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Dermal substitutes require sufficient tissue integration and vascularization to be successfully covered with split-thickness skin grafts. To rapidly achieve this, we provide the proof of principle for a novel vascularization strategy with high translational potential. Nanofat was generated from subcutaneous adipose tissue of green fluorescence protein (GFP)+ C57BL/6J donor mice and seeded onto small samples (4 mm in diameter) of the clinically approved dermal substitute Integra®. These samples and non-seeded controls were then implanted into full-thickness skin defects in the dorsal skinfold chamber of C57BL/6J wild-type mice and analyzed by intravital fluorescence microscopy, histology and immunohistochemistry over a 14-day period. Nanofat-seeded dermal substitutes exhibited an accelerated vascularization, as indicated by a significantly higher functional microvessel density on days 10 and 14 when compared to controls. This was primarily caused by the reassembly of GFP+ microvascular fragments inside the nanofat into microvascular networks. The improved vascularization promoted integration of the implants into the surrounding host tissue, which finally exhibited an increased formation of a collagen-rich granulation tissue. There were no marked differences in the inflammatory host tissue reaction to nanofat-seeded and control implants. These findings demonstrate that nanofat significantly improves the in vivo performance of dermal substitutes without affecting their biocompatibility. [ABSTRACT FROM AUTHOR]

Large surface full-thickness burns pose a significant clinical challenge to the burn surgeon. Integra® dermal matrix has now been commercially available for more than 3 decades. Over this time, its role continues to evolve, and it remains an important tool in the hands of a burn surgeon. Integra® is now being successfully used in acute burn injury, chronic wounds, and reconstructive surgery. Successful outcomes, however, are predicated on a multitude of factors. This overview serves to provide a history of the device, review data and lessons learned, and provide an algorithm for success based on the experience of the authors.

Integra® (Integra LifeSciences) is a well-known dermal regeneration template used in partial and full-thickness wound reconstruction. It can be applied directly on to vascular tissue to create a bed for a skin graft, which is often placed in a second surgery. We present our experience of its novel use in oral and maxillofacial surgery patients, using it directly on bone and cartilage (avascular tissue) without further skin grafting. Patients who required full-thickness excision of lesions down to bone or cartilage and who were treated using Integra® were included. After scalp or ear lesion resection, the collagenous dermal layer of Integra® was placed directly on to bone or cartilage and, along with its outer silicone epidermal layer, secured to the defect with absorbable sutures and a bolster dressing. The wounds were kept dry for 14 days, at which point the dressing and silicone were removed and patients continued regular wound care. Seventeen patients were included, 15 of whom had squamous cell carcinoma. One was lost to follow up. The rest achieved complete healing of the defect. Histology showed epidermis developing on the Integra® surface and at one year, the appearance of normal scarred skin. This novel approach could redefine the uses of Integra®, avoiding the need for free-flap surgery or skin grafting when reconstructing large defects. Further resection of close margins or recurrence is easier after reconstruction using dermal regeneration material than after reconstruction with a local or free flap. [ABSTRACT FROM AUTHOR]

Dermal substitutes require sufficient tissue integration and vascularization to be successfully covered with split-thickness skin grafts. To rapidly achieve this, we provide the proof of principle for a novel vascularization strategy with high translational potential. Nanofat was generated from subcutaneous adipose tissue of green fluorescence protein (GFP)+ C57BL/6J donor mice and seeded onto small samples (4 mm in diameter) of the clinically approved dermal substitute Integra®. These samples and non-seeded controls were then implanted into full-thickness skin defects in the dorsal skinfold chamber of C57BL/6J wild-type mice and analyzed by intravital fluorescence microscopy, histology and immunohistochemistry over a 14-day period. Nanofat-seeded dermal substitutes exhibited an accelerated vascularization, as indicated by a significantly higher functional microvessel density on days 10 and 14 when compared to controls. This was primarily caused by the reassembly of GFP+ microvascular fragments inside the nanofat into microvascular networks. The improved vascularization promoted integration of the implants into the surrounding host tissue, which finally exhibited an increased formation of a collagen-rich granulation tissue. There were no marked differences in the inflammatory host tissue reaction to nanofat-seeded and control implants. These findings demonstrate that nanofat significantly improves the in vivo performance of dermal substitutes without affecting their biocompatibility.

Background/Objectives: The need for surgical reconstruction of scalp defects following the excision of cutaneous skin cancers is an increasingly common procedure. Particular challenges arise when considering options for reconstruction of large defects not amenable to local skin flap coverage. The use of skin grafts poses the risk of donor site morbidity. This paper investigates the emerging use of Integra®, a synthetic acellular dermal regeneration template, as an alternative or adjunct to skin grafting in scalp reconstruction. Methods: The study presents a retrospective analysis of 101 patients who underwent Integra®-based reconstruction of scalp defects. Demographics, procedure details, complications, need for further surgery, and time to healing were evaluated. Results: The overall success rate of the one-stage Integra®-only procedure was 95%, with a minor complication rate of 30.7%. Anticoagulation medication was identified as an independent risk factor for post-operative infection, while previous head and neck radiotherapy and increased defect depth were associated with the requirement for a second-stage skin graft. Conclusions: These findings support the consideration of Integra® as a safe and viable alternative for both partial and full thickness scalp defects in a select cohort of complex highly co-morbid patients, reducing complications and the need for additional procedures. [ABSTRACT FROM AUTHOR]

