Extracorporeal shock wave therapy (ESWT) considerably improves the appearance and symptoms of post-burn hypertrophic scars (HTS). However, the mechanism underlying the observed beneficial effects is not well understood. The objective of this study was to elucidate the mechanism underlying changes in cellular and molecular biology that is induced by ESWT of fibroblasts derived from scar tissue (HTSFs). We cultured primary dermal fibroblasts derived from human HTS and exposed these cells to 1000 impulses of 0.03, 0.1, and 0.3 mJ/mm². At 24 h and 72 h after treatment, real-time PCR and western blotting were used to detect mRNA and protein expression, respectively, and cell viability and mobility were assessed. While HTSF viability was not affected, migration was decreased by ESWT. Transforming growth factor beta 1 (TGF-β1) expression was reduced and alpha smooth muscle actin (α-SMA), collagen-I, fibronectin, and twist-1 were reduced significantly after ESWT. Expression of E-cadherin was increased, while that of N-cadherin was reduced. Expression of inhibitor of DNA binding 1 and 2 was increased. In conclusion, suppressed epithelial-mesenchymal transition might be responsible for the anti-scarring effect of ESWT, and has potential as a therapeutic target in the management of post-burn scars.

Human skin incurs damage in various ways; a few of the recognizable factors are electric burns, chemical burns, scalding burns, surgery, and physical injuries, such as automobile accidents. If skin damage is extensive and severe enough [second degree and total body surface area (TBSA) involvement of >20%], the skin will lose the ability to regenerate itself. Burn wounds are treated in various ways. For full-thickness skin defects, the mainstay of treatment is an autologous split-thickness skin graft. However, there are some limitations due to scars, poor elasticity, and limitations in the joint movements due to contractures. Recently, artificial dermis has been widely used to minimize contractures. The use of dermal replacements for the treatment of burns brings new hope in maintaining the characteristics of the normal dermis. Herein, Insuregraf® was used for skin regeneration in patients who had burn injury from flames, electricity, heat, or steam. The mean take-rate values at 7 and 14 days after operation were 94.55 ± 3.02% and 97.40 ± 2.57%, respectively. Furthermore, areas covered by Insuregraf® showed higher mean values of trans-epidermal water loss (24.6 ± 3.9 g h⁻¹ m⁻²), gross elasticity (Ua/Uf = 0.76 ± 0.24), and biological elasticity (Ur/Uf = 0.55 ± 0.1). These values were much better than those of the control where Insuregraf® was not used (p = 0.030, p = 0.040, and p = 0.013, respectively). Furthermore, the biomechanical scar properties of Insuregraf® and Matriderm were very similar. Hence, we suggest that Insuregraf® can be used in the medical field.

Postburn hypertrophic scarring is a common complication in burn injuries to the hands, often associated with impaired hand function. We evaluated the effects of extracorporeal shock wave therapy (ESWT), compared to a sham stimulation therapy, on hypertrophic scars of the hand caused by burn injury and investigated its effects on hand function. This was a double-blinded, randomized, controlled trial of 48 patients with a burn to their dominant right hand. The parameters of ESWT were as follows: energy flux density, 0.05–0.30 mJ/mm²; frequency, 4 Hz; 1000 to 2000 impulses per treatment; four treatments, once a week for four weeks. The outcomes measured were as follows: a 10-point visual analogue scale pain score; Vancouver scar scale for scar vascularity, height, pliability and pigmentation; ultrasound measurement of scar thickness; Jebsen−Taylor hand function test; grip strength; Perdue pegboard test; and the Michigan hand outcomes questionnaire. The change in the score from baseline to post-treatment was compared between the two groups. ESWT improved the pain score (p = 0.001), scar thickness (p = 0.018), scar vascularity (p = 0.0015), and improved hand function (simulated card-turning, p = 0.02; picking up small objects, p = 0.004). The other measured outcomes were not different between the two groups. ESWT is effective in decreasing pain, suppressing hypertrophic scarring, and improving hand function.

