Association of Single and Dual Sensory Impairment with Falls among Medicare Beneficiaries.

Objective: The purpose of this study was to determine if dual sensory impairment (DSI) is associated with falls and fear of falling among older adults. Methods: Using data from the 2019 Medicare Current Beneficiary Survey (MCBS), we studied the cross-sectional association of self-reported hearing/vision impairment with self-reported history/number of falls over the past year, fear of falling (scale 1-6), and a fall requiring medical help using weighted multivariable regressions adjusted for demographic and clinical covariates. Results: Among 11,089 Medicare beneficiaries (mean age = 74, 55% female, 9% Black), DSI is associated with increased prevalence (prevalence ratio = 1.45 [1.28-1.65]) and incidence (incidence ratio = 2.21 [1.79-2.75]) rate of falls, and greater odds of a higher fear of falling score (odds ratio = 1.38 [1.08-1.77]). Discussion: DSI is associated with falls among older adults. Consideration of DSI as a marker to initiate fall prevention programs and inclusion of sensory interventions in these programs may be valuable.

Electrostatically Cross-Linked Bioinks for Jetting-Based Bioprinting of 3D Cell Cultures.

It has been acknowledged that thousands of drugs that passed two-dimensional (2D) cell culture models and animal studies often fail when entering human clinical trials. Despite the significant development of three-dimensional (3D) models, developing a high-throughput model that can be reproducible on a scale remains challenging. One of the main challenges is precise cell deposition and the formation of a controllable number of spheroids to achieve more reproducible results for drug discovery and treatment applications. Furthermore, when transitioning from manually generated structures to 3D bioprinted structures, the choice of material is limited due to restrictions on materials that are applicable with bioprinters. Herein, we have shown the capability of a fast-cross-linking bioink that can be used to create a single spheroid with varying diameters (660, 1100, and 1340 µm) in a high-throughput manner using a commercialized drop-on-demand bioprinter. Throughout this work, we evaluate the physical properties of printable ink with and without cells, printing optimization, cytocompatibility, cell sedimentation, and homogeneity in ink during the printing process. This work showcases the importance of ink characterization to determine printability and precise cell deposition. The knowledge gained from this work will accelerate the development of next-generation inks compatible with a drop-on-demand 3D bioprinter for various applications such as precision models to mimic diseases, toxicity tests, and the drug development process.

3D Bioprintable Hydrogel with Tunable Stiffness for Exploring Cells Encapsulated in Matrices of Differing Stiffnesses.

In vitro cell models have undergone a shift from 2D models on glass slides to 3D models that better reflect the native 3D microenvironment. 3D bioprinting promises to progress the field by allowing the high-throughput production of reproducible cell-laden structures with high fidelity. The current stiffness range of printable matrices surrounding the cells that mimic the extracellular matrix environment remains limited. The work presented herein aims to expand the range of stiffnesses by utilizing a four-armed polyethylene glycol with maleimide-functionalized arms. The complementary cross-linkers comprised a matrix metalloprotease-degradable peptide and a four-armed thiolated polymer which were adjusted in ratio to tune the stiffness. The modularity of this system allows for a simple method of controlling stiffness and the addition of biological motifs. The application of this system in drop-on-demand printing is validated using MCF-7 cells, which were monitored for viability and proliferation. This study shows the potential of this system for the high-throughput investigation of the effects of stiffness and biological motif compositions in relation to cell behaviors.

Socioeconomic Disparities in the Pursuit of Care at a High-Volume Institution for Surgical Resection of Vestibular Schwannomas.

