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Reviews and Abstracts
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Journal of Tissue Viability 1999 Vol 9 No 2
Reviews and Abstracts Review Eaglstein WH, Falanga V. Tissue engineering and the devel opment of Apligraf, a human skin equivalent. Advances in Wound Care 1998; 11 (Suppl. 4): 1-8 This review article (containing 57 references) details the rationale for the development of various skin replacement products. These include traditional skin grafts, cultured autologous keratinocyte grafts, cultured allogeneic keratinocyte grafts, autologous/allogeneic composites, acellular collagen matrices and cellular matrices, including Dermagraft (Advanced Tissue Sciences/Smith & Nephew, USA) and Apligraf (Novartis Pharma AG, USA). Biological and synthetic dressings, e.g. membranes, gels, foams and spray-on materials, are not reviewed as they do not contain living cells and do not perform like human skin. Ideally, any skin replacement should have the same proper ties as human skin. The modern tissue-engineered products have many of these properties. The use of traditional skin grafts was first recorded in 1000 BC. Autogeneic split-thickness grafts were intro duced into Europe in the late 1800s. The use of full- or split-thickness autographs and allographs is compared. Reference is made to cadaveric skin, amniotic membranes, porcine xenographs and bovine collagen. The main concern with allogenic skin is the possibility of transmit ting infection, e.g. the human immunodeficiency virus (HIV) or hepatitis. Modern attempts to develop human skin replacements began in the early 1960s as a result of advances in tissue culture technology made by workers such as Rheinwald and Green. This enabled the culture of large quantities of cells. Cultured autologous keratinocyte grafts have many advantages but their principal drawback is that they require 2-3 weeks to prepare. Alternatively, cultured allogeneic keratinocyte grafts are immediately available but there are concerns about rejection. The dermal component is important in skin grafting to lessen wound contracture and scarring and promote healing. This hastened the development of autologous/allogeneic compos ites, acellular collagen matrices and cellular matrices. Dermagraft (launched in October 1997) is a human dermal replacement consisting of newborn human fibroblast cells
cultured in vitro on a bioabsorbable scaffold under aseptic conditions. The sources of the cells are foreskins from circumcized babies. Each foreskin can make more than 23000 m 2 of dermis. As fibroblasts proliferate within the scaffold, they secrete human dermal collagen, matrix proteins and growth factors to form a human dermal tissue. Dermagraft is indicated for use as a permanent replacement dermis that provides a healthy wound bed which promotes epithe!ialization, resulting in faster healing of significantly more full-thickness diabetic foot ulcers. The recommended treatment regimen is one piece implanted in the ulcer weekly, until the ulcer is healed. Previously implanted tissue is not removed. No allergic or immunological reac tions have been reported to date but it should not be used in patients with known hypersensitivity to bovine serum albumin. Dermagraft is manufactured, frozen and supplied within the protective confines of a 'bioreactor' containing one piece of tissue measuring 5 x 7.5 cm (2 x 3 inches). The bioreactor is stored at - 70°C and supplied in an insulated container packed with dry ice. Before application, the bioreactor is thawed, opened and the dermal tissue rinsed by a medical professional. The ulcer is traced to allow sizing and shaping of the tissue to fit the wound bed which must meet the crite ria for skin grafting. Apligraf is a bovine collagen fibroblast-containing matrix integrated with a sheet of stratified human epithelium. It is also called Graftskin or Testskin (Organogenesis Inc., Canton, Massachusetts, USA). The fibroblasts in the 'dermis' and keratinocytes in the 'epidermis' are viable reproducing cells originating from screened neonatal fore skin. The total manufacturing time is about 17-20 days. Apligraf is morphologically, biochemically and metaboli cally similar to human skin. When used as a skin substitute for the in vitro testing of commercial products, Apligraf demonstrated properties similar to those of human skin. Clinical experience is available in treating wounds caused by the surgical removal of skin cancers or keratoacanthomas and in the treatment of venous ulcers. One associated product not mentioned in the review is the Vivoderm Autograft System (E.R. Squibb/ConvaTec). This is a keratinocyte delivery support matrix made from the HYAFF (Fidia Advanced Biopolymers) derivative of © Tissue Viability Society
