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Biomedical subjects

J W Siebert

Publications and source records attributed to J W Siebert.

42 records · Page 3Linked to original sources

Fetal wound healing: an in vitro explant model.

The ability of fetal skin wounds to heal without scar formation is remarkable. The mechanisms that endow the fetus with this unique healing ability remain unknown. We have developed an in vitro explant model using fetal sheep skin to investigate fetal wound healing. This model eliminates the complex systemic mechanisms that modulate in vivo wound healing. We demonstrated that using an enriched medium, midgestation fetal sheep skin explants following wounding reepithelialized within 4 days. By 7 days after wounding the confluent epidermis was thicker, but the dermal wound remained open. This model demonstrates that it is possible to achieve conditions in culture that maintain tissue viability and support reepithelialization. This model may allow us to resolve some of the individual components that participate in the process of scarless fetal skin healing.

Animals↗

Fetal wound healing: a biochemical study of scarless healing.

Human fetal surgery is being successfully performed today in a small number of highly selected patients for conditions that may lead to irreversible damage to the fetus and threaten the viability of the newborn. Following surgical repair, fetal wounds heal without scarring. This study was initiated to characterize fetal wounds both histologically and biochemically. Gore-Tex tubing was implanted into the subcutaneous tissue of the back of fetal, newborn, and adult New Zealand white rabbits. Light microscopic examination of healed wounds revealed no evidence of scar formation. Electron microscopy demonstrated a striated fibrillar structure suggestive of collagen within the lumen of the Gore-Tex tubing implants. Amino acid analysis (sensitivity 40 pmol) confirmed the presence of hydroxylysine and hydroxyproline within the Gore-Tex wound chambers indicating the presence of collagen in fetal wounds. The small amount of collagen precluded the typing of the collagen using cyanogen bromide peptide analysis. The absence of scarring and the small amounts of detectable collagen suggest a high degree of reorganization of the connective tissues involved in repair. The fetal wound matrix is rich in hyaluronic acid. Topical hyaluronic acid has been associated experimentally with a reduced amount of scarring in postnatal wound healing. Hyaluronic acid extracted from human skin and scar tissue is associated with collagen and other proteins. We propose that a hyaluronic acid-collagen-protein complex may play a role in fetal wound healing.

Amino Acids↗

Human skin and post-burn scar hyaluronan: demonstration of the association with collagen and other proteins.

Hyaluronan (HA) extracted from tissues has been demonstrated to have an enhancing effect on the process of wound healing; the question arises whether this effect is due to the HA or to associated collagen and other proteins. In this study, HA has been extracted from human skin and scar tissue under dissociative conditions and isolated by DEAE-cellulose chromatography followed by CsCl gradient and Sepharose CL-6B chromatography. This highly purified HA was found to contain between 4 and 28% protein, with collagen constituting 5% of the total protein. A functional association between HA and a collagen protein complex is proposed.

Adolescent↗

Scarless wound healing: implications for the aesthetic surgeon.

Recent developments in surgery and basic science research offer aesthetic surgeons the prospect of scarless repair. Studies in fetal wound healing provide both cellular and molecular models of optimal tissue healing without scar formation. Furthermore, craniofacial surgeons may one day operate on cleft lip, cleft palate, and other congenital malformations in utero. Cytokine research has begun to unravel possibilities for modulating the wound-healing inflammatory response in hopes of limiting scar formation. This article presents research on these developments and comments on their possible applications to aesthetic surgery.

Adult↗

Hyaluronan and wound healing: a new perspective.

Hyaluronan has long been associated with the remodelling extracellular matrix. Such remodelling occurs in development, growth and wound healing. This role has been thought to be related to the physical structure and chemical composition of the pure glycosaminoglycan chain. We question this proposition and present evidence which suggests that proteins associated with hyaluronan may be more critical determinants of tissue remodelling.

Amino Acids↗

Spatial and temporal expression of transforming growth factor-beta isoforms during ovine excisional and incisional wound repair.

To elucidate the role for transforming growth factor-beta isoforms (beta(1), -beta(2), and -beta(3)) in wound repair, we used isoform-specific antibodies to detect the spatial and temporal expression of the latent and mature/active transforming growth factor-beta isoforms by immunohistochemical localization through 21 days after excisional and incisional wounding of ovine skin. Although incisional and excisional wounds showed similar patterns of transforming growth factor-beta immunoreactivity, we found a differential temporal and spatial expression of the latent and mature transforming growth factor-beta isoforms throughout wound repair. Specifically, 1 day after wounding, there was a marked increase in transforming growth factor-beta isoforms in the epithelium adjacent to the wound, epidermal appendages, and the cells and matrix of the granulation tissue. At this time, transforming growth factor-beta(3) isoform was the most abundant. Most notably, the epidermis adjacent to the wound was intensely immunoreactive for all transforming growth factor-beta isoforms 1 day after injury. However, the migrating epithelium, derived from both the hair follicles and the wound margins, was completely devoid of immunoreactive transforming growth factor-beta until reepithelialization was complete. Within the inflammatory exudate, there was a distinct band of leukocytes that was immunoreactive for transforming growth factor-beta(2) and -beta(3) 1 day after injury and 1 day later for transforming growth factor-beta(1). Although transforming growth factor-beta(1) and -beta(2), latent transforming growth factor-beta(2), transforming growth factor-beta(3), and latent transforming growth factor-beta(3) immunostaining was present in the numerous fibroblasts and other dermal cells, latent transforming growth factor-beta(1) was only associated with the extracellular matrix. In general, immunoreactivity remained high until day 7 after wounding and slowly subsided over time. However, by day 21, immunostaining had not returned to normal and the original wound was replete with immunoreactive fibroblasts and a dense, immunostained extracellular matrix. Thus, although the dynamic presence of transforming growth factor-beta isoforms exemplifies its positive role in the wound repair process, its persistence together with its known potent effects on matrix accumulation, supports its role in scar formation.

Journal Article↗