bromochloroacetic-acid and Cicatrix--Hypertrophic

Linear hypertrophic scarring is a common surgical problem that can be difficult to manage. This article evaluates median sternotomy wounds that have often been reported to scar poorly resulting in hypertrophic scar formation.. This study is a single-blinded, open-labelled pilot study of 20 patients using keratin gel as the intervention and aqueous cream as the control, which are each applied to a different half of the wound daily over 6 months. We use the Patient and Observer Scar Assessment Scale (POSAS) and the Manchester Scar Score (MSS) to assess the scarring.. At the 6-month assessment the MSS, patient-POSAS and observer-POSAS were 12.00, 16.70 and 15.00 in the treatment half and 12.58, 17.85 and 16.55 in the control half respectively. Overall, we found that there was a decrease in all score scales after 6 months (P = 0.005). Furthermore, in the subset of patients with poor scarring, decreases in the MSS, patient-POSAS and observer-POSAS were statistically significant (P = 0.025, <0.01 and 0.01) with scores of 12.22, 17.33 and 15.33 in the treatment half and 14.22, 23.67 and 22.33 in the control half respectively.. In patients who scar more poorly than average, there were significant improvements in scarring. This demonstrates a simple, well-tolerated intervention that reduces problematic scarring following surgery.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cicatrix, Hypertrophic; Dermatologic Agents; Humans; Keratins; Middle Aged; Pilot Projects; Postoperative Complications; Single-Blind Method; Sternotomy; Wound Healing; Young Adult

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.

Topics: Cell Proliferation; Cells, Cultured; Cicatrix, Hypertrophic; Exosomes; Fibroblasts; Humans; Keratinocytes; Keratins

The majority of studies on scar formation have mainly focused on the dermis and little is known of the involvement of the epidermis. Previous research has demonstrated that the scar tissue-derived keratinocytes are different from normal cells at both the genetic and cell biological levels; however, the mechanisms responsible for the fundamental abnormalities in keratinocytes during scar development remain elusive. For this purpose, in this study, we used normal, wound edge and hypertrophic scar tissue to examine the morphological changes which occur during epidermal regeneration as part of the wound healing process and found that the histological structure of hypertrophic scar tissues differed from that of normal skin, with a significant increase in epidermal thickness. Notably, staining of the basement membrane (BM) appeared to be absent in the scar tissues. Moreover, immunofluorescence staining for cytokeratin (CK)10, CK14, CK5, CK19 and integrin-β1 indicated the differential expression of cell markers in the epidermal keratinocytes among the normal, wound edge and hypertrophic scar tissues, which corresponded with the altered BM structures. By using a panel of proteins associated with BM components, we validated our hypothesis that the BM plays a significant role in regulating the cell fate decision of epidermal keratinocytes during skin wound healing. Alterations in the structure of the BM promote basal keratinocytes to adopt a proliferative phenotype both in vivo and in vitro.

Topics: Adolescent; Adult; Basement Membrane; Biomarkers; Cell Differentiation; Cicatrix, Hypertrophic; Epidermis; Female; Gene Expression Profiling; Gene Expression Regulation; Humans; Keratinocytes; Keratins; Male; Phenotype; Wound Healing; Wounds and Injuries; Young Adult

The purpose of the present study was to evaluate the esthetic outcome using four categories of root-coverage procedures (pedicle soft tissue grafts, non-submerged grafts, submerged grafts, and envelope techniques) and to identify factors associated with esthetic assessment.. A professional panel of three observers (two periodontists and one control) used a before-after panel scoring system to evaluate the esthetics of 162 root-coverage surgeries. A five-point ordinal scale was used to evaluate the overall esthetic improvement and seven variables that may be considered in the assessment.. The intraobserver agreement of the two trained periodontists for the overall cosmetic assessment was almost perfect (kappa = 0.83), and substantial agreement was found between them (kappa = 0.68). Good to excellent overall esthetic results were found by the professionals and control in >70% of the surgical procedures. Analysis of variance indicated a statistical difference between the non-submerged grafts category and the three other surgical categories (P <10(-3)). Multivariate analysis showed that the degree of root coverage was not a significant predictive factor, whereas soft tissue appearance variables and the follow-up were significantly associated with cosmetic assessment.. The present study demonstrated that non-submerged grafts are not recommended in cases of esthetic demand. Future root-coverage trials, basing their justification on esthetics, should include overall qualitative evaluation as the primary variable. The follow-up period should not be <12 months. The before-after panel scoring system is a tool that can be used to evaluate cosmetic outcomes.

