The effects of systemic diseases, genetic disorders and lifestyle on keloids.

Keloid are a fibroproliferative disorder caused by abnormal healing of skin, specifically reticular dermis, when subjected to pathological or inflammatory scars demonstrating redness, elevation above the skin surface, extension beyond the original wound margins and resulting in an unappealing cosmetic appearance. The severity of keloids and risk of developing keloids scars are subjected to elevation by other contributing factors such as systemic diseases, general health conditions, genetic disorders, lifestyle and natural environment. In particular, recently, daily physical work interpreted into mechanical force as well as the interplay between mechanical factors such as stress, strain and stiffness have been reported to strongly modulate the cellular behaviour of keloid formation, affect their location and shape in keloids. Herein, we review the extensive literature on the effects of these factors on keloids and the contributing predisposing mechanisms. Early understanding of these participating factors and their effects in developing keloids may raise the patient awareness in preventing keloids incidence and controlling its severity. Moreover, further studies into their association with keloids as well as considering strategies to control such factors may help clinicians to prevent keloids and widen the therapeutic options.

Exclusive expression of KANK4 promotes myofibroblast mobility in keloid tissues.

Keloids are characterized by abnormal wound healing with excessive accumulation of extracellular matrix. Myofibroblasts are the primary contributor to extracellular matrix secretion, playing an essential role in the wound healing process. However, the differences between myofibroblasts involved in keloid formation and normal wound healing remain unclear. To identify the specific characteristics of keloid myofibroblasts, we initially assessed the expression levels of well-established myofibroblast markers, α-smooth muscle actin (α-SMA) and transgelin (TAGLN), in scar and keloid tissues (n = 63 and 51, respectively). Although myofibroblasts were present in significant quantities in keloids and immature scars, they were absent in mature scars. Next, we conducted RNA sequencing using myofibroblast-rich areas from keloids and immature scars to investigate the difference in RNA expression profiles among myofibroblasts. Among significantly upregulated 112 genes, KN motif and ankyrin repeat domains 4 (KANK4) was identified as a specifically upregulated gene in keloids. Immunohistochemical analysis showed that KANK4 protein was expressed in myofibroblasts in keloid tissues; however, it was not expressed in any myofibroblasts in immature scar tissues. Overexpression of KANK4 enhanced cell mobility in keloid myofibroblasts. Our results suggest that the KANK4-mediated increase in myofibroblast mobility contributes to keloid pathogenesis.

Hyperdiluted Botulinum Toxin and Intense Pulsed Light Treatment: A Case Series to Illustrate a Novel Protocol for Hypertrophic Scar Reduction.

Hypertrophic scars can have significant and far-reaching effects on patients that range from itching to creating difficulty with mobility, all of which can negatively impact the individual's quality of life. A recent study showed that many patients with recent scars report pain, burning, pruritus, erythema, in combination with psychological difficulties that impact bodily movement, choice of clothing, and participation in leisure activities. Botulinum toxin Type A (BoNTA) and intense pulsed light (IPL) have shown promise in treating such scars. We propose a novel treatment protocol involving a 4-week intervention with hyperdiluted BoNTA injections and supplemental treatment with IPL for erythema, and a 6-month scar scale assessment and photographic documentation that occurs before and 6 months after treatment. We report four cases where using hyperdiluted BoNTA, either alone or in conjunction with IPL, substantially reduced scar size, improved overall scar appearance, and diminished erythema in areas on the face and the breasts. Although this report suggests that a schedule of alternating treatments with BoNTA and IPL may be beneficial in reducing scar size and enhancing appearance, further research is necessary to better understand the most effective dosages, the relationship between BoNTA and IPL, and the optimal management of scarring.

Application and effect of tension-reducing suture in surgical treatment of hypertrophic scar.

