Alan D. Widgerow

New innovations in scar management.

Abstract. As current aesthetic surgical techniques become more standardized and results more predictable, a fine scar may be the demarcating line between acceptable and unacceptable aesthetic results. With this in mind, a scar management program has been adopted based on the modalities of wound support, hydration, and hastened maturity, all factors gleaned from scientific evidence published over the past 25 years. Tension on a scar in one axis will result in a stretched scar, probably initiated by neutrophils and their neutral proteases [18,26]. Tension on a scar from many directions or intermittently will result in a hypertrophic scar, possibly initiated by lymphocytes but definitely related to a prolongation of the inflammatory process, with increased fibroblast activity and overabundant extracellular matrix secretion [24,26]. The common initiating factor is the tension on the scar, and the critical element needed to counteract this tension is scar support. Clinical experience has shown us that the most reliable way to support a scar is by using microporous tape. Hydration is a second beneficial influence on scar control and is the basis of the use of silicone sheeting and gel [7,29,36]. Alpha Centella cream has two main components. The first is an extract from the plant Bulbine frutescens. This increases hydration under the tape by leaving a layer of fatty vesicles of glycoprotein on the skin surface. This also has antibacterial properties. The second component is the principal terpenoids extracted from the Centella asiatica plant. These include asiatic acid, madecassic acid, and asiaticoside. Centella asiatica has been documented to aid wound healing in a large number of scientific reports [5,12,21,22,33,34,40]. The most beneficial effect appears to be the stimulation of maturation of the scar by the production of type I collagen [4,19] and the resulting decrease in the inflammatory reaction and myofibroblast production. Thus these components have been incorporated into the formulation of a scar management program. This publication reviews much of the available literature relating to scar management and describes the formulation and use of a scar management program based on this information.

Regeneration of fat cells from myofibroblasts during wound healing

Hair follicles: Secret to prevent scars? Although some animals easily regenerate limbs and heal broken flesh, mammals are generally not so gifted. Wounding can leave scars, which are characterized by a lack of hair follicles and cutaneous fat. Plikus et al. now show that hair follicles in both mice and humans can convert myofibroblasts, the predominant dermal cell in a wound, into adipocytes (see the Perspective by Chan and Longaker). The hair follicles activated the bone morphogenetic protein (BMP) signaling pathway and adipocyte transcription factors in the myofibroblast. Thus, it may be possible to reduce scar formation after wounding by adding BMP. Science, this issue p. 748; see also p. 693 Hair follicles convert wound myofibroblasts to adipocytes through the bone morphogenetic protein signaling pathway, revealing a target to decrease scarring. Although regeneration through the reprogramming of one cell lineage to another occurs in fish and amphibians, it has not been observed in mammals. We discovered in the mouse that during wound healing, adipocytes regenerate from myofibroblasts, a cell type thought to be differentiated and nonadipogenic. Myofibroblast reprogramming required neogenic hair follicles, which triggered bone morphogenetic protein (BMP) signaling and then activation of adipocyte transcription factors expressed during development. Overexpression of the BMP antagonist Noggin in hair follicles or deletion of the BMP receptor in myofibroblasts prevented adipocyte formation. Adipocytes formed from human keloid fibroblasts either when treated with BMP or when placed with human hair follicles in vitro. Thus, we identify the myofibroblast as a plastic cell type that may be manipulated to treat scars in humans.

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.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.

Stem Cells in Plastic Surgery: A Review of Current Clinical and Translational Applications

Background Stem cells are a unique cell population characterized by self-renewal and cellular differentiation capabilities. These characteristics, among other traits, make them an attractive option for regenerative treatments of tissues defects and for aesthetic procedures in plastic surgery. As research regarding the isolation, culture and behavior of stem cells has progressed, stem cells, particularly adult stem cells, have shown promising results in both translational and clinical applications. Methods The purpose of this review is to evaluate the applications of stem cells in the plastic surgery literature, with particular focus on the advances and limitations of current stem cell therapies. Different key areas amenable to stem cell therapy are addressed in the literature review; these include regeneration of soft tissue, bone, cartilage, and peripheral nerves, as well as wound healing and skin aging. Results The reviewed studies demonstrate promising results, with favorable outcomes and minimal complications in the cited cases. In particular, adipose tissue derived stem cell (ADSC) transplants appear to provide effective treatment options for bony and soft tissue defects, and non-healing wounds. ADSCs have also been shown to be useful in aesthetic surgery. Conclusions Further studies involving both the basic and clinical science aspects of stem cell therapies are warranted. In particular, the mechanism of action of stem cells, their interactions with the surrounding microenvironment and their long-term fate require further elucidation. Larger randomized trials are also necessary to demonstrate the continued safety of transplanted stem cells as well as the efficacy of cellular therapies in comparison to the current standards of care.

Early postoperative mobilization of flexor tendon injuries using a modification of the Kleinert technique

The results of 99 flexor tendon repairs in all zones of injury in 36 patients are reported. Both superficialis and profundus tendons were repaired in all cases. Postoperatively patients were managed by an immediate active extension program using a modification of the Kleinert technique and physiotherapy. Results of the study are based on the Buck-Gramcko system of evaluation of flexor tendon repair. In the 70 digits that underwent operations, the results were excellent in 31% of the cases, good in 30%, fair in 20%, and poor in 19% of the cases. There were two tendon ruptures. This study corroborates evidence that early mobilization and hand therapy appear to play an important part in the postoperative management of flexor tendon injuries.

