Hope for severely injured after limb amputation

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MHH research team aims to advance replantation of arms and legs

Copyright: Karin Kaiser

Amputated, severely damaged extremities - for example as a result of accidents on the road, at work or even at home - pose major challenges for surgery in the care of these patients, who often suffer life-threatening injuries. Only a few specialized clinics are able to perform autologous replantation, i.e. to sew on these severed limbs in such a way that they are able to function at least to a limited extent afterwards. And this is only possible if the replantation is performed quickly enough, since the limbs can only survive a few hours without a blood supply.

How this so-called ischemia time can be reduced and how the severed limbs can be better cared for until surgery is being investigated by Dr. Bettina Wiegmann of the MHH Clinic for Cardiothoracic, Transplantation and Vascular Surgery (HTTG) and Professor Dr. Kirsten Haastert-Talini, head of the "Peripheral Nerve Regeneration" working group at the MHH Institute of Neuroanatomy and Cell Biology. The research project is funded by the German Federal Ministry of Defense with 520,000 euros for an initial two years.

Damage due to lack of oxygen

"Severe limb injuries and traumatic amputations, as well as increasing tumor and vascular diseases, lead to about 56,000 amputations in Germany each year," says Dr. Wiegmann, head of the "Ex-vivo Organ Perfusion" research group at the Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), where the project is based. In most cases, missing limbs are replaced by prostheses. In the case of traumatically amputated limbs, this is due on the one hand to the lack of expertise of many clinics for the complicated surgical procedure of replantation, in which bone fractures have to be treated, blood vessels reattached and nerves connected. On the other hand, time plays a decisive role, because the severely injured must be stabilized as a matter of priority in order to survive at all. Until then, the limb is kept on ice. "Until the patient is then stable enough for another operation, days can pass," says the physician. "But the extremities don't survive that, because they suffer ischemic damage after a certain amount of time without blood flow, in which the cells die from the lack of oxygen."

Preserve the ability of cells to regenerate

The surgeon is familiar with the problem of limited shelf life without a blood supply from organ transplantation. She was involved in the MHH-led INSPIRE study. This demonstrated that continuous machine flushing with a blood-like perfusion solution at body temperature results in donor lungs being preserved longer and damaged less. "The lungs are ventilated in a transportable organ care system and connected to an artificial blood circuit," Dr. Wiegmann explains. The research team now wants to develop a similar system for preserving the extremities. "However, we first need to find out under what conditions the body's cells retain their regenerative capacity so that the limb actually grows back after replantation," Professor Haastert-Talini emphasizes. The particular challenge here is that the different needs of the various cell types, such as fatty tissue, muscles, skin, connective tissue and nerve cells, must be taken into account.

Construct nerve bridges

As a first step, the scientists are now looking for the ideal perfusion solution that meets the requirements of all cells in terms of nutrient composition, temperature, and flow pressure and velocity. But it is not enough to prepare the extremities optimally and restore blood circulation in the vessels and muscles. The separated nerves must also be restored so that patients can feel and move the arm or leg again in a controlled manner after replantation. "We want to create optimal initial conditions so that the regenerating nerve fibers do not grow in an uncontrolled manner and also develop nerve bridges for an optimized connection," says Professor Haastert-Talini. There are still many unresolved questions to be answered. However, the researchers already have a clear goal in mind: a limb care system that, on the one hand, fits as a practical box in every emergency ambulance and gives severely injured people the chance of a life without amputation and prostheses. On the other hand, it should be possible to use it analogously to solid organ transplantation in the context of allogeneic limb transplantation.

Author: Kirsten Pötzke