Several dermal substitutes are available on the market, but there is no precise indication that helps surgeons choose the proper one. Few studies have tried to compare different xenogeneic bioengineered products, but no objective bio-parametric comparison has been made yet. Fifteen patients who underwent skin reconstruction with Integra® or Pelnac® were retrospectively evaluated. After at least 12 months of follow-up, an objective and quantitative assessment of several skin biophysical properties, such as color, texture, elasticity, hydration, glossiness and trans-epidermal water loss, were measured with non-invasive skin measurement devices. The grafted skin showed a reduction of the superficial hydration level and a tendency to lower values of trans-epidermal water loss with both dermal substitutes. Melanic and hemoglobin pigmentation were higher in comparison to the donor site in both groups, while a melanic pigmentation increase versus the surrounding skin was seen just with Integra®. Finally, the skin was found to be more elastic when reconstructed with Integra®. The skin barrier appeared to be intact in both groups. Hence, these substitutes are valuable means of skin regeneration. Integra® seems to be more advantageous for reconstructing areas that need more skin flexibility. [ABSTRACT FROM AUTHOR]

Since its initial design and use for the temporary coverage of severe full-thickness burn defects, Integra® (Integra LifeSciences) Dermal Regeneration Template has been increasingly used all over the body, yielding successful results in coverage of wound beds with insufficient vascularity and suboptimal conditions for proper healing. In this study, we report an institutional case series and outcomes of gender-affirming vaginoplasty revision for vaginal lengthening or reopening of the canal via placement of Integra® to assist in optimizing the wound bed for subsequent skin grafting when wound conditions were deemed to be suboptimal. A retrospective chart review was conducted in patients who underwent this technique by a single surgeon (JM) at the authors' institution. Demographics, vaginal depth, and complications were recorded and compared. Our patient population thus far includes 178 primary vaginoplasties, of which 9 of those needing revision were treated with this approach. The age at revision mean was 47 ± 13.5 years, and the body mass index mean was 31 ± 4.1. All patients had comorbidities and five were former smokers. Eight patients had prior revision conducted without Integra®, with a mean of 1.89 ± 1.76 and the time to first revision mean was 15.89 ± 14.2 months. No long-term complications after Integra® reported and most of the patients did not require further revision. The follow-up mean was 8.48 ± 8.66 months. A mean of 6.77 ± 5.35 cm was gained after the Integra® revision (4.92 ± 4.1 cm before versus 12.54 ± 3.07 cm after). The final depth after Integra® + full-thickness skin graft mean was 13.34 ± 4.65 cm. Overall, the depth gain mean was 7.48 ± 5.77 cm; in total, seven patients gained depth after revision with an average of 78% skin graft take. Overall, Integra® presents an alternative option for revision vaginoplasty with complicated wound beds potentially aiding in the healing process before grafting. [ABSTRACT FROM AUTHOR]

Several dermal substitutes are available on the market, but there is no precise indication that helps surgeons choose the proper one. Few studies have tried to compare different xenogeneic bioengineered products, but no objective bio-parametric comparison has been made yet. Fifteen patients who underwent skin reconstruction with Integra® or Pelnac® were retrospectively evaluated. After at least 12 months of follow-up, an objective and quantitative assessment of several skin biophysical properties, such as color, texture, elasticity, hydration, glossiness and trans-epidermal water loss, were measured with non-invasive skin measurement devices. The grafted skin showed a reduction of the superficial hydration level and a tendency to lower values of trans-epidermal water loss with both dermal substitutes. Melanic and hemoglobin pigmentation were higher in comparison to the donor site in both groups, while a melanic pigmentation increase versus the surrounding skin was seen just with Integra®. Finally, the skin was found to be more elastic when reconstructed with Integra®. The skin barrier appeared to be intact in both groups. Hence, these substitutes are valuable means of skin regeneration. Integra® seems to be more advantageous for reconstructing areas that need more skin flexibility.

Necrotizing fasciitis is a rare infection, often requiring large debridement's due to its rapid spread in the soft tissues. Reconstruction is always a challenge. We report the successful use of Integra® Dermal Regeneration Template, combined with Negative Pressure Wound Therapy and thin skin grafts, and a local flap, to reconstruct the abdominal skin in a 7-year-old boy who developed a necrotizing fasciitis after a trauma with his scooter. Stable coverage was achieved, without skin retraction and with a preserved range of motion at 1-year post-operatively.

Abstract Background The seeding of scaffolds with the stromal vascular fraction (SVF) of adipose tissue is a common prevascularization strategy in tissue engineering. Alternatively, adipose tissue-derived microvascular fragments (ad-MVF) may serve as vascularization units. In contrast to SVF single cells, they represent a mixture of intact arteriolar, capillary and venular vessel segments. Therefore, we herein hypothesized that the ad-MVF-based prevascularization of scaffolds is superior to the conventional SVF single cells-based approach. Results SVF single cells and ad-MVF were enzymatically isolated from epididymal fat pads of green fluorescent protein (GFP)+ donor mice to assess their viability and cellular composition using fluorescence microscopy and flow cytometry. Moreover, collagen-glycosaminoglycan matrices (Integra®) were seeded with identical amounts of the isolates and implanted into full-thickness skin defects within dorsal skinfold chambers of GFP− recipient mice for the intravital fluorescent microscopic, histological and immunohistochemical analysis of implant vascularization and incorporation throughout an observation period of 2 weeks. Non-seeded matrices served as controls. While both isolates contained a comparable fraction of endothelial cells, perivascular cells, adipocytes and stem cells, ad-MVF exhibited a significantly higher viability. After in vivo implantation, the vascularization of ad-MVF-seeded scaffolds was improved when compared to SVF-seeded ones, as indicated by a significantly higher functional microvessel density. This was associated with an enhanced cellular infiltration, collagen content and density of CD31+/GFP+ microvessels particularly in the center of the implants, demonstrating a better incorporation into the surrounding host tissue. In contrast, non-seeded matrices exhibited a poor vascularization, incorporation and epithelialization over time. Conclusions The present study demonstrates that ad-MVF are highly potent vascularization units that markedly accelerate and improve scaffold vascularization when compared to the SVF.