OBJECTIVE: Increased institutional surgical resection case volume for vestibular schwannomas (VSs) has been associated with improved patient outcomes, including reduced risk of prolonged hospital stay and readmission. Socioeconomic disparities in the pursuit of care at these high-volume institutions remain unknown. STUDY DESIGN: Retrospective cohort epidemiological study. SETTING: National Cancer Database, a hospital-based registry of over 1,500 facilities in the United States. PATIENTS: Adult VS patients (age, >18 years) treated surgically. INTERVENTIONS: High- versus low-volume facilities, defined using a facility case volume threshold of 25 cases per year. A risk-adjusted restricted cubic spline model was previously used to identify this risk threshold beyond which the incremental benefit of increasing case volume began to plateau. MAIN OUTCOME MEASURES: Sociodemographic factors, including race, ethnicity, income, insurance status, and rurality. Multivariable analyses were adjusted for patient and tumor characteristics, including age, sex, Charlson-Deyo score, and tumor size. RESULTS: A totoal of 10,048 patients were identified (median [interquartile range] age = 51 [41-60] years, 54% female, 87% Caucasian). Patients with Spanish/Hispanic ethnicity (OR = 0.71, 95% confidence interval [CI] = 0.52-0.96), income below median (OR = 0.63, 95% CI = 0.55-0.73]), and Medicare, Medicaid, or other government insurance versus private insurance (OR = 0.63, 95% CI = 0.53-0.74) had reduced odds of treatment at a high-volume facility. Further sensitivity analyses in which facility volume was operationalized continuously reinforced direction and significance of these associations. CONCLUSIONS: Socioeconomic disparities exist in the propensity for VS patients to be treated at a high-volume facility. Further work is needed to understand the nature of these associations and whether interventions can be designed to mitigate them.

Hearing Impairment and Allostatic Load in Older Adults.

Importance: Allostatic load, the cumulative strain that results from the chronic stress response, is associated with poor health outcomes. Increased cognitive load and impaired communication associated with hearing loss could potentially be associated with higher allostatic load, but few studies to date have quantified this association. Objective: To investigate if audiometric hearing loss is associated with allostatic load and evaluate if the association varies by demographic factors. Design, Setting, Participants: This cross-sectional survey used nationally representative data from the National Health and Nutrition Examination Survey. Audiometric testing was conducted from 2003 to 2004 (ages 20-69 years) and 2009 to 2010 (70 years or older). The study was restricted to participants aged 50 years or older, and the analysis was stratified based on cycle. The data were analyzed between October 2021 and October 2022. Exposure: A 4-frequency (0.5-4.0 kHz) pure tone average was calculated in the better-hearing ear and modeled continuously and categorically (<25 dB hearing level [dB HL], no hearing loss; 26-40 dB HL, mild hearing loss; ≥41 dB HL, moderate or greater hearing loss). Main Outcome and Measures: Allostatic load score (ALS) was defined using laboratory measurements of 8 biomarkers (systolic/diastolic blood pressure, body mass index [calculated as weight in kilograms divided by height in meters squared], and total serum and high-density lipoprotein cholesterol, glycohemoglobin, albumin, and C-reactive protein levels). Each biomarker was assigned a point if it was in the highest risk quartile based on statistical distribution and then summed to yield the ALS (range, 0-8). Linear regression models adjusted for demographic and clinical covariates. Sensitivity analysis included using clinical cut points for ALS and subgroup stratification. Results: In 1412 participants (mean [SD] age, 59.7 [5.9] years; 293 women [51.9%]; 130 [23.0%] Hispanic, 89 [15.8%] non-Hispanic Black, and 318 [55.3%] non-Hispanic White individuals), a modest association was suggested between hearing loss and ALS (ages 50-69 years: ß = 0.19 [95% CI, 0.02-0.36] per 10 dB HL; 70 years or older: ß = 0.10 [95% CI, 0.02-0.18] per 10 dB HL) among non-hearing aid users. Results were not clearly reflected in the sensitivity analysis with clinical cut points for ALS or modeling hearing loss categorically. Sex-based stratifications identified a stronger association among male individuals (men 70 years or older: ß = 0.22 [95% CI, 0.12-0.32] per 10 dB HL; women: ß = 0.08 [95% CI, -0.04 to 0.20] per 10 dB HL). Conclusion and Relevance: The study findings did not clearly support an association between hearing loss and ALS. While hearing loss has been shown to be associated with increased risk for numerous health comorbidities, its association with the chronic stress response and allostasis may be less than that of other health conditions.

