Mark Hayes | ANU - Academia.edu (original) (raw)
Papers by Mark Hayes
It is well known that UV radiation in particular the UVB spectrum suppresses the immune system. H... more It is well known that UV radiation in particular the UVB spectrum suppresses the immune system. However, UV does not cause a general immunosuppression but rather compromises the immune system in a specific fashion. Topical application of contact allergens onto UVexposed skin does not result in sensitization but causes hapten-specific long-term suppression. This specific immunotolerance is mediated via T cells, which suppress the immune system in an antigen-specific manner. These T Cells were previously called suppressor T cells and have been recently renamed regulatory T cells (Tr). UV-induced Tr which suppress the induction of contact hypersensitivity belong to the CD$ þ CD25 þ subtype, they express CTLA-4, bind dectin-2, and release interleukin-10 upon antigen-specific activation. It was recently shown that UV-induced Tr upon intravenous injection migrate into the lymph nodes but not into the skin. This explains why intravenously injected Tr prevent the sensitization but do not suppress the elicitation phase of contact hypersensitivity. However, when Tr are injected intracutaneously into the ears of sensitized mice the effector phase of contact hypersensitivity is efficiently suppressed. This migration behavior is due to the expression of homing receptors. Tr express the lymph node homing receptor L-selectin (CD62L) but not the ligands for the skin homing receptors E-and P-selectin.
It is well known that UV radiation in particular the UVB spectrum suppresses the immune system. H... more It is well known that UV radiation in particular the UVB spectrum suppresses the immune system. However, UV does not cause a general immunosuppression but rather compromises the immune system in a specific fashion. Topical application of contact allergens onto UVexposed skin does not result in sensitization but causes hapten-specific long-term suppression. This specific immunotolerance is mediated via T cells, which suppress the immune system in an antigen-specific manner. These T Cells were previously called suppressor T cells and have been recently renamed regulatory T cells (Tr). UV-induced Tr which suppress the induction of contact hypersensitivity belong to the CD$ þ CD25 þ subtype, they express CTLA-4, bind dectin-2, and release interleukin-10 upon antigen-specific activation. It was recently shown that UV-induced Tr upon intravenous injection migrate into the lymph nodes but not into the skin. This explains why intravenously injected Tr prevent the sensitization but do not suppress the elicitation phase of contact hypersensitivity. However, when Tr are injected intracutaneously into the ears of sensitized mice the effector phase of contact hypersensitivity is efficiently suppressed. This migration behavior is due to the expression of homing receptors. Tr express the lymph node homing receptor L-selectin (CD62L) but not the ligands for the skin homing receptors E-and P-selectin.
Journal of pediatric endocrinology & metabolism: JPEM
This study was designed to determine the intrafamilial effect of SHOX haploinsufficiency on statu... more This study was designed to determine the intrafamilial effect of SHOX haploinsufficiency on stature, by comparing the growth and phenotype of 26 SHOX haploinsufficient individuals with 45 relatives and population standards. It confirmed that SHOX haploinsufficiency leads to growth restriction from birth to final height. Compared to unaffected siblings, the SHOX haploinsufficient cohort was 2.14 SDS (3.8 cm) shorter at birth and 2.1 SDS shorter through childhood. At final height females were 2.4 SDS (14.4 cm) shorter and males 0.8 SDS (5.3 cm) shorter than normal siblings. The family height analysis suggests that the effect of SHOX haploinsufficiency on growth may have been previously underestimated at birth and overestimated in males at final height. SHOX haploinsufficiency leads to short arms in 92%, bilateral Madelung deformity in 73% and short stature in 54%. Females were more severely affected than males. We conclude that SHOX is a major growth gene and that mutations are associated with a broad range of phenotype.
Journal of pediatric endocrinology & metabolism: JPEM
This study was designed to determine the intrafamilial effect of SHOX haploinsufficiency on statu... more This study was designed to determine the intrafamilial effect of SHOX haploinsufficiency on stature, by comparing the growth and phenotype of 26 SHOX haploinsufficient individuals with 45 relatives and population standards. It confirmed that SHOX haploinsufficiency leads to growth restriction from birth to final height. Compared to unaffected siblings, the SHOX haploinsufficient cohort was 2.14 SDS (3.8 cm) shorter at birth and 2.1 SDS shorter through childhood. At final height females were 2.4 SDS (14.4 cm) shorter and males 0.8 SDS (5.3 cm) shorter than normal siblings. The family height analysis suggests that the effect of SHOX haploinsufficiency on growth may have been previously underestimated at birth and overestimated in males at final height. SHOX haploinsufficiency leads to short arms in 92%, bilateral Madelung deformity in 73% and short stature in 54%. Females were more severely affected than males. We conclude that SHOX is a major growth gene and that mutations are associated with a broad range of phenotype.
