Diabetes is a major risk factor for the progression of vascular disease, contributing to elevated levels of glycoxidation, chronic inflammation and calcification. Tissue engineering emerges as a potential solution for the treatment of vascular diseases however there is a considerable gap in the understanding of how scaffolds and stem cells will perform in patients with diabetes. We hypothesized that adipose tissue-derived stem cells (ASCs) by virtue of their immunosuppressive potential would moderate the diabetes-intensified inflammatory reactions and induce positive construct remodeling. To test this hypothesis, we prepared arterial elastin scaffolds seeded with autologous ASCs and implanted them subdermally in diabetic rats and compared inflammatory markers, macrophage polarization, matrix remodeling, calcification and bone protein expression to control scaffolds implanted with and without cells in nondiabetic rats. ASC-seeded scaffolds exhibited lower levels of CD8+ T-cells and CD68+ pan-macrophages and higher numbers of M2 macrophages, smooth muscle cell-like and fibroblast-like cells. Calcification and osteogenic markers were reduced in ASCseeded scaffolds implanted in non-diabetic rats but remained unchanged in diabetes, unless the scaffolds were first pre-treated with penta-galloyl glucose (PGG), a known anti-oxidative elastin-binding polyphenol. In conclusion, autologous ASC seeding in elastin scaffolds is effective in combating diabetes-related complications. To prevent calcification, the oxidative milieu needs to be reduced by elastin-binding antioxidants such as PGG.
Animals ; Antioxidants ; Diabetes Complications ; Elastin* ; Glucose ; Humans ; Inflammation ; Macrophages ; Muscle, Smooth ; Prostaglandins G ; Rats ; Risk Factors ; Stem Cells* ; T-Lymphocytes ; Tissue Engineering ; Vascular Diseases ; Virtues

Fecal incontinence (FI) has a significant long-term impact on patient quality of life for which there is a range of medical and surgical management alternatives. We report the preliminary outcome using the ForConti Contix Faecal Incontinence Management System (FIMS) in FI patients who had failed conservative therapy and who were recruited at 2 tertiary institutions between September 2018 and September 2020. Comparative assessments were made before and after 2 week periods of treatment using bowel diaries and subjective Wexner and Faecal Incontinence Quality of Life scores. Of 17 patients enrolled, 11 completed an 8-week assessment with a significant fall in the average percentage of FI days reported from 84% before treatment to 16.8% at the first posttreatment assessment and down to 13.2% by the second assessment period. This finding correlated with a similar reduction in the total weekly number of episodes of frank FI, minor soiling, and fecal urgency reported by patients along with concomitant improvements in the Wexner scores. For those using the device, there was less concern about accidental bowel leakage, high rates of satisfaction, and minimal problems with the device. Initial results are encouraging warranting further study.