Discussion: Mechanical Signals Induce Dedifferentiation of Mature Adipocytes and Increase the Retention Rate of Fat Grafts.

www.PRSJournal.com 1334 F grafting has become one of the most commonly performed operations in plastic and reconstructive surgery. However, the technique has been plagued by variable graft take and resorption rates that reduce the efficacy of each treatment. Basic science and clinical studies have demonstrated resorption rates of 25 to 50 percent, which can lead to the requirement for multiple fat grafting procedures and ultimate patient frustration. Significant ongoing research is currently being conducted to improve fat graft take and reduce resorption rates. Harvest site, harvest method, processing method, site of delivery, and delivery method have all been demonstrated to affect fat grafting results. Each step in the process introduces variability that can impact the overall fat grafting retention rate, and optimization of the ideal methodology for this technique has yet to be determined. In the current article, the authors should be commended for their exploration of pretreating the cells to be harvested before isolation for fat grafting.1 The concept of manipulating cells with mechanical forces before harvesting to induce a more robust population of cells for delivery is based on sound foundational principles. In developmental biology, cells and their local microenvironment, or niche, communicate through mechanical cues to regulate cell fate and cell behavior.2 In adult stem cells, the mechanical and physical interactions of cells with the extracellular matrix regulate proliferation, self-renewal, differentiation, and multipotency.2 In response to increased stiffness or load, mature cells have been shown to secrete matrix components or proteases that enhance or diminish adhesive interactions, stiffen or soften the extracellular matrix, and alter downstream signaling pathways.3 The interactions between the harvested cells and the environment may produce more robust cells that survive the fat grafting process. Although the sheer number of cells that may survive through pretreatment with various mechanical stressors can improve fat graft retention, additional signaling pathways are likely to be up-regulated through the mechanical induction and contribute to improved retention. New vascular networks are critical in the survival of the engrafted fat, as they provide nutrients to the cells. Studies have shown that neovascular network formation and growth are regulated by mechanical conditions, and changes in the surrounding matrix alter vessel formation and remodeling.4 Thus, mechanical stimulation of cells before harvest has the potential to generate an angiogenic response and promote the survival of fat grafts through the formation of new vascular networks. Although many new innovations have been described in the literature in the past decade, it remains to be determined which novel technique translates into improved fat retention in patients. Animal studies are essential as a first step to describe new techniques and to obtain histologic analysis that would otherwise be inappropriate in patients. Similarly, in vitro studies allow for further understanding of the mechanism by which these processes are occurring and possible amplification of these mechanisms for improved results. However, whereas these in vitro and in vivo studies provide important information, it is essential to determine which of these factors translate into clinical differences in patients. It will be essential to generate a large database with patients who have undergone fat grafting performed by different plastic surgeons with different techniques and evaluate the postoperative outcomes to determine