The B7:CD28 family and friends: Unraveling coinhibitory interactions.

Immune responses must be tightly regulated to ensure both optimal protective immunity and tolerance. Costimulatory pathways within the B7:CD28 family provide essential signals for optimal T cell activation and clonal expansion. They provide crucial inhibitory signals that maintain immune homeostasis, control resolution of inflammation, regulate host defense, and promote tolerance to prevent autoimmunity. Tumors and chronic pathogens can exploit these pathways to evade eradication by the immune system. Advances in understanding B7:CD28 pathways have ushered in a new era of immunotherapy with effective drugs to treat cancer, autoimmune diseases, infectious diseases, and transplant rejection. Here, we discuss current understanding of the mechanisms underlying the coinhibitory functions of CTLA-4, PD-1, PD-L1:B7-1 and PD-L2:RGMb interactions and less studied B7 family members, including HHLA2, VISTA, BTNL2, and BTN3A1, as well as their overlapping and unique roles in regulating immune responses, and the therapeutic potential of these insights.

Tracking tumor-specific CD8+ T cell responses.

In a recent article, Puig-Saus et al. computationally predict and experimentally validate neoantigen-specific T cell responses in patients with melanoma. They identify a restricted set of neoantigens recognized by polyclonal CD8+ T cells as a unique feature of anti-PD-1 responders and engineer autologous tumor-responsive T cells expressing neoantigen-specific TCRs, providing proof-of-concept for future cellular therapies.

International perspectives on procedural justice: Trust and respect matter even when body-worn cameras are present.

OBJECTIVE(S): We assessed the impact of body-worn cameras (BWCs) in two countries on perceptions of everyday encounters with police, independent of officer respectfulness and participants' preexisting trust in police. HYPOTHESES: We expected BWC presence, officer respectfulness, and preexisting trust in police to all significantly improve individuals' perceptions of a police encounter. We also expected interactions indicating that BWC presence and preexisting trust in police reduce the effect of officer respectfulness on perceptions of the encounter. METHOD: In each of three experimental studies, we measured participants' preexisting trust in police, and then presented participants with a vignette describing an encounter with a police officer in which officer respectfulness (respectful, disrespectful) and the presence/disclosure of a BWC (absent, present and disclosed by officer, present but undisclosed by officer) were independently manipulated. In Studies 1 (N = 422, Mage = 29 years, 73% women, 68% Australian) and 2 (N = 210, Mage = 19 years, 64% women, 59% Hispanic) in Australia and the United States, respectively, participants assumed the role of the driver in a traffic stop as they read the vignette. In study 3 (N = 504, Mage = 29 years, 72% women, 34% English), participants in Australia assumed the role of a citizen interacting with a police officer enforcing COVID-related restrictions. Participants then recorded their perceptions of procedural justice of and satisfaction with the encounter, legitimacy of the police, and willingness to co-operate with police. RESULTS: Across three studies and two countries, we found no support for the notion that BWC presence influenced people's perceptions of police-citizen interactions independent of officer respectfulness and preexisting trust. CONCLUSION: The effect of BWC presence, established in prior research, might operate via its effect on officer respectfulness. These findings underscore the importance of preexisting trust in police and respectful behavior by police officers, even in BWC-recorded encounters. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Enhancing the Carboxylation Efficiency of Silk Fibroin through the Disruption of Noncovalent Interactions.

Silk fibroin is a semicrystalline protein used as a renewable polymer source and as a biomaterial platform, but existing methods to synthetically modify fibroin suffer from low efficiencies that can limit the protein's utility. This work reports on a mild synthesis that results in a 2-fold increase in carboxylation through the disruption of noncovalent interactions during the reaction. Importantly, silk fibroin maintains its ability to form ß-sheets that are critical for tailoring mechanical and degradation properties, as well as for rendering solid constructs (e.g., films and scaffolds) insoluble in water. Increasing carboxyl functionalization affords control over protein charge, which permits tailoring the loading and release of small molecules using electrostatic interactions. Disruption of noncovalent interactions during aqueous carbodiimide coupling also significantly enhances conjugation efficiency of molecules containing primary amine groups, thus enabling high degrees of functionalization with biological molecules, such as proteins and peptides, for biomaterial applications.

Main-Chain Liquid Crystalline Hydrogels that Support 3D Stem Cell Culture.

