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Journal of the Royal Society, Interface Feb 2010Situations where normal autografts cannot be used to replace damaged skin often lead to a greater risk of mortality, prolonged hospital stay and increased expenditure... (Review)
Review
Situations where normal autografts cannot be used to replace damaged skin often lead to a greater risk of mortality, prolonged hospital stay and increased expenditure for the National Health Service. There is a substantial need for tissue-engineered skin bioconstructs and research is active in this field. Significant progress has been made over the years in the development and clinical use of bioengineered components of the various skin layers. Off-the-shelf availability of such constructs, or production of sufficient quantities of biological materials to aid rapid wound closure, are often the only means to help patients with major skin loss. The aim of this review is to describe those materials already commercially available for clinical use as well as to give a short insight to those under development. It seeks to provide skin scientists/tissue engineers with the information required to not only develop in vitro models of skin, but to move closer to achieving the ultimate goal of an off-the-shelf, complete full-thickness skin replacement.
Topics: Biocompatible Materials; Biomechanical Phenomena; Humans; Skin Transplantation; Skin, Artificial; Tissue Engineering; Tissue Scaffolds; Wound Healing
PubMed: 19864266
DOI: 10.1098/rsif.2009.0403 -
Journal of Investigative Medicine : the... Oct 2010Biocompatible, degradable polymer scaffolds combined with cells or biological signals are being investigated as alternatives to traditional options for tissue...
Biocompatible, degradable polymer scaffolds combined with cells or biological signals are being investigated as alternatives to traditional options for tissue reconstruction and transplantation. These approaches are already in clinical use as engineered tissues that enhance wound healing and skin regeneration. The continued enhancement of these material strategies is highly dependent on the ability to promote rapid and stable neovascularization (new blood vessel formation) within the scaffold. Whereas neovascularization therapies have shown some promise for the treatment of ischemic tissues, vascularization of polymer scaffolds in tissue engineering strategies provides a unique challenge owing to the volume and the complexity of the tissues targeted. In this article, we examine recent advances in research focused on promoting neovascularization in polymer scaffolds for tissue engineering applications. These approaches include the use of growth factors, cells, and novel surgical approaches to both enhance and control the nature of the vascular networks formed. The continued development of these approaches may lead to new tissue engineering strategies for the generation of skin and other tissues or organs.
Topics: Biocompatible Materials; Humans; Neovascularization, Physiologic; Polymers; Skin Transplantation; Tissue Engineering; Tissue Scaffolds
PubMed: 20683343
DOI: 10.231/JIM.0b013e3181f18e38 -
The Journal of Surgical Research Oct 2018Importance: Hernia surgery requires reinforcement material with few side effects when used in the intraperitoneal position. Autologous skin grafting may meet this...
BACKGROUND
Importance: Hernia surgery requires reinforcement material with few side effects when used in the intraperitoneal position. Autologous skin grafting may meet this requirement, but animal experiments are obligatory before being applied in humans.
OBJECTIVE
To compare survival and effects of isogeneic full-thickness skin grafts in the intraperitoneal onlay mesh (IPOM) position in mice, with a control group using the onlay position. Primary end point was graft survival and secondary end point adhesion formation and inflammation through NF-κB activity.
METHODS
Design: Intervention study with 8-week follow-up in accordance with ARRIVE criteria, performed between 2015 and 2016.
SETTING
Animal laboratory.
PARTICIPANTS
Transgenic C57BL/6 mice with isogeneic background were used. Recipients were female wild-type phenotype mice >3 mo (n = 24). Donors were male or female mice >7 mo, with phenotype-positive for the luciferase gene (n = 20) or positive for NF-κB-luciferase gene (n = 4).
INTERVENTION
Full-thickness skin was grafted in the IPOM position and compared with grafts in the onlay position as controls. Survival was evaluated by regular longitudinal postoperative luminescence imaging over 8 wk. Adherence formation was evaluated macroscopically after sacrifice. Inflammation of full-thickness skin grafts in IPOM position of NF-κB mice was evaluated in four additional mice. Main outcome and measure: Survival of grafts, evaluated by luminescence.
RESULTS
Ten animals received grafts in the IPOM position, and 10 in the onlay position as controls. Graft survival after 8 wk was 100% (20/20). Average luminescence at the end of the 8-week period was 999,597 flux (min 162,800, max 2,521,530) in the IPOM group (n = 10) and 769,708 flux (min 76,590, max 2,164,080) in the onlay control group (n = 10). No adhesions requiring sharp dissection (Jenkins' scale >2) were seen. Four animals with grafts in the IPOM position showed peak inflammation (NF-κB activity) 5 d after surgery subsiding toward the end of follow-up.
