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volume of soft tissues by utilizing cannulas and augmentation with fat cells. He also noted an increase in
adipose tissue under tissue expanders placed in rats below the latissimus muscle. The thought is that the
tensile pressure associated with the tissue expander leads to adipose deposits [121,122] .

Wound healing issues are a multibillion dollars business and the use of ADSCs offer potential therapeutic
options. ADSCs have been promoted as favorable candidates for wound therapies and they secrete
numerous growth factors and cytokines critical in repair. Recent studies have indicated that ADSCs may
[94]
reverse or improve radiation-induced lesions as well as atrophy and scarring . Animal studies suggest that
the release of keratinocyte growth factor and the differentiation of ADSCs toward endothelial and epithelial
cell line phenotypes may be the mechanisms of action. Further, the angiogenic properties of ADSCs may
also benefit complications secondary to ischemia. Autogenous transplantation has demonstrated some
promise in improving ankle-brachial index and transcutaneous oxygen pressure. ADSCs may also be useful
[20]
for the treatment of pathological wound healing in the context of hypertrophic scar formation .
In addition, SVF and ADSCs have been used to promote extracellular matrix (ECM) synthesis, the
groundwork for wound healing. The extracellular matrix acts as a potent scaffold in many tissue types,
accelerating the regenerative functions of nearby cells. It is comprised of structural proteins such as
[12]
collagen, laminin, fibronectin, and elastin, which are commonly secreted by the fibroblast . Furthermore,
the ECM contributes to the growth of vascular networks by mediating morphogenesis and migration
speeds during angiogenesis. Since the SVF contains matrix-secreting fibroblasts and other stromal cells, the
[11]
application of SVF is potentially advantageous for laying down the foundations for wound healing .

Finally, skin rejuvenation may have promise with ADSC use. It may be possible that these cells could
reverse atrophic and photo-damaged cells. Animals studies have demonstrated that subcutaneous ADSC
injections increase dermal thickness and collagen density in aged mice and perhaps reduced wrinkles
induced by UVB-irradiation [11,12] .

Our laboratory has also studied the mechanism of fat formation using acellularized adipose matrix by
deconstructing adipo-induction in this acellularized adipose matrix (AAM). It has been observed that
AAM injected subcutaneously in an area relatively devoid of fat may initiate lipogenesis. Because of this
observation, our global aim was to delineate the sequence of events occurring following implantation of
AAM to the final process of adipogenesis. We wanted to compare adipoinduction of adipose/fascia complex
to that of adipose fraction alone - analyzing proteomics, bioinformatics, early and late cellular infiltrates,
cytokines, adipokines, and enzymes (related to macrophage phenotype and lipoproteins). In addition, we
examined the genesis of the adipocytes required to achieve a lipofilling effect, and detailed the involvement
of stromal and stem cells in recruiting host tissue to fill the void via adipogenesis, neovascularization and
fibrosis [120] .

Recently, several groups have started to examine the use of human AAM as a scaffold for tissue
engineering, which shows great promise as a vehicle for adipose stem cell delivery as well as a construct
that promotes soft tissue regeneration though acellular mechanisms [119] . AAM secretes growth factors
with adipo- and angio-inductive characteristics [vascular endothelial growth factor, bFGF (fibroblast
growth factors), platelet-derived growth factor, and TGF-β (transforming growth factor)] and recruits
preadipocytes, pericytes, and other cells responsible for local tissue regeneration. Degradation products of
the ECM trigger a change in macrophage phenotype that can bring about progenitor cell recruitment [120] .

Micronanobubbles (MNBs) technology is another area of exploration in fat graft survival. The bubbles
afford the opportunity oxygenate tissues without the expense of utilizing hyperbaric chambers or other
nonmobile options. What are the properties that make MNBs unique? MNBs are very small bubbles