Development and evaluation of gellan gum/silk fibroin/chondroitin sulfate ternary injectable hydrogel for cartilage tissue engineering

Hydrogel is in the spotlight as a useful biomaterial in the field of drug delivery and tissue engineering due to its similar biological properties to a native extracellular matrix (ECM). Herein, we proposed a ternary hydrogel of gellan gum (GG), silk fibroin (SF), and chondroitin sulfate (CS) as a biomaterial for cartilage tissue engineering. The hydrogels were fabricated with a facile combination of the physical and chemical crosslinking method. The purpose of this study was to find the proper content of SF and GG for the ternary matrix and confirm the applicability of the hydrogel in vitro and in vivo. The chemical and mechanical properties were measured to confirm the suitability of the hydrogel for cartilage tissue engineering. The biocompatibility of the hydrogels was investigated by analyzing the cell morphology, adhesion, proliferation, migration, and growth of articular chondrocytes-laden hydrogels. The results showed that the higher proportion of GG enhanced the mechanical properties of the hydrogel but the groups with over 0.75% of GG exhibited gelling temperatures over 40 °C, which was a harsh condition for cell encapsulation. The 0.3% GG/3.7% SF/CS and 0.5% GG/3.5% SF/CS hydrogels were chosen for the in vitro study. The cells that were encapsulated in the hydrogels did not show any abnormalities and exhibited low cytotoxicity. The biochemical properties and gene expression of the encapsulated cells exhibited positive cell growth and expression of cartilage-specific ECM and genes in the 0.5% GG/3.5% SF/CS hydrogel. Overall, the study of the GG/SF/CS ternary hydrogel with an appropriate content showed that the combination of GG, SF, and CS can synergistically promote articular cartilage defect repair and has considerable potential for application as a biomaterial in cartilage tissue engineering.This research was supported by the International Research and Development Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2017K1A3A7A03089427) and by the bilateral cooperation Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2019K2A9A1A06098563)

Abstract Number ‐ 280: A Unique Case of Pial AVF Presenting as Hemispheric Cerebral Edema

Introduction To describe a unique case of pial arteriovenous fistula presenting as left hemispheric cerebral edema with hemianopsia, sensory change and ataxia. Methods Case report Results Our patient is a 38 year old male with a history of diabetes, hyperlipidemia and congenital deafness with a left cochlear implant who presented to an outside hospital for visual complaints. Non‐contrast CT of the head was negative at that time; he could not obtain an MRI due to his cochlear implant. He developed worsening right hemianopia and aphasia, prompting his transfer to our facility. Upon arrival, repeat imaging was done, including a CTA of the head and neck. This revealed a large region of hypodensity involving the left PCA and distal MCA territories. An MRI was attempted but artifact from his implant obscured visualization of the left hemisphere. Post‐contrast CT was negative for evidence of tumor. CT venogram was negative for veno‐occlusive disease. He complained of worsening headache and demonstrated worsening word‐finding ability. He received100g total of mannitol divided across 3 boluses which improved his symptoms mildly. Over the following days he began to become ataxic and clumsy in the right upper extremity and his headache worsened further and he began to develop focal seizures electrographically localized to the left parietal lobe. Repeat CTA demonstrated expanding hypodensity with marked vascular engorgement in the left hemisphere. He underwent 6‐vessel digital subtraction angiography (DSA) of the head which revealed gross left hemispheric venous congestion with early filling of the left hemispheric venous system by a parasagittal pial ateriovenous fistula believed to be responsible for his hemispheric edema. He was discharged on acetazolamide and acetaminophen for headache management and plans for outpatient follow‐up and potential intervention. Follow‐up DSA revealed improvement in his venous congestion and reduction in the degree of his early venous filling with some symptomatic improvement by medical management. Conclusions Pial arteriovenous fistulae (pAVF) are a rare entity and can present in a variety of ways, with symptomatic intracranial hemorrhage and ischemia being two of the most common. This case illustrates an unusual instance of hemispheric edema initially mistaken for venous infarct caused by a pAVF, and prompts the physician to consider angiography and further exploration when initial workup for cerebral edema and/or venous infarct is initially unrevealing

Motivational Interviewing Conversational Agent for Parents as Proxies for Their Children in Healthy Eating: Development and User Testing

BackgroundIncreased adoption of off-the-shelf conversational agents (CAs) brings opportunities to integrate therapeutic interventions. Motivational Interviewing (MI) can then be integrated with CAs for cost-effective access to it. MI can be especially beneficial for parents who often have low motivation because of limited time and resources to eat healthy together with their children. ObjectiveWe developed a Motivational Interviewing Conversational Agent (MICA) to improve healthy eating in parents who serve as a proxy for health behavior change in their children. Proxy relationships involve a person serving as a catalyst for behavior change in another person. Parents, serving as proxies, can bring about behavior change in their children. MethodsWe conducted user test sessions of the MICA prototype to understand the perceived acceptability and usefulness of the MICA prototype by parents. A total of 24 parents of young children participated in 2 user test sessions with MICA, approximately 2 weeks apart. After parents’ interaction with the MICA prototype in each user test session, we used qualitative interviews to understand parents’ perceptions and suggestions for improvements in MICA. ResultsFindings showed participants’ perceived usefulness of MICAs for helping them self-reflect and motivating them to adopt healthier eating habits together with their children. Participants further suggested various ways in which MICA can help them safely manage their children’s eating behaviors and provide customized support for their proxy needs and goals. ConclusionsWe have discussed how the user experience of CAs can be improved to uniquely offer support to parents who serve as proxies in changing the behavior of their children. We have concluded with implications for a larger context of designing MI-based CAs for supporting proxy relationships for health behavior change