ANZ Journal of Surgery
The function of the tympanic membrane (TM) in transferring energy to the middle ear is largely du... more The function of the tympanic membrane (TM) in transferring energy to the middle ear is largely due to the cellular arrangement. Three layers are distinctly recognized, namely the outer epidermal, middle lamina propria and inner mucosal layer. To maximize the functional hearing outcomes after tympanoplasty a tissue-engineered TM must closely replicate the normal human TM. The rupture pressure of the TM is an indicator of tympanic membrane strength. The mean rupture pressure of human TMs is 1.2-1.6 atm, which is significantly higher than measured in previous animal studies. Two studies were undertaken as part of a project to tissue engineer a human TM.
ANZ Journal of Surgery
The function of the tympanic membrane (TM) in transferring energy to the middle ear is largely du... more The function of the tympanic membrane (TM) in transferring energy to the middle ear is largely due to the cellular arrangement. Three layers are distinctly recognized, namely the outer epidermal, middle lamina propria and inner mucosal layer. To maximize the functional hearing outcomes after tympanoplasty a tissue-engineered TM must closely replicate the normal human TM. The rupture pressure of the TM is an indicator of tympanic membrane strength. The mean rupture pressure of human TMs is 1.2-1.6 atm, which is significantly higher than measured in previous animal studies. Two studies were undertaken as part of a project to tissue engineer a human TM.
The present invention discloses the use of fetuin and fetuin producing agents in methods and comp... more The present invention discloses the use of fetuin and fetuin producing agents in methods and compositions for treating burn injuries in animals.
The present invention discloses the use of fetuin and fetuin producing agents in methods and comp... more The present invention discloses the use of fetuin and fetuin producing agents in methods and compositions for treating burn injuries in animals.
Harding et al. US005858966A [11] Patent Number: 5,858,966 [45] Date of Patent: Jan. 12, 1999 [54]
Harding et al. US005858966A [11] Patent Number: 5,858,966 [45] Date of Patent: Jan. 12, 1999 [54]
Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand, 2001
Leri-Weill syndrome (LWS) is a dominant (pseudoautosomal) skeletal dysplasia with mesomelic short... more Leri-Weill syndrome (LWS) is a dominant (pseudoautosomal) skeletal dysplasia with mesomelic short stature and bilateral Madelung deformity, due to dyschondrosteosis of the distal radius. It results from the loss of one copy of the Short Stature Homeobox Gene (SHOX) from the tip of the short arm of the X or Y chromosome. SHOX molecular testing enabled us to evaluate the histopathology of the radial physis in LWS patients with a documented SHOX abnormality. A widespread disorganisation of physeal anatomy was revealed with disruption of the normal parallel columnar arrangement of chondrocytes. Tandem stacking of maturing chondrocytes within columns was replaced by a side-by-side arrangement. The presence of hypertrophic osteoid with micro-enchondromata in the radial metaphysis suggests abnormal endochondral ossification. The Vickers' ligament was confirmed to blend with the triangular fibrocartilage complex (TFCC). This histopathological study demonstrates that the zone of dyschond...
Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand, 2001
Leri-Weill syndrome (LWS) is a dominant (pseudoautosomal) skeletal dysplasia with mesomelic short... more Leri-Weill syndrome (LWS) is a dominant (pseudoautosomal) skeletal dysplasia with mesomelic short stature and bilateral Madelung deformity, due to dyschondrosteosis of the distal radius. It results from the loss of one copy of the Short Stature Homeobox Gene (SHOX) from the tip of the short arm of the X or Y chromosome. SHOX molecular testing enabled us to evaluate the histopathology of the radial physis in LWS patients with a documented SHOX abnormality. A widespread disorganisation of physeal anatomy was revealed with disruption of the normal parallel columnar arrangement of chondrocytes. Tandem stacking of maturing chondrocytes within columns was replaced by a side-by-side arrangement. The presence of hypertrophic osteoid with micro-enchondromata in the radial metaphysis suggests abnormal endochondral ossification. The Vickers' ligament was confirmed to blend with the triangular fibrocartilage complex (TFCC). This histopathological study demonstrates that the zone of dyschond...
