Dermal Substitute Research Articles

Potential of a Cryopreserved Cultured Dermal Substitute Composed of Hyaluronic Acid and Collagen to Release Angiogenic Cytokine

An allogeneic cultured dermal substitute (CDS) was prepared by culturing fibroblasts on a spongy matrix of hyaluronic acid (HA) and collagen (Col), which was then cryopreserved. This cryopreserved allogeneic CDS (CDS-1; cryopreserved for 1 month, CDS-6; cryopreserved for 6 months) was thawed and re-cultured for a period of 7 days to investigate the potential of the CDS for wound treatment. The cell metabolic activity in the CDS and their cytokine production were measured using an MTT assay and ELISA. Fibroblast metabolic activity in each CDS-1 and CDS-6 immediately after thawing and following 3 and 7 days of re- cultivation was 56, 67 and 93%, and 49, 64 and 86%, respectively, of that before cryopreservation. The amount of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) released from the CDS-1 on days 1, 3 and 7 of re-cultivation after thawing was 8, 44 and 92% (VEGF) and 3, 7 and 28% (HGF), respectively, of that before cryopreservation. The amount of VEGF and HGF released from the CDS-6 on days 1, 3 and 7 of re-cultivation after thawing was 9, 32 and 45% (VEGF) and 6, 10 and 27% (HGF), respectively, of that before cryopreservation. These findings showed that the potential of the CDS was restored to some extent over the first 3 days of re-cultivation after thawing. The potential of the CDS for wound treatment was then evaluated using a wound surface model, in which the each CDS-1 and CDS-6 that was re-cultured for 3 days after thawing was elevated at the air/culture medium interface, and a wound dressing was placed on top, and then cultured for 5 days. Two different types of wound dressing were tested. Fibroblasts in the CDS in Group II (placing a wound dressing with EGF) released increased amount of VEGF and HGF compared with that in Group I (placing a wound dressing without EGF). These findings suggest that re-culture of the CDS for 3 days following thawing results in a CDS with improved wound healing potential and that an EGF-incorporating wound dressing is useful as a top dressing for the CDS.

Dermal substitution with Matriderm® in burns on the dorsum of the hand

Dermal substitution with Matriderm® in burns on the dorsum of the hand

O0.4 Improved scar elasticity after dermal substitution and topical negative pressure: a multicentre controlled trial in burns

Biodegradable material is one kind of material which can be degraded by bacteria, fungi, or other biological means. It is commonly associated with environmentally friendly products, capable of decomposing back into natural elements. Reasonable modification and controllable degradation biodegradable materials can make them play an extremely important role in reducing environmental pollution.In this chapter, the history of the application of biodegradable material and the research advances of the manufacture of novel biodegradable material will be viewed including (1) definition and types of biodegradable materials; (2) properties of environmentally friendly biodegradable materials for daily life and industrial manufacturing; (3) how to meet the market need of both cost and performance of biodegradable materials; (4) the future of the production of novel biodegradable materials and their applications; and (5) biodegradable technology: microorganisms, conditions, additions, equipment, and biodegradability.

Severe Burn Injuries and the Role of Elastin in the Design of Dermal Substitutes

Severe burn injuries are a major health problem as they can compromise whole body function and result in extensive emotional trauma exacerbated by prolonged hospital stay. Burn injury treatment has improved dramatically to increase the probability of survival, but burn survivors still suffer from excessive scarring and skin contractures, which substantially compromise their health and quality of life. Elastin is historically underrepresented in commercial dermal substitutes, yet deserves consideration because of its fundamental role in skin structure and function. Dermal elastic network is a strong determinant of skin resilience, texture, and quality but is not sufficiently regenerated following burn injury. In addition to its structural and mechanical roles, elastin has inherent cell signaling properties that promote a diverse range of cellular responses including chemotaxis, cell attachment, proliferation, and differentiation. Scaffold elasticity and regeneration of the elastic fiber system is now recognized as integral to the development of functional dermal substitutes. Dermal substitutes are intended to replace damaged dermal tissue in severe burn injuries. Elastin-based dermal substitutes have the potential to decrease wound contraction, improve scar appearance and functionality, and contribute to wound healing outcomes through a combination of elastin's mechanical and cell signaling properties.