PURPOSE: To investigate the application and effectiveness of tension-reducing suture in the repair of hypertrophic scars. METHODS: A retrospective analysis of clinical data was conducted on 82 patients with hypertrophic scars treated at the Department of Burns and Plastic Surgery of Nanjing Drum Tower Hospital from September 2021 to December 2022. Patients were operated with combination of heart-shaped tension-reducing suturing technique and looped, broad, and deep buried (LBD) suturing technique or conventional suture method. Outcomes of surgical treatment were assessed before and 6 months after surgery using the Patient and Observer Scar Assessment Scale (POSAS) and the Vancouver Scar Scale (VSS). RESULTS: Improvements were achieved on scar quality compared to that preoperatively, with a reduction in scar width (1.7 ± 0.6 cm vs. 0.7 ± 0.2 cm, P < 0.001). Assessment using the POSAS and VSS scales showed significant improvements in each single parameter and total score compared to preoperative values (P < 0.05). The Combination method group achieved better score in total score of VSS scale, in color, stiffness, thickness and overall opinion of PSAS scale, and in vascularity, thickness, pliability and overall opinion of OSAS scale. CONCLUSION: The amalgamation of the heart-shaped tension-reducing suturing technique and the LBD suturing technique has shown promising outcomes, garnering notably high levels of patient satisfaction in the context of hypertrophic scar repair. Patients have exhibited favorable postoperative recoveries, underscoring the clinical merit and the prospective broader applicability of this approach in the realm of hypertrophic scar management.

Effective keloid management using a combinatorial continuous-wave and repeat fractionated ablative CO2 laser regimen.

BACKGROUND: Keloids are benign proliferative scars that form as a result of dysregulated growth and collagen deposition in response to cutaneous injury. Laser therapies have emerged as promising options for the treatment of keloids, with performance varying by laser type and lesion characteristics. PURPOSE: To assess the combined continuous wave and repetitive fractionated CO2 laser treatment of keloids. METHODS: A retrospective chart review of 22 cases of keloid scars treated with combined CO2 laser modes. A single session of continuous wave followed by five sessions of fractional delivery. Efficacy was assessed using the Patient and Observer Scar Assessment Scale (POSAS) and the Vancouver Scar Scale. The Numeric Rating Scale was used to assess patient satisfaction and pain. RESULTS: Most patients were female (77.3%) with skin type IV (72.7%), age was 24.3 ± 9.3 years, most keloids were located on the earlobe (56.5%) or arm or hand (17.4%), size ranged from 5 to 10 cm, and time since injury ranged from 3 months to 35 years. No serious adverse events were reported. At 6 months, significant improvements from baseline occurred in all characteristics, scar color (4.8 ± 2.8 to 1.9 ± 1.1), rigidity (5.0 ± 2.8 vs. 5.4 ± 2.8), thickness (5.4 ± 2.8 vs. 2.0 ± 1.1), and irregularity (5.9 ± 2.4 vs. 1.9 ± 0.9). The Vancouver scores followed a similar trend. Patient-rated overall improvement from 37 ± 17.6 at baseline to 16.1 ± 8.5 at 6 months, and improvement in associated pain and pruritus. CONCLUSION: Combination of two ablative laser delivery modes within a single laser platform provided for effective and safe keloid management and left patients highly satisfied.

Effects of botulinum toxin type A in the prevention and treatment of facial hypertrophic scars: A meta-analysis.

A meta-analysis was conducted to comprehensively evaluate the prophylactic and therapeutic efficacy of botulinum toxin type A (BTX-A) in the treatment of facial hypertrophic scars. Computerised searches were performed in databases, from their inception to November 2023, including Embase, Google Scholar, Cochrane Library, Wanfang, PubMed and China National Knowledge Infrastructure databases, focusing on randomised controlled trials (RCTs) that investigated the use of BTX-A for treating facial hypertrophic scars. Two researchers independently screened the literature, extracted data and conducted quality assessments. Stata 17.0 software was employed for data analysis. Seventeen RCTs were ultimately included, involving 1605 patients who underwent facial cosmetic surgery. The analysis revealed that compared with conventional treatments, BTX-A significantly reduced visual analogue scale (VAS) scores (standardized mean difference [SMD]: -3.50, 95% confidence interval [CI]: -5.16 to -1.84, p < 0.001) and Vancouver scar scale (VSS) scores (SMD: -2.86, 95% CI: -4.03 to -1.68, p < 0.001), and narrowed scar width (SMD: -1.80, 95% CI: -2.48 to -1.13, p < 0.001), while also enhancing the overall effectiveness of the treatment. This study indicates that BTX-A is an effective modality in the prophylaxis and treatment of facial hypertrophic scars, significantly alleviating scar-related pain and preventing scar widening, and is thus worthy of broader clinical application.

Photo-crosslinkable polyester microneedles as sustained drug release systems toward hypertrophic scar treatment.