Topics: Adult; Cicatrix, Hypertrophic; Color; Esthetics, Dental; Female; Follow-Up Studies; Gingiva; Gingival Recession; Humans; Image Processing, Computer-Assisted; Keratins; Male; Observer Variation; Photography, Dental; Plastic Surgery Procedures; Predictive Value of Tests; Retrospective Studies; Surgical Flaps; Tooth Root; Treatment Outcome

In hypertrophic scar tissue, no sweet gland and hair follicle exist usually because of the dermal and epidermal damage in extensive thermal skin injury, thus imparing regulation of body temperature. This study was designed to reveal the morphological and distributional characteristics of the sweat glands in normal skin and hypertrophic scar obtained from children and adults, and to study the possible interfering effects of the scar on regeneration of the sweat gland after burn injury.. Biopsies of hypertrophic scar were taken from four children (4 - 10 years) and four adults (35 - 51 years). Normal, uninjured full-thickness skin adjacent to the scar of each patient was used as control. Keratin 19 (K19) was used as the marker for epidermal stem cells and secretory portion of the sweat glands, and keratin 14 (K14) for the tube portion, respectively. Immunohistochemical and histological evaluations were performed.. Histological and immunohistochemical staining of skin tissue sections from both the children and adults showed K19 positive cells in the basement membrane of epidermis of normal skin. These cells were seen only single layer and arranged regularly. The secretory or duct portion of the eccrine sweat glands was situated in the dermis and epidermal layer. However, in the scar tissue, K19 positive cells were scant in the basal layer, and the anatomic location of the secretory portion of sweat glands changed. They were located between the border of the scar and reticular layer of the dermis. These secretory portions of sweat glands were expanded and were organized irregularly. But a few K14 positive cells were scattered in the scar tissues in cyclic form.. There are some residual sweat glands in scar tissues, in which the regeneration process of active sweat glands is present. Possibly the sweat glands could regenerate from adult epidermal stem cells or residual sweat glands in the wound bed after burn injury.

Topics: Adult; Burns; Child; Child, Preschool; Cicatrix, Hypertrophic; Epidermal Cells; Humans; Immunohistochemistry; Keratin-14; Keratins; Middle Aged; Regeneration; Skin; Stem Cells; Sweat Glands

To investigate the abnormalities of human epiderm in keloids and hypertrophic scars.. Biopsies from ten untreated keloids (duration of disease 3 - 30 years) and ten hypertrophic scars (duration of disease 6 - 10 months) and five normal adult skin specimens. Total RNA was isolated from normal adult skin. A cDNA fragment (base 5941 - 6481 bp) of the full-length human Tenascin-C cDNA was synthesized by polymerase chain reaction and subcloned in pGEM-T-easy. Dioxigen-labeled anti-sense and sense probes were synthesized by using a Sp6/T7 in vitro RNA synthesis kit in the present of Dig-UTP. In situ hybridization was performed on 4% paraformaldehyde-fixed and wax-embedded sections of keloids and hypertrophic scars. NBT-NCIP was used in color detection. Immunohistochemical procedure. The sections were incubated with antibodies (anti-Tenascin-C, anti-CK-16 and anti-Ki-67). Ultrasensitive Streptavidin Peroxidase staining was performed following established procedures.. The study show that the proliferation of epidermal keratinocytes in keloids and hypertrophic scars is very clear. The expressions of Tenascin-C mRNA in keloids epidermal keratinocytes markedly increased in contrast with epidermal keratinocytes of hypertrophic scars and adult skin. The CK-16 and Ki-67 stainings significantly enhanced in the epidermal keratinocytes of keloids and hypertrophic scars.. The different expressions of Tenascin-C, CK-16 and Ki-67 among normal adult skin, keloids and hypertrophic scars show the abnormalities of epidermal keratinocytes proliferation and differentiation in keloids and hypertrophic scars.

Topics: Cicatrix, Hypertrophic; Epidermis; Female; Humans; Hyperplasia; Immunohistochemistry; In Situ Hybridization; Keloid; Keratins; Ki-67 Antigen; Male; Tenascin

Keloids and hypertrophic scars are a result of aberrations of the normal wound healing processes of the skin. The expression of keratins, the proteins of an intermediate filament supergene family, closely parallel the division/differentiation of epithelial cells and therefore offer excellent molecular markers to examine wound healing. In this study, the expression of K5/K14, proliferation specific keratin polypeptides in normal skin, keloids and hypertrophic scars was analysed. Results indicated that unlike normal wounds and hypertrophic scars, keloid epidermis displayed increased expression of K5 and K14 at both the translational and transcriptional levels. The molecular mechanisms in the pathogenesis of keloids appear to be different from those of hypertrophic scars.

Topics: Adolescent; Adult; Biomarkers; Cicatrix, Hypertrophic; Epidermis; Female; Humans; Keloid; Keratins; Male; RNA; Skin; Wound Healing