Hydrogels are frequently utilized as three-dimensional matrices for the culture and regeneration of soft tissues, but one challenge with the existing hydrogels is that, though the natural extracellular matrix of tissues may be ordered, there are few biocompatible ways to incorporate anisotropy within hydrogels. Liquid crystalline (LC) polymers are well suited for this because of their combination of molecular ordering and polymer elasticity; however, the hydrophobic nature of LC monomers has hindered their polymerization into hydrogels under cytocompatible conditions. This work reports on the generation of main-chain LC hydrogels in aqueous media and the ability of LC phases to affect mesenchymal stem cell behavior. The synthesis results in high gel fraction materials, and calorimetry, thermomechanical analysis, and X-ray scattering show that the networks organize into LC phases in the dry and hydrogel states. Human mesenchymal stem cells (hMSCs) cultured within the hydrogels show excellent viability, and hMSC proliferation proceeds at a faster rate in LC hydrogels compared to non-LC hydrogels. TThe result is a new synthetic approach for calamitic liquid crystalline hydrogels, which support the encapsulation and culture of human stem cells and are expected to enable applications as anisotropic and responsive substrates for tissue engineering and regenerative medicine.

Assessment of venous thromboembolism treatment in patients with cancer on low molecular weight heparin, warfarin, and the direct oral anticoagulants.

BACKGROUND: Direct oral anticoagulants (DOACs) are not recommended for venous thromboembolism (VTE) treatment in patients with cancer because their safety and efficacy have not been compared to low molecular weight heparin (LMWH) in large trials. Routine anti-Xa monitoring in cancer patients on LMWH is also not recommended due to limited data correlating anti-Xa levels and outcomes. OBJECTIVE: Compare the safety and efficacy of DOACs to LMWH and warfarin and assess the relationship of anti-Xa monitoring and outcomes in patients with cancer taking LMWH in an urban university setting. METHODS: This retrospective, cohort study analyzed the recurrence of VTE and number of bleeding events in patients with cancer. RESULTS: There were 131 patients included in the analysis. There was no difference seen in the rate of recurrent VTEs between the LMWH, warfarin and DOAC groups (9.3%, 5.9%, 9.1%, p = 0.89). There was also no difference in the rate of bleeding between groups (10.5%, 14.7%, 9.1%, p = 0.576). There was an increased rate of mortality seen in the LMWH group (26.7% vs. 2.9% vs. 18.2%, p = 0.006). There was no difference seen in recurrent VTE (10.3% vs. 8.5%, p = 0.53) or bleeding (10.3% vs. 10.7%, p = 0.661) between the monitored and unmonitored LMWH patients. CONCLUSION: Results of this analysis suggest DOACs may be as safe and effective as LMWH and warfarin for the treatment of VTE in patients with cancer, and there may be no clinical benefit to routine anti-Xa monitoring in patients on LMWH treatment. However, larger studies are needed to confirm these observations.

The effects of body-worn camera footage and eyewitness race on jurors' perceptions of police use of force.

Police use of body-worn cameras (BWCs) is increasingly common in the USA. This article reports the results of one of the first experimental examinations of the effects of three BWC status conditions (absent, transcribed, viewed) and eyewitness race (Black, White) on mock jurors' case judgments, in a case in which a community member (defendant) was charged with resisting arrest but where the officer's use of force in conducting the arrest was controversial. Results provide evidence of significant main effects of both eyewitness race and BWC status. When the eyewitness supporting the defendant was White, mock jurors were less likely to vote the defendant guilty of resisting arrest, as well as more likely to consider the defendant credible and the officer culpable for the incident. In addition, when BWC footage of the arrest was viewed, compared with transcribed or absent, participants were less likely to vote the defendant guilty of resisting arrest, and also rated the officer's use of force less justifiable, and the officer more culpable and less credible. Follow-up analyses demonstrated that these relationships between BWC condition and case judgments were all mediated by moral outrage toward the officer.

Phase behavior of main-chain liquid crystalline polymer networks synthesized by alkyne-azide cycloaddition chemistry.