Burn injuries can result in a significant inflammatory response, often leading to hypertrophic scarring (HTS). Local drug therapies e.g. corticoid injections are advised to treat HTS, although they are invasive, operator-dependent, extremely painful and do not permit extended drug release. Polymer-based microneedle (MN) arrays can offer a viable alternative to standard care, while allowing for direct, painless dermal drug delivery with tailorable drug release profile. In the current study, we synthesized photo-crosslinkable, acrylate-endcapped urethane-based poly(ε-caprolactone) (AUP-PCL) toward the fabrication of MNs. Physico-chemical characterization (1H-NMR, evaluation of swelling, gel fraction) of the developed polymer was performed and confirmed successful acrylation of PCL-diol. Subsequently, AUP-PCL, and commercially available PCL-based microneedle arrays were fabricated for comparative evaluation of the constructs. Hydrocortisone was chosen as model drug. To enhance the drug release efficiency of the MNs, Brij®35, a nonionic surfactant was exploited. The thermal properties of the MNs were evaluated via differential scanning calorimetry. Compression testing of the arrays confirmed that the MNs stay intact upon applying a load of 7 N, which correlates to the standard dermal insertion force of MNs. The drug release profile of the arrays was evaluated, suggesting that the developed PCL arrays can offer efficient drug delivery for up to two days, while the AUP-PCL arrays can provide a release up to three weeks. Finally, the insertion of MN arrays into skin samples was performed, followed by histological analysis demonstrating the AUP-PCL MNs outperforming the PCL arrays upon providing pyramidical-shaped perforations through the epidermal layer of the skin.

AUP-PCL MN arrays provide long-term transdermal drug delivery of hydrocortisoneAUP-PCL-based MN arrays provide superior drug release profiles compared to PCL MNsEffective skin penetration AUP-PCL-based MNs on skin was achieved.

Androgenic steroids induce pathologic scarring in a preclinical porcine model via dysfunctional extracellular matrix deposition.

Hypertrophic scarring is a major source of morbidity. Sex hormones are not classically considered modulators of scarring. However, based on increased frequency of hypertrophic scarring in patients on testosterone, we hypothesized that androgenic steroids induce abnormal scarring and developed a preclinical porcine model to explore these effects. Mini-swine underwent castration, received no testosterone (noT) or biweekly testosterone therapy (+T), and underwent excisional wounding. To create a delayed wound healing model, a subset of wounds were re-excised at 2 weeks. Scars from postoperative day 42 (POD42) and delayed wounds (POD28) were harvested 6 weeks after initial wounding for analysis via histology, bulk RNA-seq, and mechanical testing. Histologic analysis of scars from +T animals showed increased mean fibrosis area (16 mm2noT, 28 mm2+T; p = .007) and thickness (0.246 mm2noT, 0.406 mm2+T; p < .001) compared to noT. XX+T and XY+T scars had greater tensile burst strength (p = .024 and p = .013, respectively) compared to noT swine. Color deconvolution analysis revealed greater deposition of type I and type III collagen as well as increased collagen type I:III ratio in +T scars. Dermatopathologist histology scoring showed that +T exposure was associated with worse overall scarring (p < .05). Gene ontology analysis found that testosterone exposure was associated with upregulation of cellular metabolism and immune response gene sets, while testosterone upregulated pathways related to keratinization and laminin formation on pathway analysis. In conclusion, we developed a preclinical porcine model to study the effects of the sex hormone testosterone on scarring. Testosterone induces increased scar tissue deposition and appears to increase physical strength of scars via supraphysiologic deposition of collagen and other ECM factors. The increased burst strength seen in both XX and XY animals suggests that hormone administration has a strong influence on scar mechanical properties independent of chromosomal sex. Anti-androgen topical therapies may be a promising future area of research.

Endogenous stimuli-responsive separating microneedles to inhibit hypertrophic scar through remodeling the pathological microenvironment.

