonic acid (PSS) and verified the Janus character by subsequent labelling with cationic nanoparticles. Finally, we show that the sulfonated Janus discs are amphiphilic and can be used as efficient colloidal stabilizers for oil-in-water (O/W) emulsions.

How structural subtleties lead to molecular diversity for the type III polyketide synthases.

Type III polyketide synthases (PKSs) produce an incredibly diverse group of plant specialized metabolites with medical importance despite their structural simplicity compared with the modular type I and II PKS systems. The type III PKSs use homodimeric proteins to construct the molecular scaffolds of plant polyketides by iterative condensations of starter and extender CoA thioesters. Ever since the structure of chalcone synthase (CHS) was disclosed in 1999, crystallographic and mutational studies of the type III PKSs have explored the intimate structural features of these enzyme reactions, revealing that seemingly minor alterations in the active site can drastically change the catalytic functions and product profiles. New structures described in this review further build on this knowledge, elucidating the detailed catalytic mechanism of enzymes that make curcuminoids, use extender substrates without the canonical CoA activator, and use noncanonical starter substrates, among others. These insights have been critical in identifying structural features that can serve as a platform for enzyme engineering via structure-guided and precursor-directed engineered biosynthesis of plant polyketides. In addition, we describe the unique properties of the recently discovered "second-generation" type III PKSs that catalyzes the one-pot formation of complex molecular scaffolds from three distinct CoA thioesters or from "CoA-free" substrates, which are also providing exciting new opportunities for synthetic biology approaches. Finally, we consider post-type III PKS tailoring enzymes, which can also serve as useful tools for combinatorial biosynthesis of further unnatural novel molecules. Recent progress in the field has led to an exciting time of understanding and manipulating these fascinating enzymes.

Vesicular Polymer Hexosomes Exhibit Topological Defects.

Polymer hexosomes are block copolymer solution morphologies that adopt an internal structure composed of an inverse hexagonal (HII) phase. To date, most polymer hexosomes are reportedly rotationally symmetric solid structures that possess a common feature where hexagonally ordered inverted cylinders rotate along a central axis of symmetry to form circular hoops. Here, we report on the formation of polymer hexosomes whose inverted cylinders orient in an unusual manner, forming hoops that are noncircular. For topological reasons, this led to the generation of four defects in the resulting hexosome structure. We find that these defect-bearing hexosomes are hollow, thereby resembling polymer vesicles or polymersomes with an inverse hexagonal cylindrical morphology in the shell. The topological defects of these so-called "vesicular hexosomes" are enticing as they could serve as a platform to spatially anchor targeting ligands or biomolecules on the surface, while the hollow cylindrical shell and the vesicular lumen could spatially accommodate cargoes within the different domains. We propose that these vesicular hexosomes do not form via a conventional nucleation-growth self-assembly pathway, but rather via a two-step process involving first liquid-liquid phase separation followed by polymer microphase separation.