One Successful Case of Wound Treatment for Leg Ulcer: Application of Allogeneic Cultured Dermal Substitute

One Successful Case of Wound Treatment for Leg Ulcer: Application of Allogeneic Cultured Dermal Substitute

Dermal substitution with Matriderm ® in burns on the dorsum of the hand

Background Dermal substitutes are used increasingly in deep partial and full-thickness burn wounds in order to enhance elasticity and pliability. In particular, the dorsum of the hand is an area requiring extraordinary mobility for full range of motion. The aim of this comparative study was to evaluate intra-individual outcomes among patients with full-thickness burns of the dorsum of both hands. One hand was treated with split-thickness skin grafts (STSG) alone, and the other with the dermal substitute Matriderm ® and split-thickness skin grafts. Material and Methods In this study 36 burn wounds of the complete dorsum of both hands in 18 patients with severe burns (age 45.1 ± 17.4 years, 43.8 ± 11.8% TBSA) were treated with the simultaneous application of Matriderm ®, a bovine based collagen I, III, V and elastin-hydrolysate based dermal substitute, and split-thickness skin grafting (STSG) in the form of sheets on one hand, and STSG in the form of sheets alone on the other hand. The study was designed as a prospective comparative study. Using both objective and subjective assessments, data were collected at one week and 6 months after surgery. The following parameters were included: After one week all wounds were assessed for autograft survival. Skin quality was measured 6 months postoperatively using the Vancouver Burn Skin Score (VBSS). Range of motion was measured by Finger-Tip-Palmar-Crease-Distance (FPD) and Finger-Nail-Table-Distance (FNTD). Results Autograft survival was not altered by simultaneous application of the dermal matrix ( p > 0.05). The VBSS demonstrated a significant increase in skin quality in the group with dermal substitutes ( p = 0.02) compared to the control group with non-substituted wounds. Range of motion was significantly improved in the group treated with the dermal substitute ( p = 0.04). Conclusion From our results it can be concluded that simultaneous use of Matriderm ® and STSG is safe and feasible, leading to significantly better results in respect to skin quality of the dorsum of the hand and range of motion of the fingers. Skin elasticity was significantly improved by the collagen/elastin dermal substitute in combination with sheet-autografts.

Dermal Substitution in Acute Burns and Reconstructive Surgery: A 12-Year Follow-Up

Application of dermal substitutes has been reported to improve the outcome of burns. However, the long-term effectiveness of dermal substitutes has not been investigated objectively. The aim of this study was to evaluate long-term effectiveness of a collagen-elastin dermal substitute in acute and reconstructive burn surgery. From 1996 to 1998, an intraindividual comparison was carried out between a dermal substitute with a split-skin graft and a split-skin graft alone in patients with acute and reconstructive wounds. In this follow-up, scar elasticity, vascularization, pigmentation, and surface roughness were determined objectively. In addition, a subjective scar assessment was performed. In 46 patients, 69 pairs of substituted and conventionally treated sites were measured, consisting of acute and reconstructive burn scars. In reconstructive scars, one surface roughness parameter was significantly better in substituted scars. Subjective assessment in acute and reconstructive burn scars showed several statistically significant differences in favor of substituted scars, such as pliability, relief, and the general observer score. Elasticity measurements showed higher scores for substituted scars, although the difference was not statistically significant. For the subcategory of scars treated with a largely expanded meshed skin graft, a significantly higher elasticity was found for the substituted area. In this first long-term and objective follow-up of dermal substitution, the authors found improved scar parameters in both acute and reconstructive wounds treated with the substitute, indicating a long-lasting effect on scar quality.

Matriderm ® in depth-adjusted reconstruction of necrotising fasciitis defects

Necrotising fasciitis (NF) and Fournier's gangrene are still a source of high morbidity and mortality and a significant health-care resource consumption. These difficult cases are increasingly being referred to burn centres for specialised wound and critical care issues. Besides the total body surface area (TBSA) affected, location, co-morbidities, age and an immediate surgical treatment are important prognostic factors. The treatment of these patients is challenging and best performed by prompt diagnosis, immediate radical surgical debridement and aggressive critical care management. Referral to a major burn centre may help provide optimal surgical intervention, wound care and critical care management.As soon as the patient is stabilised, reconstruction of the injured areas becomes the main focus. As often seen, complete loss of dermal structures needs a depth adjusted – ‘multilayer’ – reconstruction especially in critical areas. In modern reconstructive surgery, concepts of layer-specific reconstruction, including dermal substitution have to be considered. In this article, we present our recent experiences of five patients with NF who underwent dermal reconstruction with Matriderm ® not only for better skin quality but also in some cases as an alternative to flap surgery when joint capsules or tendons were exposed.

