Increased oxygen enhances bone degradation and promotes bone regeneration after digit amputation in mice

Abstract

In 2005, approximately 1.6 million persons in the United States were living with the loss of a limb. That number is projected to increase to 3.6 million by 2050. While full limb replacement is not yet a possibility, prosthetic limb replacement is common amongst amputees, and the ability to control bone regeneration is highly favorable for comfortable fit. The capacity to regenerate bone post‐amputation is limited to only the distal 1/3 of the third phalangeal element (P3) of rodents, monkeys, and humans. Regeneration in adult mice is defined as three distinct steps: 1) wound healing and bone degradation, 2) formation of the blastema, and 3) differentiation of the blastema into bone and tissue. Our hypothesis is that P3 regeneration is facilitated by temporally specific fluctuations in oxygen. The objective of this study is to apply hyperbaric oxygen treatment (HBOT) to our well‐characterized P3 regenerative model to evaluate the effects of increased oxygen during P3 regeneration. Our data show that digits treated with HBOT immediately after amputation display elevated levels of bone degradation. These digits are then able to fully regenerate P3, demonstrating an expansion of regenerative capacity to the proximal P3 bone stump. Our findings strongly support that oxygen is able to act as a primary signaling event to influence bone regeneration in vivo. Research funded by grant 1F32HD071763–01A1 from the NIH