CONCLUSIONS
Full-thickness skin survives as well in the IPOM position as in the onlay control position, and few adherences develop. Further studies are required to fully characterize the tissue remodeling and repair processes associated with IPOM skin grafting. The result is relevant in the search for alternative reinforcement materials to be used in complex hernia surgery in humans.
Topics: Animals; Animals, Genetically Modified; Disease Models, Animal; Female; Follow-Up Studies; Graft Survival; Hernia, Abdominal; Herniorrhaphy; Humans; Male; Mice; Mice, Inbred C57BL; Postoperative Complications; Prostheses and Implants; Skin Transplantation; Surgical Mesh; Transplantation, Isogeneic; Treatment Outcome
PubMed: 30100033
DOI: 10.1016/j.jss.2018.04.041 -
Journal of Burn Care & Research :... 2017Stable closure of full-thickness burn wounds remains a limitation to recovery from burns of greater than 50% of the total body surface area (TBSA). Hypothetically,... (Comparative Study)
Comparative Study Randomized Controlled Trial
Stable closure of full-thickness burn wounds remains a limitation to recovery from burns of greater than 50% of the total body surface area (TBSA). Hypothetically, engineered skin substitutes (ESS) consisting of autologous keratinocytes and fibroblasts attached to collagen-based scaffolds may reduce requirements for donor skin, and decrease mortality. ESS were prepared from split-thickness skin biopsies collected after enrollment of 16 pediatric burn patients into an approved study protocol. ESS and split-thickness autograft (AG) were applied to 15 subjects with full-thickness burns involving a mean of 76.9% TBSA. Data consisted of photographs, tracings of donor skin and healed wounds, comparison of mortality with the National Burn Repository, correlation of TBSA closed wounds with TBSA full-thickness burn, frequencies of regrafting, and immunoreactivity to the biopolymer scaffold. One subject expired before ESS application, and 15 subjects received 2056 ESS grafts. The ratio of closed wound to donor areas was 108.7 ± 9.7 for ESS compared with a maximum of 4.0 ± 0.0 for AG. Mortality for enrolled subjects was 6.25%, and 30.3% for a comparable population from the National Burn Repository (P < .05). Engraftment was 83.5 ± 2.0% for ESS and 96.5 ± 0.9% for AG. Percentage TBSA closed was 29.9 ± 3.3% for ESS, and 47.0 ± 2.0% for AG. These values were significantly different between the graft types. Correlation of % TBSA closed with ESS with % TBSA full-thickness burn generated an R value of 0.65 (P < .001). These results indicate that autologous ESS reduce mortality and requirements for donor skin harvesting, for grafting of full-thickness burns of greater than 50% TBSA.
Topics: Adolescent; Biopsy, Needle; Body Surface Area; Burns; Child; Child, Preschool; Female; Follow-Up Studies; Graft Survival; Humans; Immunohistochemistry; Infant; Injury Severity Score; Male; Prospective Studies; Risk Assessment; Skin Transplantation; Skin, Artificial; Survival Rate; Tissue and Organ Harvesting; Transplantation, Autologous; Treatment Outcome; Wound Healing
PubMed: 27404165
DOI: 10.1097/BCR.0000000000000401 -
Hand Clinics May 2014Dermal skin substitutes are a group of biologically engineered materials composed of collagen and glycosaminoglycans and are devoid of cellular structures. These... (Review)
Review
Dermal skin substitutes are a group of biologically engineered materials composed of collagen and glycosaminoglycans and are devoid of cellular structures. These biodegradable materials act as an artificial dermis to promote neovascularization and neodermis formation. Their applications in soft tissue reconstructions are rapidly expanding. In this article, the indications, advantages, and limitations of dermal skin substitutes for reconstruction of soft tissue defects of the upper extremity are reviewed.
Topics: Arm Injuries; Humans; Neovascularization, Physiologic; Plastic Surgery Procedures; Skin Transplantation; Skin, Artificial; Soft Tissue Injuries; Surgical Flaps; Tissue Expansion
PubMed: 24731613
DOI: 10.1016/j.hcl.2014.02.001 -
Burns : Journal of the International... Aug 2023Autologous split-thickness skin grafts (STSGs) are the standard of care for closure of deep and large burns. However, perforation and extensive fishnet-like expansion of...