Hypertrophic scars are a common complication of burns treated both conservatively and surgically. The etiology of their formation depends on many factors. The location of the affected area, depth, surface area, individual predispositions, age, nutritional status and therapeutic actions play a crucial role here. A particular tendency to develop hypertrophic scars was found in patients with deep burns whose treatment process was prolonged for more than 2-3 weeks. The risk of occurrence of hypertrophic scars in burns is defined in a wide range between 32-94%. Early treatment of burns, appropriate surgical techniques that minimize damage to healthy tissues; the use of modern dressings and appropriate preventive measures minimizes the risk of hypertrophic scars. The following article presents the stories of two patients in whom a matrix was used for skin regeneration. In the first case, it was used to improve treatment - a massive hypertrophic scar on the neck causing head flexion due to contraction, therefore limiting function. In the second case, the use of a matrix for skin regeneration as prevention of hypertrophic scars was described. In both cases the desired effect was obtained - a flexible and pleasing in terms of aesthetics and functionality area of skin. [ABSTRACT FROM AUTHOR]

Adipose tissue-derived microvascular fragments (ad-MVF) represent promising vascularisation units for bioengineered Integra® matrix wound dressing (MWD). However, due to the sheet-like structure with small pore sizes, the seeding of this matrix with ad-MVF is mainly limited to its surface. Integra® flowable wound matrix (FWM) may be suitable to achieve a more homogeneous distribution and, thus, improved vascularisation, because this gel-like matrix allows for the direct admixture of ad-MVF during sample preparation. To test this hypothesis, we seeded MWD and FWM with an identical number of ad-MVF and assessed their distribution and inter-fragment distance within both matrices. Moreover, ad-MVF-seeded MWD and FWM were implanted into full-thickness skin defects within mouse dorsal skinfold chambers to analyse their vascularisation, epithelialisation and tissue incorporation using intravital fluorescence microscopy, histology and immunohistochemistry. Seeded FWM exhibited a more homogeneous ad-MVF distribution, when compared to MWD. This resulted in a significantly increased inter-fragment distance, preventing the reassembly of ad-MVF into new microvascular networks. Accordingly, the vascularisation of FWM was diminished after implantation, as indicated by a reduced functional microvessel density and blood perfusion. This was associated with a decreased tissue incorporation and epithelialisation of the matrix, when compared to ad-MVF-seeded MWD. Hence, the use of FWM as a carrier system may require a tremendous amount of ad-MVF to shorten their inter-fragment distance and, thus, to maintain their vascularisation capacity for tissue engineering applications.

Soft tissue covering of degloving injuries of fingers remains a common challenge in trauma. In this case, we report the good long-term results after the use of Integra ® Dermal Regeneration Template in combination with a split-thickness skin graft as an alternative treatment option for a patient with a traumatic degloving injury of multiple fingers.

Introduction: The goal of lower extremity reconstruction after trauma is the coverage of defects to give patients a healed wound and to let them resume their life, ambulate and return to work, while preventing amputation. In this article, we describe an innovative use of Integra® for free flap pedicle coverage in lower extremity reconstruction. Materials and methods: Between January 2011 and December 2015, ten patients, four women and six men, underwent a lower limb reconstruction with an association of free flap and Integra® to cover the flap pedicle. The mean age of the patients was 38.8±15.6 years at the time of surgery (range of 14-59 years). The mean defect size was 102±54 cm2 (range of 40-160 cm2). The bone and/or tendons were exposed at the level of the middle third of the leg in 2 cases, at the level of the distal leg in 5 cases and at the level of the foot in 3 cases. Results: There were no intra-operative complications. Mean size of Integra® needed for flap pedicle coverage was 12.8±2.3 cm2 (range 10-15 cm2). The mean follow-up was 41±19 months (range 21-70 months). Revision surgery was necessary in three cases due to haematoma of the pedicle. In these cases, the dermal substitute was easily removed while awaiting revision. This allowed flap survival in all cases. A skin graft was performed after a mean time of 3.4±0.8 weeks post-operatively. Complications at the donor site level included one seroma and a case of hypertrophic scar. Complete healing of both the donor and recipient sites was achieved in all cases. Conclusions: The combination of free flap and Integra® appears to be a useful option in covering complex defects in the lower limb. The dermal substitute avoids skin tension and compression of the pedicle. Haematomas of the pedicle, if they occur, are highly visible and thus easy to manage. We hypothesize that the use of dermal substitute for this specific indication of pedicle coverage will expand in the near future. [ABSTRACT FROM AUTHOR]

