Spinal cord injury (SCI) is a devastating condition with no curative therapy currently available. Immunomodulation can be applied as a therapeutic strategy to drive alternative immune cell activation and promote a proregenerative injury microenvironment. Locally injected hydrogels carrying immunotherapeutic cargo directly to injured tissue offer an encouraging treatment approach from an immunopharmacological perspective. Gelatin methacrylate (GelMA) hydrogels are promising in this regard, however, detailed analysis on the immunogenicity of GelMA in the specific context of the SCI microenvironment is lacking. Here, the immunogenicity of GelMA hydrogels formulated with a translationally relevant photoinitiator is analyzed in vitro and ex vivo. 3% (w/v) GelMA, synthesized from gelatin type‐A, is first identified as the optimal hydrogel formulation based on mechanical properties and cytocompatibility. Additionally, 3% GelMA‐A does not alter the expression profile of key polarization markers in BV2 microglia or RAW264.7 macrophages after 48 h. Finally, it is shown for the first time that 3% GelMA‐A can support the ex vivo culture of primary murine organotypic spinal cord slices for 14 days with no direct effect on glial fibrillary acidic protein (GFAP+) astrocyte or ionized calcium‐binding adaptor molecule 1 (Iba‐1+) microglia reactivity. This provides evidence that GelMA hydrogels can act as an immunotherapeutic hydrogel‐based platform for preclinical SCI.
AbstractThis study aimed to investigate (1) the accuracy of resting metabolic rate (RMR) prediction equations in female rugby players on a group and individual level; and (2) whether individual differences in the accuracy of prediction equations is associated with muscle damage or energy availability.RMR was assessed in 14 female provincial and club rugby players (Age: 20–34 years, FFM: 47–63 kg, FM: 15–37%) training a minimum of twice per week. Participants attended the laboratory following an overnight fast and having avoided strenuous exercise for 24 hours. RMR was measured over 30 minutes by indirect calorimetry, and taken as the 10 minutes with the lowest variation. Body composition was assessed by air displacement plethysmography, muscle damage indicated by creatine kinase (CK) and risk of low energy availability assessed by the Low Energy Availability in Females Questionnaire. Accuracy of RMR prediction equations relevant to the general population and athletes were assessed including the Harris Benedict (1919), Cunningham (1980) and Ten Haaf FFM (2014) based equations.Measured RMR was 1748 ± 146 kcal/day (range: 1474–2010 kcal/day). Predicted RMR determined by the Harris-Benedict equation (1601 ± 120 kcal/day) was significantly lower than measured RMR (p < 0.001), whereas predicted RMR using the Cunningham (1753 ± 146 kcal/day, p = 0.89) and the Ten Haaf (1781 ± 115 kcal/day, p = 0.33) equations did not differ from measured RMR. On an individual level, 50% (n = 7), 86% (n = 12) and 79% (n = 11) of participants fell within 10% of the measured RMR value when RMR was predicted by Harris-Benedict, Cunningham and Ten Haaf equations respectively. CK values were 182 ± 155U/L (range: 25–490U/L). When correlations of the whole group were studied, the difference between predicted and measured RMR was not associated with CK (r = 0.13). However, in the two individuals who fell outside the 10% range of that predicted by the Cunningham equation, one above and one below, CK values were 428U/L and 166U/L respectively. Muscle damage (as indicated by a high CK value) could therefore be one potential explanation for the higher measured RMR in the individual who was above the Cunningham predicted value.In this cohort of female rugby players, the Cunningham equation showed the best accuracy on a group and individual level, suggesting this may be the most suitable prediction equation for this population. Further studies with larger sample sizes and investigating underlying reasons for why RMR measured values may differ from predicted values are needed.
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