Effects of macrophage regulation on fat grafting survival: Improvement, mechanisms, and potential application—A review

Abstract

Background Autologous fat grafting has become a popular tool in plastic surgery to solve soft tissue defects and achieve skin rejuvenation, but the volume loss after transplantation remains a disturbing problem. In recent years, some new strategies have improved the outcome to some extent, but the fat graft retention is still far from ideal, so there remains a wide development prospect in this field. Macrophages are closely related to the local microenvironment and tissue regeneration, and their role in fat grafting has been increasingly highlighted. Aims This article was aimed to review the efficacy, possible mechanisms, and potential application of macrophage regulation on fat grafting, as well as concerns and future perspectives of this filed. Methods A retrospective review of the published data was conducted. Results Most studies indicated that up‐regulating M2 macrophages during fat grafting would improve fat retention via promoting neovascularization. M2 macrophages could secrete several pro‐angiogenic factors, accelerate extracellular matrix (ECM) remodeling, and directly function on endothelial cells to encourage vascular expansion. In addition, macrophages could influence the proliferation, apoptosis, and adipogenic differentiation of preadipocytes. Conclusions During autologous fat grafting, appropriately regulating macrophages may become a promising method to increase fat retention. Nevertheless, the M2 macrophage polarizing agents, treatment opportunity, and contraindications require further discussion. We hope our work could promote more in‐depth studies in this field, and we are looking forward to a standard procedure for the macrophage therapy in clinical practice.

Disulfiram Improves Fat Graft Retention by Modulating Macrophage Polarization With Inhibition of NLRP3 Inflammasome-Mediated Pyroptosis

“…The polarization state of macrophages plays a significant role in angiogenesis of fat grafts. 39 , 40 We therefore analyzed the effect of DSF on neovascularization. Angiogenesis was evaluated by analyzing CD31, a biomarker of endothelial cells, to determine whether inhibition of pyroptosis facilitated angiogenesis in fat grafts.…”

“… 39 , 41 Macrophages undergo apoptosis during the repair process after fat grafting, which is consistent with our electron microscopy observations. 40 In addition, the cytoplasmic membrane of macrophages was fragmented, membrane pores formed, and nuclei were crumpled. We hypothesized that macrophages activate pyroptosis (an inflammatory form of cell death) in addition to apoptosis.…”

PPAR‐γ regulates the polarization of M2 macrophages to improve the microenvironment for autologous fat grafting

“…First, macrophages affect the vascularization process, 54 thus affecting the survival and regeneration of adipocytes. Studies have shown that in a hypoxic environment, M2 macrophages can produce proteases such as MMP‐2 and MMP‐9, which can cause the hydrolysis of ECM, induce the invasion and fusion of nearby tip cells, and form neovasculature 55 . In addition, when M2 macrophages aggregate in large quantities, they can produce interleukins (IL‐1, 5, 6, 8, and 17) and their receptors to interact with VECs to accelerate revascularization in a paracrine manner 56 .…”

“…Studies have shown that in a hypoxic environment, M2 macrophages can produce proteases such as MMP-2 and MMP-9, which can cause the hydrolysis of ECM, induce the invasion and fusion of nearby tip cells, and form neovasculature. 55 In addition, when M2 macrophages aggregate in large quantities, they can produce interleukins (IL-1, 5, 6, 8, and 17) and their receptors to interact with VECs to accelerate revascularization in a paracrine manner. 56 We observed that the grafts in Group R had a strong regeneration ability, and the LSCI results also suggested that the grafts in this group had good blood perfusion.…”

Xenogenic induction of adipose tissue and maintenance through pre- and post-conditioning using external volume expansion

“…Previous research described the process of inflammation that occurs following fat grafting as comprising an 'initial,' 'peak,' and 'declining' stage [56,57]. During the initial stage, which occurs within hours of grafting, macrophages, of a predominant M1 phenotype, infiltrate the recipient site and mediate an inflammatory cascade.…”