Efficacy and Safety of a Nanofat-seeded Biological Scaffold in Healing Lower Limb Surgical Defects

Large full-thickness skin defects, such as those resulting from trauma, large and giant
congenital nevi, disfiguring scars, or tumor resection remain major clinical problems to
patients and physicians. Skin flaps and grafts represent the current standard of care (SOC),
but often present limitations associated with surgical morbidity and donor site availability.
To overcome these limitations, cultured epidermal autografts consisting of keratinocytes were
developed to provide enough autologous skin. However, the routine use of these cultured
epidermal autografts was hampered by its high risk of recurrent wound opening, long-term
fragility, and increased rates of scar contractures.

Tissue-engineered dermal skin substitutes containing complex dermal layers have also been
developed to produce large, near-natural skin substitutes. They promote healing and avoid
scar contracture; however, the healing times are long as they lack the active cellular and
paracrine components of healing, and they often need a second delayed surgical procedure, a
split-thickness skin graft, to obtain complete epithelization.

The term "nanofat grafting" was first used by Tonnard et al. and constitutes a rich reservoir
of regenerative precursor cells (including stromal vascular fraction cells, among which
adipose-derived stem cells) with pro-angiogenic capabilities. The many proprieties of nanofat
and the stromal vascular fraction in regenerative and aesthetic surgery are just being
discovered. In particular, numerous in vitro and in vivo studies have demonstrated the
ability of these cells to differentiate into various skin cell lineages. Moreover, they are
recognized as a powerful source for tissue regeneration because of their capability to
secrete paracrine factors, initiating tissue repair and accelerating wound closure by skin
regeneration instead of fibrotic scar formation.

Few anecdotal reports have documented the efficacy of the stromal vascular fraction in acute
as well as chronic wounds. However, no observation has explored the efficacy of nanofat in
healing surgical defects. Of note, nanofat is substantially easier, faster, and remarkably
less expensive to obtain when compared to the mechanically- or enzymatically-isolated stromal
vascular fraction. At present, there is a noticeable lack of randomized-controlled evidence
in the international literature. Thus, this would represent the most comprehensive and the
first randomized, controlled experience documenting the use of nanofat for wound healing.

Inclusion Criteria:

- Subjects who need to undergo a surgical intervention resulting in complex lower limb
surgical defects that cannot be closed primarily, and thus need a reconstructive phase

- Willing to undertake all study procedures, including nanofat harvesting from stomach
site

- Willing to sign an informed consent form

Exclusion Criteria:

- Age less than 18 years of age

- Pregnant women

- Any contraindications to use of nanofat or collagen scaffold