Wound Repair and Regeneration, 2005
Our group has developed an ovine model of deep dermal, partial-thickness burn where the fetus hea... more Our group has developed an ovine model of deep dermal, partial-thickness burn where the fetus heals scarlessly and the lamb heals with scar. The comparison of collagen structure between these two different mechanisms of healing may elucidate the process of scarless wound healing. Picrosirius staining followed by polarized light microscopy was used to visualize collagen fibers, with digital capture and analysis. Collagen deposition increased with fetal age and the fibers became thicker, changing from green (type III collagen) to yellow/red (type I collagen). The ratio of type III collagen to type I was high in the fetus (166), whereas the lamb had a much lower ratio (0.2). After burn, the ratios of type III to type I collagen did not differ from those in control skin for either fetus or lamb. The fetal tissue maintained normal tissue architecture after burn while the lamb tissue showed irregular collagen organization. In conclusion, the type or amount of collagen does not alter significantly after injury. Tissue architecture differed between fetal and lamb tissue, suggesting that scar development is related to collagen cross-linking or arrangement. This study indicates that healing in the scarless fetal wound is representative of the normal fetal growth pattern, rather than a ''response'' to burn injury. (WOUND REP REG 2005;13:198-204) Collagen is the major component of extracellular matrix and provides tensile strength to skin. During the wound healing process, it acts to modulate cell proliferation and migration and is important in the wound contraction process. The patterns of collagen deposition in healing fetal and adult wounds differ markedly. Fetal skin regenerates collagen fibers in neat, well-organized patterns with close to perfect tissue architecture, whereas postnatal and adult skin heals with collagen laid down in thick disorganized patterns and scar formation. 1 The scarless healing properties of fetal skin are lost in many animal models in late gestation. The study of collagen structure, distribution, and levels before and after this critical fetal time point may contribute to our understanding of the process of scarless fetal wound healing.
Wound Repair and Regeneration, 2005
Our group has developed an ovine model of deep dermal, partial-thickness burn where the fetus hea... more Our group has developed an ovine model of deep dermal, partial-thickness burn where the fetus heals scarlessly and the lamb heals with scar. The comparison of collagen structure between these two different mechanisms of healing may elucidate the process of scarless wound healing. Picrosirius staining followed by polarized light microscopy was used to visualize collagen fibers, with digital capture and analysis. Collagen deposition increased with fetal age and the fibers became thicker, changing from green (type III collagen) to yellow/red (type I collagen). The ratio of type III collagen to type I was high in the fetus (166), whereas the lamb had a much lower ratio (0.2). After burn, the ratios of type III to type I collagen did not differ from those in control skin for either fetus or lamb. The fetal tissue maintained normal tissue architecture after burn while the lamb tissue showed irregular collagen organization. In conclusion, the type or amount of collagen does not alter significantly after injury. Tissue architecture differed between fetal and lamb tissue, suggesting that scar development is related to collagen cross-linking or arrangement. This study indicates that healing in the scarless fetal wound is representative of the normal fetal growth pattern, rather than a ''response'' to burn injury. (WOUND REP REG 2005;13:198-204) Collagen is the major component of extracellular matrix and provides tensile strength to skin. During the wound healing process, it acts to modulate cell proliferation and migration and is important in the wound contraction process. The patterns of collagen deposition in healing fetal and adult wounds differ markedly. Fetal skin regenerates collagen fibers in neat, well-organized patterns with close to perfect tissue architecture, whereas postnatal and adult skin heals with collagen laid down in thick disorganized patterns and scar formation. 1 The scarless healing properties of fetal skin are lost in many animal models in late gestation. The study of collagen structure, distribution, and levels before and after this critical fetal time point may contribute to our understanding of the process of scarless fetal wound healing.