Journal of Tissue Viability 1999 Vol 9 No 2
hyaluronic acid. It is the first CE-marked biomaterial created for tissue engineering. Vivoderm allows skin cultures to be grafted onto wounds while the cells are actively proliferating, without having to wait for 3 weeks for a complete epithelial sheet to form before grafting. This enables early grafting which could make a difference in the management of severely damaged skin, e.g. severe bums or diabetic foot ulcers. David Morgan Director of Pharmaceutical Public Health North Wales Health Authority
Abstract Poster presented at the Society's 31st Conference in Edinburgh on 16/17 September 1998 Effects of external compression on sub-bandage pressures
Shyam VS Rithalia, Department of Rehabilitation, University of Salford, Salford, UK, Adrienne Taylor, Salford Community Health Care NHS Trust, Salford, UK, and Laurence Kenney, Department of Rehabilitation, University of Salford, Salford, UK
Intermittent pneumatic compression (IPC) has been success fully used to reduce chronic oedema and lymphoedema, thus improving the chances of prevention and treatment of leg ulcers 1. The procedure involves enclosing the arms or legs in airtight double-walled garments which are periodically inflated to a pre-set pressure. Gauges on IPC devices display air pressure which may be substantially different from the interface pressure caused by the action of the garment on the leg. The objective of this study was to investigate the effect on interface pressure of IPC garment pressures applied on top of compression bandaging. Measurements of sub-bandage pressures were taken at three different sites on the left leg of a healthy adult volunteer: (1) 3 cm above the lateral malleolus (ankle site); (2) maximum diameter around the mid-calf (calf site); and (3) 2 cm below the head of the fibula (knee site). Bandaging using a four layer technique 2 was carried out sequentially by eight differ ent nurses trained in bandaging skills. Interface pressure sensors were taped to the skin at sites (1)-(3) and connected to a calibrated Oxford Pressure Monitor (OPM), model Mkll (Talley Group Ltd, Hampshire). Interface pressures were measured for (a) bandaging without IPC, (b) bandag ing with IPC, and (c) IPC alone. Applying IPC garments involved enclosing the limb from toes to upper thigh level in a double-walled, single-compartment garment, which was periodically inflated by an air pump (Flowtron Plus,
73
Huntleigh Technology, Luton, Bedfordshire) to a pre-set pressure of 40 mmHg. Data are expressed as the mean ± standard deviation. We tested the assumption that the net result of bandage and IPC garment pressures would be additive. This was approx imately the case only in fleshy areas of the leg, namely the calf muscle region (2); giving an average interface pressure in case (a) of 36 ± 5 mmHg, case (b) of 71 ± 6 mmHg and case (c) of 45 ± 6 mmHg. We also observed that only three of the eight nurses generated a negative gradient from ankle to knee when bandaging the same leg, the remainder gener ating null or reverse gradient. This seems to confirm that the sub-bandage pressure produced in vivo depends largely upon the technique of the bandager3 . Additionally, contact pressures measured on the skin using IPC alone only approximately matched the air inflation pressures on fleshy parts of the leg, but variations in interface pressure were not as large as those produced by bandaging. Thus, variations in pressure and gradient may be minimized by the selective use of IPC devices in place of or with compression bandaging, as the former can be used with confidence even by an in experienced user. We conclude that garment air inflation pressures do not correlate well with leg interface pressures,which are sensi tive to local bone/muscle presence and the design of the gradient garment. We caution against the use of high air pressures in IPC systems used in conjunction with high compression bandaging or hosiery, since the combined pres sures could cause occlusion in some patients. These findings are being investigated further using a larger sample of nurses.
References
1 Hazarika EZ, Wright DE. Chronic leg ulcers; the effect of pneu matic intermittent compression. Practitioner 1981; 225: 189-192. 2 Taylor AD, Taylor RJ, Said SSS. Using a pressure monitor as an aid in improving bandaging skills. Journal of Wound Care 1998; 7: 131-133. 3 Logan RA, Thomas S, Harding EF, Collyer GH. A comparison of sub-bandage pressures produced by experienced and inexperienced bandagers. Journal of Wound Care 1992; 1: 23-26.