Integra® matrix wound dressing (MWD) is used for the reconstruction of full-thickness skin defects. For the treatment of complex wounds, this dermal substitute is available as a flowable wound matrix (FWM) of identical composition. To clarify whether variations in sample preparation and consistency affect the biocompatibility and tissue incorporation, we herein compared MWD and FWM. The matrices were characterized using scanning electron microscopy and histology. Moreover, they were implanted in mouse dorsal skinfold chambers to analyze their in vivo performance over 2 weeks. Scanning electron microscopy showed a planar surface of MWD whereas FWM presented an irregular, fissured morphology. However, histology of the two matrices revealed an identical fiber thickness, fiber length, and interfiber distance. Repetitive stereo-microscopy and immunohistochemical analyses of MWD and FWM showed a comparable epithelialization of the implants in the dorsal skinfold chamber model. At day 14, both matrices exhibited a low collagen content and microvessel density. Moreover, they were infiltrated by a high number of myeloperoxidase (MPO)-positive neutrophilic granulocytes and a lower number of MAC387-positive macrophages and CD3-positive lymphocytes. These findings demonstrate that differences in preparation and consistency do not affect the tissue response to MWD and FWM, indicating a comparable regenerative capacity in wound healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 52-60, 2018. [ABSTRACT FROM AUTHOR]

Introduction: Much attention has been directed towards understanding the phenomena of angiogenesis and lymphangiogenesis in wound healing. Thanks to the manifold dermal substitute available nowadays, wound treatment has improved greatly. Many studies have been published about angiogenesis and cell invasion in INTEGRA®. On the other hand, the development of the lymphatic network in acellular dermal matrix (ADM) is a more obscure matter. In this article, we aim to characterize the different phases of host cell invasion in ADM. Special attention was given to lymphangiogenic aspects. Materials and Methods: Among 57 rats selected to analyse the role of ADM in lymphangiogenesis, we created four groups. We performed an excision procedure on both thighs of these rats: On the left one we did not perform any action except repairing the borders of the wound; while on the right one we used INTEGRA® implant. The excision biopsy was performed at four different times: First group after 7 days, second after 14 days, third after 21 days and fourth after 28 days. For our microscopic evaluation, we used the classical staining technique of haematoxylin and eosin and a semi-quantitative method in order to evaluate cellularity counts. To assess angiogenesis and lymphangiogenesis development we employed PROX-1 Ab and CD31/PECAM for immunohistochemical analysis. Results: We found remarkable wound contraction in defects that healed by secondary intention while minor wound contraction was observed in defects treated with ADM. At day 7, optical microscopy revealed a more plentiful cellularity in the granulation tissue compared with the dermal regeneration matrix. The immunohistochemical process highlighted vascular and lymphatic cells in both groups. After 14 days a high grade of fibrosis was noticeable in the non-treated group. At day 21, both lymphatic and vascular endothelial cells were better developed in the group with a dermal matrix application. At day 28, lymphatic endothelial cells had organized themselves, engineering the pseudocylindrical structure better disposed in the ADM group than in the control group, and the lymphatic cells were detectable inside the vessels’ lumen in this group. Conclusion: This study has made it possible to demonstrate the absolute importance of an ADM in proper wound healing and has shown better definition of both the qualitative and quantitative aspects of lymphangiogenesis compared to the second intention healing. A major grade of organization of the extracellular matrix and a minor grade of fibrosclerosis in ADM allowed a well-structured morphologic and functional development of the endothelial and lymphatic vascular structures. This study hopes to represent a clinical basis for a wider use of ADM in lesions where lymphatic complications are common.

The major challenge for stem cell translation regenerative medicine is the regeneration of damaged tissues by creating biological substitutes capable of recapitulating the missing function in the recipient host. Therefore, the current paradigm of tissue engineering strategies is the combination of a selected stem cell type, based on their capability to differentiate toward committed cell lineages, and a biomaterial, that, due to own characteristics (e.g., chemical, electric, mechanical property, nano-topography, and nanostructured molecular components), could serve as active scaffold to generate a bio-hybrid tissue/organ. Thus, effort has been made on the generation of in vitro tissue engineering modeling. Here, we present an in vitro model where human adipose stem cells isolated from lipoaspirate adipose tissue and breast adipose tissue, cultured on polymeric INTEGRA® Meshed BilayerWound Matrix (selected based on conventional clinical applications) are evaluated for their potential application for reconstructive surgery toward bone and adipose tissue. We demonstrated that human adipose stem cells isolated from lipoaspirate and breast tissue have similar stemness properties and are suitable for tissue engineering applications. Finally, the overall results highlighted lipoaspirate adipose tissue as a good source for the generation of adult adipose stem cells. [ABSTRACT FROM AUTHOR]

Introduction: Much attention has been directed towards understanding the phenomena of angiogenesis and lymphangiogenesis in wound healing. Thanks to the manifold dermal substitute available nowadays, wound treatment has improved greatly. Many studies have been published about angiogenesis and cell invasion in INTEGRA®. On the other hand, the development of the lymphatic network in acellular dermal matrix (ADM) is a more obscure matter. In this article, we aim to characterize the different phases of host cell invasion in ADM. Special attention was given to lymphangiogenic aspects. Materials and Methods: Among 57 rats selected to analyse the role of ADM in lymphangiogenesis, we created four groups. We performed an excision procedure on both thighs of these rats: On the left one we did not perform any action except repairing the borders of the wound; while on the right one we used INTEGRA® implant. The excision biopsy was performed at four different times: First group after 7 days, second after 14 days, third after 21 days and fourth after 28 days. For our microscopic evaluation, we used the classical staining technique of haematoxylin and eosin and a semi-quantitative method in order to evaluate cellularity counts. To assess angiogenesis and lymphangiogenesis development we employed PROX-1 Ab and CD31/PECAM for immunohistochemical analysis. Results: We found remarkable wound contraction in defects that healed by secondary intention while minor wound contraction was observed in defects treated with ADM. At day 7, optical microscopy revealed a more plentiful cellularity in the granulation tissue compared with the dermal regeneration matrix. The immunohistochemical process highlighted vascular and lymphatic cells in both groups. After 14 days a high grade of fibrosis was noticeable in the non-treated group. At day 21, both lymphatic and vascular endothelial cells were better developed in the group with a dermal matrix application. At day 28, lymphatic endothelial cells had organized themselves, engineering the pseudocylindrical structure better disposed in the ADM group than in the control group, and the lymphatic cells were detectable inside the vessels' lumen in this group. Conclusion: This study has made it possible to demonstrate the absolute importance of an ADM in proper wound healing and has shown better definition of both the qualitative and quantitative aspects of lymphangiogenesis compared to the second intention healing. A major grade of organization of the extracellular matrix and a minor grade of fibrosclerosis in ADM allowed a well-structured morphologic and functional development of the endothelial and lymphatic vascular structures. This study hopes to represent a clinical basis for a wider use of ADM in lesions where lymphatic complications are common. [ABSTRACT FROM AUTHOR]

