Anti-CTGF Oligonucleotide Reduces Severity of Postsurgical Hypertrophic Scars in a Randomized, Double-Blind, Within-Subject, Placebo-Controlled Study.

BACKGROUND: Connective tissue growth factor (CTGF) levels are up-regulated in wounded skin and are thought to play a major role in scar formation. An antisense oligonucleotide targeting CTGF was evaluated in adult patients undergoing hypertrophic scar revision surgery, to determine effects on reducing the severity of subsequent scars. METHODS: In a randomized, double-blind, within-subject, placebo-controlled study, 23 female subjects (aged 28 to 55 years) with bilateral, symmetric, hypertrophic surgical scars of the breast underwent scar revision surgery. The resulting breast incisions were randomized to receive EXC 001 (5 mg/cm) or placebo injected intradermally at postsurgery weeks 2, 5, 8, and 11. Scar severity assessments were performed at weeks 12 and 24 by an expert panel using blinded photographs, and by physicians and subjects using a scar scoring scale, the Patient and Observer Scar Assessment Scale. An assumption of the design is that within-subject variance would be small and that whatever within-subject variance there was would be controlled through the randomization process. RESULTS: EXC 001 significantly reduced scar severity at both 12 and 24 weeks after scar revision surgery in all three measures (expert panel and physician Patient and Observer Scar Assessment Scale, p < 0.001; Patient and Observer Scar Assessment Scale, p < 0.003). CONCLUSIONS: This study provided positive preliminary data that intradermal injection of EXC 001 produced a significant reduction in severity of postsurgical skin scars, as measured by physicians, subjects, and an expert panel. This study provided evidence that suppression of CTGF could be a viable strategy for hypertrophic scar reduction therapy and that further study of the antisense oligonucleotide EXC 001 was indicated. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Point-of-Care Adipose-Derived Stromal Vascular Fraction Cell Isolation and Expanded Polytetrafluoroethylene Graft Sodding.

Adipose-derived stromal vascular fraction (SVF) cell populations are being evaluated for numerous clinical applications. The current study evaluated a point-of-care technology, the Tissue Genesis "TGI 1000" Cell Isolation System™, to perform an automated isolation of adipose-derived SVF cells to be used in the fabrication of a tissue-engineered vascular graft in the operating room. A total of seven patients were enrolled in this study and received femoral to tibial expanded polytetrafluoroethylene bypass grafts to treat peripheral arterial disease. Lipoaspiration of fat was performed on five patients, and the fat sample was processed immediately in the automated system in the operating room. The mean processing time, from the point of fat delivery into the instrument to removal of the SVF-containing syringe, was 70 min. The SVF cell population was evaluated for cell yield, cell viability, endotoxin levels, and microbial contamination. Samples of the SVF preparation were further subjected to microbiologic evaluation both microscopically before implantation of the graft and through a microbiologic screening using aerobic and anaerobic culture conditions. Mean cell yield was 1E5 cells per cc of fat, and endotoxin levels were below the FDA recognized standards. All SVF preparations were released for graft preparation, and the intimal surface of 90-cm-long grafts was pressure sodded with cells at a concentration of 2E5 cells/cm2. The sodded grafts (n = 5) and control grafts (n = 2) were immediately implanted and graft patency assessed for 1 year. One year patency was 60% for sodded grafts and 50% for control grafts. Automated preparation of autologous adipose-derived SVF cells for immediate use to create cellular linings on vascular grafts is feasible and safe.