Use of Adipose Stem Cells Against Hypertrophic Scarring or Keloid

Hypertrophic scars or keloid form as part of the wound healing reaction process, and its formation mechanism is complex and diverse, involving multi-stage synergistic action of multiple cells and factors. Adipose stem cells (ASCs) have become an emerging approach for the treatment of many diseases, including hypertrophic scarring or keloid, owing to their various advantages and potential. Herein, we analyzed the molecular mechanism of hypertrophic scar or keloid formation and explored the role and prospects of stem cell therapy, in the treatment of this condition.

Pulse dye laser therapy and superficial cryotherapy as a novel combination treatment for hypertrophic scars and keloids

Background: Hypertrophic scars are benign and fibrotic skin lesions caused by defects in the regulation of cellularity during the wound-healingprocess, in which there is higher collagen production and less degradation. Genetic predisposing factors and different skin injuries may play a role in developing these types of lesions. On the other hand, keloids are overgrowths of fibrous tissue outside the original boundaries of trauma, yet these may also occur spontaneously. There are numerous treatment options for both conditions, including silicone gel sheeting, pressure therapy, intralesional triamcinolone acetonide, radiation, laser therapy, cryosurgery, interferon, 5-fluorouracil, and surgical excision as well as a multitude of extracts and topical agents. Objective: The objective was to evaluate the effectiveness of pulse dye laser (PDL) therapy and superficial cryotherapy as a combination treatment for hypertrophic scars and keloids. Method: Four Arabic female patients were seen at the outpatient clinic of the Department of Dermatology at the King Fahd Hospital of the University in Khobar, Saudi Arabia. The patients had keloids and hypertrophic scars. Treatment with cryotherapy every week for three weeks followed by one session of pulsed dye laser was administered rotationally for three to six months until the lesions displayed remarkable physical improvement or complete resolution. Results: All patients experienced significant improvement, showing a reduction in the size, erythema, pliability, and pruritus. None of the hypertrophic scars or keloids deteriorated during the one year of treatment. No complications were noted during the treatment period. Conclusion: Sequential PDL therapy combined with superficial cryotherapy may be an option for treating hypertrophic scars and keloids.

CO2 laser resurfacing for burn and traumatic scars of the hand and upper extremity

Background Scar formation is a normal part of the proliferative phase in wound healing where collagen is remodelled to better approximate normal skin. When collagen is not effectively redistributed, excessive scarring may occur. Recently, CO2 laser has emerged as an adjunct in improving scar quality via remodelling and redistribution of dermal collagen fibres. Due to the paucity of literature related to its use in the hands and upper extremities, we created a study to examine its effects on hypertrophic scars focused on the hands and upper extremities. Methods Patients treated with CO2 laser for hypertrophic scars of the hand and upper extremity were included. The Vancouver Scar Scale (VSS) and Patient and Observer Scar Assessment Scale (POSAS) were used to assess the progression of scar quality. Unpaired t-tests were performed to determine statistical difference between pre- and post-treatment scores on each scale. Pearson correlation coefficients were used to understand the relationship between number of treatments and scar quality. Results Of the 90 patients enrolled, 54 patients completed serial scar assessment forms. All patient and observer-reported POSAS domains showed improvement ( P < 0.05) apart from Itching. All VSS domains showed improvement ( P < 0.05). There was moderate correlation between overall patient-reported opinion of scar quality and Discoloration, Stiffness and Thickness, and strong correlation between overall patient opinion and Irregularity (r = 0.715). All observer-reported domains were strongly correlated (r = 7.56–8.74) with overall observer opinion of scar quality. Conclusion The results of this study may further substantiate CO2 laser as a treatment modality for excessive scarring in a variety of surgical subspecialties. Lay Summary Complex trauma and burns that impact the skin sometimes result in abnormal healing of the skin called, “hypertrophic scarring”. In our study we assessed how using focused CO2 laser therapy impacts patients and health care provider assessment of wound progression. Our results were based upon patient reported and healthcare provider observations based upon two standardized forms the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS). What we found is that after CO2 Laser Therapy, our 64 patients with 77 treated scars received on average almost 3 treatments and these treatments helped them with physical function and improved aesthetic appearance of their scars. The health care providers also found that the treatments improved functional and aesthetic end points. Overall, our study helps substantiate the body of evidence that using CO2 laser therapy improves aesthetics and function of hypertrophic scars in the upper extremity.

