Surgical Advancements for Individuals with Limb Amputation

Doctoral thesis, 2025

Individuals facing major limb amputation confront two primary challenges: restoring lost function and managing amputation-related pain. In recent decades, surgical and engineering innovations have significantly advanced rehabilitation in both areas. However, their full potential has yet to be realized in terms of optimization and widespread adoption, underscoring the need for continued research.

One breakthrough in functional restoration is the development of bone-anchored "osseointegrated" limb prostheses, which involve directly attaching a prosthesis to the skeleton. This approach enhances functionality by addressing the limitations of traditional socket prostheses, such as skin irritation and nerve compression. However, achieving a successful bone-implant interface is critical for long-term efficacy, and in some cases, the osseointegration process must be enhanced. In pain management, surgical advancements such as selective nerve transfers and muscle reconstruction have become increasingly common, driven by techniques designed to promote healthy nerve regeneration after neuroma removal. The two most widely used methods, Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interface (RPNI), have shown promising results in treating and preventing postamputation pain. Despite encouraging results, rigorous comparative studies against the current standard of care are lacking, and clear guidelines for standardized application of these procedures remain undeveloped.

This doctoral thesis explores a potential advancement in osseointegration while also contributing to the dissemination and implementation of existing surgical techniques. To address the functional challenge, we introduced a novel concept that uses pulsed electrical stimulation, mimicking peripheral nerve stimulation in artificial limbs, to enhance osseointegration. This concept leverages existing hardware and well-established stimulation paradigms within known safety parameters. This approach shows promise in accelerating healing, restoring early function, and reestablishing osseointegration in failing bone-anchored implants.

To address the knowledge gap in pain treatments, we designed a multicenter, international randomized controlled trial (RCT) comparing TMR and RPNI to each other and to a standard procedure, in order to evaluate their effectiveness in treating postamputation pain. This represents the first and largest RCT directly comparing these techniques. As part of the study, we convened leading global experts in the field to standardize the surgical procedures, resulting in comprehensive written protocols and video recordings. Each step was thoroughly discussed and defined by the experts to ensure clarity and consistency. This work also contributes to the dissemination of these techniques, facilitating their implementation and providing a valuable resource for clinicians seeking to integrate them into amputation care practices.