Hypertrophic scar (HS) considerably affects the appearance and causes tissue dysfunction in patients. The low bioavailability of 5-fluorouracil poses a challenge for HS treatment. Here we show a separating microneedle (MN) consisting of photo-crosslinked GelMA and 5-FuA-Pep-MA prodrug in response to high reactive oxygen species (ROS) levels and overexpression of matrix metalloproteinases (MMPs) in the HS pathological microenvironment. In vivo experiments in female mice demonstrate that the retention of MN tips in the tissue provides a slowly sustained drug release manner. Importantly, drug-loaded MNs could remodel the pathological microenvironment of female rabbit ear HS tissues by ROS scavenging and MMPs consumption. Bulk and single cell RNA sequencing analyses confirm that drug-loaded MNs could reverse skin fibrosis through down-regulation of BCL-2-associated death promoter (BAD), insulin-like growth factor 1 receptor (IGF1R) pathways, simultaneously regulate inflammatory response and keratinocyte differentiation via up-regulation of toll-like receptors (TOLL), interleukin-1 receptor (IL1R) and keratinocyte pathways, and promote the interactions between fibroblasts and keratinocytes via ligand-receptor pair of proteoglycans 2 (HSPG2)-dystroglycan 1(DAG1). This study reveals the potential therapeutic mechanism of drug-loaded MNs in HS treatment and presents a broad prospect for clinical application.

[Influences and mechanism of extracellular vesicles from dermal papilla cells of mice on human hypertrophic scar fibroblasts].

Objective: To investigate the influences and mechanism of extracellular vesicles from dermal papilla cells (DPC-EVs) of mice on human hypertrophic scar fibroblasts (HSFs). Methods: The study was an experimental research. The primary dermal papilla cells (DPCs) of whiskers were extracted from 10 6-week-old male C57BL/6J mice and identified successfully. The DPC-EVs were extracted from the 3rd to 5th passage DPCs by ultracentrifugation, and the morphology was observed through transmission electron microscope and the particle diameter was detected by nanoparticle tracking analyzer (n=3) at 24 h after culture. The 3rd passage of HSFs were divided into DPC-EV group and phosphate buffer solution (PBS) group, which were cultured with DPC-EVs and PBS, respectively. The cell scratch test was performed and cell migration rate at 24 h after scratching was calculated (n=5). The cell proliferation levels at 0 (after 12 h of starvation treatment and before adding DPC-EVs or PBS), 24, 48, 72, and 96 h after culture were detected by using cell counting kit 8 (n=4). The protein expressions of α-smooth muscle actin (α-SMA) and collagen typeⅠ (ColⅠ) in cells at 24 h after culture were detected by immunofluorescence method and Western blotting, and the protein expression of Krüppel-like factor 4 (KLF4) in cells at 24 h after culture was detected by Western blotting. After the 3rd passage of HSFs were cultured with DPC-EVs for 24 h, the cells were divided into blank control group, KLF4 knockdown group, and KLF4 overexpression group according to the random number table. The cells in blank control group were only routinely cultured for 48 h. The cells in KLF4 knockdown group and KLF4 overexpression group were incubated with KLF4 knockdown virus for 24 h, then the cells in KLF4 knockdown group were routinely cultured for 24 h while the cells in KLF4 overexpression group were incubated with KLF4 overexpression virus for 24 h. The protein expressions of KLF4, α-SMA, and ColⅠ in cells were detected by Western blotting at 48 h after culture. Results: At 24 h after culture, the extracted DPC-EVs showed vesicular structure with an average particle diameter of 108.8 nm. At 24 h after scratching, the migration rate of HSFs in PBS group was (54±10)%, which was significantly higher than (29±8)% in DPC-EV group (t=4.37, P<0.05). At 48, 72, and 96 h after culture, the proliferation levels of HSFs in DPC-EV group were significantly lower than those in PBS group (with t values of 4.06, 5.76, and 6.41, respectively, P<0.05). At 24 h after culture, the protein expressions of α-SMA and ColⅠ of HSFs in DPC-EV group were significantly lower than those in PBS group, while the protein expression of KLF4 was significantly higher than that in PBS group. At 48 h after culture, compared with those in blank control group, the protein expression of KLF4 of HSFs in KLF4 knockdown group was down-regulated, while the protein expressions of α-SMA and ColⅠ were both up-regulated; compared with those in KLF4 knockdown group, the protein expression of KLF4 of HSFs in KLF4 overexpression group was up-regulated, while the protein expressions of ColⅠ and α-SMA were down-regulated. Conclusions: The DPC-EVs of mice can inhibit the proliferation and migration of human HSFs and significantly inhibit the expressions of fibrosis markers α-SMA and ColⅠ in human HSFs by activating KLF4.