Keloid-Specific Gene Expression Profiling for Accurate Diagnostic and Therapeutic Applications

Scars are a heterogeneous disease including normotrophic scars, hypertrophic scars, and keloids. Of these lesions, keloids are a distinct subtype from any other type of scar. Clinically, it causes pain, itching, or tenderness, causing life discomfort and characteristically irreversible. Despite various treatment modalities, restoring keloids to normal tissues is difficult, and frequent recurrences have been reported. Therefore, it is essential to identify keloid-specific genes for accurate diagnosis and treatment of keloids. In an effort to find out keloid-specific genes, several studies compared keloids with scar-free normal skin, which leading general scar-related genes to be chosen rather than keloid-specific genes. To select for highly accurate keloid-specific genes and pathways, we compared the transcriptome profile of keloids with those of normotrophic scars and hypertrophic scars, which acquired from formalin-fixed paraffin-embedded human skin samples using high-throughput RNA-sequencing techniques. Differential expression analyses and over-representation analyses revealed that genes related to nervous system process were upregulated in keloids, whereas genes related with immune responses were downregulated in keloids. Additionally, the extracellular matrix related processes were highlighted in both hypertrophic scars and keloids. Finally, we highlight potential keloid-specific biomarkers and expression changes that can be employed for future therapeutics of keloids.

Correlation between elastic modulus and clinical severity of pathological scars: a cross-sectional study

Though widely used to assess pathological scars, the modified Vancouver Scar Scale (mVSS) is neither convenient nor objective. Shear wave elastography (SWE) is used to evaluate the stiffness of pathological scars. We aimed to determine the correlation between mVSS score and elastic modulus (EM) measured by SWE for pathological scars. Clinical information including ultrasound (US) results of the enrolled patients with pathological scars was analyzed. The clinical severity of the pathological scars was evaluated by mVSS. Skin stiffness, as represented by EM, was calculated using SWE. The average EM of the whole scar (EMWHOLE), hardest part of the scar (EMHARDEST), and normal appearance of the skin around the scar (EMNORMAL) were also recorded. Enrolled in this study were 69 pathological scars, including 28 hypertrophic scars and 41 keloids. The univariable regression analyses showed that the EM of pathological scars was closely related to mVSS score, while the linear multivariable regression analyses showed no significantly correlation. Curve fitting and threshold effect analysis revealed that when EMWHOLE was less than 166.6 kPa or EMHARDEST was less than 133.07 kPa, EM was positively correlated with mVSS score. In stratified analysis, there was no significant linear correlation and threshold effect between EMWHOLE and mVSS score in hypertrophic scars or keloids. However, the fully adjusted smooth curves presented a linear association between mVSS score and EMHARDEST in keloids (the adjusted β [95% CI] was 0.010 [0.001, 0.018]), but a threshold and nonlinear association were found in hypertrophic scars. When EMHARDEST was less than 156.13 kPa, the mVSS score increased along with the hardest scar part stiffness; the adjusted β (95% CI) was 0.024 (0.009, 0.038). In conclusion, EM of pathological scars measured by SWE were correlated with mVSS within a threshold range, and showed different association patterns in hypertrophic scars and keloids.

Effects and mechanisms of medicinal plants on healing scars: A systematic review

Background: Scars can be a cosmetic disfigurement and can tremendously impact psychological, emotional, and social well-being. Some medicinal plants exert anti-scar properties via various mechanisms of action, many of which have not been clearly defined. Objective: This study will evaluate the effects of these medicinal plants with anti-scar properties and review the known underlying mechanisms related to the treatment and prevention of hypertrophic scars. Methods: The keywords used in the literature search included ((Wound healing OR Re-epithelialization OR Regeneration)) AND ((Medicinal plants OR Phyto* OR herb)) AND ((Cytokines OR Collagen OR Fibroblasts)). Publications indexed in the Institute for Scientific Information (ISI) and PubMed databases were included in the review. Articles with no accessible full texts, non-English language articles, review articles, studies with non-positive effects, and studies that were not related to the study’s aim were excluded from the study. The agreement for exclusion required all authors to concur. Finally, after reviewing all available literature, 61 articles were included in this systematic review. Results: Currently available evidence shows that medicinal plants and their derivatives seem to have properties that can prevent hypertrophic scars. This is achieved by accelerating the scar healing process, reducing inflammatory cytokines, suppressing proliferation, and inducing apoptosis in scar fibroblasts by regulating several signaling pathways. Additionally, they can reduce collagen deposition and have antimicrobial effects at the wound site. Conclusion: Topical use of medicinal plants as complementary medicine with varying mechanisms of action can reduce scar formation. They exert these properties mainly due to their anti-inflammatory, antioxidant, and antimicrobial properties. Therefore, these mechanisms reduce the healing time of the wound and thus prevent the formation of hypertrophic scars. Medicinal plants can be used safely and efficiently when applied topically to improve or prevent hypertrophic scars.