Liquid crystalline polymer networks (LCNs) couple polymer chain organization to molecular ordering, the switching of which has been shown to impart stimuli-responsive properties, including actuation and one-way shape memory, to the networks. While LCNs have long been proposed as artificial muscles, recent reports have also suggested potential as dynamic biomaterial substrates. In contrast to many existing LCNs synthesized using hydrophobic spacers, this work investigates networks synthesized using more hydrophilic spacers to promote interaction with water. A challenge with such materials is liquid crystalline phases could be disrupted in hydrated networks. This work thus investigates the impact of polyether spacers and mesogen composition on the phase behavior of LCNs. Main-chain LCNs were synthesized using alkyne-azide cycloaddition ("click" chemistry), where two different mesogens (5yH and 5yMe) and a non-LC monomer (5yTe) were coupled with one of two different polyether spacers, poly(ethylene glycol) and poly(propylene glycol), and a crosslinker. The chemistry led to high gel fraction materials, the workup of which resulted in networks that displayed no difference in cellular toxicity due to leachable components compared to tissue culture plastic control. Calorimetric analysis, dynamic mechanical analysis, and X-ray scattering revealed the LC microstructure and temperature-responsive properties of the networks. The use of low molecular weight polyether spacers was found to prevent their crystallization within the LC network, and adjusting mesogen composition to enhance its LC phase stability allowed the use of spacers with larger molecular weights and pendant groups. Hydrated networks were found to rearrange their structure compared to dry networks, while maintaining their LC phases. Like other crosslinked LC materials, the networks display shape changes (actuation) that are tied to changes in LC ordering. The result is a new synthetic approach for polydomain networks that form stable LC phases that are tailorable using polyether spacers and may enable future application as hydrated, stimuli-responsive materials.

Levels of combatant control and the patterns of non-incumbent/insurgent violence experienced by civilians living in Sunni-Arab communities in Iraq (2004-2009).

This study explores how one social-structural variable, control over Sunni-Arab communities during the Iraq civil war, affected the types of violence used by insurgent/non-government actors that killed and injured civilians in these communities from January 2004 to December 2009. The study classifies three levels of control: (1) incumbent (government-supported) control, (2) insurgent control and (3) actively contested control. It uses Iraq Body Count (IBC) fatality data to characterize two general types of violence (selective and indiscriminate) evident during the Iraq conflict. It demonstrates that the type of violence committed by non-government actors was significantly (P > .01) different as related to the level of control insurgents had over territory. Primarily, insurgents/non-governmental actors used more selective forms of violence when insurgents controlled territory and more indiscriminate violence when incumbent (government-supported) forces controlled territory. Also, acts of indiscriminate violence cause considerably more injuries and death per act as compared to selective violence. Importantly, if control over territory has broadly generalizable effects on the types of violence that civilian's experience during civil war, than understanding this relationship could be useful when determining the types of medical assistance, medical supplies and training most needed in combat zones.

Silk Fibroin Aqueous-Based Adhesives Inspired by Mussel Adhesive Proteins.

Silk fibroin from the domesticated silkworm Bombyx mori is a naturally occurring biopolymer with charged hydrophilic terminal regions that end-cap a hydrophobic core consisting of repeating sequences of glycine, alanine, and serine residues. Taking inspiration from mussels that produce proteins rich in L-3,4-dihydroxyphenylalanine (DOPA) to adhere to a variety of organic and inorganic surfaces, the silk fibroin was functionalized with catechol groups. Silk fibroin was selected for its high molecular weight, tunable mechanical and degradation properties, aqueous processability, and wide availability. The synthesis of catechol-functionalized silk fibroin polymers containing varying amounts of hydrophilic polyethylene glycol (PEG, 5000 g/mol) side chains was carried out to balance silk hydrophobicity with PEG hydrophilicity. The efficiency of the catechol functionalization reaction did not vary with PEG conjugation over the range studied, although tuning the amount of PEG conjugated was essential for aqueous solubility. Adhesive bonding and cell compatibility of the resulting materials were investigated, where it was found that incorporating as little as 6 wt % PEG prior to catechol functionalization resulted in complete aqueous solubility of the catechol conjugates and increased adhesive strength compared with silk lacking catechol functionalization. Furthermore, PEG-silk fibroin conjugates maintained their ability to form ß-sheet secondary structures, which can be exploited to reduce swelling. Human mesenchymal stem cells (hMSCs) proliferated on the silks, regardless of PEG and catechol conjugation. These materials represent a protein-based approach to catechol-based adhesives, which we envision may find applicability as biodegradable adhesives and sealants.