Epidermal keratinocytes are highly activated, hyper-proliferated, and abnormally differentiated in the post-burn hypertrophic scar (HTS); however, the effects of scar fibroblasts (SFs) on keratinocytes through cell–cell interaction in HTS remain unknown. Here, we investigated the effects of HTSF-derived exosomes on the proliferation and differentiation of normal human keratinocytes (NHKs) compared with normal fibroblasts (NFs) and their possible mechanism to provide a reference for clinical intervention of HTS. Fibroblasts were isolated and cultured from HTS and normal skin. Both HTSF-exosomes and NF-exosomes were extracted via a column-based method from the cell culture supernatant. NHKs were treated for 24 or 48 h with 100 μg/mL of cell-derived exosomes. The expression of proliferation markers (Ki-67 and keratin 14), activation markers (keratins 6, 16, and 17), differentiation markers (keratins 1 and 10), apoptosis factors (Bax, Bcl2, caspase 14, and ASK1), proliferation/differentiation regulators (p21 and p27), and epithelial–mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, and vimentin) was investigated. Compared with NF-exosomes, HTSF-exosomes altered the molecular pattern of proliferation, activation, differentiation, and apoptosis, proliferation/differentiation regulators of NHKs, and EMT markers differently. In conclusion, our findings indicate that HTSF-derived exosomes may play a role in the epidermal pathological development of HTS.

Low-temperature plasma (LTP; 3 min/day), negative pressure wound therapy (NPWT; 4 h/day), and bone marrow mesenchymal stem cells (MSCs; 1 × 10⁶ cells/day) were used as mono- and combination therapy in an acute excisional skin wound-healing ICR mouse model. These therapies have been beneficial in treating wounds. We investigated the effectiveness of monotherapy with LTP, NPWT, and MSC and combination therapy with LTP + MSC, LTP + NPWT, NPWT + MSC, and LTP + NPWT + MSC on skin wounds in mice for seven consecutive days. Gene expression, protein expression, and epithelial thickness were analyzed using real time polymerase chain reaction (RT-qPCR), western blotting, and hematoxylin and eosin staining (H&E), respectively. Wound closure was also evaluated. Wound closure was significantly accelerated in monotherapy groups, whereas more accelerated in combination therapy groups. Tumor necrosis factor-α (TNF-α) expression was increased in the LTP monotherapy group but decreased in the NPWT, MSC, and combination therapy groups. Expressions of vascular endothelial growth factor (VEGF), α-smooth muscle actin (α-SMA), and type I collagen were increased in the combination therapy groups. Re-epithelialization was also considerably accelerated in combination therapy groups. Our findings suggest that combination therapy with LPT, NPWT, and MSC exert a synergistic effect on wound healing, representing a promising strategy for the treatment of acute wounds.

Burn injuries and their treatment are extremely painful. This study aimed to determine whether virtual reality (VR) could reduce pain during robot-assisted gait training (RAGT) in burn patients by analyzing the cerebral blood flow (CBF) in the prefrontal cortex over time using functional near-infrared spectroscopy (fNIRS). The patients included in this study complained of a pain score ≥5 on a visual analog scale (VAS) during RAGT, which was performed 10 times for 2 weeks. Each session consisted of 15 min of VR application, with a 2-min break, and 15 min without VR. The average values of oxyhemoglobin and deoxyhemoglobin concentrations in the prefrontal cortex on fNIRS were calculated at four stages: temporal delay time with only RAGT, RAGT without VR, temporal delay time with RAGT and VR, and RAGT with VR. The pain scores and CBF were evaluated in sessions 1, 5, and 10 of the RAGT. The mean VAS pain scores were significantly lower (p < 0.05) in the experimental condition than in the control condition. Oxyhemoglobin in the prefrontal lobe significantly increased when RAGT was performed with VR. In conclusion, VR may be a strong nonpharmacological pain reduction technique for burn patients during physical therapy.