chondroitin-sulfates and Keloid

Topics: Chondroitin Sulfates; Collagen; Humans; Keloid; Male; Plastic Surgery Procedures; Skin, Artificial; Young Adult

Over the past two decades the treatment of hypertrophic scars and keloids has seen substantial changes due to the evolution of current and establishment of new conservative and surgical methods. This review gives an overview of the current research with respect to the multifactorial etiology and pathophysiology of keloids and hypertrophic scars, discusses conservative surgical treatment options and provides an outlook on novel treatment strategies.

Topics: Adult; Burns; Cell Proliferation; Child; Chondroitin Sulfates; Cicatrix, Hypertrophic; Collagen; Combined Modality Therapy; Diagnosis, Differential; Facial Injuries; Female; Free Tissue Flaps; Granulation Tissue; Humans; Keloid; Male; Microsurgery; Middle Aged; Plastic Surgery Procedures; Reoperation; Tissue Expansion Devices

Keloids are dermal fibroproliferative tumors that arise beyond the boundary of the original wound edges and invades adjacent tissue. Keloids are characterized by the extensive production of extracellular matrix (ECM) and abnormal fibroblast proliferation. Chondroitin sulfate (CS) is one of the major structural components of cartilage and ECM. Recently, we reported the over-accumulation of CS in keloid lesions. Keloid-derived fibroblasts (KFs) and normal dermal fibroblasts (NFs) were incubated with CS. The fibroblast proliferation rate was analyzed using a tetrazolium salt colorimetric assay. The activation of the intracellular signaling pathway was analyzed by Western blotting. Wortmannin, a PI3K inhibitor, and anti-integrin antibodies were tested to investigate the mechanism of the CS-induced cell proliferation. CS strongly stimulated the proliferation of KFs, but not NFs. The analysis of the intracellular signal transduction pathway revealed that the stimulation effect of CS on KF proliferation was due to the activation of the protein kinase B (AKT) pathway and that integrin α1 was responsible for this phenomenon. We revealed that CS probably activates the AKT pathway through integrin to induce KF proliferation. CS may be a novel clinical therapeutic target in keloids.

Topics: Adult; Aged; Aged, 80 and over; Cell Proliferation; Cells, Cultured; Chondroitin Sulfates; Female; Fibroblasts; Humans; Integrins; Keloid; Male; Middle Aged; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction

Integra Artificial Skin, a biosynthetic dermal template, is well established in acute burn surgery. The aim of the study was to determine the role of Integra in the surgical treatment of postburn scars in a younger population. Between March 1998 and November 2004, 17 patients (n=17; mean age=13.15 years) underwent complete excision of hypertrophic scars or keloids (1-4% TBSA; extremities=47%, head/neck=35%, trunk=18%) with subsequent implantation of Integra for defect closure. Split thickness skin grafting (STSG) of the Integra-derived neodermis was performed 3 weeks after the first operation. Scar excision and primary Integra implantation was successful in all but one patient (94%) who (6%) needed reimplantation once. Integra's mean take rate was 99.7% for all primarily successful patients. Complications occurred in three patients (18%), including minor problems without long-term consequences in 12% (seroma formation), and major problems in 6% (hematoma formation). Take rate of STSG ranged from 50% to 100% (mean 94%). Functional and cosmetic long-term outcome showed results scored "excellent" in 53%, "good" in 36%, and "fair" in 11%. Comparison of pre- and postoperative findings revealed a significant functional improvement in all and a considerable cosmetic improvement in all but two patients. These results suggest that Integra is a valid new treatment modality for extensive burn scar revision in younger patients.

Topics: Adolescent; Burns; Child; Chondroitin Sulfates; Cicatrix, Hypertrophic; Collagen; Esthetics; Female; Humans; Keloid; Male; Plastic Surgery Procedures; Reoperation; Skin, Artificial; Treatment Outcome

Keloids occurring on the chest can be deforming with significant painful sequelae for patients. These lesions can pose a therapeutic dilemma for the dermatologic surgeon as certain excision defects may be too large to close primarily and recurrences tend to be high (40-100%). A collagen-glycosaminoglycan copolymer (Integra) has been found to be useful in the surgical treatment of scar excisions as the bovine collagen and glycosaminoglycans provide a template for neocollagenesis. Additionally, this dermal regeneration template concomitantly reduces tensile forces on the wound.. The authors' group has followed five patients with chronic chest keloids refractory to myriad of interventions and treated these patients with surgical excision followed by Integra placement into the wound bed on the chest. Split-thickness grafts were applied shortly thereafter. Patients were followed at regular intervals and all patients received adjuvant therapy with single-dose radiation and intralesional chemotherapy (triamcinolone and/or 5 fluorouracil).. This treatment protocol has provided a cure rate of 100% over an average of 43 months follow-up. The symptoms often accompanied by these chest keloids also appear to improve.. The authors believe that this study provides the groundwork for further investigation of Integra for surgical management of keloids. A placebo-controlled study should be performed to adequately determine if this data holds true.