Letter: The Use of a Dermal Substitute and Thin Skin Grafts in the Cure of “Complex” Leg Ulcers

Letter: The Use of a Dermal Substitute and Thin Skin Grafts in the Cure of “Complex” Leg Ulcers

Long‐Term Followup of Dermal Substitution with Acellular Dermal Implant in Burns and Postburn Scar Corrections

Full-thickness burn and other types of deep skin loss will result in scar formation. For at least partial replacement of the lost dermal layer, there are several options to use biotechnologically derived extracellular matrix components or tissue scaffolds of cadaver skin origin. In a survey, we have collected data on 18 pts who have previously received acellular dermal implant Alloderm. The age of these patients at the injury varied between 16 months and 84 years. The average area of the implants was 185 cm2. Among those, 15 implant sites of 14 patients were assessed at an average of 50 months after surgery. The scar function was assessed by using the modified Vancouver Scar Scale. We have found that the overall scar quality and function was significantly better over the implanted areas than over the surrounding skin. Also these areas received a better score for scar height and pliability. Our findings suggest that acellular dermal implants are especially useful tools in the treatment of full-thickness burns as well as postburn scar contractures.

Response of Intractable Skin Ulcers in Recessive Dystrophic Epidermolysis Bullosa Patients to an Allogeneic Cultured Dermal Substitute

Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited skin disorder caused by mutations in the COL7A1 gene, which encodes collagen VII (COL7). Skin ulcers in RDEB patients are sometimes slow to heal. We describe here the therapeutic response of intractable skin ulcers in two patients with generalized RDEB to treatment with an allogeneic cultured dermal substitute (CDS). Skin ulcers in both patients epithelialized by 3-4 weeks after this treatment. Immunohistochemical studies demonstrated that the COL7 expression level remained reduced with respect to the control skin and that it did not differ significantly between graft-treated and untreated areas. Electron microscopy showed aberrant anchoring fibrils beneath the lamina densa of both specimens. In conclusion, CDS is a promising modality for treatment of intractable skin ulcers in patients with RDEB, even though it does not appear to increase COL7 expression.

Design of a Matrix for Cultured Dermal Substitute Suitable for Simultaneous Transplantation with Auto-Skin Graft: Evaluation in Animal Test

This study focused on the design of a matrix for a cultured dermal substitute (CDS). Two types of cross-linked spongy matrix were designed. The weight ratio of hyaluronic acid (HA) to a cross-linking agent was adjusted to 5:1 (c-5) or 15:1 (c-15). Each HA spongy matrix was combined with collagen (Col) gel, forming 4 groups: Group I, c-5 sponge and Col gel; Group II, c-5 sponge and Col gel with human fibroblasts; Group III, c-15 sponge and Col gel; and Group IV, c-15 sponge and Col gel with human fibroblasts. The physical properties of the matrix depend on the cross-linking conditions. In animal tests using T-cell-deficient F344 rats, materials from Groups I–IV were transplanted onto a full-thickness skin defect, followed by auto-skin grafting. Commercially available artificial dermis composed of collagen sponge was employed as a control. Grafted skin survival in all groups was evaluated according to macroscopic and histological appearances 2 weeks after transplantation. The take rate of auto-skin was higher in Groups I–IV than in control. The take rate of auto-skin was also higher for Groups II and IV than for Groups I and III. This finding indicates that CDS containing human fibroblasts is able to provide more suitable conditions for rat's auto-skin engraftment. The take rate of auto-skin in Group IV was >84%, showing the best results. This finding suggests that CDS comprising highly biodegradable matrix is acceptable for the engraftment of auto-skin, creating no physical barrier to interactions between the wound bed and auto-skin.

