Thiol-Methylsulfone-Based Hydrogels for Cell Encapsulation: Reactivity Optimization of Aryl-Methylsulfone Substrate for Fine-Tunable Gelation Rate and Improved Stability.

Hydrogels are widely used as hydrated matrices for cell encapsulation in a number of applications, spanning from advanced 3D cultures and tissue models to cell-based therapeutics and tissue engineering. Hydrogel formation in the presence of living cells requires cross-linking reactions that proceed efficiently under close to physiological conditions. Recently, the nucleophilic aromatic substitution of phenyl-oxadiazole (Ox) methylsulfones (MS) by thiols was introduced as a new cross-linking reaction for cell encapsulation. Reported poly(ethylene glycol) (PEG)-based hydrogels featured tunable gelation times within seconds to a few minutes within pH 8.0 to 6.6 and allowed reasonably good mixing with cells. However, their rapid degradation prevented cell cultures to be maintained beyond 1 week. In this Article, we present the reactivity optimization of the heteroaromatic ring of the MS partner to slow down the cross-linking kinetics and the degradability of the derived hydrogels. New MS substrates based on phenyl-tetrazole (Tz) and benzothiazole (Bt) rings, with lower electrophilicity than Ox, were synthesized by simple pathways. When mixed with PEG-thiol, the novel PEG-MS extended the working time of precursor mixtures and allowed longer term cell culture. The Tz-based MS substrate was identified as the best candidate, as it is accessible by simple chemical reactions from cost-effective reactants, hydrogel precursors show good stability in aqueous solution and keep high chemoselectivity for thiols, and the derived Tz gels support cell cultures for >2 weeks. The Tz system also shows tunable gelation kinetics within seconds to hours and allows comfortable manipulation and cell encapsulation. Our findings expand the toolkit of thiol-mediated chemistry for the synthesis of hydrogels with improved properties for laboratory handling and future automatization.

Knowledge, attitude, and practice of medical interns and postgraduate residents on American Geriatric Society updated Beers criteria.

BACKGROUND: Potentially inappropriate medication (PIM) prevalence in older adults is increasing day by day due to lack of knowledge among medical students and professionals. OBJECTIVE: To determine the knowledge of medical students toward American Geriatric Society (AGS) Beers criteria for PIM prescribing. MATERIALS AND METHODS: This cross-sectional study employed a self-administered questionnaire which was validated and designed to assess the knowledge, attitude, and practice of medical interns and postgraduate residents on Beers criteria for PIMs in older adults. The study was conducted in Faridkot region of Punjab in 2019. This study will utilize a purposive sampling strategy and a convenience sampling of up to 183 participants. Mann-Whitney U or Kruskal-Wallis tests were used to compare different issues as appropriate. P values of <0.05 were considered significant. RESULTS: Out of 183 questionnaires distributed, only 155 participants (response rate 84.6%) had filled the survey and were included in the study. 61.3% (n = 95) of the respondents were males. The mean knowledge score of 155 participants was (5.16 ± 1.56), where the highest score was 9 and the lowest score was 2 out of 10. 15.5% (n = 24) of the participant strongly agreed that Beers criteria use is necessary in clinical setting and would be very helpful. While 22.5% (n = 35) of the participants strongly agreed that PIMs cause adverse drug event (ADE) and drug-related problems (DRPs) in older adults. Age of the participant had a significant effect on the knowledge score (p = 0.009), and participant aged between 31 and 40 years had significantly higher knowledge scores compared with participants falls under 20-30 years. CONCLUSION: Medical students and postgraduate residents had average knowledge of PIMs and are unaware of the standard guidelines in older adults such as the Beers criteria. Lack of formal education or training about Beers guidelines was the main reason responsible for average knowledge among participants.