Long term perfusion system supporting adipogenesis.

Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogenesis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight.

Highly tunable elastomeric silk biomaterials.

Elastomeric, fully degradable and biocompatible biomaterials are rare, with current options presenting significant limitations in terms of ease of functionalization and tunable mechanical and degradation properties. We report a new method for covalently crosslinking tyrosine residues in silk proteins, via horseradish peroxidase and hydrogen peroxide, to generate highly elastic hydrogels with tunable properties. The tunable mechanical properties, gelation kinetics and swelling properties of these new protein polymers, in addition to their ability to withstand shear strains on the order of 100%, compressive strains greater than 70% and display stiffness between 200 - 10,000 Pa, covering a significant portion of the properties of native soft tissues. Molecular weight and solvent composition allowed control of material mechanical properties over several orders of magnitude while maintaining high resilience and resistance to fatigue. Encapsulation of human bone marrow derived mesenchymal stem cells (hMSC) showed long term survival and exhibited cell-matrix interactions reflective of both silk concentration and gelation conditions. Further biocompatibility of these materials were demonstrated with in vivo evaluation. These new protein-based elastomeric and degradable hydrogels represent an exciting new biomaterials option, with a unique combination of properties, for tissue engineering and regenerative medicine.

Immunogenicity and cross-reactivity of a representative ancestral sequence in hepatitis C virus infection.

Vaccines designed to prevent or to treat hepatitis C viral infection must achieve maximum cross-reactivity against widely divergent circulating strains. Rational approaches for sequence selection to maximize immunogenicity and minimize genetic distance across circulating strains may enhance vaccine induction of optimal cytotoxic T cell responses. We assessed T cell recognition of potential hepatitis C virus (HCV) vaccine sequences generated using three rational approaches: combining epitopes with predicted tight binding to the MHC, consensus sequence (most common amino acid at each position), and representative ancestral sequence that had been derived using bayesian phylogenetic tools. No correlation was seen between peptide-MHC binding affinity and frequency of recognition, as measured by an IFN-γ T cell response in HLA-matched HCV-infected individuals. Peptides encoding representative, consensus, and natural variant sequences were then tested for the capacity to expand CD8 T cell populations and to elicit cross-reactive CD8 T cell responses. CD8(+) T cells expanded with representative sequence HCV generally more broadly and robustly recognized highly diverse circulating HCV strains than did T cells expanded with either consensus sequence or naturally occurring sequence variants. These data support the use of representative sequence in HCV vaccine design.

Legal Decision-Making in an Adult Rape Case Involving DNA Evidence.

This study investigated how jurors use deoxyribonucleic acid (DNA) evidence in an adult rape trial with a female victim and a male stranger defendant. Community members read a trial summary and then made case judgments (e.g., verdict). Results showed: (a) DNA evidence led to more pro-victim judgments (e.g., more guilty verdicts) than those who did not receive DNA evidence; (b) women were more pro-victim than men; (c) pro-victim judgments indirectly affected the presence of DNA evidence and verdict; and (d) the reason for a guilty verdict when DNA evidence was present typically noted a focus on the victim and DNA evidence.

PD-1 Expression on Intratumoral Regulatory T Cells Is Associated with Lack of Benefit from Anti-PD-1 Therapy in Metastatic Clear-Cell Renal Cell Carcinoma Patients.