The regulatory role of the apelin/APJ axis in scarring: Identification of upstream and downstream mechanisms.

Scarring, a prevalent issue in clinical settings, is characterized by the excessive generation of extracellular matrix within the skin tissue. Among the numerous regulatory factors implicated in fibrosis across various organs, the apelin/APJ axis has emerged as a potential regulator of fibrosis. Given the shared attribute of heightened extracellular matrix production between organ fibrosis and scarring, we hypothesize that the apelin/APJ axis also plays a regulatory role in scar development. In this study, we examined the expression of apelin and APJ in scar tissue, normal skin, and fibroblasts derived from these tissues. We investigated the impact of the hypoxic microenvironment in scars on apelin/APJ expression to identify the transcription factors influencing apelin/APJ expression. Through overexpressing or knocking down apelin/APJ expression, we observed their effects on fibroblast secretion of extracellular matrix proteins. We further validated these effects in animal experiments while exploring the underlying mechanisms. Our findings demonstrated that the apelin/APJ axis is expressed in fibroblasts from keloid, hypertrophic scar, and normal skin. The regulation of apelin/APJ expression by the hypoxic environment in scars plays a significant role in hypertrophic scar and keloid development. This regulation promotes extracellular matrix secretion through upregulation of TGF-ß1 expression via the PI3K/Akt/CREB1 pathway.

Erbium: YAG laser treatment efficacy and association with histologic features for giant congenital melanocytic nevi management.

BACKGROUND: Limited research exists on laser treatment of giant congenital melanocytic nevus (GCMN). OBJECTIVE: We sought to elucidate the efficacy of the Erbium: YAG laser on GCMN and the histologic factors associated with a positive clinical response. METHODS AND MATERIALS: Between 2019 and 2022, we enrolled 30 medium-to-giant CMN patients who underwent Er: YAG laser treatment. All patients received biopsies before and after laser treatments. Clinical efficacy outcomes were evaluated by the investigator's global assessment (IGA), 5-point scale of depigmentation, and Vancouver Scar Scale (VSS) scores at least 6 months after treatment. RESULTS: Of the 30 cases, 18 (60.0%) showed improvement (IGA score ≥3). Eight (26.7%) patients showed repigmentation. Eight (26.7%) patients developed hypertrophic scars. The average IGA, depigmentation, and VSS scores were 2.93, 3.57, and 3.20. The IGA score was higher (3.24 ± 1.18 vs. 2.22 ± 0.97, p = 0.031) and a lower repigmentation rate (14.3% vs. 55.6%, p = 0.032) was observed in the cases with Grenz zone. The IGA score was higher (3.33 ± 1.24 vs. 2.13 ± 0.89, p = 0.023) and the repigmentation rate was lower (11.1% vs. 50.0%, p = 0.034) also in the cases with the melanocytes nests with aggregation of melanin. Lesions with superficial ablation resulted in less hypertrophic scar formation than those with deep ablation (5.9% vs. 53.8%, p < 0.05). CONCLUSION: The Er: YAG laser demonstrated effective clinical results for GCMNs. The grenz zone and the melanocytes nests with aggregation of melanin are promising predictors of laser efficacy.

Efficacy and safety of 1064-nm fractional picosecond laser for the treatment of postmastectomy scars in transgender men: A randomized controlled trial.

OBJECTIVES: Subcutaneous mastectomy is a crucial component of gender affirmation therapy for transgender men (TM), but the scars that result from this procedure can frequently impair their quality of life. This study aimed to assess the efficacy and safety of 1064-nm fractional picosecond laser (FxPico) treatment for hypertrophic and atrophic postmastectomy scars in TM. METHODS: Twenty-two patients with a total of 35 pairs of bilateral symmetric mastectomy scars were enrolled. One of each pair of symmetric scars was randomly assigned to receive four FxPico treatments at 4-week intervals. All scars were evaluated using the modified Vancouver Scar Scale (mVSS) and three-dimensional imaging for scar roughness, melanin index, and hemoglobin index before each treatment session and at 1, 3, and 6 months following the last treatment. Additionally, participant-rated scar satisfaction (PSS) and scar improvement (Global Assessment Score, GAS), as well as adverse events were recorded. RESULTS: During the 6-month follow-up period after the end of laser treatment sessions, the treated scars showed significant reductions in the mVSS compared to the untreated controls (p < 0.001), whereas the melanin index and hemoglobin index were not significantly different. Subgroup analysis of hypertrophic scars demonstrated statistically significant reductions in mVSS at 1 (p = 0.003) and 3 months (p = 0.041) after the end of laser treatments. PSS was significantly higher on the laser-treated scars than the controls (p = 0.008), and a participant-rated GAS of 2.95 ± 0.65 was found. There were no serious adverse events reported. CONCLUSIONS: 1064-nm FxPico could be utilized to treat mastectomy scars among TM, particularly the hypertrophic type.