Topics: Adult; Aged; Anti-Inflammatory Agents; Chondroitin Sulfates; Chronic Disease; Collagen; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Keloid; Middle Aged; Plastic Surgery Procedures; Severity of Illness Index; Thorax; Treatment Outcome; Triamcinolone

Integra (Integra Lifesciences Corporation, Plainsboro, NJ) has been used in a variety of reconstructive surgical procedures. The application of Integra using subatmospheric pressure (V.A.C., Kinetic Concepts, Inc, San Antonio, TX) has been suggested to be easier, faster, and more consistent than previous dressings, allowing grafting as soon as 1 week after Integra placement. Ten patients were chosen for outpatient reconstructive surgery with Integra and subatmospheric pressure with skin grafting 7-10 days (mean = 8 days) post-Integra. Skin graft take was 75% to 100% (mean = 91.5%). No patients required additional grafting or reconstruction. Integra may be successfully used for reconstruction of difficult areas as an outpatient in combination with subatmospheric pressure (V.A.C.). This allows for expedited treatment, decreased morbidity, and lower cost versus standard Integra application.

Topics: Adult; Ambulatory Surgical Procedures; Atmospheric Pressure; Burns; Child; Child, Preschool; Chondroitin Sulfates; Collagen; Female; Humans; Keloid; Male; Middle Aged; Plastic Surgery Procedures; Soft Tissue Injuries

Keloid is a fibrotic disease characterized by abnormal accumulation of extracellular matrix in the dermis. The keloid matrix contains excess collagen and glycosaminoglycans (GAGs), but lacks elastic fiber. However, the roles of these matrix components in the pathogenesis of keloid are largely unknown. Here, we show that elastin and DANCE (also known as fibulin-5), a protein required for elastic fiber formation, are not deposited in the extracellular matrix of keloids, due to excess accumulation of chondoitin sulfate (CS), although the expression of elastin and DANCE is not affected. Amount of CS accumulated in the keloid legion was 6.9-fold higher than in normal skin. Fibrillin-1, a scaffold protein for elastic fiber assembly, was abnormally distributed in the keloid matrix. Addition of purified CS to keloid fibroblast culture resulted in abnormal deposition of fibrillin-1, concomitant with significantly decreased accumulation of elastin and DANCE in the extracellular matrix. We propose that CS plays a crucial role in the development of keloid lesions through inhibition of elastic fiber assembly.

Topics: Adolescent; Adult; Aged; Child; Chondroitin Sulfates; Elastic Tissue; Female; Humans; Keloid; Male; Middle Aged; Skin Diseases; Young Adult

Studies have been made of the glycosaminoglycan (GAG) composition of implants of keloid and hypertrophic scars in athymic nude mice in order to evaluate these implants as a model for studies of causation and therapy of these abnormal human scars. Changes in weight of implanted tissue were also recorded. Pieces of keloid, hypertrophic scar or normal human skin were placed in subcutaneous pockets of athymic nude mice and left for various times up to 246 days. The uronic acid content of the scar implants did not change significantly until after 80 days when the level decreased; the uronic acid level of normal skin increased slightly during the 110 days studied. The initially high percentage of chondroitin-4-sulfate of keloid and hypertrophic scar tissue decreased in the implants (averaging a 50% decrease at 164 days for keloids and at 176 days for hypertrophic scars). The average weight of the scar implants increased slightly after implantation and then decreased when expressed either as wet or dry weight. The regression lines of weight on time indicated an average loss of 50% dry weight at 66 days for keloid implants and 68 days for hypertrophic scars. Normal human skin increased in net weight until 20 days and dry weight until 40 days and then decreased, losing about 20% of weight (either wet or dry) at 110 days. On the basis of the glycosaminoglycan changes, the model should be useful for short term studies of therapy and causation.

Topics: Adolescent; Adult; Animals; Chondroitin Lyases; Chondroitin Sulfates; Cicatrix; Female; Glycosaminoglycans; Humans; Keloid; Male; Mice; Mice, Nude; Middle Aged; Regression Analysis; Skin Transplantation; Uronic Acids