BACKGROUND
Autologous split-thickness skin grafts (STSGs) are the standard of care for closure of deep and large burns. However, perforation and extensive fishnet-like expansion of the grafts to achieve greater area wound coverage can lead to treatment failures or esthetically poor healing outcomes and scarring. The purpose of this study was to validate an autologous advanced therapy medicinal product (ATMP)-compliant skin cell suspension and evaluate its efficacy to promote epithelialization.
METHODS
Cells isolated from a piece of STSG according to ATMP classification requirements were sprayed onto 20 patients during a single operation in a validation study. Comparative evaluation of treatment efficacy was carried out using side-by-side skin graft donor site wounds that were standardized in depth. Firstly, we characterized wound healing transcriptomes at 14 and 21 days from serial wound biopsies in seven patients. Then, side-by-side wounds in four patients were treated with or without the skin cells. The wounds were photographed, clinical outcomes assessed, and the treatment and control wound transcriptomes at 14 days were compared to the untreated wounds' healing transcriptomes.
RESULTS
The average cell yield after isolation from the STSG was 2.4 × 10 cells/cm with 96 % viability. The product contained mainly keratinocytes and their precursors but also other skin cells such as fibroblasts were present. As compared to vehicle-treated donor site wounds, the wounds treated with cells demonstrated improved epithelialization by both direct comparison and machine learning analysis of the transcriptomes.
CONCLUSIONS
We showed that rapid and scalable ATMP-classified processing of skin cells is feasible, and application of the skin cells effectively promotes healing and epithelization of donor site wounds.
Topics: Humans; Transplantation, Autologous; Burns; Wound Healing; Skin; Skin Transplantation; Soft Tissue Injuries
PubMed: 36195485
DOI: 10.1016/j.burns.2022.09.006 -
Burns : Journal of the International... Jun 2024The current standard management of full-thickness or deep dermal burns is early tangential excision and skin grafting. A conservative approach to deep burns without the...
INTRODUCTION
The current standard management of full-thickness or deep dermal burns is early tangential excision and skin grafting. A conservative approach to deep burns without the option of skin grafting results in delayed wound healing, possibly leading to wound infection and is associated with hypertrophic scarring and increased morbidity and mortality. The aim of this study was to improve the understanding of the management and availability to perform skin grafting for burns on the African continent. It also sought to identify challenges and perceived improvements.
METHODS
A web-based, structured, closed-formatted, multinational survey was designed to gather information on the current state and availability of skin grafting of burn wounds on the African continent. The questionnaire consisted of 27 questions, available in English and French. It was reviewed within the GAP-Burn collaboration network and sent to 271 health care professionals who had participated in a previous study and had initially been recruited by means of the snowball system.
RESULTS
The questionnaire was completed 84 times (response rate: 31.0%), of which 3 were excluded. Responses originated from 22 African countries. The majority 71 (87.7%) resulted from countries with a low Human Development Index (HDI), 7 (8.6%) from medium HDI countries. Split thickness skin grafting (STSG) is performed in 51 (63.0%) centers. The majority considers STSG to reduce length of stay (72.8%) and improve scarring (54.3%), yet some indicated that STSG is associated with increased risk of donor site infection (8.6%) and severe bleeding (7.4%). Factors preventing increased grafting included lack of equipment and training.
CONCLUSION
Skin grafting is not performed in a significant number of hospitals treating burns. The majority of the staff believe that more skin grafting would lead to a better outcome. Advocacy and improved infrastructure, human resources coupled with introduction to well-structured health coverage for all in African countries could help to better access and affordability in burn care.
Topics: Humans; Burns; Skin Transplantation; Africa; Surveys and Questionnaires; Health Services Accessibility
PubMed: 38490835
DOI: 10.1016/j.burns.2024.02.012 -
Transplantation Mar 2010Transplantation of human skin on immunodeficient mice that support engraftment with functional human immune systems would be an invaluable tool for investigating...
BACKGROUND
Transplantation of human skin on immunodeficient mice that support engraftment with functional human immune systems would be an invaluable tool for investigating mechanisms involved in wound healing and transplantation. Nonobese diabetic (NOD)-scid interleukin-2 gamma chain receptor (NSG) readily engraft with human immune systems, but human skin graft integrity is poor. In contrast, human skin graft integrity is excellent on CB17-scid bg (SCID.bg) mice, but they engraft poorly with human immune systems.
METHODS
Human skin grafts transplanted onto immunodeficient NSG, SCID.bg, and other immunodeficient strains were evaluated for graft integrity, preservation of graft endothelium, and their ability to be rejected after engraftment of allogeneic peripheral blood mononuclear cells.