Electrostatic Assembly of Multiarm PEG-Based Hydrogels as Extracellular Matrix Mimics: Cell Response in the Presence and Absence of RGD Cell Adhesive Ligands.

Synthetic hydrogels have been used widely as extracellular matrix (ECM) mimics due to the ability to control and mimic physical and biochemical cues observed in natural ECM proteins such as collagen, laminin, and fibronectin. Most synthetic hydrogels are formed via covalent bonding resulting in slow gelation which is incompatible with drop-on-demand 3D bioprinting of cells and injectable hydrogels for therapeutic delivery. Herein, we developed an electrostatically crosslinked PEG-based hydrogel system for creating high-throughput 3D in vitro models using synthetic hydrogels to mimic the ECM cancer environment. A 3-arm PEG-based polymer backbone was first modified with either permanent cationic charged moieties (2-(methacryloyloxy)ethyl trimethylammonium) or permanent anionic charged moieties (3-sulfopropyl methacrylate potassium salt). The resulting charged polymers can be conjugated further with various amounts of cell adhesive RGD motifs (0, 25, 75, and 98%) to study the influences of RGD motifs on breast cancer (MCF-7) spheroid formation. Formation, stability, and mechanical properties of hydrogels were tested with, and without, RGD to evaluate the cellular response to material parameters in a 3D environment. The hydrogels can be degraded in the presence of salts at room temperature by breaking the interaction of oppositely charged polymer chains. MCF-7 cells could be released with high viability through brief exposure to NaCl solution. Flow cytometry characterization demonstrated that embedded MCF-7 cells proliferate better in a softer (60 Pa) 3D hydrogel environment compared to those that are stiffer (1160 Pa). As the stiffness increases, the RGD motif plays a role in promoting cell proliferation in the stiffer hydrogel. Flow cytometry characterization demonstrated that embedded MCF-7 cells proliferate better in a softer (60 Pa) 3D hydrogel environment compared to those that are stiffer (1160 Pa). As the stiffness increases, the RGD motif plays a role in promoting cell proliferation in the stiffer hydrogel. Additionally, cell viability was not impacted by the tested hydrogel stiffness range between 60 to 1160 Pa. Taken together, this PEG-based tuneable hydrogel system shows great promise as a 3D ECM mimic of cancer extracellular environments with controllable biophysical and biochemical properties. The ease of gelation and dissolution through salt concentration provides a way to quickly harvest cells for further analysis at any given time of interest without compromising cell viability.

Tuning the Mechanical Properties of Multiarm RAFT-Based Block Copolyelectrolyte Hydrogels via Ionic Cross-Linking for 3D Cell Cultures.

Hydrogels that serve as native extracellular matrix (ECM) mimics are typically naturally derived hydrogels that are physically cross-linked via ionic interactions. This means rapid gelation of synthetic polymers, which give control over the chemical and physical cues in hydrogel formation. Herein, we combine the best of both systems by developing a synthetic hydrogel with ionic cross-linking of block copolyelectrolytes to rapidly create hydrogels. Reversible addition-fragmentation chain-transfer (RAFT) polymerization was used to synthesize oppositely charged polyelectrolyte molecules and, in turn, modulate the mechanical property of stiffness. The mechanical stiffness of a range of 900-3500 Pa was tuned by varying the number of charged ionic groups, the length of the polymer arms, and the polymer concentration. We demonstrate the synthetic polyelectrolyte hydrogel as an ECM mimic for three-dimensional (3D) in vitro cell models using MCF-7 breast cancer cells.

Epidemiology and Prognostic Indicators of Survival in Tongue Lymphoma.