Résumé: Nous présentons le cas d’une patiente atteinte d’épidermolyse bulleuse dystrophique dominante. Les lésions cutanées de cette patiente, multigreffée et suivie pendant dix ans, ont été traitées par Integra® et greffe de peau mince. L’expérience nous a montré que la qualité de la prise de greffe était subordonnée à l’exérèse complète des tissus lésés et indurés, à savoir non seulement celle du derme très épaissi, mais également celle d’une partie du tissu sous-cutané. [ABSTRACT FROM AUTHOR]

Background: Large full thickness skin defects caused by trauma or surgery require skin grafting, often in conjunction with dermal scaffolds such as INTEGRA®. Due to the size and severity of these procedures, complications such as infection may occur. This can lead to poor healing outcomes. Objective: To identify early biomarkers of complications during INTEGRA® healing. Methods: Levels of EGF, TGF-β1, FGF-2, VEGF, IFN-α, GM-CSF, IL-4 and IL-8 were measured pre-surgery and at days 1, 7 and 25 post-surgery in peripheral blood of 15 pediatric patients treated with INTEGRA® for reconstructive procedures. The levels of these molecules were analysed with respect to the occurrence of complications. Results: Complications (local infection) occurred in a group of 4 patients. This resulted in a reduced INTEGRA® take rate comparing to the group without complications (71.5±5.4% vs. 98.1±0.7%). In cases with complications there were significantly higher plasma concentrations of IL-4 and FGF-2 on day 7 (p =0.037 and p =0.008 respectively). Other markers were not significantly different between groups or at very low level at all time-points. WCC and CRP remained within normal ranges at all time-points. Conclusions: This data suggests that elevated levels of IL-4 and FGF-2 at early time-points after surgery may predict the development of complications in patients with INTEGRA®. This may enable early interventions to prevent complications in procedures involving the use of INTEGRA®. [Copyright &y& Elsevier]

We report our experience with the use of Integra® for the management of severe traumatic wounds of the hand. Fifteen patients were treated with follow-up ranging from 10 to 37 months. Wounds were associated with an osseous and/or joint and/or tendon exposure. Following Integra® placement, patients were managed with dressings and subsequent split-thickness skin grafting an average of 26 days later. Integra® was successful in achieving durable, functional and aesthetic definitive coverage in 13 of 15 applications while allowing a satisfying pollicidigital prehension. Regarding our clinical experience, Integra® is an effective technique to deal with severe wounds of the hand with exposed tendon and/or bone and/or joint, even in the absence of paratenon or periosteum. This can potentially lessen the need for local rotational or free flap coverage and should be taken into consideration as a viable alternative in traumatic reconstruction of the hand. [ABSTRACT FROM PUBLISHER]

Summary: The reconstruction of large full-thickness scalp defects remains a challenge, particularly when dura is exposed. Various reconstructive methods have been described in the past. Dermal Regeneration Templates (DRTs) are becoming increasingly popular in the management of acute wounds as well as the reconstruction of burn scars, oncological defects and various other complex reconstructive problems. We describe a case where Integra® was successfully used together with a Vacuum-Assisted Closure (VAC) dressing to reconstruct a full-thickness scalp defect with exposed dura. Surgical technique is discussed as well as problems encountered during the case and possible solutions. [ABSTRACT FROM AUTHOR]

Wounds with exposed vessels, especially in artery bypass procedures, can pose a barrier to adequate skin healing. Skin grafts or flaps are sometimes difficult to perform in the face of the ischaemia that is often present in such cases. We report a case of a 73-year-old man who presented with grade IV peripheral arterial disease necessitating salvage of the lower limb using artery bypass surgery. Immediate exposure of femorotibial artery secondary to skin necrosis following the bypass led us to propose an innovative means of wound coverage using Integra®, a well-known dermal regeneration template. The wound healed uneventfully with an appearance similar to that of the adjacent skin. Integra® seems to be less demanding in terms of the vascular wound bed and the degree of oxygenation than a conventional skin graft. This finding could support further indications for this dermal regeneration template. [ABSTRACT FROM AUTHOR]

Summary: Xeroderma pigmentosum is a rare and severe photodermatitis without cure. Skin cancers are inevitable and give rise to iterative skin resections often mutilating especially in the face. We report the case of two sisters suffering from severe forms of xeroderma pigmentosum. Given the rapid emergence of multicancerous lesions, we opted for a radical approach entailing successively all aesthetic sub-units of the face. The reconstruction uses an original method used initially in the great burned: the artificial dermis. This simple method, providing a quality sub-soil, has helped us in these two complex cases to ensure coverage of a large defect providing a tissue recovery of excellent trophic and aesthetics quality. Thanks to this treatment strategy, we were able to significantly delay the development of this disease. With a retreat of 35months, the quality of reconstruction by artificial dermis is considered to be satisfactory for its elasticity and its trophicity. [Copyright &y& Elsevier]

