Effect of mesh width on apical support after sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: We evaluated the effect of polypropylene mesh width on vaginal apical support, mesh elongation, and mesh tensile strength for abdominal sacrocolpopexy. METHODS: Abdominal sacrocolpopexy was performed on ten cadavers using pieces of polypropylene mesh of width 1, 2, and 3 cm. Weights of 1, 2, 3, and 4 kg were sequentially applied to the vagina. The total distance moved by the vaginal apex, and the amount of stretch of the intervening mesh segment between the sacrum and the vagina were recorded for each width. The failure strengths of additional single and double layer sets of each width were also tested using a tensiometer. Data were analyzed with analysis of variance using a random effects model. RESULTS: The mean (standard error of the mean) maximum distance moved by the vaginal apex was 4.63 cm (0.37 cm) for the 1 cm mesh compared to 3.67 cm (0.26 cm) and 2.73 cm (0.14 cm) for the 2 and 3 cm meshes, respectively (P < 0.0001). The 1 cm width ruptured during testing in four of the ten cadavers. The results were similar for mesh elongation, with the 1 cm mesh stretching the most and the 3 cm mesh stretching the least. Mesh failure loads for double-layer mesh were 52.9 N (2.5 N), 124.4 N (2.7 N), and 201.2 N (4.5 N) for the 1, 2, and 3 cm meshes, respectively, and were higher than the failure loads for single mesh (P < 0.001). CONCLUSIONS: In a cadaver model, increasing mesh width is associated with better vaginal apical support, less mesh elongation, and higher failure loads. Mesh widths of 2-3 cm provide sufficient repair strength for sacrocolpopexy.

Genome editing of mouse fibroblasts by homologous recombination for sustained secretion of PDGF-B and augmentation of wound healing.

BACKGROUND: Exogenous cytokines, such as platelet-derived growth factor (PDGF)-B, can augment wound healing, but sustained delivery to maintain therapeutic levels remains a problem. "Genome editing" is a new technology in which precise genome modifications are made within cells using engineered site-specific nucleases. Genome editing avoids many of the complications associated with traditional gene therapy and the use of viral vectors, including random integration, imprecise gene expression, and inadvertent oncogene activation. METHODS: This study demonstrates site-specific nuclease-mediated integration of a PDGF-B transgene into a predefined locus within the genome of primary mouse fibroblasts. Engineered fibroblasts were applied to splinted mouse wounds and evaluated after 14 days and 5 months for the retention of engineered fibroblasts, wound healing morphology, angiogenesis, and systemic PDGF-B expression. RESULTS: The application of engineered PDGF-B-expressing fibroblasts enhanced wound healing compared with controls. Low-level, constitutive expression of PDGF-B was achieved without detectable levels of systemic PDGF-B. The mechanism of improved wound healing is, at least in part, the result of increased wound vascularization, as the wounds treated with PDGF-B fibroblasts had a blood vessel density 2.5 times greater than controls. After 5 months, the engineered fibroblasts persisted in the wound bed. No adverse effects were detected from the application of these fibroblasts after 5 months as assessed by hematoxylin and eosin staining of wounds and by mouse necropsy. CONCLUSIONS: These data support that site-specific genome editing allows for sustained cell-based cytokine delivery. Furthermore, sustained release of PDGF-B increases the speed and quality of wound healing after a single application.

The differing adipocyte morphologies of deep versus superficial midfacial fat compartments: a cadaveric study.

BACKGROUND: Anatomical studies show that facial fat is partitioned into distinct compartments, with the nasolabial fat pad in a superficial compartment and the deep medial cheek fat in a deep compartment. Gross morphologic differences may exist between these fat depots, but this has never been established at the cellular level. METHODS: Adipose tissue specimens from nasolabial fat and deep medial cheek fat pads were obtained from 63 cadaveric specimens (38 female and 25 male cadavers) aged 47 to 101 years (mean, 71 years). Thirty-seven cadavers had a normal body mass index (≤25 kg/m) and 26 cadavers had a high body mass index (>25 kg/m). Cross-sectional areas of individual adipocytes were calculated digitally and averaged from histologic sections of the adipose tissue samples. RESULTS: The average adipocyte size of nasolabial fat is significantly (p < 0.0001) larger than that of deep medial cheek fat. The average adipocyte size in both nasolabial and deep medial cheek fat is significantly (p < 0.0001) larger in subjects with high compared with low body mass index. Although the overall average adipocyte size is significantly (p < 0.0001) larger in female than in male subjects, this sexual dimorphism is lost in the nasolabial fat depots of overweight subjects and in the deep medial cheek depots of normal-weight subjects. CONCLUSIONS: The significantly smaller adipocyte size in deep medial cheek fat relative to nasolabial fat in elderly subjects supports the theory that deep and superficial facial fat pads are morphologically different. Future investigation of the metabolic and structural properties of these fat compartments will help us understand the different patterns of volumetric facial aging.