OBJECTIVES: Lymphoma, categorized as either non-Hodgkin's lymphoma or Hodgkin's lymphoma, is the second most common malignancy in the head and neck. Primary tongue lymphoma is exceedingly rare, with only case reports or small case series in the literature. This population-based analysis is the first to report the epidemiology and prognostic factors of survival in patients with primary tongue lymphoma. METHODS: The Surveillance, Epidemiology, and End Results 18 database from the National Cancer Institute was queried for patients diagnosed between the years 2000 and 2016 with tongue lymphoma. Outcomes of interest were overall and disease-specific survival. Independent variables included age at diagnosis, sex, race, marital status, primary subsite, histologic subtype, stage, and treatment type. RESULTS AND CONCLUSION: Seven hundred forty patients met criteria; the male-female ratio was 1.5:1 and the mean age at diagnosis was 67.8 years. The majority of lesions localized to the base of tongue (90.0%), were histologically diffuse large B-cell lymphoma (59.5%), and presented at stage I or II (77.9%). Most early-stage lymphomas were treated with chemotherapy only (40.5%) or a combination of both chemotherapy and radiation (31.3%), while late-stage cancers were primarily treated with chemotherapy alone (68.5%). In multivariate analysis, younger age at diagnosis, female sex, married/partnered marital status, mucosa-associated lymphoid tissue histologic subtype, and earlier cancer stage were found to be associated with improved survival. Chemotherapy treatment with or without radiation was also associated with better survival compared to no treatment or radiation alone, though data regarding immunotherapy was unavailable.

Factors Shifting Preference Toward Telemedicine in the Delivery of Skin Cancer Reconstruction Care.

OBJECTIVES: Identify which delivery modality for skin reconstruction care, face-to-face (FTF) in-person versus two telemedicine modalities, store-and-forward (S&F) and live video chat (LVC), is patient preferred and how cost, access, wait time, and demographics influence this preference. STUDY DESIGN: Cross-sectional survey. METHODS: A 16-question survey querying demographics and five scenario-specific preferences questions for the delivery of skin cancer reconstruction care was created and distributed via Amazon Mechanical Turk (MTurk), a crowdsourcing online marketplace, and in-person to Mohs micrographic surgery patients. RESULTS: 1394 MTurk and 55 in-person responses were included. While 82.1% of online respondents prefer FTF clinic visits, this decreases to 58.3% with an in-person visit cost (p < 0.01) and furthermore to a minority 43.5% with both an in-person visit cost and wait time (p < 0.01) despite 77.8% believing that usefulness to the surgeon would improve FTF. Both the MTurk and in-person cohorts demonstrated similar response patterns despite considerable demographic differences. Multivariable analyses revealed that telemedicine was preferred by MTurk respondents with Medicaid (adjusted OR [95% CI]: 1.97 [1.18-3.31]) or Medicare (1.69 [1.10-2.59]) versus private insurance, and prior skin cancer (2.01 [1.18-3.42]) and less preferred by those earning $140,000+ per year (0.49 [0.29-0.82]) compared to those earning <$20,000 per year. CONCLUSIONS: FTF visits are preferred for skin cancer reconstruction care; this shifts toward virtual care with a cost and wait time in spite of the perceived quality of care. Individuals with socioeconomic barriers to access prefer telemedicine. MTurk can be a valuable tool for behavioral research in FPRS. LEVEL OF EVIDENCE: NA Laryngoscope, 133:294-301, 2023.

Volumetric analysis of the aging auditory pathway using high resolution magnetic resonance histology.

