Skin regeneration is an important area of research in the field of tissue-engineering, especially for cases involving loss of massive areas of skin, where current treatments are not capable of inducing permanent satisfying replacements. Human adipose-derived stem cells (ASC) have been shown to differentiate in-vitro into both mesenchymal lineages and non-mesenchymal lineages, confirming their transdifferentiation ability. This versatile differentiation potential, coupled with their ease of harvest, places ASC at the advancing front of stem cell-based therapies. In this study, we hypothesized that ASC also have the capacity to transdifferentiate into keratinocyte-like cells and furthermore are able to engineer a stratified epidermis. ASC were successfully isolated from lipoaspirates and cell sorted (FACS). After sorting, ASC were either co-cultured with human keratinocytes or with keratinocyte conditioned media. After a 14-day incubation period, ASC developed a polygonal cobblestone shape characteristic of human keratinocytes. Western blot and q-PCR analysis showed the presence of specific keratinocyte markers including cytokeratin-5, involucrin, filaggrin and stratifin in these keratinocyte-like cells (KLC); these markers were absent in ASC. To further evaluate if KLC were capable of stratification akin to human keratinocytes, ASC were seeded on top of human decellularized dermis and cultured in the presence or absence of EGF and high Ca2+ concentrations. Histological analysis demonstrated a stratified structure similar to that observed in normal skin when cultured in the presence of EGF and high Ca2+. Furthermore, immunohistochemical analysis revealed the presence of keratinocyte markers such as involucrin, cytokeratin-5 and cytokeratin-10. In conclusion this study demonstrates for the first time that ASC have the capacity to transdifferentiate into KLC and engineer a stratified epidermis. This study suggests that adipose tissue is potentially a readily available and accessible source of keratinocytes, particularly for severe wounds encompassing large surface areas of the body and requiring prompt epithelialization.
Bacteriophages can be an effective topical therapy against S. aureus biofilm-infected wounds in the setting of a deficient (mutant) or disrupted (débridement) biofilm structure. Combination treatment aimed at disturbing the extracellular biofilm matrix, allowing for increased penetration of species-specific bacteriophages, represents a new and potentially effective approach to chronic wound care. These results establish principles for biofilm therapy that may be applied to several different clinical and surgical problems.
Diabetic patients exhibit dysregulated inflammatory and immune responses that predispose them to chronic wound infections and the threat of limb loss. The molecular underpinnings responsible for this have not been well elucidated, particularly in the setting of wound biofilms. This study evaluates host responses in biofilm-impaired wounds using the TallyHo mouse, a clinically relevant polygenic model of type 2 diabetes. No differences in cytokine or Toll-like receptor (TLR) expression were noted in unwounded skin or noninoculated wounds of diabetic and wild-type mice. However, diabetic biofilm-containing wounds had significantly less TLR 2, TLR 4, interleukin-1β, and tumor necrosis factor-α expression than wild-type wounds with biofilm (all p < 0.001). Both groups had similar bacterial burden and neutrophil infiltration after development of biofilms at 3 days postwounding, but diabetic wounds had significantly less neutrophil oxidative burst activity. This translated into a log-fold greater bacterial burden and significant delay of wound epithelization for biofilm-impaired diabetic wounds at 10 days postwounding. These results suggest that impaired recognition of bacterial infection via the TLR pathway leading to inadequate cytokine stimulation of antimicrobial host responses may represent a potential mechanism underlying diabetic susceptibility to wound infection and ulceration.
By expanding the analysis of BMI to include patients who do not meet the traditional definition of obesity (BMI ≥ 30 kg/m), we demonstrated that simply overweight patients (25 ≤ BMI < 30 kg/m) had an elevated complication rate. Moreover, through regression analysis, we established that BMI as a continuous variable predicts outcomes from expander-based breast reconstruction.
Background: Facial feminization surgery entails a series of surgical procedures that help the transwoman pass as their affirmed gender. Although virtual surgical planning, with intraoperative cutting guides, and custom plates have been shown to be helpful for craniomaxillofacial reconstruction, they have not yet been studied for facial feminization surgery. The authors used cadaveric analysis for morphologic typing and to demonstrate the utility of virtual surgical planning in facial feminization surgery procedures. Methods: Male cadaveric heads underwent morphologic typing analysis of the frontal brow, lateral brow, mandibular angle, and chin regions (n = 50). Subsequently, the cadavers were split into two groups: (1) virtual surgical planning intraoperative cutting guides and (2) no preoperative planning. Both groups underwent (1) anterior frontal sinus wall setback, (2) lateral supraorbital recontouring, (3) mandibular angle reduction, and (4) osseous genioplasty narrowing. Efficiency (measured as operative time), safety (determined by dural or nerve injury), and accuracy (scored with three-dimensional computed tomographic preoperative plan versus postoperative result) were compared between groups, with significance being p < 0.05. Results: For frontal brow and lateral lower face, morphologic type 3 (severe) predominated; for lateral brow and chin, type 2 (moderate) predominated. For frontal sinus wall setback, virtual surgical planning improved efficiency (19 minutes versus 44 minutes; p < 0.05), safety (100 percent versus 88 percent; p < 0.05; less intracranial entry), and accuracy (97 percent versus 79 percent; p < 0.05) compared with no preoperative planning. For mandibular angle reduction, virtual surgical planning improved safety (100 percent versus 88 percent; p < 0.05; less inferior alveolar nerve injury) and accuracy (95 percent versus 58 percent; p < 0.05). Conclusions: Preoperative planning for facial feminization surgery is helpful to determine morphologic typing. Virtual surgical planning with the use of cutting guides/custom plates improved efficiency, safety, and accuracy when performing four key craniofacial techniques for facial feminization.
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