Summary: Integra® dermal substitute is used as biomaterial after thermal injury. This artificial skin allows temporary coverage after burns excision, transformation of matrix in neo dermis and definitive engraftment. Infections are the most common complication of this technique. The objectives were to evaluate incidence of sepsis, to analyse microbiology and risk factors of developing Integra® infections. Patients with acute burns and indications of Integra® during five years were retrospectively enrolled. Demographic data, surgical procedures and microbiologic biopsies were collected. Fifty patients (40±15 years) were studied and 71surgical procedures using Integra® were performed. Burns were extended 45±21% total body surface area. Placement of Integra® was made 15±11days after burns and autografts 31±9days after placement of Integra®. Twenty-one patients had infected Integra® (42% of population). A total of 23Integra® infected sites were observed (15local and eight invasive). Diagnosis of infection was made after 13±5days using quantitative cultures. Other sites of infection were respiratory tract (46pneumonias) and others burned wounds (17infections outside of Integra®). Any risk factor was identified between burns who developed Integra® infections and the others. Incidence of infected Integra® was higher than in previous studies. Delayed application of Integra® after burns could explain higher incidence of infection. Pseudomonas aeruginosa and Staphylococcus aureus were more frequently isolated than other pathogens. Standardized technique for wounds coverage with Integra® is necessary to reduce incidence of infections and improve functional results in burns patients. [Copyright &y& Elsevier]

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Abstract: Aim: To compare engraftment rates and vascularisation in a rat model using either Integra Artificial Skin® or Matriderm®. Methods: Matriderm® and the dermal part of Integra® were compared in a two-step procedure including matrix implantation and subsequent epidermal grafting. Neonatal rat epidermis was used as coverage to test for rapid and complete take. Results: Efficiency and quality of vascularisation expressed by take rate of epidermis, and thickness of resulting neodermis, were identical for both matrices. Conclusion: This first comparison of Matriderm® with Integra® in a rat model revealed no major differences in engraftment rates or vascularisation. [Copyright &y& Elsevier]

Integra has been shown to be very useful in accelerating the growth of neodermis. It has found extensive use in case of burns as a primary dressing immediately after a burn, after release of contractures and following scar revision. It has been used to achieve cover after the debridement of extensive infective processes involving the skin. Encouraged by these results we have assessed the application of Integra to augment and/or patch defects of the urinary bladder, diaphragm and the abdominal wall in the rat model. This was a pilot study and involved the incorporation of Integra in the diaphragm, the urinary bladder (extramucosal) and the muscle layer of the abdominal wall. Eight adult Wistar rats were given general anaesthesia and Integra was implanted with absorbable sutures at the sites mentioned. The omentum was hitched to the collagen matrix surface to revascularise the graft. The silicone was left in situ. The operative period was covered with antibiotics. The anaesthesia was then reversed. Postoperatively the rats were given analgesia and feeds started immediately. The rats were sacrificed after 3 weeks. The abdominal cavity was examined for adhesions. The Integra implant along with adjacent tissue was harvested and examined histologically. There were no visible intra-abdominal adhesions. The histology revealed good degree of neovascularisation and fibrosis in and adjacent to the implant. This was comparable to the changes seen in the skin. This pilot study has shown that implanting Integra invokes a similar response in deeper tissues and it can develop neovascularisation from the omentum. Hence, this could find some application in treating congenital conditions such as diaphragmatic hernias, abdominal wall defects and for bladders requiring augmentation. Our initial results are quite encouraging and we feel that this field should be further explored. [ABSTRACT FROM AUTHOR]

Abstract: Management of deep facial burns remains one of the greatest challenges in burn care. We have developed a protocol over the past 20 years for management of facial burns that includes excision and coverage with thick autograft. However, the results were not perfect. Deformities of the eyelids, nose and mouth as well as the prominence of skin graft junctures demonstrated the need to explore novel approaches. Integra® has been used with success in the management of burns of the trunk and extremities. The purpose of this study was to prospectively evaluate the aesthetic outcome of the use of Integra® for deep facial burns. Twelve consecutive patients underwent excision of large, deep facial burns and placement of Integra®. Integra® provides excellent color and minimally visible skin graft junctures. The texture is good but not as supple as thick autograft. Integra® is not well suited for use in the coverage of eyelid burns due to the need to wait 2 weeks for adequate vascularization. In summary, thick autograft remains the gold standard for deep facial burns. However, for patients with extensive burns and limited donor sites, Integra® provides an acceptable alternative. [Copyright &y& Elsevier]

This case report describes the successful wound management of a 19-year-old patient with 76% of his body surface burnt. Due to the severity of the burns and the limited availability of native skin, 63% of the body surface were covered with Integra®, a dermis equivalent. This material has been developed for the reconstruction of dermal structures and is designed as a bilayer. It consists of a modified, bovine collagen matrix and a silastic membrane facing toward the body surface. After vascularization of Integra®, the epidermal skin replacement was created in a second step. In four different therapy procedures autologous, cultivated keratinocytes were combined with autologous fibroblast suspensions of various concentration and split-thickness skin as a 1:6 mesh graft. Rapid and largely complication-free wound healing could be achieved despite the limited availability of native skin. A correlation could be observed between the time of complete wound closure and the number of fibroblasts applied. The patient was monitored over a period of 1 year and showed good functional and cosmetic results. [Copyright &y& Elsevier]