PURPOSE: Programmed cell death protein 1 (PD-1) expression on CD8+TIM-3-LAG-3- tumor-infiltrating cells predicts positive response to PD-1 blockade in metastatic clear-cell renal cell carcinoma (mccRCC). Because inhibition of PD-1 signaling in regulatory T cells (Treg) augments their immunosuppressive function, we hypothesized that PD-1 expression on tumor-infiltrating Tregs would predict resistance to PD-1 inhibitors. EXPERIMENTAL DESIGN: PD-1+ Tregs were phenotyped using multiparametric immunofluorescence in ccRCC tissues from the CheckMate-025 trial (nivolumab: n = 91; everolimus: n = 90). Expression of CD8, PD-1, TIM-3, and LAG-3 was previously determined (Ficial and colleagues, 2021). Clinical endpoints included progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). RESULTS: In the nivolumab (but not everolimus) arm, high percentage of PD-1+ Tregs was associated with shorter PFS (3.19 vs. 5.78 months; P = 0.021), shorter OS (18.1 vs. 27.7 months; P = 0.013) and marginally lower ORR (12.5% vs. 31.3%; P = 0.059). An integrated biomarker (PD-1 Treg/CD8 ratio) was developed by calculating the ratio between percentage of PD-1+Tregs (marker of resistance) and percentage of CD8+PD-1+TIM-3-LAG-3- cells (marker of response). In the nivolumab (but not everolimus) arm, patients with high PD-1 Treg/CD8 ratio experienced shorter PFS (3.48 vs. 9.23 months; P < 0.001), shorter OS (18.14 vs. 38.21 months; P < 0.001), and lower ORR (15.69% vs. 40.00%; P = 0.009). Compared with the individual biomarkers, the PD-1 Treg/CD8 ratio showed improved ability to predict outcomes to nivolumab versus everolimus. CONCLUSIONS: PD-1 expression on Tregs is associated with resistance to PD-1 blockade in mccRCC, suggesting that targeting Tregs may synergize with PD-1 inhibition. A model that integrates PD-1 expression on Tregs and CD8+TIM-3-LAG-3- cells has higher predictive value.

Computational reconstruction of Bole1a, a representative synthetic hepatitis C virus subtype 1a genome.

Hepatitis C virus (HCV) research is hampered by the use of arbitrary representative isolates in cell culture and immunology. The most replicative isolate in vitro is a subtype 2a virus (JFH-1); however, genotype 1 is more prevalent worldwide and represents about 70% of infections in the United States, and genotypes differ from one another by 31% to 33% at the nucleotide level. For phylogenetic and immunologic analyses, viruses H77 and HCV-1 (both subtype 1a) are commonly used based on their historic importance. In an effort to rationally design a representative subtype 1a virus (Bole1a), we used Bayesian phylogenetics, ancestral sequence reconstruction, and covariance analysis on a curated set of 390 full-length human HCV 1a sequences from GenBank. By design, Bole1a contains variations present in widely circulating strains and matches more epitope-sized peptides in a full-genome comparison to subtype 1a isolates than any other sequence studied. Parallel analyses confirm that selected epitopes from the Bole1a genome were able to elicit a robust T cell response. In a proof of concept for infectivity, the envelope genes (E1 and E2) of Bole1a were expressed in an HIV pseudoparticle system containing HCV envelope genes and HIV nonenvelope genes with luciferase expression. The resulting Bole1a pseudoparticle robustly infected Hep3B cells. In this study, we demonstrate that a rationally designed, fully synthetic HCV genome contains representative epitopes and envelope genes that assemble properly and mediate entry into target cells.

Immune checkpoint receptors in autoimmunity.

Immune checkpoint receptors such as programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), and T cell immunoglobulin and ITIM domain (TIGIT) have distinct and overlapping inhibitory functions that regulate Tcell activation, differentiation, and function. These inhibitory receptors also mediate tolerance, and dysregulation of these receptors can result in a breach of tolerance and the development of autoimmune syndromes. Similarly, antibody blockade of immune checkpoint receptors or their ligands for cancer immunotherapy may trigger a spectrum of organ inflammation that resembles autoimmunity, termed immune-related adverse events (irAE). In this review, we discuss recent advances in the regulation of autoimmunity by immune checkpoint receptors. We highlight coordinated gene expression programs linking checkpoint receptors, heterogeneity within autoreactive T-cell populations, parallels between irAE and autoimmunity, and bidirectional functional interactions between immune checkpoint receptors and their ligands.

Combined PD-1, BRAF and MEK inhibition in BRAFV600E colorectal cancer: a phase 2 trial.

