Antecedent thermal injury worsens split-thickness skin graft quality: A clinically relevant porcine model of full-thickness burn, excision and grafting.

Current standard of care for full-thickness burn is excision followed by autologous split-thickness skin graft placement. Skin grafts are also frequently used to cover surgical wounds not amenable to linear closure. While all grafts have potential to contract, clinical observation suggests that antecedent thermal injury worsens contraction and impairs functional and aesthetic outcomes. This study evaluates the impact of antecedent full-thickness burn on split-thickness skin graft scar outcomes and the potential mediating factors. Full-thickness contact burns (100°C, 30s) were created on the backs of anesthetized female Yorkshire Pigs. After seven days, burn eschar was tangentially excised and covered with 12/1000th inch (300µm) split-thickness skin graft. For comparison, unburned wounds were created by sharp excision to fat before graft application. From 7 to 120days post-grafting, planimetric measurements, digital imaging and biopsies for histology, immunohistochemistry and gene expression were obtained. At 120days post-grafting, the Observer Scar Assessment Scale, colorimetry, contour analysis and optical graft height assessments were performed. Twenty-nine porcine wounds were analyzed. All measured metrics of clinical skin quality were significantly worse (p<0.05) in burn injured wounds. Histological analysis supported objective clinical findings with marked scar-like collagen proliferation within the dermis, increased vascular density, and prolonged and increased cellular infiltration. Observed differences in contracture also correlated with earlier and more prominent myofibroblast differentiation as demonstrated by α-SMA staining. Antecedent thermal injury worsens split-thickness skin graft quality, likely by multiple mechanisms including burn-related inflammation, microscopically inadequate excision, and dysregulation of tissue remodeling. A valid, reliable, clinically relevant model of full-thickness burn, excision and skin replacement therapy has been demonstrated. Future research to enhance quality of skin replacement therapies should be directed toward modulation of inflammation and assessments for complete excision.

Autologous Graft Thickness Affects Scar Contraction and Quality in a Porcine Excisional Wound Model.

BACKGROUND: Texture, color, and durability are important characteristics to consider for skin replacement in conspicuous and/or mobile regions of the body such as the face, neck, and hands. Although autograft thickness is a known determinant of skin quality, few studies have correlated the subjective and objective characters of skin graft healing with their associated morphologic and cellular profiles. Defining these relationships may help guide development and evaluation of future skin replacement strategies. METHODS: Six-centimeter-diameter full-thickness wounds were created on the back of female Yorkshire pigs and covered by autografts of variable thicknesses. Skin quality was assessed on day 120 using an observer scar assessment score and objective determinations for scar contraction, erythema, pigmentation, and surface irregularities. Histological, histochemical, and immunohistochemical assessments were performed. RESULTS: Thick grafts demonstrated lower observer scar assessment score (better quality) and decreased erythema, pigmentation, and surface irregularities. Histologically, thin grafts resulted in scar-like collagen proliferation while thick grafts preserves the dermal architecture. Increased vascularity and prolonged and increased cellular infiltration were observed among thin grafts. In addition, thin grafts contained predominately dense collagen fibers, whereas thick grafts had loosely arranged collagen. α-Smooth muscle actin staining for myofibroblasts was observed earlier and persisted longer among thinner grafts. CONCLUSIONS: Graft thickness is an important determinant of skin quality. High-quality skin replacements are associated with preserved collagen architecture, decreased neovascularization, and decreased inflammatory cellular infiltration. This model, using autologous skin as a metric of quality, may give a more informative analysis of emerging skin replacement strategies.

Burn wound healing and treatment: review and advancements.

Burns are a prevalent and burdensome critical care problem. The priorities of specialized facilities focus on stabilizing the patient, preventing infection, and optimizing functional recovery. Research on burns has generated sustained interest over the past few decades, and several important advancements have resulted in more effective patient stabilization and decreased mortality, especially among young patients and those with burns of intermediate extent. However, for the intensivist, challenges often exist that complicate patient support and stabilization. Furthermore, burn wounds are complex and can present unique difficulties that require late intervention or life-long rehabilitation. In addition to improvements in patient stabilization and care, research in burn wound care has yielded advancements that will continue to improve functional recovery. This article reviews recent advancements in the care of burn patients with a focus on the pathophysiology and treatment of burn wounds.

The Streptococcus pneumoniae adhesin PsrP binds to Keratin 10 on lung cells.

Pneumococcal serine-rich repeat protein (PsrP) is a pathogenicity island-encoded adhesin that mediates attachment to lung cells. It is a member of the serine-rich repeat protein family and the largest bacterial protein known. PsrP production by S. pneumoniae was confirmed by immunoblotting and a truncated version of the protein was determined to be glycosylated. Using isogenic psrP mutants complemented with various PsrP constructs and competitive inhibition assays with recombinant proteins, we determined that PsrP requires an extended SRR2 domain for function and that adhesion is mediated through amino acids 273-341 of its basic region (BR) domain. Affinity chromatography, immunoprecipitation, enzyme-linked immunosorbent assay (ELISA), fluorescent-activated cell sorting (FACS) and immunofluorescent colocalization studies determined that PsrP binds to Keratin 10 (K10) on the surface of lung but not nasopharyngeal epithelial cells. Unglycosylated K10 bound to wild type but not psrP deficient pneumococci; suggesting that unlike other serine-rich repeat proteins, PsrP-mediated adhesion is independent of lectin activity. Finally, mice immunized with recombinant (r)PsrP(BR) had significantly less bacteria in their blood and improved survival versus controls following intranasal challenge. We conclude that the BR domain of PsrP binds to K10 in a lectin-independent manner, that K10 is expressed on lung cells and that vaccination with rPsrP(BR) is protective against pneumococcal disease.