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Page 2 of 13 Yang et al. Plast Aesthet Res 2020;7:8 I http://dx.doi.org/10.20517/2347-9264.2019.63

immunofluorescent staining was performed. Real-time quantitative polymerase chain reaction was performed for
adipogenic, inflammatory and apoptotic genes.

Results: The range of fat particle diameters harvested with four commonly used cannulas was 2-7 mm. In vitro studies
showed that 5-7-mm particles had significantly increased VEGF secretion normalized to weight, indicating increased
tissue hypoxia in these particles compared to 2-4-mm particles. Surprisingly, in vivo comparison in two unique studies
showed 2-4-mm and 5-7-mm fat particles had comparable graft retention (P = 0.5329). Masson’s trichrome staining
revealed increased extracellular matrix and fibrosis in the 5-7-mm particle group (P = 0.0115). Adipocyte survival
with perilipin demonstrated comparable viability. Gene expression showed large particles experienced increased
inflammation and apoptosis at one week after grafting, but overall there were no significant differences between groups.

Conclusion: The ideal fat particle size should be large enough to contain adequate mesenchyme while not so thick as to
preclude imbibition. This study suggests that, despite changes in hypoxia and VEGF levels, differing fat particles (2-4-mm
and 5-7-mm) can achieve similar graft retention.

Keywords: Fat grafting, particle size, lipofilling, lipoharvesting, adipocyte viability, clinical translation

INTRODUCTION
Autologous adipose tissue transfer, or fat grafting, is a common procedure in aesthetic and reconstructive
[1]
plastic surgery with approximately 90,000 patients treated each year in the US alone . Fat grafting allows
permanent tissue volume augmentation and correction of contour irregularities in a minimally invasive
[2]
and safe manner . However, studies have demonstrated unpredictable and unsatisfactory graft retention
[3]
in some patients that can range between 40% and 90% . Thus, significant efforts have been undertaken to
understand the biology of fat grafting and optimize each step of the fat grafting process from end-to-end
[4-9]
(harvesting, processing, and injection) .
In modern liposuction, excess adipose tissue is extracted through a hollow-bore cannula, typically between
12 and 14 G, with variable numbers and sizes of holes. The resulting lipoaspirate product is a suspension of
solid adipose tissue particles in liquid comprised of tumescent fluid, blood, and oil from lysed cells. From
this lipoaspirate, additional processing steps may be added to remove fluid and oil, ultimately producing a
collection of fat particles that are then grafted into the volume void. It is well known in the literature that
fat grafts depend on diffusion of oxygen and nutrients from the recipient bed until new blood vessels are
formed [10,11] . According to work by Khouri et al. , when fat particles are very large (greater than 0.16 cm in
[12]
radius), oxygen and nutrient diffusion to the interior particle core is insufficient to maintain tissue viability
resulting in central necrosis and potentially oil cyst formation. These oil cysts are eventually resorbed
through macrophage clearance, resulting in overall graft tissue loss and inferior long-term fat grafting
outcomes.

The predominate theory in fat graft preparation is therefore to minimize particle size to as small as possible
to reduce central necrosis and ultimately increase graft retention. However, other groups have challenged
this assertion, hypothesizing that small cannula diameters increase shear stress in tissue, thereby damaging
[16]
[15]
viability and increasing graft resorption [13,14] . In two unique studies, Erdim et al. and Kirkham et al.
demonstrated that large diameter cannulas lead to higher graft retention, improved adipocyte survival, and
less inflammatory infiltrate and fibrosis. In another comparative study in rabbits, fat was harvested with
a regular 4.5-mm, 1-mL syringe with a sharp steel sleeve, excised ,and cut into 1-mg pieces and aspirated
[17]
with a 2-mm harvesting cannula, and long-term retention was equal in all groups . Therefore, the impact
of fat particle size on survival and resorption outcomes remains controversial.