Journal of Tissue Viability 1999 Vol 9 No 2
Reviews and Abstracts Review Eaglstein WH, Falanga V. Tissue engineering and the devel opment of Apligraf, a human skin equivalent. Advances in Wound Care 1998; 11 (Suppl. 4): 1-8 This review article (containing 57 references) details the rationale for the development of various skin replacement products. These include traditional skin grafts, cultured autologous keratinocyte grafts, cultured allogeneic keratinocyte grafts, autologous/allogeneic composites, acellular collagen matrices and cellular matrices, including Dermagraft (Advanced Tissue Sciences/Smith & Nephew, USA) and Apligraf (Novartis Pharma AG, USA). Biological and synthetic dressings, e.g. membranes, gels, foams and spray-on materials, are not reviewed as they do not contain living cells and do not perform like human skin. Ideally, any skin replacement should have the same proper ties as human skin. The modern tissue-engineered products have many of these properties. The use of traditional skin grafts was first recorded in 1000 BC. Autogeneic split-thickness grafts were intro duced into Europe in the late 1800s. The use of full- or split-thickness autographs and allographs is compared. Reference is made to cadaveric skin, amniotic membranes, porcine xenographs and bovine collagen. The main concern with allogenic skin is the possibility of transmit ting infection, e.g. the human immunodeficiency virus (HIV) or hepatitis. Modern attempts to develop human skin replacements began in the early 1960s as a result of advances in tissue culture technology made by workers such as Rheinwald and Green. This enabled the culture of large quantities of cells. Cultured autologous keratinocyte grafts have many advantages but their principal drawback is that they require 2-3 weeks to prepare. Alternatively, cultured allogeneic keratinocyte grafts are immediately available but there are concerns about rejection. The dermal component is important in skin grafting to lessen wound contracture and scarring and promote healing. This hastened the development of autologous/allogeneic compos ites, acellular collagen matrices and cellular matrices. Dermagraft (launched in October 1997) is a human dermal replacement consisting of newborn human fibroblast cells
cultured in vitro on a bioabsorbable scaffold under aseptic conditions. The sources of the cells are foreskins from circumcized babies. Each foreskin can make more than 23000 m 2 of dermis. As fibroblasts proliferate within the scaffold, they secrete human dermal collagen, matrix proteins and growth factors to form a human dermal tissue. Dermagraft is indicated for use as a permanent replacement dermis that provides a healthy wound bed which promotes epithe!ialization, resulting in faster healing of significantly more full-thickness diabetic foot ulcers. The recommended treatment regimen is one piece implanted in the ulcer weekly, until the ulcer is healed. Previously implanted tissue is not removed. No allergic or immunological reac tions have been reported to date but it should not be used in patients with known hypersensitivity to bovine serum albumin. Dermagraft is manufactured, frozen and supplied within the protective confines of a 'bioreactor' containing one piece of tissue measuring 5 x 7.5 cm (2 x 3 inches). The bioreactor is stored at - 70°C and supplied in an insulated container packed with dry ice. Before application, the bioreactor is thawed, opened and the dermal tissue rinsed by a medical professional. The ulcer is traced to allow sizing and shaping of the tissue to fit the wound bed which must meet the crite ria for skin grafting. Apligraf is a bovine collagen fibroblast-containing matrix integrated with a sheet of stratified human epithelium. It is also called Graftskin or Testskin (Organogenesis Inc., Canton, Massachusetts, USA). The fibroblasts in the 'dermis' and keratinocytes in the 'epidermis' are viable reproducing cells originating from screened neonatal fore skin. The total manufacturing time is about 17-20 days. Apligraf is morphologically, biochemically and metaboli cally similar to human skin. When used as a skin substitute for the in vitro testing of commercial products, Apligraf demonstrated properties similar to those of human skin. Clinical experience is available in treating wounds caused by the surgical removal of skin cancers or keratoacanthomas and in the treatment of venous ulcers. One associated product not mentioned in the review is the Vivoderm Autograft System (E.R. Squibb/ConvaTec). This is a keratinocyte delivery support matrix made from the HYAFF (Fidia Advanced Biopolymers) derivative of © Tissue Viability Society