Numerous shown consequences of age-related hearing loss have been unveiled; however, the relationship of the cortical and subcortical structures of the auditory pathway with aging is not well known. Investigations into neural structure analysis remain sparse due to difficulties of doing so in animal models; however, recent technological advances have been able to achieve a resolution adequate to perform such studies even in the small mouse. We utilize 12 members of the BXD family of recombinant inbred mice and aged separate cohorts. Utilizing novel magnetic resonance histology imaging techniques, we imaged these mice and generated high spatial resolution three dimensional images which were then comprehensively labeled. We completed volumetric analysis of 12 separate regions of interest specific to the auditory pathway brainstem nuclei and cortical areas with focus on the effect of aging upon said structures. Our results showed significant interstrain variation in the age-related effect on structure volume supporting a genetic influence in this interaction. Through multivariable modeling, we observed heterogenous effects of aging between different structures. Six of the 12 regions of interests demonstrated a significant age-related effect. The auditory cortex and ventral cochlear nucleus were found to decrease in volume with age, while the medial division of the medial geniculate nucleus, lateral lemniscus and its nucleus, and the inferior colliculus increased in size with age. Additionally, no sex-based differences were noted, and we observed a negative relationship between auditory cortex volume and mouse weight. This study is one of the first to perform comprehensive magnetic resonance imaging and quantitative analysis in the mouse brain auditory pathway cytoarchitecture, offering both novel insights into the neuroanatomical basis of age-related changes in hearing as well as evidence toward a genetic influence in this interaction. High resonance magnetic resonance imaging provides a promising efficacious avenue in future mouse model hearing loss investigations.

Use of a Novel Clinical Decision-Making Tool in Vestibular Schwannoma Treatment.

OBJECTIVE: To determine the usefulness of a personalized tool and its effect on the decision-making process for those with vestibular schwannoma (VS). STUDY DESIGN: Prospective study. SETTING: Single institution, academic tertiary care lateral skull base surgery program. PATIENTS: Patients diagnosed with VS. INTERVENTIONS: A comprehensive clinical decision support (CDS) tool was constructed from a previously published retrospective patient-reported data obtained from members of the Acoustic Neuroma Association from January to March 2017. Demographic, tumor, and treatment modality data, including associated side effects, were collected for 775 patients and integrated in an interactive and personalized web-based tool. MAIN OUTCOME MEASURES: Pre- and posttool questionnaires assessing the process of deciding treatment for VS using a decisional conflict scale (DCS) and satisfaction with decision (SWD) scale were compared. RESULTS: A pilot study of 33 patients evaluated at a single institution tertiary care center with mean ± SD age of 63.9 ± 13.5 years and with average tumor size of 7.11 ± 4.75 mm were surveyed. CDS implementation resulted in a mean ± SD total DCS score decrease from 43.6 ± 15.5 to 37.6 ± 16.4 ( p < 0.01) and total SWD score increase from 82.8 ± 16.1 to 86.2 ± 14.4 ( p = 0.04), indicating a significant decrease in decisional conflict and increase in satisfaction. CONCLUSIONS: Implementing a decision-making tool after diagnosis of VS reduced decisional conflict and improved satisfaction with decision. Patients considered the tool to be an aid to their medical knowledge, further improving their comfort and understanding of their treatment options. These findings provide a basis for developing predictive tools that will assist patients in making informed medical decisions in the future.

Medical students' knowledge of HPV, HPV vaccine, and HPV-associated head and neck cancer.

On the basis of their training, medical students are considered "the best case scenario" among university students in knowledge of the human papillomavirus (HPV). We evaluated differences in knowledge of HPV, HPV vaccine, and head and neck cancer (HNC) among medical students. A previously validated questionnaire was completed by 247 medical students at a Midwestern university. Outcomes of interest were knowledge score for HPV and HPV vaccine, and HNC, derived from combining questionnaire items to form HPV knowledge and HNC scores, and analyzed using multivariate linear regression. Mean scores for HPV knowledge were 19.4 out of 26, and 7.2 out of 12 for HNC knowledge. In the final multivariate linear regression model, sex, race, and year of study were independently associated with HPV and HPV vaccine knowledge. Males had significantly lower HPV vaccine knowledge than females (ß = -1.53; 95% CI: -2.53, -0.52), as did nonwhite students (ß = -1.05; 95% CI: -2.07, -0.03). There was a gradient in HPV vaccine knowledge based on the year of study, highest among fourth year students (ß = 6.75; 95% CI: 5.17, 8.33). Results were similar for factors associated with HNC knowledge, except for sex. HNC knowledge similarly increased based on year of study, highest for fourth year students (ß = 2.50; 95% CI: 1.72, 3.29). Among medical students, gaps remain in knowledge of HPV, HPV vaccine, and HPV-linked HNC. Male medical students have significantly lower knowledge of HPV. This highlights the need to increase medical student knowledge of HPV and HPV-linked HNC.