Fabrication and Evaluation of Gellan Gum/Hyaluronic Acid Hydrogel for Retinal Tissue Engineering Biomaterial and the Influence of Substrate Stress Relaxation on Retinal Pigment Epithelial Cells

Cell therapies for age-related macular degeneration (AMD) treatment have been developed by integrating hydrogel-based biomaterials. Until now, cell activity has been observed only in terms of the modulus of the hydrogel. In addition, cell behavior has only been observed in the 2D environment of the hydrogel and the 3D matrix. As time-dependent stress relaxation is considered a significant mechanical cue for the control of cellular activities, it is important to optimize hydrogels for retinal tissue engineering (TE) by applying this viewpoint. Herein, a gellan Gum (GG)/Hyaluronic acid (HA) hydrogel was fabricated using a facile physical crosslinking method. The physicochemical and mechanical properties were controlled by forming a different composition of GG and HA. The characterization was performed by conducting a mass swelling study, a sol fraction study, a weight loss test, a viscosity test, an injection force study, a compression test, and a stress relaxation analysis. The biological activity of the cells encapsulated in 3D constructs was evaluated by conducting a morphological study, a proliferation test, a live/dead analysis, histology, immunofluorescence staining, and a gene expression study to determine the most appropriate material for retinal TE biomaterial. Hydrogels with moderate amounts of HA showed improved physicochemical and mechanical properties suitable for injection into the retina. Moreover, the time-dependent stress relaxation property of the GG/HA hydrogel was enhanced when the appropriate amount of HA was loaded. In addition, the cellular compatibility of the GG/HA hydrogel in in vitro experiments was significantly improved in the fast-relaxing hydrogel. Overall, these results demonstrate the remarkable potential of GG/HA hydrogel as an injectable hydrogel for retinal TE and the importance of the stress relaxation property when designing retinal TE hydrogels. Therefore, we believe that GG/HA hydrogel is a prospective candidate for retinal TE biomaterial

Proactive strategy for long-term biological research aimed at low-dose radiation risk in Korea

<p><b>Purpose:</b> Since the 2011 Fukushima nuclear power plant accident, Korean radiation experts have agreed that reliable data on health risks of low-dose radiation (LDR) are needed to ease the anxiety of lay people. The intent of this study was to devise a sustainable biological program suited for the research environment in Korea and aimed at the health effects of radiation exposures <100 millisieverts (mSv). To address pressing public concerns over LDR risk, we investigated the current understanding of LDR effects by analyzing the previous reports of international authorities for radiation protection and research publications that appeared after the Chernobyl accident. A research program appropriate for societal and scientific inclinations of Korea was then devised based on input from Korean radiation scientists.</p> <p><b>Conclusions:</b> After review by our advisory committee, program priorities were set, calling for an agenda that focused on dose-response relationships in carcinogenesis, health span responses to lifestyle variations, and systemic metabolic changes. Our long-term biological research program may contribute scientific evidence to reduce the uncertainties of LDR health risks and help stakeholders formulate policies for radiation protection.</p

Serum Antibody Response Comparison and Adverse Reaction Analysis in Healthcare Workers Vaccinated with the BNT162b2 or ChAdOx1 COVID-19 Vaccine

The COVID-19 pandemic is changing rapidly and requires different strategies to maintain immunization. In Korea, different COVID-19 vaccines are recommended and available for various populations, including healthcare workers (HCWs) at high risk of SARS-CoV-2 infection. We plan to evaluate the adverse events (AEs) and immunogenicity of the BNT162b2 and ChAdOx1 vaccines in HCWs at a single center. This cohort study included HCWs fully vaccinated with either BNT162b2 or ChAdOx1. Blood samples were taken eight weeks after the second vaccination with both COVID-19 vaccines and six months after the second vaccination from participants with the BNT162b2 vaccine. The primary endpoint for immunogenicity was the serum neutralizing antibody responses eight weeks after vaccination. The secondary endpoint was the incidence of various AEs within 28 days of each vaccination. Between 16 March and 23 June 2021, 115 participants were enrolled (65 in the ChAdOx1 group and 50 in the BNT162b2 group). Significantly higher surrogate virus neutralization test (sVNT) inhibition was observed in participants vaccinated with two doses of BNT162b2 (mean (SD) 91.4 (9.68)%) than in those vaccinated with ChAdOx1 (mean (SD) 73.3 (22.57)%). The effectiveness of the BNT162b2 vaccine was maintained across all age and gender categories. At six months after the second dose, serum antibody levels declined significantly in the BNT162b2 group. The main adverse events, including fever, myalgia, fatigue, and headache, were significantly higher in the ChAdOx1 group after the first dose, whereas, after the second dose, those AEs were significantly higher in the BNT162b2 group (p < 0.05). Two doses of either the ChAdOx1 or the BNT162b2 COVID-19 vaccine resulted in very high seropositivity among the HCWs at our center. The quality of the antibody response, measured by sVNT inhibition, was significantly better with the BNT162b2 vaccine than with the ChAdOx1 vaccine. There was no significant association between neutralizing antibody response and AE after each vaccination in our cohort