The efficacy of NPWT in promoting wound healing has been largely accepted by clinicians, yet the number of high-level clinical studies demonstrating its effectiveness is small and much more can be learned about the mechanisms of action. In the future, hopefully we will have the data to assist clinicians in selecting optimal parameters for specific wounds including interface material, waveform of suction application, and the amount of suction to be applied. Further investigation into specific interface coatings and instillation therapy are also needed. We believe that advances in mechanobiology, the science of wound healing, the understanding of biofilms, and advances in cell therapy will lead to better care for our patients.

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.

No abstract

The role of pathological angiogenesis on liver fibrogenesis is still unknown. Here, we developed fibrotic microniches (FμNs) that recapitulate the interaction of liver sinusoid endothelial cells (LSECs) and hepatic stellate cells (HSCs). We investigated how the mechanical properties of their substrates affect the formation of capillary-like structures and how they relate to the progression of angiogenesis during liver fibrosis. Differences in cell response in the FμNs were synonymous of the early and late stages of liver fibrosis. The stiffness of the early-stage FμNs was significantly elevated due to condensation of collagen fibrils induced by angiogenesis, and led to activation of HSCs by LSECs. We utilized these FμNs to understand the response to anti-angiogenic drugs, and it was evident that these drugs were effective only for early-stage liver fibrosis in vitro and in an in vivo mouse model of liver fibrosis. Late-stage liver fibrosis was not reversed following treatment with anti-angiogenic drugs but rather with inhibitors of collagen condensation. Our work reveals stage-specific angiogenesis-induced liver fibrogenesis via a previously unrevealed mechanotransduction mechanism which may offer precise intervention strategies targeting stage-specific disease progression.

Despite the wide applications, systematic mechanobiological investigation of 3D porous scaffolds has yet to be performed due to the lack of methodologies for decoupling the complex interplay between structural and mechanical properties. Here, we discover the regulatory effect of cryoprotectants on ice crystal growth and use this property to realize separate control of the scaffold pore size and stiffness. Fibroblasts and macrophages are sensitive to both structural and mechanical properties of the gelatin scaffolds, particularly to pore sizes. Interestingly, macrophages within smaller and softer pores exhibit pro-inflammatory phenotype, whereas anti-inflammatory phenotype is induced by larger and stiffer pores. The structure-regulated cellular mechano-responsiveness is attributed to the physical confinement caused by pores or osmotic pressure. Finally, in vivo stimulation of endogenous fibroblasts and macrophages by implanted scaffolds produce mechano-responses similar to the corresponding cells in vitro, indicating that the physical properties of scaffolds can be leveraged to modulate tissue regeneration.

Mechanotransduction is the process by which physical forces are converted into biochemical signals that are then integrated into cellular responses. It plays a crucial role in bone repair and regeneration and thus has attracted a great deal of interest from researchers in various fields. This report reviews the current clinical evidence that shows the role mechanotransduction plays in bone processes such as physical adaptation, pathological fracture healing, and therapeutic distraction osteogenesis. We also outline the progress that has been made in understanding bone mechanotransduction from both the macro- and microperspectives. Specifically, we describe the theories that postulate how mechanical force exhibits effects on bone repair and regeneration (i.e., the tensegrity and mechanosome theories). We also summarize the recent advances in our understanding of the molecular signaling pathways of mechanotransduction, which include calcium ion channels, integrins, Wnt/β-catenin, prostaglandin, and nitric oxide. A better understanding of skeletal mechanotransduction will facilitate research into this promising field and could lead to the development of applications that improve bone structures and functions.

No abstract

Hypertrophic scars (HSs) and keloids are commonly seen as two different diseases by both clinicians and pathologists. However, as supported by histological evidence showing they share increased numbers of fibroblasts and accumulate collagen products, HS and keloid might be different forms of the same pathological entity, rather than separate conditions. To test this hypothesis, keloids from patients who underwent scar excisions (n = 20) in Nippon Medical School from 2005 to 2010 were examined histologically. The proportion and distribution of cellular and matrix collagen components were evaluated at the centre and periphery of each sample. In keloid samples, coexistence of hyalinised collagen, which is the most important pathognomonic characteristic of a keloid and dermal nodules that are considered to be characteristic of HS, was found. Moreover, hyalinised fibres appeared to initiate from the corner of the dermal nodules. Key features of inflammation such as microvessels, fibroblasts and inflammatory cells all decreased gradually from the periphery to the centre of keloids, indicative of reduced inflammation in the centre. Thus, we hypothesise that HS and keloid can be considered as successive stages of the same fibroproliferative skin disorder, with differing degrees of inflammation that might be affected by genetic predisposition.