Summary Non-specific re-innervation of target organs caused by misdirected axonal growth at the repair site is regarded as one reason for a poor functional outcome after peripheral nerve transsection and repair. This study investigates the rate of aberrant re-innervation and its influence on motor recovery in the rat sciatic nerve using artificial sheets as barrier between tibial and peroneal nerves. The sciatic nerve was transsected and repaired as follows: epineural sutures (A×6), fascicular repair of tibial and peroneal nerves respectively (B×8), and the same as in group B, but separating both nerves using an Integra®-sheet with silicone (C×8), or Integra® without silicone (D×8). As control, solely the tibial nerve was transsected and repaired (E×5). Final investigations after 4 months revealed that in group C, 50% of the Integra®-silicone sheets were dislocated. No dislocation was found in group D. Muscle contraction force of the gastrocnemius muscle was significantly higher in group E as compared to all other groups. However although not significant, group D showed a consistently higher muscle contraction force than groups A, B, and C. Histology in groups A, B, and C with dislocated sheets demonstrated multiple axons growing from the tibial to the peroneal nerve and vice versa. In groups D and E, no such axonal growth was visible. These findings were confirmed by a significantly higher rate of specific re-innervation of the soleus muscle using sequential retrograde double labelling technique. Results of this study suggest that an artificial sheet such as Integra® bears the potential of preventing aberrant re-innervation between repaired adjacent nerves resulting in improved motor recovery. Clinically, this technique may be of importance for brachial plexus, sciatic nerve, and facial nerve repair. [ABSTRACT FROM AUTHOR]

Summary: Traumatic injuries of male external genitalia are rare and not usually life threatening; however, they can have psychological repercussions. The reconstructive management of these lesions is challenging and articulated. We report the case of a 38-year-old farmer suffering from a degloving wound on the external genitalia. The first reconstructive step used to treat the wound was the incorporation of a dermal regeneration template (Integra®) and accordingly partial-thickness skin grafts and local flaps. The follow-up 16 months after the first treatment was satisfying; sexual function had been restored. [Copyright &y& Elsevier]

Necrotizing fasciitis is a rare infection, often requiring large debridement's due to its rapid spread in the soft tissues. Reconstruction is always a challenge. We report the successful use of Integra® Dermal Regeneration Template, combined with Negative Pressure Wound Therapy and thin skin grafts, and a local flap, to reconstruct the abdominal skin in a 7-year-old boy who developed a necrotizing fasciitis after a trauma with his scooter. Stable coverage was achieved, without skin retraction and with a preserved range of motion at 1-year post-operatively. [ABSTRACT FROM AUTHOR]

Engineered dermal templates have revolutionised the repair and reconstruction of skin defects. Their interaction with the wound microenvironment and linked molecular mediators of wound repair is still not clear. This study investigated the wound bed and acellular "off the shelf" dermal template interaction in a mouse model. Full-thickness wounds in nude mice were grafted with allogenic skin, and either collagen-based or fully synthetic dermal templates. Changes in the wound bed showed significantly higher vascularisation and fibroblast infiltration in synthetic grafts when compared to collagen-based grafts (P ≤ 0.05). Greater tissue growth was associated with higher prostaglandin-endoperoxide synthase 2 (Ptgs2) RNA and cyclooxygenase-2 (COX-2) protein levels in fully synthetic grafts. Collagen-based grafts had higher levels of collagen III and matrix metallopeptidase 2. To compare the capacity to form a double layer skin substitute, both templates were seeded with human fibroblasts and keratinocytes (so-called human skin equivalent or HSE). Mice were grafted with HSEs to test permanent wound closure with no further treatment required. We found the synthetic dermal template to have a significantly greater capacity to support human epidermal cells. In conclusion, the synthetic template showed advantages over the collagen-based template in a short-term mouse model of wound repair. [ABSTRACT FROM AUTHOR]

Wstęp Stopień dysfunkcji ręki po głębokim oparzeniu zależy głównie od stopnia oparzenia, prawidłowości leczenia oraz od wieku pacjenta. Chirurgia rekonstrukcyjna w ciężkich przykurczach pooparzeniowych jest ogromnym wyzwaniem. O ile u dorosłych można przewidzieć liczbę zabiegów czy ich zakres, o tyle leczenie przykurczu ręki rosnącego dziecka jest dużo trudniejsze do precyzyjnego zaplanowania. Wymaga nie tylko umiejętności, lecz także doświadczenia. Możliwość zastosowania różnych technik operacyjnych, jak i ich kombinacji jest koniecznym elementem służącym poprawie jakości życia pacjentów po głębokim oparzeniu ręki. Cel Praca przedstawia wybrane rozwiązania chirurgiczne zastosowane w leczeniu ciężkich przykurczów pooparzeniowych - zarówno u dorosłych, jak i u dzieci. Przedstawiony materiał kliniczny opiera się na dwudziestoletnim doświadczeniu w chirurgicznym leczeniu konsekwencji ciężkich oparzeń u dzieci i dorosłych. Materiał i metody Prezentacja przedstawia najbardziej skomplikowane przypadki, w których zastosowano rozmaite rozwiązania rekonstrukcyjne. Praca dotyczy wtórnych operacji korekcyjnych przeprowadzonych u chorych w różnym okresie czasu od oparzenia. W zabiegach tych stosowano między innymi: płaty miejscowe, przeszczepy skórne, Integrę® czy rekonstrukcję ścięgien prostowników lub artrodezę. Wyniki Zastosowanie odpowiednich technik chirurgicznych z uwzględnieniem wieku i wzrostu pacjentów pozwoliło na uzyskanie poprawy funkcji ręki. Wnioski Przedłużanie leczenia zachowawczego w leczeniu oparzenia ręki, unikanie przeszczepów skóry czy stosowanie nieprawidłowych opatrunków może doprowadzić do poważnego kalectwa. Umiejętność wykorzystania rozmaitych technik rekonstrukcyjnych związanych zarówno z wiedzą dotyczącą leczenia blizn, jak i chirurgii ręki pozwala na poprawę jakości życia pacjentów dotkniętych pooparzeniową dysfunkcją ręki. [ABSTRACT FROM AUTHOR]