Journal of Tissue Viability 1999 Vol 9 No 2
hyaluronic acid. It is the first CE-marked biomaterial created for tissue engineering. Vivoderm allows skin cultures to be grafted onto wounds while the cells are actively proliferating, without having to wait for 3 weeks for a complete epithelial sheet to form before grafting. This enables early grafting which could make a difference in the management of severely damaged skin, e.g. severe bums or diabetic foot ulcers. David Morgan Director of Pharmaceutical Public Health North Wales Health Authority
Abstract Poster presented at the Society's 31st Conference in Edinburgh on 16/17 September 1998 Effects of external compression on sub-bandage pressures
Shyam VS Rithalia, Department of Rehabilitation, University of Salford, Salford, UK, Adrienne Taylor, Salford Community Health Care NHS Trust, Salford, UK, and Laurence Kenney, Department of Rehabilitation, University of Salford, Salford, UK
Intermittent pneumatic compression (IPC) has been success fully used to reduce chronic oedema and lymphoedema, thus improving the chances of prevention and treatment of leg ulcers 1. The procedure involves enclosing the arms or legs in airtight double-walled garments which are periodically inflated to a pre-set pressure. Gauges on IPC devices display air pressure which may be substantially different from the interface pressure caused by the action of the garment on the leg. The objective of this study was to investigate the effect on interface pressure of IPC garment pressures applied on top of compression bandaging. Measurements of sub-bandage pressures were taken at three different sites on the left leg of a healthy adult volunteer: (1) 3 cm above the lateral malleolus (ankle site); (2) maximum diameter around the mid-calf (calf site); and (3) 2 cm below the head of the fibula (knee site). Bandaging using a four layer technique 2 was carried out sequentially by eight differ ent nurses trained in bandaging skills. Interface pressure sensors were taped to the skin at sites (1)-(3) and connected to a calibrated Oxford Pressure Monitor (OPM), model Mkll (Talley Group Ltd, Hampshire). Interface pressures were measured for (a) bandaging without IPC, (b) bandag ing with IPC, and (c) IPC alone. Applying IPC garments involved enclosing the limb from toes to upper thigh level in a double-walled, single-compartment garment, which was periodically inflated by an air pump (Flowtron Plus,
73
Huntleigh Technology, Luton, Bedfordshire) to a pre-set pressure of 40 mmHg. Data are expressed as the mean ± standard deviation. We tested the assumption that the net result of bandage and IPC garment pressures would be additive. This was approx imately the case only in fleshy areas of the leg, namely the calf muscle region (2); giving an average interface pressure in case (a) of 36 ± 5 mmHg, case (b) of 71 ± 6 mmHg and case (c) of 45 ± 6 mmHg. We also observed that only three of the eight nurses generated a negative gradient from ankle to knee when bandaging the same leg, the remainder gener ating null or reverse gradient. This seems to confirm that the sub-bandage pressure produced in vivo depends largely upon the technique of the bandager3 . Additionally, contact pressures measured on the skin using IPC alone only approximately matched the air inflation pressures on fleshy parts of the leg, but variations in interface pressure were not as large as those produced by bandaging. Thus, variations in pressure and gradient may be minimized by the selective use of IPC devices in place of or with compression bandaging, as the former can be used with confidence even by an in experienced user. We conclude that garment air inflation pressures do not correlate well with leg interface pressures,which are sensi tive to local bone/muscle presence and the design of the gradient garment. We caution against the use of high air pressures in IPC systems used in conjunction with high compression bandaging or hosiery, since the combined pres sures could cause occlusion in some patients. These findings are being investigated further using a larger sample of nurses.
References
1 Hazarika EZ, Wright DE. Chronic leg ulcers; the effect of pneu matic intermittent compression. Practitioner 1981; 225: 189-192. 2 Taylor AD, Taylor RJ, Said SSS. Using a pressure monitor as an aid in improving bandaging skills. Journal of Wound Care 1998; 7: 131-133. 3 Logan RA, Thomas S, Harding EF, Collyer GH. A comparison of sub-bandage pressures produced by experienced and inexperienced bandagers. Journal of Wound Care 1992; 1: 23-26.