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Page 8 of 16 Shaaban et al. Plast Aesthet Res 2023;10:12 https://dx.doi.org/10.20517/2347-9264.2022.91

FAT GRAFTING FOR PAIN REDUCTION
Some of the most current and emerging uses for autologous fat grafts are scar and pain treatment following
mastectomy and/or radiation therapy [23,102-105] . Post-mastectomy pain syndrome (PMPS) entails more than
just post-surgical pain; it is neuropathic, lasts at least 6 months, occurs at least 50% of the time and presents
as dull, burning, and aching sensations involving the chest, axilla, and ipsilateral upper extremity [23,72,88,106-108] .
Activities such as movement, straining, overhead activity, and cold weather can exacerbate symptoms and
cause further disability, reduced quality of life, and emotional distress. Jung et al. classified PMPS into four
categories; phantom breast pain, intercostobrachial neuralgia stemming from intercostobrachial nerve
damage, neuroma pain, and other nerve injury pain from surrounding nerves’ damage [60,106,107] .

The current leading hypotheses on PMPS etiology include intraoperative nerve damage to any of the
primary nerves affected during mastectomy or breast surgeries in general, i.e., the intercostobrachial, medial
and lateral pectoral, thoracodorsal, long thoracic, and intercostal nerves [108,109] , and subsequent entrapment
in cicatricial fibrosis, which may incite continuous nervous excitement. Additional hypotheses include
decreased circulation, scarring/fibrosis, and injury to fibroblasts after radiation [60,106,110] .

Autologous fat grafting is believed to help with scar remodeling, enhance angiogenesis, reduce nerve
entrapment within adhesions, and provide local analgesia by inhibiting the inflammatory
response [60,105,106,110] . Several Level I/II clinical studies have shown that fat grafting significantly reduces
PMPS-related pain compared to control cohorts [87,105,111-113] . Lisa et al. analyzed patient demographic factors
affecting fat grafting clinical efficacy and found no significant association between age, BMI, the
menopausal status of patients, time from oncologic surgery to autologous fat grafting and reduction of the
[87]
Visual Analogue Scale (VAS) values over time . Smoking and axillary dissection were the main factors
[87]
significantly associated with reduced fat grafting efficacy (respectively, P = 0227 and P = 0066) .
There have been very few mechanistic rationales provided as to why fat grafting improves fibrosis; however,
the above studies postulated regenerative factors produced by tissue after grafting. This aligns well with
preclinical research showing that lipoaspirate particles continue to secrete high concentrations of growth
factors such as vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and anti-
inflammatory cytokines such as IL-10 in hypoxic environments that occur immediately after graft
injection [114-116] , which may improve the recipient tissue health. However, significantly more research is
needed in this area.

FAT GRAFTING FOR CAPSULAR CONTRACTURE
Despite advancements in biomaterial’s texture and composition, implant-based breast reconstruction
remains challenging due to the prevalence of postoperative complications; one of the most common is
capsular contracture, especially in patients who have received radiation therapy as part of their cancer
treatment . The development of a thin capsule around foreign objects is a normal immune response
[117]
following implant placement and typically has minimal effects on the appearance or consistency of the
operated breast. However, over-activation of the immune response can cause inflammatory cell recruitment
and excessive fibrosis, which results in the synthesis of a matrix around the implant. Fibroblast proliferation
and organization into structured capsules in proximity to frustrated, overactive phagocytes lead to chronic
inflammation and differentiation of fibroblasts into myofibroblasts, inducing contractile scar tissue. Fat
grafting purportedly ameliorates capsular contracture through the same mechanism mentioned by reducing
nerve entrapment and also helps to improve skin quality and sensation after contracture [49,60,105] . An early
preclinical study demonstrated that autologous fat transfer reversed capsule severity following pericapsular
[118]
injection by promoting neovascularization of adjacent tissue and softening of the capsule . Subsequent