Wound Repair and Regeneration, 2005
Early to mid-term fetuses heal cutaneous incisional wounds without scars; however, fetal response... more Early to mid-term fetuses heal cutaneous incisional wounds without scars; however, fetal response to burn injury has not been ascertained. We present a fetal model of thermal injury and subsequent analysis of fetal and lamb response to burn injury. A reproducible deep dermal burn injury was created in the fetus by application of water at 66˚C for 7 seconds, and at 82˚C for 10 seconds to the lamb. Macroscopically, the area of fetal scald was undetectable from day 7 post injury, while all lamb scalds were readily identified and eventually healed with scarring. Using a five-point histopathology scoring system for alteration in tissue morphology, differences were detected between control and scalded skin at all stages in lamb postburn, but no difference was detected in the fetal model after day 7. There were also large differences in content of a-smooth muscle actin and transforming growth factor-b1 between control and scalded lamb and these differences were statistically significant at day 14 (P < 0.01). This novel model of fetal and lamb response to deep dermal injury indicates that the fetus heals a deep burn injury in a scarless fashion. Further elucidation of this specific fetal process of burn injury repair may lead to improved outcome for patients with burn injury. (WOUND REP REG 2005;13:189-197)
Wound Repair and Regeneration, 2005
Early to mid-term fetuses heal cutaneous incisional wounds without scars; however, fetal response... more Early to mid-term fetuses heal cutaneous incisional wounds without scars; however, fetal response to burn injury has not been ascertained. We present a fetal model of thermal injury and subsequent analysis of fetal and lamb response to burn injury. A reproducible deep dermal burn injury was created in the fetus by application of water at 66˚C for 7 seconds, and at 82˚C for 10 seconds to the lamb. Macroscopically, the area of fetal scald was undetectable from day 7 post injury, while all lamb scalds were readily identified and eventually healed with scarring. Using a five-point histopathology scoring system for alteration in tissue morphology, differences were detected between control and scalded skin at all stages in lamb postburn, but no difference was detected in the fetal model after day 7. There were also large differences in content of a-smooth muscle actin and transforming growth factor-b1 between control and scalded lamb and these differences were statistically significant at day 14 (P < 0.01). This novel model of fetal and lamb response to deep dermal injury indicates that the fetus heals a deep burn injury in a scarless fashion. Further elucidation of this specific fetal process of burn injury repair may lead to improved outcome for patients with burn injury. (WOUND REP REG 2005;13:189-197)
It is well known that UV radiation in particular the UVB spectrum suppresses the immune system. H... more It is well known that UV radiation in particular the UVB spectrum suppresses the immune system. However, UV does not cause a general immunosuppression but rather compromises the immune system in a specific fashion. Topical application of contact allergens onto UVexposed skin does not result in sensitization but causes hapten-specific long-term suppression. This specific immunotolerance is mediated via T cells, which suppress the immune system in an antigen-specific manner. These T Cells were previously called suppressor T cells and have been recently renamed regulatory T cells (Tr). UV-induced Tr which suppress the induction of contact hypersensitivity belong to the CD$ þ CD25 þ subtype, they express CTLA-4, bind dectin-2, and release interleukin-10 upon antigen-specific activation. It was recently shown that UV-induced Tr upon intravenous injection migrate into the lymph nodes but not into the skin. This explains why intravenously injected Tr prevent the sensitization but do not suppress the elicitation phase of contact hypersensitivity. However, when Tr are injected intracutaneously into the ears of sensitized mice the effector phase of contact hypersensitivity is efficiently suppressed. This migration behavior is due to the expression of homing receptors. Tr express the lymph node homing receptor L-selectin (CD62L) but not the ligands for the skin homing receptors E-and P-selectin.
It is well known that UV radiation in particular the UVB spectrum suppresses the immune system. H... more It is well known that UV radiation in particular the UVB spectrum suppresses the immune system. However, UV does not cause a general immunosuppression but rather compromises the immune system in a specific fashion. Topical application of contact allergens onto UVexposed skin does not result in sensitization but causes hapten-specific long-term suppression. This specific immunotolerance is mediated via T cells, which suppress the immune system in an antigen-specific manner. These T Cells were previously called suppressor T cells and have been recently renamed regulatory T cells (Tr). UV-induced Tr which suppress the induction of contact hypersensitivity belong to the CD$ þ CD25 þ subtype, they express CTLA-4, bind dectin-2, and release interleukin-10 upon antigen-specific activation. It was recently shown that UV-induced Tr upon intravenous injection migrate into the lymph nodes but not into the skin. This explains why intravenously injected Tr prevent the sensitization but do not suppress the elicitation phase of contact hypersensitivity. However, when Tr are injected intracutaneously into the ears of sensitized mice the effector phase of contact hypersensitivity is efficiently suppressed. This migration behavior is due to the expression of homing receptors. Tr express the lymph node homing receptor L-selectin (CD62L) but not the ligands for the skin homing receptors E-and P-selectin.
