The study of an age-dependent spectrum of scar formation is driven by the desire to understand and recapitulate scarless healing. Although focus in the past has been directed toward scarring in the fetus, less exuberant scarring is a common clinical observation in the elderly. Cell turnover is a major contributor to the development of scar tissue and is governed by the proliferative and apoptotic cellular fractions within a healing wound. We hypothesize that the balance between cell proliferation and apoptosis during late stages of excisional wound healing is, at least in part, responsible for age-related variations in scarring potential. Full-thickness 7-mm ulcers (four per ear), exposing bare cartilage, were made on the inner surface of the ear on 12 young and 12 aged New Zealand White rabbits. Analyses were performed at days 15, 21, and 28 postwounding. A previously described Scar Elevation Index was derived from histomorphometric analysis, along with the quantification of epithelial ingrowth and total cellularity. Apoptotic cellular fractions were derived from TdT-mediated dUTP nick end-labeling assay-stained histologic sections; proliferative fractions were derived from proliferating cell nuclear antigen-labeled serial sections. Young rabbits demonstrated significantly greater scar elevation/area. Apoptosis was strongly associated with progress of epithelialization in both groups. Significantly higher proliferative indices were seen in the young and were sustained through day 28, by which time levels had substantially declined in the aged. No differences in apoptotic indices were demonstrated between groups at any time point. The clinical observation of less exuberant scarring with aging is supported by this animal model. Apoptosis follows the progression of epithelialization but does not appear to independently influence scar morphology. A diminished proliferative response during later stages of healing is an important contributing mechanism for the decrease in scar formation seen in the elderly.

Hypothesis:Although hyperbaric oxygen (HBO) has been used clinically for 3 decades, there have been few controlled clinical trials. Animal models have not been adequate to test the efficacy of HBO in the treatment of chronic wounds, either by itself or in combination with growth factors. We hypothesize that HBO is as efficacious as a prototype growth factor in improving wound healing in a new animal model of ischemic chronic wounds.Design: Twenty-five aged rabbits and 3 young rabbits had their ears rendered chronically ischemic and ulcers were created down to the level of cartilage. These ulcers were treated in 1 of 3 ways: with HBO, 90 minutes per day, Monday through Friday, for 4 weeks; with transforming growth factor ␤ 3 at 1 µg/cm 2 ; or with both modalities combined. Controls were treated with vehicle or hyperbaric room air or both. Results: This model created an aged/ischemic wound that failed to heal spontaneously up to 26 days after wounding (88% reduction compared with aged/nonischemic controls). Hyperbaric oxygen alone and transforming growth factor ␤ 3 alone both improved healing rate (only 38% reduction in healing compared with aged/ nonischemic controls). Combined therapy produced no additional improvement over either modality by itself. Conclusions:In aged animals, HBO and transforming growth factor ␤ 3 were equally effective in improving wound healing. Our data suggest that HBO alone may be more effective in the chronic wound than in the acute wound. There was no additive benefit to combining modalities as has been reported in the same wound model in young rabbits.

A majority of surgeons preferably do not use the CVS method of identification during LC. A large percentage of practicing surgeons are unable to describe or visually identify the CVS. These results suggest an urgent need to reexamine the tenets of how LC is being taught and disseminated and present a clear target for improvement to reduce BDI.