Global proteomic analysis reveals lysine succinylation is involved in the pathogenesis of hypertrophic scar.

Lysine succinylation (Ksucc) is a recently identified posttranslational modification that is involved in many diseases. This study examined the role of Ksucc in the pathogenesis of hypertrophic scar (HS). The presence of Ksucc in human skin was measured by immunoblotting. Ksucc occurs in many skin proteins ranging from 25 to 250 kDa, and higher levels of Ksucc are found in HS skin than in normal skin. An immunoaffinity approach coupled with LC-MS/MS was used to characterize the first succinylome of human skin, and 159 Ksucc sites in 79 proteins were identified. Among these, there were 38 increased succinylated sites in 29 proteins but no decreased succinylated sites in HS compared with normal skin. A parallel reaction monitoring assay was performed to validate the results of the succinylome and showed that the levels of Ksucc in decorin and collagens, which are involved in the pathogenesis of HS, were increased in HS than in normal skin. In addition, increasing the level of Ksucc enhanced cell proliferation and upregulated the expression of fibrosis markers (α-SMA, COL1, and COL3) in human skin fibroblasts. Our results provide global insights into the functional role of Ksucc in hypertrophic scarring.

Fractional CO2 Laser Therapy for Effective Treatment of Facial Traumatic Hypertrophic Scar: A Case Report.

BACKGROUND Hypertrophic scars occur when there is an excessive wound-healing response in the skin. Fractional, or fractionated, carbon dioxide (CO2) laser therapy uses narrow shafts of light to smooth the skin surface and stimulate dermal collagen, which tightens the skin. This case report describes a 57-year-old woman with a traumatic hypertrophic scar of the face treated with fractional carbon dioxide laser therapy. The purpose of this case report was to highlight the role of fractional CO2 laser therapy in treatment of a facial traumatic hypertrophic scar in a patient after a motor vehicle crash. CASE REPORT A 57-year-old female patient presented with a hypertrophic, rigid, post-traumatic scar on the left side of her face following a motor vehicle crash. For the hypertrophic scar removal, the patient underwent 1 treatment session with fractional CO2 laser using the µ-Scan DOT scanning system. After 1 laser treatment session, the photographic documentation, which permits monitoring the treatment's effectiveness in esthetic improvement, showed a significant improvement in scar texture and color. In addition, a significant reduction in scar height was observed following laser therapy. Fractional laser treatment with the device was very well tolerated by the patient, who reported no pain or discomfort, complications, or adverse effects either during treatment or in the follow-up period (3 months). CONCLUSIONS This report demonstrates the cosmetic application of fractional carbon dioxide laser therapy in a case of hypertrophic scar with the use of an effective therapeutic protocol that did not require the use of suturing.

Zeolitic imidazolate framework-90 loaded with methylprednisolone sodium succinate effectively reduces hypertrophic scar in vivo.

Hypertrophic scar (HS) is characterized by an abnormal fibroblast-myofibroblast transformation; non-apoptosis of fibroblasts; and redundant expression of TGF-ß1, VEGF, α-SMA, and collagen I/III. An HS affects patients' physical and psychological quality of life, leading to joint dysfunction and skin cancer. However, there is currently no satisfactory drug to treat this disorder. In this study, we constructed methylprednisolone sodium succinate (MPSS) encapsulated ZIF-90 (MPSS@ZIF-90) for the effective treatment of an HS. The encapsulation of MPSS in ZIF-90 can achieve the controllable drug release of MPSS and prolong its effective treatment time. MPSS@ZIF-90 enhanced the apoptosis of human hypertrophic scar fibroblasts and downregulated the overexpression of TGF-ß1, VEGF, α-SMA, and collagen I/III both in vitro and in vivo. The instant injection of MPSS@ZIF-90 effectively intervened with the formation of the HS after 28 days. On the contrary, MPSS@ZIF-90 greatly reduced the HS with two injections and 14 days of treatment after the HS was formed. This work provides evidence of effective intervention in the formation of an HS and the therapeutic effectiveness of MPSS@ZIF-90 with short treatment periods in vivo. It suggests that MPSS@ZIF-90 can be used as a biomedical option in the treatment of skin wounds and may reveal the potential molecular basis for promising future antifibrotic agents against scarring.