The Use of a Dermal Substitute (Integra) to Preserve Maximal Foot Length in a Diabetic Foot Wound With Bone and Tendon Exposure Following Urgent Surgical Debridement for an Acute Infection

In this report, the authors present the case of a 62-year-old female patient who was admitted to our hospital with an acute deep foot infection. The patient was taken immediately to the operating room where she underwent surgical debridement to completely remove all infected tissues; at the end of this first surgical step, all 5 metatarsal bones remained exposed dorsally. Once eradication of infection was completed, we had to decide whether to perform a transmetatarsal amputation at proximal levels, which would have allowed healing by first intention but would have left the patient with a smaller foot stump, or amputation at more distal levels followed by coverage of healthy tendon and bone tissues with a dermal regeneration template (Integra, Integra Life Sciences Corporation, Plainsboro, NJ), which would have preserved the foot stump length and allowed better walking. We opted for the second choice, and the use of a dermal template actually enabled our patient to maintain a considerable foot stump length, much longer than would have resulted from an amputation with immediate primary closure.

Concentrated collagen hydrogels as dermal substitutes

Collagen hydrogels first appeared promising for skin repair. Unfortunately, their extensive contraction and their poor mechanical properties constituted major disadvantages toward their utilization as permanent graft. The present study has investigated a way to correct these drawbacks by increasing the collagen concentration in controlled conditions. Concentrated collagen hydrogels (CCH) at 1.5, 3 and 5 mg/ml were obtained. The effect of raised collagen concentration on contraction, cell growth and remodeling activities was evaluated for 21 days in culture. Subsequently, in vivo integration of CCH and normal collagen hydrogels (NCH) was assessed. Compared to NCH, CCH contraction was delayed and smaller. At day 21, surface area of CCH at 3 mg/ml was 18 times more important than that of NCH. Whatever the initial fibroblast density, CCH favored cell growth that reached about 10 times the initial cell number at day 21; cell proliferation was inhibited in NCH. Gelatinase A activities appeared lower in CCH than within NCH. In vivo studies in rats revealed a complete hydrolysis of NCH 15 days after implantation. In contrast, CCH at 3 mg/ml was still present after 30 days. Moreover, CCH showed cell colonization, neovascularization and no severe inflammatory response. Our results demonstrate that concentrated collagen hydrogels can be considered as new candidates for dermal substitution because they are is easy to handle, do not contract drastically, favor cell growth, and can be quickly integrated in vivo.

Dermal substitution in acute burns and reconstructive surgery: A 12-year follow-up with a collagen–elastin matrix

Dermal substitution in acute burns and reconstructive surgery: A 12-year follow-up with a collagen–elastin matrix

A New Strategy of Using Keratinocytes for Skin Graft: Animal Experimental Study of Keratinocyte Suspension Combined with the Dermal Substitutes

Objective: To provide a new and simple strategy for keratinocyte transplantation. Methods: Keratinocyte suspension and dermal substitutes including acellular dermal matrix (ADM) and collagen membrane were prepared. Full-thickness skin defect wounds of Balb/c-nu mice were created and the mice were assigned into 5 groups: the control group, where the wound was grafted with keratinocyte suspension only; the one-step ADM and collagen membrane groups, where the wound was grafted with ADM or collagen membrane plus dripping of keratinocyte suspension; the two-step ADM and collagen membrane groups, where keratinocyte suspension was dripped 2 weeks after ADM or collagen membrane grafting. The percentage of epithelium was observed. Results: Two weeks after grafting, no evidence of re-epithelialization was seen in the one-step ADM group, and the re-epithelialization rate in the one-step collagen membrane group, two-step ADM group and two-step collagen membrane group was 54.1, 41.8 and 76.8%, respectively, indicating that the re-epithelialization rate in the two-step collagen membrane group was higher than that in the other two groups (p < 0.01). Conclusions: Keratinocyte suspension combined with dermal substitutes grafting offers a more flexible way of making use of keratinocytes. Compared with ADM, microporous collagen membrane is a more preferable option for combined use with keratinocyte suspension for skin grafting.

