Wound healing during hibernation by black bears (Ursus americanus) in the wild: elicitation of reduced scar formation

Abstract

Even mildly hypothermic body or limb temperatures can retard healing processes in mammals. Despite this, we observed that hibernating American black bears (Ursus americanus Pallas, 1780) elicit profound abilities in mounting inflammatory responses to infection and/or foreign bodies. In addition, they resolve injuries during hibernation while maintaining mildly hypothermic states (30-35 °C) and without eating, drinking, urinating or defecating. We describe experimental studies on free-ranging bears that document their abilities to completely resolve cutaneous cuts and punctures incurred during or prior to hibernation. We induced small, full-thickness cutaneous wounds (biopsies or incisions) during early denning, and re-biopsied sites 2-3 months later (near the end of denning). Routine histological methods were used to characterize these skin samples. All biopsied sites with respect to secondary intention (open circular biopsies) and primary intention (sutured sites) healed, with evidence of initial eschar (scab) formation, completeness of healed epidermis and dermal layers, dyskeratosis (inclusion cysts), and abilities to produce hair follicles. These healing abilities of hibernating black bears are a clear survival advantage to animals injured before or during denning. Bears are known to have elevated levels of hibernation induction trigger (delta-opioid receptor agonist) and ursodeoxycholic acid (major bile acid within plasma, mostly conjugated with taurine) during hibernation, which may relate to these wound-healing abilities. Further research as to the underlying mechanisms of wound healing during hibernation could have applications in human medicine. Unique approaches may be found to improve healing for malnourished, hypothermic, diabetic and elderly patients or to reduce scarring associated with burns and traumatic injuries.

Hibernating bears (Ursidae): metabolic magicians of definite interest for the nephrologist

“…47 The American black bear, on the other hand, appears to be able to completely resolve cutaneous cuts and punctures incurred during or before hibernation despite being anuric. 48 The ability to heal wounds is a survival advantage in hibernating species in which decreased peripheral blood flow during hypothermia and immobilization may impede delivery of oxygen and nutrients to the wound site. Iaizzo et al 48 have speculated that elevated levels of delta-opioid receptor antagonist and the major bile acid ursudeoxycholic acid (UDCA) observed during hibernation contribute to the amazing wound healing capacity of American black bears.…”

“…48 The ability to heal wounds is a survival advantage in hibernating species in which decreased peripheral blood flow during hypothermia and immobilization may impede delivery of oxygen and nutrients to the wound site. Iaizzo et al 48 have speculated that elevated levels of delta-opioid receptor antagonist and the major bile acid ursudeoxycholic acid (UDCA) observed during hibernation contribute to the amazing wound healing capacity of American black bears. The fact that hibernating bears secrete markedly higher concentrations of UDCA in their bile than non-hibernating bears is interesting since this remarkable molecule has been proposed as a remedy for many human diseases.…”

Recent advances on the δ opioid receptor: from trafficking to function

“…A similar protective effect of DOPr agonists in maintaining cellular integrity has been seen during mammalian hibernation, a state of low‐energy stores and oxygen depletion. Indeed circulating opioid peptides are considered a ‘trigger of hibernation’ (Oeltgen et al ., ) and may play an important role in cell proliferation, scar formation and wound healing in hibernating black bears (Iaizzo et al ., ).…”

Development and utilization of implantable cardiac monitors in free-ranging American black and Eurasian brown bears: system evolution and lessons learned

“…In addition to transmission from remote telemetry stations, physiological information will soon be transmitted in real time from free-ranging animals using custom designed radio collars linked with Bluetooth ™ technologies [22]. Despite improvements, the performance and integrity of these devices may still be compromised by the animals themselves (e.g., slipping off or damaging collars or the elicitation of a dramatic foreign body response to implantable devices) [23,24].…”