RESULTS
Human skin transplanted onto NSG mice develops an inflammatory infiltrate, consisting predominately of host Gr1(+) cells, that is detrimental to the survival of human endothelium in the graft. Treatment of graft recipients with anti-Gr1 antibody reduces this cellular infiltrate, preserves graft endothelium, and promotes wound healing, tissue development, and graft remodeling. Excellent graft integrity of the transplanted skin includes multilayered stratified human epidermis, well-developed human vasculature, human fibroblasts, and passenger leukocytes. Injection of unfractionated, CD4 or CD8 allogeneic human peripheral blood mononuclear cell induces a rapid destruction of the transplanted skin graft.
CONCLUSIONS
NSG mice treated with anti-Gr1 antibody provide a model optimized for both human skin graft integrity and engraftment of a functional human immune system. This model provides the opportunity to investigate mechanisms orchestrating inflammation, wound healing, revascularization, tissue remodeling, and allograft rejection and can provide guidance for improving outcomes after clinical transplantation.
Topics: Animals; Antigens, CD; Erythrocytes; Flow Cytometry; Graft Rejection; Humans; Leukocyte Common Antigens; Leukocyte Transfusion; Mice; Mice, Inbred NOD; Mice, SCID; Receptors, Interleukin-2; Skin Transplantation; Spleen; Transplantation, Heterologous; Transplantation, Homologous; Wound Healing
PubMed: 20134397
DOI: 10.1097/TP.0b013e3181c90242 -
Journal of Feline Medicine and Surgery Sep 2021Open wounds and their treatment present a common challenge in veterinary practice. Approaching 15 years ago negative pressure wound therapy (NPWT) started to be... (Review)
Review
PRACTICAL RELEVANCE
Open wounds and their treatment present a common challenge in veterinary practice. Approaching 15 years ago negative pressure wound therapy (NPWT) started to be incorporated into clinical veterinary medicine, and its availability is becoming more widespread in Europe and the USA. Use of this therapy has the potential to significantly increase the healing rate of open wounds as well as free skin grafts in small animals, and it has been occasionally described for the management of feline wounds.
AIM
This review describes the mechanisms of action of, and indications for, NPWT, and offers recommendations for NPWT specific to feline patients.
EVIDENCE BASE
The information presented is based on the current evidence and the author's clinical experience of the technique gained over the past 12 years. Comparative studies of different treatment options are lacking and, since wound healing in cats and dogs differs, cat-specific studies are especially needed. Well-designed wound healing studies comparing different advanced techniques will improve open wound healing in cats in the future, and potentially allow better understanding of the role of NPWT in this setting.
Topics: Animals; Cats; Europe; Negative-Pressure Wound Therapy; Skin Transplantation; Vacuum; Wound Healing
PubMed: 34428942
DOI: 10.1177/1098612X211037873 -
Cells Jul 2020Chronic wounds occur as a consequence of a prolonged inflammatory phase during the healing process, which precludes skin regeneration. Typical treatment for chronic... (Review)
Review
Chronic wounds occur as a consequence of a prolonged inflammatory phase during the healing process, which precludes skin regeneration. Typical treatment for chronic wounds includes application of autografts, allografts collected from cadaver, and topical delivery of antioxidant, anti-inflammatory, and antibacterial agents. Nevertheless, the mentioned therapies are not sufficient for extensive or deep wounds. Moreover, application of allogeneic skin grafts carries high risk of rejection and treatment failure. Advanced therapies for chronic wounds involve application of bioengineered artificial skin substitutes to overcome graft rejection as well as topical delivery of mesenchymal stem cells to reduce inflammation and accelerate the healing process. This review focuses on the concept of skin tissue engineering, which is a modern approach to chronic wound treatment. The aim of the article is to summarize common therapies for chronic wounds and recent achievements in the development of bioengineered artificial skin constructs, including analysis of biomaterials and cells widely used for skin graft production. This review also presents attempts to reconstruct nerves, pigmentation, and skin appendages (hair follicles, sweat glands) using artificial skin grafts as well as recent trends in the engineering of biomaterials, aiming to produce nanocomposite skin substitutes (nanofilled polymer composites) with controlled antibacterial activity. Finally, the article describes the composition, advantages, and limitations of both newly developed and commercially available bioengineered skin substitutes.
Topics: Biocompatible Materials; Humans; Skin Transplantation; Skin, Artificial; Tissue Engineering; Wound Healing
PubMed: 32640572
DOI: 10.3390/cells9071622