Journal of pediatric endocrinology & metabolism: JPEM
This study was designed to determine the intrafamilial effect of SHOX haploinsufficiency on statu... more This study was designed to determine the intrafamilial effect of SHOX haploinsufficiency on stature, by comparing the growth and phenotype of 26 SHOX haploinsufficient individuals with 45 relatives and population standards. It confirmed that SHOX haploinsufficiency leads to growth restriction from birth to final height. Compared to unaffected siblings, the SHOX haploinsufficient cohort was 2.14 SDS (3.8 cm) shorter at birth and 2.1 SDS shorter through childhood. At final height females were 2.4 SDS (14.4 cm) shorter and males 0.8 SDS (5.3 cm) shorter than normal siblings. The family height analysis suggests that the effect of SHOX haploinsufficiency on growth may have been previously underestimated at birth and overestimated in males at final height. SHOX haploinsufficiency leads to short arms in 92%, bilateral Madelung deformity in 73% and short stature in 54%. Females were more severely affected than males. We conclude that SHOX is a major growth gene and that mutations are associated with a broad range of phenotype.
Journal of pediatric endocrinology & metabolism: JPEM
This study was designed to determine the intrafamilial effect of SHOX haploinsufficiency on statu... more This study was designed to determine the intrafamilial effect of SHOX haploinsufficiency on stature, by comparing the growth and phenotype of 26 SHOX haploinsufficient individuals with 45 relatives and population standards. It confirmed that SHOX haploinsufficiency leads to growth restriction from birth to final height. Compared to unaffected siblings, the SHOX haploinsufficient cohort was 2.14 SDS (3.8 cm) shorter at birth and 2.1 SDS shorter through childhood. At final height females were 2.4 SDS (14.4 cm) shorter and males 0.8 SDS (5.3 cm) shorter than normal siblings. The family height analysis suggests that the effect of SHOX haploinsufficiency on growth may have been previously underestimated at birth and overestimated in males at final height. SHOX haploinsufficiency leads to short arms in 92%, bilateral Madelung deformity in 73% and short stature in 54%. Females were more severely affected than males. We conclude that SHOX is a major growth gene and that mutations are associated with a broad range of phenotype.
ANZ Journal of Surgery
The function of the tympanic membrane (TM) in transferring energy to the middle ear is largely du... more The function of the tympanic membrane (TM) in transferring energy to the middle ear is largely due to the cellular arrangement. Three layers are distinctly recognized, namely the outer epidermal, middle lamina propria and inner mucosal layer. To maximize the functional hearing outcomes after tympanoplasty a tissue-engineered TM must closely replicate the normal human TM. The rupture pressure of the TM is an indicator of tympanic membrane strength. The mean rupture pressure of human TMs is 1.2-1.6 atm, which is significantly higher than measured in previous animal studies. Two studies were undertaken as part of a project to tissue engineer a human TM.
ANZ Journal of Surgery
The function of the tympanic membrane (TM) in transferring energy to the middle ear is largely du... more The function of the tympanic membrane (TM) in transferring energy to the middle ear is largely due to the cellular arrangement. Three layers are distinctly recognized, namely the outer epidermal, middle lamina propria and inner mucosal layer. To maximize the functional hearing outcomes after tympanoplasty a tissue-engineered TM must closely replicate the normal human TM. The rupture pressure of the TM is an indicator of tympanic membrane strength. The mean rupture pressure of human TMs is 1.2-1.6 atm, which is significantly higher than measured in previous animal studies. Two studies were undertaken as part of a project to tissue engineer a human TM.
The present invention discloses the use of fetuin and fetuin producing agents in methods and comp... more The present invention discloses the use of fetuin and fetuin producing agents in methods and compositions for treating burn injuries in animals.
The present invention discloses the use of fetuin and fetuin producing agents in methods and comp... more The present invention discloses the use of fetuin and fetuin producing agents in methods and compositions for treating burn injuries in animals.