Introduction: The goal of lower extremity reconstruction after trauma is the coverage of defects to give patients a healed wound and to let them resume their life, ambulate and return to work, while preventing amputation. In this article, we describe an innovative use of Integra® for free flap pedicle coverage in lower extremity reconstruction., Materials and Methods: Between January 2011 and December 2015, ten patients, four women and six men, underwent a lower limb reconstruction with an association of free flap and Integra® to cover the flap pedicle. The mean age of the patients was 38.8±15.6 years at the time of surgery (range of 14-59 years). The mean defect size was 102±54 cm 2 (range of 40-160 cm 2 ). The bone and/or tendons were exposed at the level of the middle third of the leg in 2 cases, at the level of the distal leg in 5 cases and at the level of the foot in 3 cases., Results: There were no intra-operative complications. Mean size of Integra® needed for flap pedicle coverage was 12.8±2.3 cm 2 (range 10-15 cm 2 ). The mean follow-up was 41±19 months (range 21-70 months). Revision surgery was necessary in three cases due to haematoma of the pedicle. In these cases, the dermal substitute was easily removed while awaiting revision. This allowed flap survival in all cases. A skin graft was performed after a mean time of 3.4±0.8 weeks post-operatively. Complications at the donor site level included one seroma and a case of hypertrophic scar. Complete healing of both the donor and recipient sites was achieved in all cases., Conclusions: The combination of free flap and Integra® appears to be a useful option in covering complex defects in the lower limb. The dermal substitute avoids skin tension and compression of the pedicle. Haematomas of the pedicle, if they occur, are highly visible and thus easy to manage. We hypothesize that the use of dermal substitute for this specific indication of pedicle coverage will expand in the near future.

Integra ® matrix wound dressing (MWD) is used for the reconstruction of full-thickness skin defects. For the treatment of complex wounds, this dermal substitute is available as a flowable wound matrix (FWM) of identical composition. To clarify whether variations in sample preparation and consistency affect the biocompatibility and tissue incorporation, we herein compared MWD and FWM. The matrices were characterized using scanning electron microscopy and histology. Moreover, they were implanted in mouse dorsal skinfold chambers to analyze their in vivo performance over 2 weeks. Scanning electron microscopy showed a planar surface of MWD whereas FWM presented an irregular, fissured morphology. However, histology of the two matrices revealed an identical fiber thickness, fiber length, and interfiber distance. Repetitive stereo-microscopy and immunohistochemical analyses of MWD and FWM showed a comparable epithelialization of the implants in the dorsal skinfold chamber model. At day 14, both matrices exhibited a low collagen content and microvessel density. Moreover, they were infiltrated by a high number of myeloperoxidase (MPO)-positive neutrophilic granulocytes and a lower number of MAC387-positive macrophages and CD3-positive lymphocytes. These findings demonstrate that differences in preparation and consistency do not affect the tissue response to MWD and FWM, indicating a comparable regenerative capacity in wound healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 52-60, 2018., (© 2016 Wiley Periodicals, Inc.)

Introduction: Integra® dermal replacement has a wide spectrum of use both in burn medicine as well as in reconstructive plastic surgery and traumatology. Since 2002, it has been a part of surgical treatment of patients at Prague Burns Centre of the Královské Vinohrady Teaching Hospital., Study Group: Integra® was used in 47 patients in total between years 2002 and 2016. In this group there were 28 paediatric patients and 19 adult patients. Eleven children were operated during the reconstructive period, 8 children had an acute injury. There were 11 adult patients with Integra® applied within the trauma treatment, another 9 during reconstructive surgery. In 2016, we examined 11 patients treated by Integra®, at least 2 years ago. The average time since the application was 9 years. All examined patients had Integra® primarily applied to treat an acute injury., Method: Scars after the application of Integra® were compared with scars after dermoepidermal grafts (DE) in respective patients. Evaluation was performed on the basis of subjective and objective assessment by means of the modified Vancouver Scale (VSS). Samples were submitted for a histological and immunohistochemical analysis., Results: Areas with Integra® coverage scored 1.4 points on average on the VSS. The scars after dermoepidermal graft scored 4 points on the same scale. Subjective assessment of functional and cosmetic quality of scars by patients was better in all cases in comparison to DE grafting. Notable differences were found between scars following Integra® application and those after DE grafting on histological assessment, namely in the organization and quality of collagen and elastin fibres as well as in tissue revascularization., Conclusion: The Integra® artificial skin replacement is a part of surgical strategy in management of extensive burn trauma and plays an important role in reconstructive surgery. The resulting scar quality when using Integra® seems to be better than in DE grafting both from an objective and subjective points of view..