A high-throughput 3D bioprinted cancer cell migration and invasion model with versatile and broad biological applicability.

Understanding the underlying mechanisms of migration and metastasis is a key focus of cancer research. There is an urgent need to develop in vitro 3D tumor models that can mimic physiological cell-cell and cell-extracellular matrix interactions, with high reproducibility and that are suitable for high throughput (HTP) drug screening. Here, we developed a HTP 3D bioprinted migration model using a bespoke drop-on-demand bioprinting platform. This HTP platform coupled with tunable hydrogel systems enables (i) the rapid encapsulation of cancer cells within in vivo tumor mimicking matrices, (ii) in situ and real-time measurement of cell movement, (iii) detailed molecular analysis for the study of mechanisms underlying cell migration and invasion, and (iv) the identification of novel therapeutic options. This work demonstrates that this HTP 3D bioprinted cell migration platform has broad applications across quantitative cell and cancer biology as well as drug screening.

Large-scale phenotyping and characterization of age-related hearing loss in outbred CFW mice.

Age-related hearing loss (ARHL), or presbycusis, is one of the most prevalent conditions affecting the global population. A substantial fraction of patients with ARHL have no identifiable mutation despite over a hundred having been discovered, suggesting unidentified monogenic or polygenic causes. In this study, we investigated the hearing function of the aging outbred CFW mice through auditory brainstem response (ABR) thresholds. Through the characterization of 1,132 ABRs, we observed significant variation in both absolute thresholds and the effect of aging. We identify eight distinct patterns of hearing loss and were able to categorize nearly all data within these eight categories. Proportions within each category varied immensely between aging timepoints. We observe a small but consistent hearing deficit in female CFW mice. The resulting phenotypic data are a necessity for ARHL association mapping at a higher resolution than has previously been achieved and provides a new resource for studying ARHL.

Advances in 3D Bioprinting for Cancer Biology and Precision Medicine: From Matrix Design to Application.

The tumor microenvironment is highly complex owing to its heterogeneous composition and dynamic nature. This makes tumors difficult to replicate using traditional 2D cell culture models that are frequently used for studying tumor biology and drug screening. This often leads to poor translation of results between in vitro and in vivo and is reflected in the extremely low success rates of new candidate drugs delivered to the clinic. Therefore, there has been intense interest in developing 3D tumor models in the laboratory that are representative of the in vivo tumor microenvironment and patient samples. 3D bioprinting is an emerging technology that enables the biofabrication of structures with the virtue of providing accurate control over distribution of cells, biological molecules, and matrix scaffolding. This technology has the potential to bridge the gap between in vitro and in vivo by closely recapitulating the tumor microenvironment. Here, a brief overview of the tumor microenvironment is provided and key considerations in biofabrication of tumor models are discussed. Bioprinting techniques and choice of bioinks for both natural and synthetic polymers are also outlined. Lastly, current bioprinted tumor models are reviewed and the perspectives of how clinical applications can greatly benefit from 3D bioprinting technologies are offered.

Cheek Donor Site for Full-Thickness Skin Graft Repair of the Nasal Ala: Outcomes of a Retrospective Cohort Study.