The reconstruction of epidermal architecture over time in normotrophic and hypertrophic scars in untransplanted, spontaneously healed partial-thickness burns has scarcely been studied, unlike the regeneration of epidermal grafts used to cover burn wounds and the regeneration of the dermis during hypertrophic scarring. The expression of markers of epidermal proliferation, differentiation and activation in normotrophic and hypertrophic scars in spontaneously healed partial-thickness burns was assessed and compared with the expression of these markers in normal control skin of healthy persons to determine whether hypertrophic scarring is associated with abnormalities in the phenotype of keratinocytes. Punch biopsies were taken both of partial-thickness burns after re-epithelialisation and of matched unburned skin. At 4 and 7 months post-burn, biopsies were taken of normotrophic and hypertrophic scars that had developed in these wounds. The biopsies were analysed using immunostaining for markers of keratinocyte proliferation, differentiation and activation (keratins 5, 10, 16 and 17, filaggrin, transglutaminase and CD36). We observed a higher expression of markers for proliferation, differentiation and activation in the epidermis of scars at 1 month post-burn than in normal control skin of healthy persons. There was a striking difference between normotrophic and hypertrophic scars at 4 months post-burn. Keratinocytes in hypertrophic scars displayed a higher level of proliferation, differentiation and activation than did normotrophic scars. At 7 months post-burn all keratinocyte proliferation and differentiation markers showed normal expression, but the activation marker CD36 remained upregulated in both normotrophic and hypertrophic scars. Surprisingly, in matched unburned skin of burn patients, a state of hyperactivation was observed at 1 month. Our results suggest that keratinocytes may be involved in the pathogenesis of hypertrophic scarring.

Topics: Adult; Aged; Burns; CD36 Antigens; Cicatrix; Cicatrix, Hypertrophic; Epidermis; Filaggrin Proteins; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Middle Aged; Reference Values; Skin; Time Factors

The etiology of hypertrophic scarring, a pathological end point of wound healing, is unknown. The scars most commonly occur when epithelialization has been delayed during, for example, the healing of deep dermal burn wounds. Hypertrophic scars are conventionally described as a dermal pathology in which the epidermis has only a passive role. In this study, the expression of keratin intermediate filament proteins and filaggrin has been investigated in the epidermis of hypertrophic scars and site-matched controls from the same patients. Hypertrophic scar epidermis was found to express the hyperproliferative keratins K6 and K16 in interfollicular epidermis in association with K17 and precocious expression of filaggrin. K16 mRNA was localized by in situ hybridization using a highly specific cRNA probe. In contrast to the immunohistochemical location of K16 protein, the K16 mRNA was found to be expressed in the basal cell layer of normal skin. In hypertrophic scars the mRNA distribution corroborated the abnormal K16 protein distribution. These results suggest the keratinocytes in hypertrophic scar epidermis have entered an alternative differentiation pathway and are expressing an activated phenotype. Activated keratinocytes are a feature of the early stages of wound healing producing growth factors that influence fibroblasts, endothelial cells, and the inflammatory response. We propose that cellular mechanisms in the pathogenesis of hypertrophic scarring are more complex than isolated dermal phenomena. The persistence of activated keratinocytes in hypertrophic scar epidermis implicates abnormal epidermal-mesenchymal interactions.

Topics: Adult; Aged; Animals; Antibodies, Monoclonal; Cell Differentiation; Child; Child, Preschool; Cicatrix, Hypertrophic; DNA Primers; Epidermis; Female; Filaggrin Proteins; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Intermediate Filament Proteins; Keratinocytes; Keratins; Male; Mice; Mice, Inbred BALB C; Middle Aged; Polymerase Chain Reaction; RNA, Messenger; Wound Healing

The role of epidermal keratinocytes in the early phases of normal unimpaired wound healing has been studied extensively. However, little is known about the cell biological processes in the epidermis and the basal membrane zone during the later phases of dermal matrix formation and remodelling of the scar tissue. This study investigated epidermal growth and differentiation and maturation of the basal membrane zone. Biopsies were taken from (clinically) hypertrophic and non-hypertrophic scars at 3 and 12 months after a breast-reduction operation. Tissues were analysed using immunohistochemical techniques. The data showed that epidermal abnormalities with respect to differentiation persist up to 3 months, as witnessed by the expression of cytokeratin 16. Remarkably, hypertrophic scars that remained hypertrophic throughout the period of analysis (up to 12 months) showed significantly more cytokeratin 16 expression at 3 months, when compared either with normal scars or with hypertrophic scars that became normal after 12 months. Staining for Ki-67 antigen, a marker for cell proliferation, revealed an increase in basal keratinocyte proliferation rate in 3-month-old hypertrophic scars compared with non-hypertrophic scars. After 12 months, this difference had disappeared completely and the number of cycling basal cells had returned to normal values. Three-month-old hypertrophic scars showed more acanthosis than non-hypertrophic scars of the same age, irrespective of whether they remained hypertrophic or became normal scars. After 12 months, this difference was no longer present. Staining for various heparan sulphate proteoglycan epitopes revealed that restoration of the basal membrane was incomplete at 3 months, but was complete at 12 months with respect to this component. No differences in the expression of several components of the basal membrane zone (heparan sulphate proteoglycan, laminin, tenascin) were noted between hypertrophic and non-hypertrophic scars. These data show that in the early phase of hypertrophic scarring, epidermal abnormalities are found compared with normal wound healing. In addition, early (3 months) epidermal abnormalities are associated with the clinical outcome at 12 months. These findings raise the possibility that the epidermal compartment is involved in the pathogenic process.

Topics: Adolescent; Adult; Cell Differentiation; Cell Division; Cicatrix, Hypertrophic; Epidermis; Female; Heparan Sulfate Proteoglycans; Humans; Immunoenzyme Techniques; Keratinocytes; Keratins; Ki-67 Antigen; Middle Aged; Tenascin; Time Factors