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Ultimately, the ethical considerations surrounding limb salvage, replantation, and VCA of the lower
extremity are profoundly nuanced. It must be reinforced that the data discussed above are from available
evidence on the upper extremity. Lower extremity alternatives to amputation carry more substantial
burdens relative to upper extremity equivalents, given the higher and excellent level of function that
available prosthetics provide for the lower extremity. With increasingly effective prosthetics, this ethical
discussion must be revisited based on the latest science.

HOW MEDICAL INNOVATION CHANGES THE CONVERSATION
Prosthetic alternatives
Specific to VCA of the extremity, the function and benefits provided by the allograft must be weighed
against those of prosthetics. A recent survey found that for hand transplantation, recipients experience
increased satisfaction driven by social and aesthetic values and a greater sense of independence with the
allograft compared with available prosthetic options. Caregivers similarly report less unease with leaving
transplanted patients alone due to the superior functionality provided . Again, contrary to options for the
[113]
upper extremity, lower extremity prosthetic devices are more effective constructs that have demonstrated
excellent outcomes with a high rate of return to independent ambulation . Yet, patients still often reject
[3,4]
them due to discomfort, weight, or limited usefulness - especially for above-knee amputees [114-116] . Rejection
rates are as high as 1 in 3 for lower limb prostheses, compared with over 1 in 2 for upper limb
constructs [117,118] .

Ongoing research has been focused on enhancing the functionality and applicability of prosthetic devices.
In addition to technological innovations that address socket, interface, and alignment concerns, advanced
[119]
options include targeted sensory and muscle innervation, bionics, and bone-anchored prostheses . The
use of microprocessor-controlled components has enabled greater functional achievements in above-knee
amputees, allowing real-time dynamic gait and ambulation management that permits adjustments with
advancing progress during postoperative rehabilitation. Potential merits include reduced effort during
ambulation, improved symmetry and natural gait, and a lower risk of falls [120,121] . Targeted sensory
innervation transfers peripheral sensory nerves to denervated proximal skin and allows restoration of tactile
feedback, pain, temperature, and proprioception, thus addressing a key pitfall of traditional prosthetic
constructs [52,122,123] . Similarly, targeted muscle innervation, which involves the transfer of functioning nerves
that have lost their operational target to intact proximal muscles, can confer additional degrees of active
[124]
motion to myoelectric prostheses and has gained considerable momentum in recent years . This
technique also has the added benefit of reduced phantom limb pain , considerable morbidity in patients
[125]
with lower extremity amputations. Moreover, actively powered prosthetic joints (i.e., bionics) have become
more sophisticated, with new technology allowing a wider range of movements and easier transition
between ambulation modes [126-128] . Osseointegration, which involves the attachment of titanium implants to
the residual bone as an anchor for prostheses, has further been explored as a solution to complications
regarding socket fit and comfort with encouraging early results [129,130] . More than functional benefits,
recipients have reported that osseointegrated prostheses have strengthened their sense of body integrity .
[131]
However, despite these improvements, cosmetic values have not been a major focus of current research
initiatives, especially for the lower extremity. Despite being less visible than upper extremity prostheses,
studies have shown that having a lower limb device with an appearance in line with one’s body perception
induces prosthesis embodiment and satisfaction [132,133] . Advanced constructs are also costly, and patients’
accessibility to these newer technologies is questionable . As prosthetics become more advanced and able
[134]
to meet the goal of a replacement with near-identical function and appearance as the missing limb,
indications for VCA may shift out of favor due to its higher risk profile.