Adipose-Derived Tissue in the Treatment of Dermal Fibrosis: Antifibrotic Effects of Adipose-Derived Stem Cells.

Treatment of hypertrophic scars and other fibrotic skin conditions with autologous fat injections shows promising clinical results; however, the underlying mechanisms of its antifibrotic action have not been comprehensively studied. Adipose-derived stem cells, or stromal cell-derived factors, inherent components of the transplanted fat tissue, seem to be responsible for its therapeutic effects on difficult scars. The mechanisms by which this therapeutic effect takes place are diverse and are mostly mediated by paracrine signaling, which switches on various antifibrotic molecular pathways, modulates the activity of the central profibrotic transforming growth factor ß/Smad pathway, and normalizes functioning of fibroblasts and keratinocytes in the recipient site. Direct cell-to-cell communications and differentiation of cell types may also play a positive role in scar treatment, even though they have not been extensively studied in this context. A more thorough understanding of the fat tissue antifibrotic mechanisms of action will turn this treatment from an anecdotal remedy to a more controlled, timely administered technology.

Lipotransfer: the potential from bench to bedside.

The development of autologous fat grafting to augment or reconstruct tissue defects has become an increasingly popular modality among plastic surgeons. Despite its popularity, a standardized fat grafting protocol has yet to be developed. Great variations exist with regard to almost all the technical features, yielding a reported fat graft survivability that ranges from 40% to 80%. Recent bench approaches have been proposed to improve the long-term viability of fat grafts: although promising results have been shown, empirical evidence has yet to prove the superiority of one particular method. Nevertheless, currently available literature still provides some evidence for optimal results in differing clinical scenarios, in the wait of validating and ultimate studies.The issues of enriched fat grafting techniques and variations in harvesting and delivery in the background of US regulatory constraints demand alterations and variations in techniques. These only complicate the process of validation of any single technique. However, recent studies have brought us closer to making informed decisions on technical choices in lipotransfer. These are elaborated on in this review.

Bioengineered skin substitute considerations in the diabetic foot ulcer.

Diabetes constitutes a global emergency with case numbers increasing exponentially every year. Diabetic foot ulcers are the leading cause of nontraumatic lower limb amputations. A complex background of pathophysiologic events has been identified with advances in molecular biology such that newer interventions are possible. Bioengineered skin substitutes currently play an important role in the diabetic foot ulcer, particularly in the "stalled" wounds that fail to show progress in their healing trajectory. However, newer designs and scaffold incorporation may herald a new generation of products with more focused targeting of these pathophysiologic events. The major background impairment is that of vasculogenesis brought about as a direct result of hyperglycemia, advanced glycation end product/methylglyoxal generation, and its direct effect on endothelial progenitor cell production and attraction to the wound site. At the same time, glycation end products affect immunity and inflammation, increasing the susceptibility to infection. Thus, reactive oxygen species scavengers, methylglyoxal scavengers, vascular endothelial growth factor stimulators as well as various lipids and neuropeptides are all potential agents that could be incorporated into such templates. The logical sequence of events and possible interventions is detailed. In this manner, intrinsic healing is encouraged in preference to our current attempts at adding unknown quantities of specialized cellular and growth factor components which seem to provide very temporary advantages.

Deconstructing the stalled wound.

 The stalled wound refers to a wound that has entered a nonhealing or intransigent phase. This can occur as a progression of an acute wound to one of chronicity dictated by events within the wound milieu or following alterations in host immunity. The occurrence may be related by a number of variable factors that collectively or individually can halt the process of orderly healing. A number of biologic events occurring at the wound bed interface, outside the wound (exudate), and related to systemic chronic disease profiles have been identified. This assists clinicians and researchers in developing a systematic approach to managing and reversing this undesired event. First, host factors related to any background chronic disease are checked and controlled. Second, the focus turns to local wound factors adopting accepted principles of wound care to control the wound environment, adding systemic therapies where necessary. If this fails to change the healing milieu, more sophisticated, specialized local wound interventions are introduced. This systematic approach to the stalled wound in individual steps, or collectively, would be expected to re-advance the wound to a normal healing pattern. .

Scar management practice and science: a comprehensive approach to controlling scar tissue and avoiding hypertrophic scarring.

A meta-analysis of the literature forms the basis of a treatment regimen focused on the principles of support, controlled inflammation, hydration, and hastened collagen remodeling. The presented clinical trial avoided hypertrophic scarring in more than 80% of cases, validating the theory of targeting many areas of scar control in 1 approach.

Chronic wound fluid--thinking outside the box.

Chronic wounds are associated with an altered wound milieu that results from an imbalance in extracellular matrix (ECM) homeostasis. This alteration is characterized by an increased destruction and degradation of components of the ECM with a concomitant lack of synthesis of these elements. Traditionally wound fluid has been considered a reflection of the internal wound milieu. It has been used to monitor and reflect on the chronic status of a wound or to measure the efficacy of wound treatment. However, on closer inspection of chronic wound fluid, certain components of the fluid, particularly matrix metalloproteinases (MMPs) and their subcomponents (MMP-9) have been found to exist at higher levels in wound fluid than in the corresponding wound. There is mounting evidence that much of the destructive effects observed in chronic wounds may be compounded by components of the wound exudate which are corrosive in nature resulting in a continuum of ECM breakdown. Isolation of these components has identified MMPs, in particular MMP-9 as dominant in this destructive process. Additionally an association has been made between high bacterial levels and elevated MMP9 in chronic wounds. Agents that have efficacy against MMP-9 and significant antibacterial potency thus provide a dual defense against chronic wounds. It is likely that these agents cause a change in the chronic wound fluid components that more closely resemble the balance of proteases and growth factors seen acute wounds, thus triggering a positive wound healing process. Nanocrystalline silver appears to fulfill these criteria. A strategy is suggested whereby wound fluid is directly targeted to diminish the corrosive wound fluid elements in an attempt to break the ongoing destructive inflammatory cycle. This presents a relatively new treatment paradigm attempting to influence wound healing by working from without to initiate changes within.