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Page 8 of 13 Rajaram et al. Plast Aesthet Res. 2025;12:6 https://dx.doi.org/10.20517/2347-9264.2024.147

Fragmentation of lymph nodes is a technique that involves cutting whole lymph nodes into multiple parts
in order to increase the number of regeneration centres without increasing the number of explanted lymph
[15]
nodes from the donor site . This is imperative from a lymphoedema standpoint due to the necessity to
preserve the lymphatic drainage of the donor site and prevent an iatrogenic donor site lymphoedema. While
it has been shown by Hadamitzky et al. that the engraftment of whole lymph nodes produces the greatest
level of regeneration per given regeneration centre, fragmenting lymph nodes has become common practice
in experimental studies investigating NVLNT . As a result, multiple fragmentation methods have been
[12]
developed in an attempt to increase the number of potential regeneration centres while maintaining the
ability of each fragment centre to induce lymphangiogenesis. Currently, there are four established
fragmentation techniques [12,15] .

· Salami slice: where the lymph node is cut axially multiple times before having fragments sutured together
end to end.
· Butterfly: where the lymph node is cut in half coronally but is still left attached by the lymph node capsule.
· Transverse fragmentation: where the lymph node is cut axially and completely in half.
· Transverse fragmentation with capsulectomy.

Hadamitzky et al. in their three-stage large-scale minipig experimental model demonstrated that after whole
node grafting, it was transverse fragmentation without capsulectomy that provided superior regeneration of
lymph nodes in recipient animals .
[12]

An earlier work on Lewis Rats by Hadamitzky et al. in 2009 demonstrated that the addition of PRP
[13]
enhanced the rate of regrowth of lymphatic networks in NVLNT. They demonstrated that the
postoperative subdermal addition of PRP induced enhanced regeneration of lymphatics compared to a
negative control group of rats.

Hamiditzky et al. would then examine the impact of the most lymphangiogenic platelet-derived
compound, VEGF-C, in a minipig model . VEGF-C would prove to be superior in generating new
[12]
growth of lymphatics compared to two other purportedly lymphangiogenic compounds: Streptococcus
suis and tetanol. These findings were buttressed by an experimental study conducted by Sommer et
al. in Lewis rats, which demonstrated the functional benefit of VEGF-C augmented grafting . Not only
[19]
were rats in the VEGF-C group able to produce more histologically robust lymphatic networks, but
these were also shown to be superior at lymphatic drainage and regenerate in irradiated tissue as well.
These studies lend credence to the idea that VEGF-C is an important growth factor in the proliferation,
differentiation, and organisation of de novo lymphatic channels in grafted areas.

Finally, due to concerns about VEGF-mediated cancer recurrence in the intended post-cancer
lymphoedema population, the induction of non-carcinogenic sterile inflammation prior to lymph node
grafting was explored by Joseph et al. . The hypothesis for this was factors such as TGF-beta and
[14]
interferon-gamma, despite playing an important role in lymphatic remodelling, were largely anti-
lymphangiogenic compounds, and the induction of inflammation in lymph nodes would downregulate
these factors and potentially induce greater rates of lymphatic growth . Furthermore, the increased
[14]
differentiation of B cells, implicated in lymph node growth, by this inflammation would further reinforce a
pro-angiogenic state. Joseph et al. induced sterile inflammation in murine lymph nodes prior to harvesting
[14]
and grafting these lymph nodes at a distant site . They found that both the rate of lymphangiogenesis and
the drainage capability of the new lymphatic networks in the sterile inflammation group were significantly
superior to the negative control.