The Use of a Dermal Substitute and Thin Skin Grafts in the Cure of “Complex” Leg Ulcers

In some chronic leg ulcers, a reconstructive operation using skin grafts may be extremely difficult or is quite likely to fail as a result of the position, the width, and the depth of the lesions. To evaluate the effectiveness of a dermal substitute and thin skin grafts in the treatment of patients suffering from deep and wide chronic leg ulcers. Twenty-six consecutive patients with leg ulcers at least 1 year old were admitted to the study. The ulcers were large (>100 cm2) and deep (>3 mm) over at least 50% of the surface area. After surgical debridement of the wounds, the dermal matrix was modeled and applied. After 21 days, the attachment of the artificial dermis was tested, and in positive cases, the patient was re-admitted for "thin" skin grafting. In all patients, at the first follow-up, a notable reduction in pain, exudate, and perilesional edema was ascertained. After 2 weeks, the progressive substitution of granulation tissue with new yellow or gold derma became evident in all patients. After 21 days, the dermal matrix was completely integrated with the guest tissue. In 23 patients (88.5%), attachment of the skin graft was complete, and in three patients (11.5%), it was partial but nevertheless larger than 70% of the surface. Even in these cases, complete healing of the lesions was achieved within 4 weeks at most. All patients were checked for a minimum of 3 months, and none suffered an ulcerous recurrence. In our series, the use of this dermal matrix allowed for the complete refilling of the loss of tissue, the rapid disappearance of pain, and the rapid regeneration of a permanent dermis.

Bioartificial Dermal Substitute: A Preliminary Report on Its Use for the Management of Complex Combat-Related Soft Tissue Wounds

Bioartificial Dermal Substitute: A Preliminary Report on Its Use for the Management of Complex Combat-Related Soft Tissue Wounds

Development of a dermal matrix from glycerol preserved allogeneic skin

Dermal substitutes can be used to improve the wound healing of deep burns when placed underneath expanded, thin autologous skin grafts. Such dermal matrix material can be derived from xenogeneic or human tissue. Antigenic structures, such as cells and hairs must be removed to avoid adverse inflammatory response after implantation. In this study, a cost-effective method using low concentrations of NaOH for the de-cellularization of human donor skin preserved in 85% glycerol is described. The donor skin was incubated into NaOH for different time periods; 2, 4, 6 or 8 weeks. These dermal matrix prototypes were analyzed using standard histology techniques. Functional tests were performed in a rat subcutaneous implant model and in a porcine transplantation model; the prototypes were placed in full thickness excision wounds covered with autologous skin grafts.An incubation period of 6 weeks was most optimal, longer periods caused damage to the collagen fibers. Elastin fibers were well preserved. All prototypes showed intact biocompatibility in the rat model by the presence of ingrowing blood vessels and fibroblasts at 4 weeks after implantation. An inflammatory response was observed in the prototypes that were treated for only 2 or 4 weeks with NaOH. The prototypes treated with 6 or 8 weeks NaOH were capable to reduce wound contraction in the porcine model. In neo-dermis of these wounds, elastin fibers derived from the prototype could be observed at 8 weeks after operation, surrounded by more random orientated collagen fibers. Thus, using this effective low cost method, a dermal matrix can be obtained from human donor skin. Further clinical studies will be performed to test this material for dermal substitution in deep (burn) wounds.

Decellularized dermis in combination with cultivated keratinocytes in a short‐ and long‐term animal experimental investigation

Decellularized human dermis as a potentially ideal scaffold for dermal substitution in severe burns was examined in a two-staged animal experiment. In an initial step, an in vitro generated composite graft consisting of human keratinocytes and decellularized dermis (AlloDerm) was transplanted onto nude mice in a short-term trial (n = 20, 14 days). Subsequently, a combined one-step grafting of full thickness wounds with both decellularized dermis (in part preincubated with fibroblasts) and cultivated autologous keratinocytes as a cell suspension in fibrin glue was done in a long-term porcine animal model (n = 10, 6 months). In both series, macroscopic wound healing was evaluated by planimetry. Histological investigations included morphological as well as immunohistochemical parameters. The short-term study showed both successful integration of the composite grafts and reduction of wound contraction compared with the control group (epithelial grafts). The long-term porcine study displayed reduced myofibroblast formation and contraction in the wounds that had been treated with fibroblast-preincubated dermis. After 4 weeks, a decline of the structural integrity of the dermal matrix could be noticed. The utility of decellularized dermis as template for both dermal reconstitution and keratinocyte delivery vehicle was shown. The closure of full thickness wounds by a single-step combination of an autologous keratinocyte fibrin sealant suspension and acellular dermis in a pig animal model could be shown. Incorporation of fibroblasts led to reduced wound contraction but could not prevent the loss of dermal integrity. The engineered 'skin' remained viable and stable over a period of 6 months.