Harding et al. US005858966A [11] Patent Number: 5,858,966 [45] Date of Patent: Jan. 12, 1999 [54]
Harding et al. US005858966A [11] Patent Number: 5,858,966 [45] Date of Patent: Jan. 12, 1999 [54]
Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand, 2001
Leri-Weill syndrome (LWS) is a dominant (pseudoautosomal) skeletal dysplasia with mesomelic short... more Leri-Weill syndrome (LWS) is a dominant (pseudoautosomal) skeletal dysplasia with mesomelic short stature and bilateral Madelung deformity, due to dyschondrosteosis of the distal radius. It results from the loss of one copy of the Short Stature Homeobox Gene (SHOX) from the tip of the short arm of the X or Y chromosome. SHOX molecular testing enabled us to evaluate the histopathology of the radial physis in LWS patients with a documented SHOX abnormality. A widespread disorganisation of physeal anatomy was revealed with disruption of the normal parallel columnar arrangement of chondrocytes. Tandem stacking of maturing chondrocytes within columns was replaced by a side-by-side arrangement. The presence of hypertrophic osteoid with micro-enchondromata in the radial metaphysis suggests abnormal endochondral ossification. The Vickers' ligament was confirmed to blend with the triangular fibrocartilage complex (TFCC). This histopathological study demonstrates that the zone of dyschond...
Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand, 2001
Leri-Weill syndrome (LWS) is a dominant (pseudoautosomal) skeletal dysplasia with mesomelic short... more Leri-Weill syndrome (LWS) is a dominant (pseudoautosomal) skeletal dysplasia with mesomelic short stature and bilateral Madelung deformity, due to dyschondrosteosis of the distal radius. It results from the loss of one copy of the Short Stature Homeobox Gene (SHOX) from the tip of the short arm of the X or Y chromosome. SHOX molecular testing enabled us to evaluate the histopathology of the radial physis in LWS patients with a documented SHOX abnormality. A widespread disorganisation of physeal anatomy was revealed with disruption of the normal parallel columnar arrangement of chondrocytes. Tandem stacking of maturing chondrocytes within columns was replaced by a side-by-side arrangement. The presence of hypertrophic osteoid with micro-enchondromata in the radial metaphysis suggests abnormal endochondral ossification. The Vickers' ligament was confirmed to blend with the triangular fibrocartilage complex (TFCC). This histopathological study demonstrates that the zone of dyschond...
Wound Repair and Regeneration, 2005
Our group has developed an ovine model of deep dermal, partial-thickness burn where the fetus hea... more Our group has developed an ovine model of deep dermal, partial-thickness burn where the fetus heals scarlessly and the lamb heals with scar. The comparison of collagen structure between these two different mechanisms of healing may elucidate the process of scarless wound healing. Picrosirius staining followed by polarized light microscopy was used to visualize collagen fibers, with digital capture and analysis. Collagen deposition increased with fetal age and the fibers became thicker, changing from green (type III collagen) to yellow/red (type I collagen). The ratio of type III collagen to type I was high in the fetus (166), whereas the lamb had a much lower ratio (0.2). After burn, the ratios of type III to type I collagen did not differ from those in control skin for either fetus or lamb. The fetal tissue maintained normal tissue architecture after burn while the lamb tissue showed irregular collagen organization. In conclusion, the type or amount of collagen does not alter significantly after injury. Tissue architecture differed between fetal and lamb tissue, suggesting that scar development is related to collagen cross-linking or arrangement. This study indicates that healing in the scarless fetal wound is representative of the normal fetal growth pattern, rather than a ''response'' to burn injury. (WOUND REP REG 2005;13:198-204) Collagen is the major component of extracellular matrix and provides tensile strength to skin. During the wound healing process, it acts to modulate cell proliferation and migration and is important in the wound contraction process. The patterns of collagen deposition in healing fetal and adult wounds differ markedly. Fetal skin regenerates collagen fibers in neat, well-organized patterns with close to perfect tissue architecture, whereas postnatal and adult skin heals with collagen laid down in thick disorganized patterns and scar formation. 1 The scarless healing properties of fetal skin are lost in many animal models in late gestation. The study of collagen structure, distribution, and levels before and after this critical fetal time point may contribute to our understanding of the process of scarless fetal wound healing.
