Exuberant fibroproliferation is a common complication after injury for reasons that are not well understood1. One key component of wound repair that is often overlooked is mechanical force, which regulates cell-matrix interactions through intracellular focal adhesion components, including focal adhesion kinase (FAK)1,2. Here we report that FAK is activated after cutaneous injury and that this process is potentiated by mechanical loading. Fibroblast-specific FAK knockout mice have substantially less inflammation and fibrosis than control mice in a model of hypertrophic scar formation. We show that FAK acts through extracellular-related kinase (ERK) to mechanically trigger the secretion of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), a potent chemokine that is linked to human fibrotic disorders3–5. Similarly, MCP-1 knockout mice form minimal scars, indicating that inflammatory chemokine pathways are a major mechanism by which FAK mechanotransduction induces fibrosis. Small-molecule inhibition of FAK blocks these effects in human cells and reduces scar formation in vivo through attenuated MCP-1 signaling and inflammatory cell recruitment. These findings collectively indicate that physical force regulates fibrosis through inflammatory FAK–ERK–MCP-1 pathways and that molecular strategies targeting FAK can effectively uncouple mechanical force from pathologic scar formation.

Keloids tend to occur on highly mobile sites with high tension. This study was designed to determine whether body surface areas exposed to large strain during normal activities correlate with areas that show high rates of keloid generation after wounding. Eight adult Japanese volunteers were enrolled to study the skin stretching/contraction rates of nine different body sites. Skin stretching/contraction was measured by marking eight points on each region and measuring the change in location of the marked points after typical movements. The distribution of 1,500 keloids on 483 Japanese patients was mapped. The parietal region and anterior lower leg were associated with the least stretching/contraction, while the suprapubic region had the highest stretching/contraction rate. With regard to keloid distribution, there were 733 on the anterior chest region (48.9%) and 403 on the scapular regions (26.9%). No keloids were reported on the scalp or anterior lower leg. Because these sites are rarely subjected to skin stretching/contraction, it appears that mechanical force is an important trigger that drives keloid generation even in patients who are genetically predisposed to keloids. Thus, mechanotransduction studies are useful for developing clinical approaches that reduce the skin tension around wounds or scars for the prevention and treatment of not only keloids but also hypertrophic scars.

Human skin is a highly specialized mechanoresponsive interface separating our bodies from the external environment. It must constantly adapt to dynamic physical cues ranging from rapid expansion during embryonic and early postnatal development to ubiquitous external forces throughout life. Despite the suspected role of the physical environment in cutaneous processes, the fundamental molecular mechanisms responsible for how skin responds to force remain unclear. Intracellular pathways convert mechanical cues into biochemical responses (in a process known as mechanotransduction) via complex mechanoresponsive elements that often blur the distinction between physical and chemical signaling. For example, cellular focal adhesion components exhibit dual biochemical and scaffolding functions that are critically modulated by force. Moreover, the extracellular matrix itself is increasingly recognized to mechanically regulate the spatiotemporal distribution of soluble and matrix-bound ligands, underscoring the importance of bidirectional crosstalk between cells and their physical environment. It seems likely that a structural hierarchy exists to maintain both cells and matrix in mechanical homeostasis and that dysregulation of this architectural integrity may underlie or contribute to various skin disorders. An improved understanding of these interactions will facilitate the development of novel biophysical materials and mechanomodulatory approaches to augment wound repair and regeneration.

Crystalline structure and morphology of poly(L-lactide) (PLLA) formed under high-pressure CO 2 were studied by comparing the CO 2 -treated PLLA and the annealed one in terms of the crystallization behavior, crystalline forms, and crystalline superstructures. The crystallization temperature dependence of the diffraction peak position (2θ ≈ 16°) and crystallinity for the CO 2 -treated PLLA indicates that the crystal modification changes continuously from the disorder R (R′′) to R forms not through the R′ one with increasing temperature. By using light scattering technique, we clarified that the morphological transition from spherulites on a micrometer scale to rodlike crystalline superstructures on a nanometer scale occurs around 15 °C under 7-15 MPa CO 2 and around 30 °C under 3 MPa CO 2 . By introducing the parameters η and ∆ in the theoretical calculation for Vv light scattering from spherulites, it is indicated that there is a distinct difference in the arrangement of crystalline lamellae within spherulite between the CO 2 -treated PLLA and the annealed one.

There has been a long-standing need for guidelines on the diagnosis and treatment of keloids and hypertrophic scars that are based on an understanding of the pathomechanisms that underlie these skin fibrotic diseases. This is particularly true for clinicians who deal with Asian and African patients because these ethnicities are highly prone to these diseases. By contrast, Caucasians are less likely to develop keloids and hypertrophic scars, and if they do, the scars tend not to be severe. This ethnic disparity also means that countries vary in terms of their differential diagnostic algorithms. The lack of clear treatment guidelines also means that primary care physicians are currently applying a hotchpotch of treatments, with uneven outcomes. To overcome these issues, the Japan Scar Workshop (JSW) has created a tool that allows clinicians to objectively diagnose and distinguish between keloids, hypertrophic scars, and mature scars. This tool is called the JSW Scar Scale (JSS) and it involves scoring the risk factors of the individual patients and the affected areas. The tool is simple and easy to use. As a result, even physicians who are not accustomed to keloids and hypertrophic scars can easily diagnose them and judge their severity. The JSW has also established a committee that, in cooperation with outside experts in various fields, has prepared a Consensus Document on keloid and hypertrophic scar treatment guidelines. These guidelines are simple and will allow even inexperienced clinicians to choose the most appropriate treatment strategy. The Consensus Document is provided in this article. It describes (1) the diagnostic algorithm for pathological scars and how to differentiate them from clinically similar benign and malignant tumors, (2) the general treatment algorithms for keloids and hypertrophic scars at different medical facilities, (3) the rationale behind each treatment for keloids and hypertrophic scars, and (4) the body site-specific treatment protocols for these scars. We believe that this Consensus Document will be helpful for physicians from all over the world who treat keloids and hypertrophic scars.