Biomedical subjects

T M Krummel

Publications and source records attributed to T M Krummel.

96 records · Page 6Linked to original sources

PubMedDate not supplied

Exposure to amniotic fluid inhibits closure of open wounds in the fetal rabbit.

In many species, open cutaneous fetal wounds do not heal in utero. Such open wounds have been shown to close only after their exclusion from amniotic fluid, thus leading to the hypothesis that amniotic fluid inhibits open wound healing. Therefore the effect of amniotic fluid exposure on the healing of open fetal skin wounds was studied. Fetuses of New Zealand White rabbits received a full-thickness circular 4 mm diameter skin punch biopsy wound. Wounds were left uncovered, covered with a latex patch, or covered with a latex patch with a central hole (doughnut). This third group provided for wound exposure to amniotic fluid while controlling for any wound splinting effect of the patch. Wounds were harvested after 5 days, the wound area was determined planimetrically, and wound edges were examined by means of light microscopy. Analysis of glycosaminoglycans in the wound extra-cellular matrix was performed on a separate group of wounds treated similarly. Uncovered wounds enlarged by an average of 60%, whereas wounds covered with the doughnut patch enlarged by an average of 24%. In contrast, the wounds in the patch-covered group decreased in size by an average of 84%. Histologically all groups contained proliferating fibroblasts and epithelial migration at the wound edge but also an absence of granulation tissue. The patch-covered wounds, which had decreased wound area, were significantly enriched in hyaluronic acid. These results suggest that the healing of the patch-covered wounds occurs without the formation of granulation tissue, presumably through a process of cellular migration and proliferation and that healing was inhibited by exposure to amniotic fluid. Hyaluronic acid has been shown to be permissive of cellular migration and to play a key role in tissue regeneration. Therefore, we speculate that direct exposure of open wounds to amniotic fluid during the late stages of fetal development in the rabbit prevents hyaluronic acid deposition, which in turn may alter wound closure.

Journal Article↗

PubMedDate not supplied

Regulation of wound healing from a connective tissue perspective.

Tissue injury resulting in irreversible tissue loss initiates the repair process. The restoration of dermal loss is by scarring, where a new cell population resides in a new connective tissue matrix. The chemical composition of a scar is similar to normal dermis, but the organization of that tissue is altered. The inability of the organism to reassemble collagen into a normal dermal pattern is an attribute of a scar, but in most cases it restores normal function. With impaired scarring, wound dehiscence or chronic wounds arise, whereas the overproduction of scar tissue results in keloid or hypertrophic scarring. In both situations a catastrophic end point occurs. The volume of scar tissue deposited, as well as its organization, is critical for determining the scar's integrity, stability, and restoration of function. The maturation of scar depends on the character of its resident cell populations, the quality of deposited connective tissue, and the interactions between those components. In this Perspective article, the focus will be on the repair process in terms of collagen fiber organization. As our knowledge of cell-cell and cell-matrix interactions in the repair process increases, we may be able to direct the pattern of scar collagen fibers to resemble that of dermis and thereby provide better wound care to the patient of the future.

Journal Article↗

PubMedDate not supplied

Transition from fetal to adult repair occurring in mouse forelimbs maintained in organ culture.

In previous wound healing experiments with the use of midgestation murine fetal forelimb explants, wounds were made before or immediately after amputation from the fetus. This experimental technique allows one to ask the question: do circulatory elements initiate or sustain the repair process in vitro? The hypotheses tested in the current study were that repair occurs in organ culture in the absence of systemic influences and that the in vivo transition from fetal-like to adult-type repair persists in an unperfused in vitro system. Gestational day-14 mouse forelimbs were harvested and placed in serum-free culture medium. Before amputation, control forelimbs received linear full-incision microscalpel wounds that were closed primarily. The animals in the other group were not immediately wounded but cultured for 4 days and then wounded with primary wound closure. All limbs were cultured for 7 days after wounding and then processed for histologic analysis. In the immediately wounded limbs, scarless healing occurred with collagen fibers deposited in a reticular form. In contrast, the delay-wounded limbs had collagen organized in parallel arrays (disordered), constituting repair by scarring. Wound repair proceeded as a local phenomenon in the absence of systemic mediators. We conclude that day-14 gestation forelimbs undergo maturation in culture, causing a transition from scarless to adult scar repair.