Risk factors for local recurrence of keloids and hypertrophic scars after postoperative electron beam radiotherapy.

OBJECTIVE: Keloids and hypertrophic scars are benign fibroproliferative lesions that occur as a result of skin injury. Postoperative radiation therapy is used to reduce the recurrence rate because of the high recurrence rate with surgical treatment alone. This study aimed to identify the risk factors for recurrence after postoperative electron beam radiotherapy. MATERIALS AND METHODS: Patients with keloid or hypertrophic scars with at least one lesion and who underwent postoperative electron beam radiotherapy at our institution from June 2013 to March 2022 were included in the study, while patients with a follow-up period of fewer than three months were excluded. RESULTS: A retrospective analysis was performed on 94 lesions in 81 patients. Exactly two years after the treatment, the actuarial local control rate was 86.4%. The chest wall, shoulder, and suprapubic area were identified as high-risk recurrence sites. Compared to other body sites, these sites had significantly lower local control rates (two-year local control rates: 75.5% vs. 95.2%, P = 0.005). After multivariate analysis, treatment site (P = 0.014), male gender (P = 0.019), and younger age (P = 0.029) were revealed to be statistically significant risk factors for local recurrence. Risk factors for keloid recurrence after postoperative electron beam radiotherapy were therefore identified. CONCLUSION: This result could be used for follow-up and as a determinant for the optimal dose/fractionation of postoperative radiotherapy.

Parecoxib decreases cellular growth and Bcl-2 protein levels in primary cultures of keloid fibroblasts.

Keloids seem to overexpress cyclo-oxygenase-2 (COX-2), suggesting a role in its deregulated pathway in inducing an altered epithelial-mesenchymal interaction, which may be responsible for the overgrowth of dermal components resulting in scars or keloid lesions. This study aimed to evaluate the effect of Parecoxib, a COX-2 inhibitor, on cell growth in fibroblast primary cultures obtained from human keloid tissues. Tissue explants were obtained from patients who underwent intralesional excision of untreated keloids; central fractions were isolated from keloid tissues and used for establishing distinct primary cultures. Appropriate aliquots of Parecoxib, a COX-2 inhibitor were diluted to obtain the concentration used in the experimental protocols in vitro (1, 10 or 100 µM). Treatment with Parecoxib (at all concentrations) caused a significant decrease in cellular growth from 24 hours onwards, and with a maximum at 72 hours (P < .02). Moreover, at 72 hours Parecoxib significantly reduced cellular vitality. Parecoxib treatment also induced an increase in fragmented nuclei with a maximum effect at 100 µM and a significant decrease in Bcl-2 and an increase in activated caspase-3 protein levels at 72 hours compared with control untreated cultures. Our findings suggest a potential use of the COX-2 inhibitor, Parecoxib, as the therapy for keloids.

The role of positional information in determining dermal fibroblast diversity.

The largest mammalian organ, skin, consisting of a dermal connective tissue layer that underlies and supports the epidermis, acts as a protective barrier that excludes external pathogens and disseminates sensory signals emanating from the local microenvironment. Dermal connective tissue is comprised of a collagen-rich extracellular matrix (ECM) that is produced by connective tissue fibroblasts resident within the dermis. When wounded, a tissue repair program is induced whereby fibroblasts, in response to alterations in the microenvironment, produce new ECM components, resulting in the formation of a scar. Failure to terminate the normal tissue repair program causes fibrotic conditions including: hypertrophic scars, keloids, and the systemic autoimmune connective tissue disease scleroderma (systemic sclerosis, SSc). Histological and single-cell RNA sequencing (scRNAseq) studies have revealed that fibroblasts are heterogeneous and highly plastic. Understanding how this diversity contributes to dermal homeostasis, wounding, fibrosis, and cancer may ultimately result in novel anti-fibrotic therapies and personalized medicine. This review summarizes studies supporting this concept.