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The spinal cord has a poor ability to regenerate after an injury, which may be due to cell loss, cyst formation, inflammation, and scarring. A promising approach to treating a spinal cord injury (SCI) is the use of biomaterials. We have developed a novel hydrogel scaffold fabricated from oligo(poly(ethylene glycol) fumarate) (OPF) as a 0.08 mm thick sheet containing polymer ridges and a cell-attractive surface on the other side. When the cells are cultured on OPF via chemical patterning, the cells attach, align, and deposit ECM along the direction of the pattern. Animals implanted with the rolled scaffold sheets had greater hindlimb recovery compared to that of the multichannel scaffold control, which is likely due to the greater number of axons growing across it. The immune cell number (microglia or hemopoietic cells: 50–120 cells/mm2 in all conditions), scarring (5–10% in all conditions), and ECM deposits (Laminin or Fibronectin: approximately 10–20% in all conditions) were equal in all conditions. Overall, the results suggest that the scaffold sheets promote axon outgrowth that can be guided across the scaffold, thereby promoting hindlimb recovery. This study provides a hydrogel scaffold construct that can be used in vitro for cell characterization or in vivo for future neuroprosthetics, devices, or cell and ECM delivery. [ABSTRACT FROM AUTHOR]

This commentary is on the original article by Kruse et al. on pages 902–909 [ABSTRACT FROM AUTHOR]

Aim: Neonatal encephalopathy (NE) is associated with an increased risk of multi‐organ injury. The lack of standardised definitions for multi‐organ dysfunction in NE hinders accurate quantification of these complications. Methods: A simple multi‐organ dysfunction in neonatal encephalopathy scoring (MODE) system was created to include the cardiovascular, respiratory, gastrointestinal, haematological and neurological systems with a maximum score of 15. The MODE score was then compared with the grade of NE, Bayley Scales of Infant Development (Bayley‐III) at 2 years of age and mortality. The Bayley score was used as it gave an objective score making it easier to compare the MODE score. Bayley score of <90 and/or abnormal MRI as an adverse outcome. Results: Infants with perinatal asphyxia (PA:n = 85) were prospectively enrolled (PA only n = 9; NE I = 23; NE II = 42; NE III = 11). Infants with higher MODE scores were significantly more likely to have moderate/severe NE (NE II/III: median scores (IQR) 7(5–10) versus mild NE 2 (1–3); p‐value < 0.001) The MODE score was highly predictive of mortality (AUC 0.96, p‐value = 0.002). Infants who had an abnormal neurological examination at discharge or abnormal Bayley‐III scores had significantly higher MODE scores (p‐value = 0.001). Conclusion: Quantifying multi‐organ injury is important to plan optimal early management and long‐term follow‐up. Additional use of clinical biomarkers may be useful as surrogate endpoints in future clinical trials and link to multi‐organ longer‐term developmental follow‐up. [ABSTRACT FROM AUTHOR]

Aim: To examine pro‐ and anti‐inflammatory cytokines in children with cerebral palsy (CP) at baseline and in response to endotoxin (lipopolysaccharide), and correlate outcomes compared with age‐matched comparisons, to evaluate their ability to mount an immune response. Method: Serum cytokines were assessed in 12 children (eight males, four females; mean age 10y 1mo [SD 1y 8mo], 6–16y) with CP against 12 age‐matched comparisons (eight males, four females; mean age 9y 1mo [SD 1y 1mo]). Pro‐ and anti‐inflammatory cytokines (interleukin‐1β, interleukin‐2, interleukin‐6, interleukin‐8, interleukin‐10, interleukin‐18, tumour necrosis factor [TNF]‐α, TNF‐β, interferon‐γ, granulocyte‐macrophage colony‐stimulating factor [GM‐CSF], vascular endothelial growth factor [VEGF], erythropoietin, and interleukin‐1 receptor antagonist) were measured at baseline and in response to in vitro simulation with lipopolysaccharide by multiplex enzyme‐linked immunosorbent assay. Results: Significantly higher erythropoietin was found at baseline in children with CP compared with the comparison group. There was a strong response to lipopolysaccharide for interleukin‐8, VEGF, TNF‐α, and GM‐CSF in both children with CP and the comparison group; however, there was significant lipopolysaccharide hyporesponsiveness in children with CP compared with the comparison group for interleukin‐1α, interleukin‐1β, interleukin‐2, and interleukin‐6. Interpretation: Altered cytokine responses in children with CP compared with the comparison group demonstrate an altered inflammatory state that may contribute to ongoing sequelae and could be a target for therapy. What this paper adds: Altered inflammatory responses persist in children with cerebral palsy (CP).Erythropoietin is elevated in children with CP compared with the comparison group.Children with CP have reduced interleukin‐1α, interleukin‐1β, interleukin‐2, and interleukin‐6 inflammatory responses to lipopolysaccharide. What this paper adds: Altered inflammatory responses persist in children with cerebral palsy (CP).Erythropoietin is elevated in children with CP compared with the comparison group.Children with CP have reduced interleukin‐1α, interleukin‐1β, interleukin‐2, and interleukin‐6 inflammatory responses to lipopolysaccharide. This article is commented on by Schleiss on pages 365–366 of this issue. [ABSTRACT FROM AUTHOR]