Journal Article↗

PubMedDate not supplied

Ultrastructural analysis of fetal rabbit wounds.

Fetal wound healing proceeds rapidly with minimal inflammation and fibroplasia and little or no scar formation. These observations have led to the hypothesis that fetal wound healing more closely resembles regeneration rather than adult wound repair. To test this hypothesis, this study used ultrastructural analysis of fetal and adult fibroblasts and collagen to gain greater insight into differences in the healing processes. Full-thickness, primarily closed linear incisions were created dorsally on 24-day gestational age fetal rabbits (n = 9). The fetuses were killed 5 days later, and the wounds were excised and evaluated with transmission electron microscopy. Similarly, uninjured fetal skin of the same gestational age was obtained and analyzed. Adult rabbit dermal wounds were analyzed after 8 days of healing. Resting adult dermal fibroblasts had features of quiescent, inactive cells, whereas adult wound fibroblasts were highly active and filled with secretory vesicles. In contrast, both fetal normal dermal and wound fibroblasts appeared highly active and contained numerous secretory vesicles. In the adult wound, collagen fibril diameter was only 45% of the diameter of normal dermal collagen. However, fetal wound collagen fibrils were basically the same as normal dermal collagen, having a diameter that was 82% of the size of dermal collagen. These observations suggest that fetal wound fibroblasts do not require activation from an inactivated state and that fetal wound collagen deposition undergoes more rapid organization and maturation. These findings have significance in extending our understanding of the rapidity and functional superiority of fetal wound healing compared with adult wound healing.

Journal Article↗

PubMedDate not supplied

Repeated additions of hyaluronan alters granulation tissue deposition in sponge implants in mice.

The role for the metabolism of hyaluronic acid in the repair process is uncertain. Fetal dermal wounds do not heal by scarring and have sustained high levels of hyaluronic acid. In contrast, adult dermis is repaired by scarring and has less hyaluronic acid. Initially after injury, hyaluronic acid is elevated in both adult and fetal wounds, and although it remains elevated in fetal repair, it is rapidly degraded in adult wounds. The chronic addition of hyaluronic acid or hyaluronidase to polyvinyl alcohol sponge implants in adult mice was investigated in this study. Polyvinyl alcohol sponge implants containing a central reservoir were placed subcutaneously in the dorsum of adult male CD-1 mice. Mice were divided into three groups: a phosphate-buffered saline control, a 20 microgram hyaluronic acid treatment group, and a 10 U hyaluronidase treatment group. The central reservoir of each sponge implant received appropriate compound every 3 days for 2 weeks via transdermal injection and were then evaluated histologically. At 2 weeks, the cellular density and the quantity of granulation tissue deposition were the greatest in the hyaluronidase group and were lowest in the hyaluronic acid group. In addition, the organization of collagen fiber bundles was the most dense in the hyaluronidase group and least in the hyaluronic acid group. In a second experiment, polyvinyl alcohol sponge implants in mice received either phosphate-buffered saline solution or 20 microgram hyaluronic acid every 3 days for 1 week. On day 5, an aliquot of fluorescently tagged native collagen was injected into the sponges. Sponges were harvested at day 7, cryosections made, and the presence of autofluorescent collagen fibers assessed. The autofluorescent collagen fiber bundles in the phosphate-buffered saline solution group were organized in thick parallel bundles, whereas the collagen bundles from hyaluronic acid-treated implants were organized in fine lacelike structures. Chronic addition of hyaluronic acid appears to mimic the fetal dermal connective tissue matrix in which repair proceeds with diminished collagen deposition, organized in finer collagen fiber bundles in granulation tissue. On the other hand, the removal of hyaluronic acid by the chronic administration of hyaluronidase increases the amount of granulation tissue. Elevated levels of hyaluronic acid in granulation tissue appear to modulate the ability of resident fibroblasts to organize collagen fiber bundles.

Adjuvants, Immunologic↗

PubMedDate not supplied

Fetal rhabdomyoma and nevoid basal cell carcinoma syndrome.

A 6-year-old white female presented with a fetal rhabdomyoma of the posterior mediastinum and retroperitoneum. Radiologic evaluation and family history revealed features of the nevoid basal cell carcinoma syndrome (NBS). Literature review disclosed two other children with NBS and fetal rhabdomyoma, which should be regarded as one of the soft tissue tumors associated with NBS.

Basal Cell Nevus Syndrome↗