Wound Repair and Regeneration, 2005
Our group has developed an ovine model of deep dermal, partial-thickness burn where the fetus hea... more Our group has developed an ovine model of deep dermal, partial-thickness burn where the fetus heals scarlessly and the lamb heals with scar. The comparison of collagen structure between these two different mechanisms of healing may elucidate the process of scarless wound healing. Picrosirius staining followed by polarized light microscopy was used to visualize collagen fibers, with digital capture and analysis. Collagen deposition increased with fetal age and the fibers became thicker, changing from green (type III collagen) to yellow/red (type I collagen). The ratio of type III collagen to type I was high in the fetus (166), whereas the lamb had a much lower ratio (0.2). After burn, the ratios of type III to type I collagen did not differ from those in control skin for either fetus or lamb. The fetal tissue maintained normal tissue architecture after burn while the lamb tissue showed irregular collagen organization. In conclusion, the type or amount of collagen does not alter significantly after injury. Tissue architecture differed between fetal and lamb tissue, suggesting that scar development is related to collagen cross-linking or arrangement. This study indicates that healing in the scarless fetal wound is representative of the normal fetal growth pattern, rather than a ''response'' to burn injury. (WOUND REP REG 2005;13:198-204) Collagen is the major component of extracellular matrix and provides tensile strength to skin. During the wound healing process, it acts to modulate cell proliferation and migration and is important in the wound contraction process. The patterns of collagen deposition in healing fetal and adult wounds differ markedly. Fetal skin regenerates collagen fibers in neat, well-organized patterns with close to perfect tissue architecture, whereas postnatal and adult skin heals with collagen laid down in thick disorganized patterns and scar formation. 1 The scarless healing properties of fetal skin are lost in many animal models in late gestation. The study of collagen structure, distribution, and levels before and after this critical fetal time point may contribute to our understanding of the process of scarless fetal wound healing.
Wound Repair and Regeneration, 2005
Early to mid-term fetuses heal cutaneous incisional wounds without scars; however, fetal response... more Early to mid-term fetuses heal cutaneous incisional wounds without scars; however, fetal response to burn injury has not been ascertained. We present a fetal model of thermal injury and subsequent analysis of fetal and lamb response to burn injury. A reproducible deep dermal burn injury was created in the fetus by application of water at 66˚C for 7 seconds, and at 82˚C for 10 seconds to the lamb. Macroscopically, the area of fetal scald was undetectable from day 7 post injury, while all lamb scalds were readily identified and eventually healed with scarring. Using a five-point histopathology scoring system for alteration in tissue morphology, differences were detected between control and scalded skin at all stages in lamb postburn, but no difference was detected in the fetal model after day 7. There were also large differences in content of a-smooth muscle actin and transforming growth factor-b1 between control and scalded lamb and these differences were statistically significant at day 14 (P < 0.01). This novel model of fetal and lamb response to deep dermal injury indicates that the fetus heals a deep burn injury in a scarless fashion. Further elucidation of this specific fetal process of burn injury repair may lead to improved outcome for patients with burn injury. (WOUND REP REG 2005;13:189-197)
Wound Repair and Regeneration, 2005
Early to mid-term fetuses heal cutaneous incisional wounds without scars; however, fetal response... more Early to mid-term fetuses heal cutaneous incisional wounds without scars; however, fetal response to burn injury has not been ascertained. We present a fetal model of thermal injury and subsequent analysis of fetal and lamb response to burn injury. A reproducible deep dermal burn injury was created in the fetus by application of water at 66˚C for 7 seconds, and at 82˚C for 10 seconds to the lamb. Macroscopically, the area of fetal scald was undetectable from day 7 post injury, while all lamb scalds were readily identified and eventually healed with scarring. Using a five-point histopathology scoring system for alteration in tissue morphology, differences were detected between control and scalded skin at all stages in lamb postburn, but no difference was detected in the fetal model after day 7. There were also large differences in content of a-smooth muscle actin and transforming growth factor-b1 between control and scalded lamb and these differences were statistically significant at day 14 (P < 0.01). This novel model of fetal and lamb response to deep dermal injury indicates that the fetus heals a deep burn injury in a scarless fashion. Further elucidation of this specific fetal process of burn injury repair may lead to improved outcome for patients with burn injury. (WOUND REP REG 2005;13:189-197)