Cellular/extracellular matrix cross-talk in scar evolution and control

The principles of scar evolution and control are recognized and defined. Further clarity has been shed on these principles with the elucidation and elaboration of the sequence of events occurring at a molecular level. Cellular cross‐talk among structures in the cell cytosol, in the cellular nucleus, and outside the cell within in the extracellular matrix is continuous and controlling in nature. This interaction or “dynamic reciprocity” takes place via a series of signals, ionic messenger shifts, protein activation, and receptor transactions. The described principles are now able to be defined in terms of cellular/extracellular matrix interactions and the identification of the cross‐talk involved in scar evolution and maturation presents the possibility of influencing the “wording” of this cross‐talk to improve scar outcome. The principles of mechanostimulation and scar support, hydration occlusion, controlled inflammation, and collagen/extracellular remodeling are discussed with possible interventions in each category.

Stromal vascular fraction: A regenerative reality? Part 1: Current concepts and review of the literature

Stromal Vascular Fraction (SVF) is a heterogeneous collection of cells contained within adipose tissue that is traditionally isolated using enzymes such as collagenase. With the removal of adipose cells, connective tissue and blood from lipoaspirate, comes the SVF, a mix including mesenchymal stem cells, endothelial precursor cells, T regulatory cells, macrophages, smooth muscle cells, pericytes and preadipocytes. In part 1 of our 2-part series, we review the literature with regards to the intensifying interest that has shifted toward this mixture of cells, particularly due to its component synergy and translational potential. Trials assessing the regenerative potential of cultured Adipose Derived Stem Cells (ADSCs) and SVF demonstrate that SVF is comparably effective in treating conditions ranging from radiation injuries, burn wounds and diabetes, amongst others. Aside from their use in chronic conditions, SVF enrichment of fat grafts has proven a major advance in maintaining fat graft volume and viability. Many SVF studies are currently in preclinical phases or are moving to human trials. Overall, regenerative cell therapy based on SVF is at an early investigative stage but its potential for clinical application is enormous.

Stromal vascular fraction: A regenerative reality? Part 2: Mechanisms of regenerative action

Adipose tissue is a rich source of cells with emerging promise for tissue engineering and regenerative medicine. The stromal vascular fraction (SVF), in particular, is an eclectic composite of cells with progenitor activity that includes preadipocytes, mesenchymal stem cells, pericytes, endothelial cells, and macrophages. SVF has enormous potential for therapeutic application and is being investigated for multiple clinical indications including lipotransfer, diabetes-related complications, nerve regeneration, burn wounds and numerous others. In Part 2 of our review, we explore the basic science behind the regenerative success of the SVF and discuss significant mechanisms that are at play. The existing literature suggests that angiogenesis, immunomodulation, differentiation, and extracellular matrix secretion are the main avenues through which regeneration and healing is achieved by the stromal vascular fraction.

Implications for human adipose‐derived stem cells in plastic surgery

Adipose‐derived stem cells (ADSCs) are a subset of mesenchymal stem cells (MSCs) that possess many of the same regenerative properties as other MSCs. However, the ubiquitous presence of ADSCs and their ease of access in human tissue have led to a burgeoning field of research. The plastic surgeon is uniquely positioned to harness this technology because of the relative frequency in which they perform procedures such as liposuction and autologous fat grafting. This review examines the current landscape of ADSC isolation and identification, summarizes the current applications of ADSCs in the field of plastic surgery, discusses the risks associated with their use, current barriers to universal clinical translatability, and surveys the latest research which may help to overcome these obstacles.

Nanocrystalline silver, gelatinases and the clinical implications

Nanocrystalline silver (NCS) has proven to be an important wound dressing particularly in chronic infected wounds. However, debate still rages around its use in the case of partially epithelialized wounds, particularly when these are non-infected. Much of the debate has revolved around seemingly contradictory research publications that blurred the use of NCS in these clinical situations, primarily based on reported cytotoxic effects of NCS on cell lines in vitro. MMPs, in particular MMP-9 (gelatinase) has been demonstrated to be pivotal in the progression from keratinocyte cleavage, to migration and re-epithelialisation. High levels promote increases in TNF-α; IL-8 and TGFβ, all associated with exaggerated ongoing inflammation and chronicity. Low levels impede the process of keratinocyte migration. Thus, as in so many clinical situations, a balance of MMP level is extremely important. NCS has been demonstrated to decrease these undesirable high levels of MMP-9 making it an ideal dressing for chronic infected wounds, acute inflamed wounds and burn wounds of all types which are associated with protracted raised MMP-9 levels. The converse applies too-NCS used in a situation of minimal inflammation may undesirably decrease the low levels of MMP-9 and adversely affect epithelialisation. NCS would be contra-indicated in conjunction with cell lines in vitro, cell cultured lines in vivo and integrated artificial matrices with added cell lines. Therapeutic decisions for different clinical situations may thus be made more predictably.