Outcome predictors for wound healing in patients with a diabetic foot ulcer.

The aim of this study was to identify diabetic foot ulcer (DFU) patients at risk for the development of a hard-to-heal wound. This is a post-hoc analysis of a prospective cohort study including a total of 208 patients with a DFU. The primary endpoints were time to healing and the development of a hard-to-heal-wound. Univariable and multivariable logistic and Cox regression analysis were used to study the associations of patient characteristics with the primary endpoints. The number of previous DFUs [odds ratio (OR): 1.42, 95% confidence interval (CI): 1.01-1.99, P = .04], University of Texas (UT) classification grade 2 (OR: 2.93, 95% CI: 1.27-6.72, P = .01), UT classification grade 3 (OR: 2.80, 95% CI: 1.17-6.71, P = .02), and a diagnosis of foot stand deformation (OR: 1.54, 95% CI: 0.77-3.08, P = .05) were significantly associated with the development of a hard-to-heal wound. Only UT classification grade 3 (HR: 0.61, 95% CI: 0.41-0.90, P = .01) was associated with time to healing. The number of previous DFUs, UT classification grade, and a diagnosis of foot deformation are significantly associated with development of a hard-to-heal wound in patients with a DFU. The only predictor significantly associated with time to healing was UT classification grade 3. These patient characteristics can be used to identify patients at risk for the development of hard-to-heal wounds, who might need an early intervention to prevent wound problems.

High-throughput assessment of mechanical properties of stem cell derived red blood cells, toward cellular downstream processing.

Stem cell products, including manufactured red blood cells, require efficient sorting and purification methods to remove components potentially harmful for clinical application. However, standard approaches for cellular downstream processing rely on the use of specific and expensive labels (e.g. FACS or MACS). Techniques relying on inherent mechanical and physical properties of cells offer high-throughput scalable alternatives but knowledge of the mechanical phenotype is required. Here, we characterized for the first time deformability and size changes in CD34+ cells, and expelled nuclei, during their differentiation process into red blood cells at days 11, 14, 18 and 21, using Real-Time Deformability Cytometry (RT-DC) and Atomic Force Microscopy (AFM). We found significant differences (p < 0.0001; standardised mixed model) between the deformability of nucleated and enucleated cells, while they remain within the same size range. Expelled nuclei are smaller thus could be removed by size-based separation. An average Young's elastic modulus was measured for nucleated cells, enucleated cells and nuclei (day 14) of 1.04 ± 0.47 kPa, 0.53 ± 0.12 kPa and 7.06 ± 4.07 kPa respectively. Our identification and quantification of significant differences (p < 0.0001; ANOVA) in CD34+ cells mechanical properties throughout the differentiation process could enable development of new routes for purification of manufactured red blood cells.