BACKGROUND: Full-thickness skin grafts (FTSGs) are useful repairs for reconstructing nasal alar defects. Traditional donor sites include the preauricular, postauricular, and supraclavicular skin. OBJECTIVE: To evaluate esthetic outcomes and complications of nasal alar defects repaired with FTSGs from the medial cheek. MATERIALS AND METHODS: A retrospective chart review of Mohs surgery patients who had FTSG repair of the nasal ala between January 2015 and August 2020 was performed. Demographic, surgery, and follow-up visit data were reviewed. Cosmesis was rated by a facial plastic surgeon, a Mohs surgeon, and a plastic surgeon using baseline, defect, and follow-up visit photographs. RESULTS: Sixty-nine patients with FTSG repairs of nasal alar defects were identified. 51 of 69 patients (73.9%) had the cheek donor site, and 18 of 69 patients (26.1%) had a noncheek donor site. The mean (SD) rater visual analog score for both cohorts was good with no significant difference (cheek: 65.9 [13.8]; noncheek: 66.1 [15.3]; p = .96). A notable difference in the complication rate by donor site was observed (cheek: 6.9%, noncheek: 16.7%; p = .13), although it did not reach significance. CONCLUSION: The cheek is a reliable FTSG donor site for nasal alar defects after Mohs micrographic surgery, with a trend toward fewer complications.

A Covalently Crosslinked Ink for Multimaterials Drop-on-Demand 3D Bioprinting of 3D Cell Cultures.

In vitro 3D cell models have been accepted to better recapitulate aspects of in vivo organ environment than 2D cell culture. Currently, the production of these complex in vitro 3D cell models with multiple cell types and microenvironments remains challenging and prone to human error. Here, a versatile ink comprising a 4-arm poly(ethylene glycol) (PEG)-based polymer with distal maleimide derivatives as the main ink component and a bis-thiol species as the activator that crosslinks the polymer to form the hydrogel in less than a second is reported. The rapid gelation makes the polymer system compatible with 3D bioprinting. The ink is combined with a novel drop-on-demand 3D bioprinting platform, designed specifically for producing 3D cell cultures, consisting of eight independently addressable nozzles and high-throughput printing logic for creating complex 3D cell culture models. The combination of multiple nozzles and fast printing logic enables the rapid preparation of many complex 3D cell cultures comprising multiple hydrogel environments in one structure in a standard 96-well plate format. The platform's compatibility for biological applications is validated using pancreatic ductal adenocarcinoma cancer (PDAC) and human dermal fibroblast cells with their phenotypic responses controlled by tuning the hydrogel microenvironment.

Correction: Non-reversible heat-induced gelation of a biocompatible Fmoc-hexapeptide in water.

Correction for 'Non-reversible heat-induced gelation of a biocompatible Fmoc-hexapeptide in water' by Jonathan P. Wojciechowski et al., Nanoscale, 2020, 12, 8262-8267, DOI: .

Effect of polar amino acid incorporation on Fmoc-diphenylalanine-based tetrapeptides.

Peptide hydrogels show great promise as extracellular matrix mimics due to their tuneable, fibrous nature. Through incorporation of polar cationic, polar anionic or polar neutral amino acids into the Fmoc-diphenylalanine motif, we show that electrostatic charge plays a key role in the properties of the subsequent gelators. Specifically, we show that an inverse relationship exists for biocompatibility in the solution state versus the gel state for cationic and anionic peptides. Finally, we use tethered bilayer lipid membrane (tBLM) experiments to suggest a likely mode of cytotoxicity for tetrapeptides which exhibit cytotoxicity in the solution state.

Non-reversible heat-induced gelation of a biocompatible Fmoc-hexapeptide in water.

Hydrogel materials which respond to changes in temperature are widely applicable for injectable drug delivery or tissue engineering applications. Here, we report the unsual heat-induced gelation behaviour of a low molecular weight gelator based on an Fmoc-hexapeptide, Fmoc-GFFRGD. We show that Fmoc-GFFRGD forms kinetically stable fibres when mixed with divalent cations (e.g. Ca2+). Gelation of the mixture occurs upon heating of the mixture which enables electrostatic screening by the divalent cations and hydrophobic collapse of the fibres to give a self-supporting hydrogel network that shows good biocompatibility with L929 fibroblast cells. This work highlights a unique mechanism to initiate heat-induced gelation which should find opportunities as a gelation trigger for injectable hydrogels or fundamental self-assembly applications.