While BRAF inhibitor combinations with EGFR and/or MEK inhibitors have improved clinical efficacy in BRAFV600E colorectal cancer (CRC), response rates remain low and lack durability. Preclinical data suggest that BRAF/MAPK pathway inhibition may augment the tumor immune response. We performed a proof-of-concept single-arm phase 2 clinical trial of combined PD-1, BRAF and MEK inhibition with sparatlizumab (PDR001), dabrafenib and trametinib in 37 patients with BRAFV600E CRC. The primary end point was overall response rate, and the secondary end points were progression-free survival, disease control rate, duration of response and overall survival. The study met its primary end point with a confirmed response rate (24.3% in all patients; 25% in microsatellite stable patients) and durability that were favorable relative to historical controls of BRAF-targeted combinations alone. Single-cell RNA sequencing of 23 paired pretreatment and day 15 on-treatment tumor biopsies revealed greater induction of tumor cell-intrinsic immune programs and more complete MAPK inhibition in patients with better clinical outcome. Immune program induction in matched patient-derived organoids correlated with the degree of MAPK inhibition. These data suggest a potential tumor cell-intrinsic mechanism of cooperativity between MAPK inhibition and immune response, warranting further clinical evaluation of optimized targeted and immune combinations in CRC. ClinicalTrials.gov registration: NCT03668431.

Do the materials matter? A review of the literature and analysis of the materials properties of urethral stents for hypospadias repair.

INTRODUCTION: Despite the prevalence of hypospadias surgery and the common use of postoperative urethral stents, there has been no evaluation of the material properties of common stents. Our study sets out to close this gap with a literature review of recent publications comparing outcomes after hypospadias surgery for different urethral stent types and an evaluation of the material properties of four common urethral stents. STUDY DESIGN: A review of the English language literature from 2011 to 2021 was performed. Thermal analysis and mechanical analysis of the Zaontz Urethral Stent, the Firlit-Kluge Urethral Stent, the Koyle Diaper Stent, and the Bard Premature Infant Feeding Tube was also undertaken. RESULTS: Out of 165 papers, four met inclusion criteria. There was limited research on this topic, and no significant evidence that different stent materials impacted surgical complication rates. One study found improved comfort with the Zaontz stent, and another found a reduction emergency room visits with the Koyle stent. Using a foley balloon was associated with increased fistula rates, though this was likely due to the balloon design and not the material. Analysis of stents shows that all four are rubbery polymers at body temperature (Summary Table). The Zaontz and Koyle stents are thermoplastic elastomers with strong melting transitions above body temperature, but the Firlit-Kluge stent is amorphous at 37 °C and is likely covalently cross-linked to generate the network. The Bard feeding tube was the stiffest, with a Young's Modulus of 14.0 ± 0.78 (compared to 4.12 ± 0.56 for Zaontz, 4.92 ± 0.63 for Firlit-Kluge, and 4.09 ± 0.49 for Koyle). The Bard Feeding Tube is also the least extensible, fracturing at just over 300% strain compared to the other stents that can be stretched to greater than 2000% strain before fracture. Cyclic deformation studies demonstrate that the Zaontz, Firlit-Kluge, and Koyle stents are able to stretch and recover their shape more completely, a finding determined by the lower amount of plastic deformation those stents display compared to the Bard Feeding Tube. DISCUSSION: While there is little information associating urethral stent type with outcomes after hypospadias surgery, material properties may account for findings of prior studies. Stiffer stents may contribute to decreased postoperative comfort, while a stent that is too soft and extensible may have issues with dislodgement, kinking and breaking. CONCLUSION: This study provides the foundation for future work optimizing urethral stents, designing support for regenerative medicine applications, and improving hypospadias outcomes.

Solvent-Free Direct PEGylation of Collagen Fibers.

The addition of poly(ethylene glycol) (PEG) to biomolecules and biomaterials is a well-established approach to modify their properties for therapeutic applications. For biomaterials, the approach is typically to blend or electrospray the synthetic polymer with the biomaterial. Effective surface modification approaches such as surface-initiated polymer brushes are challenging since the harsh solvents required for brush synthesis may destroy the biomaterial. Herein, we describe the PEGylation of collagen fibers by surface-initiated PEG brushes using a living anionic grafting-from mechanism. This brush synthesis is done in the absence of solvents to minimize the degradation of the native collagen structure. We quantify the effect the brush synthesis has on the native structure of the collagen fiber using differential scanning calorimetry (DSC) and find that even at long reaction times a significant fraction of the native structure remains. Dynamic mechanical analysis indicates the collagen undergoes only modest structural degradation, while adhesion studies find a significant improvement of antifouling properties. Further, our approach opens the way for further chemistry, as the growing polymer chain is a potassium alkoxy group that can be functionalized by termination or by subsequent reaction by a wide variety of molecules.