Radiation therapy is not only a mainstay in the treatment of many malignancies but also results in collateral obliteration of microvasculature and dermal/subcutaneous fibrosis. Soft tissue reconstruction of hypovascular, irradiated recipient sites through fat grafting remains challenging; however, a coincident improvement in surrounding skin quality has been noted. Cell-assisted lipotransfer (CAL), the enrichment of fat with additional adipose-derived stem cells (ASCs) from the stromal vascular fraction, has been shown to improve fat volume retention, and enhanced outcomes may also be achieved with CAL at irradiated sites. Supplementing fat grafts with additional ASCs may also augment the regenerative effect on radiation-damaged skin. In this study, we demonstrate the ability for CAL to enhance fat graft volume retention when placed beneath the irradiated scalps of immunocompromised mice. Histologic metrics of fat graft survival were also appreciated, with improved structural qualities and vascularity. Finally, rehabilitation of radiation-induced soft tissue changes were also noted, as enhanced amelioration of dermal thickness, collagen content, skin vascularity, and biomechanical measures were all observed with CAL compared to unsupplemented fat grafts. Supplementation of fat grafts with ASCs therefore shows promise for reconstruction of complex soft tissue defects following adjuvant radiotherapy.

An invaluable part of the plastic surgeon's technical arsenal for soft tissue contouring, fat grafting continues to be plagued by unpredictable outcomes, resulting in either reoperation and/or patient dissatisfaction. Thus, extensive research has been conducted into the effects of adipose tissue procurement, processing, and placement on fat graft quality at both the cellular level and in terms of overall volume retention. Herein, we present an overview of the vast body of literature in these areas, with additional discussion of cell-assisted lipotransfer as a therapy to improve volume retention, and on the controversial use of autologous fat in the setting of prior irradiation.

Soft tissue reconstruction to restore volume to damaged or deficient tissue beneath the skin remains a challenging endeavor. Current techniques are centered around autologous fat transfer, or the use of synthetic substitutes, however, a great deal of scientific inquiry has been made into both the molecular mechanisms involved in, and limitations of, de novo adipogenesis, that is, the formation of new adipose tissue from precursor cells. To best comprehend these mechanisms, an understanding of defined markers for adipogenic differentiation, and knowledge of both commercially available and primary cell lines that enable in vitro and in vivo studies is necessary. We review the growth factors, proteins, cytokines, drugs, and molecular pathways that have shown promise in enhancing adipogenesis and vasculogenesis, in addition to the multitude of scaffolds that act as delivery vehicles to support these processes. While progress continues on these fronts, equally important is how researchers are optimizing clinically employed strategies such as autologous fat transfer through cell-based intervention, and the potential to augment this approach through isolation of preferentially adipogenic or angiogenic precursor subpopulations, which exists on the horizon. This review will highlight the novel molecular and synthetic modifications currently being studied for inducing adipose tissue regeneration on a cellular level, which will expand our arsenal of techniques for approaching soft tissue reconstruction.

Chronic diabetic ulcers are a common complication in patients with diabetes, often leading to lower limb amputations and even mortality. Stem cells have shown promise in promoting cutaneous wound healing by modulating inflammation, angiogenesis, and re-epithelialization. However, more effective delivery and engraftment strategies are needed to prolong transplanted stem cell lifespan and their pro-healing functions in a chronic wound environment to improve skin regeneration. In this study, an injectable poly(ethylene glycol) (PEG)-gelatin-based hydrogel system is examined to create a functional stem cell niche for the delivery of adipose-derived stem cells (ASCs) into diabetic wounds. Human ASCs are encapsulated into the in situ crosslinked hydrogels and cultured in a 3D topography. The encapsulated cells are well attached and spread inside the hydrogels, retaining viability, proliferation, and metabolic activity up to three weeks in vitro. Allogeneic ASCs are delivered to diabetic wounds by this hydrogel vehicle. It is found that stem cell retention is significantly improved in vivo with vehicle-mediated delivery. The ASC-hydrogel-based treatment decreases inflammatory cell infiltration, enhances neovascularization, and remarkably accelerates wound closure in diabetic mice. Together, these findings suggest this conveniently-applicable ASC-hydrogel-based skin substitute provides a promising potential for the treatment of chronic diabetic wounds.

The regenerative abilities of adipose-derived mesenchymal stem cells (ASCs) harvested via a third-generation ultrasound-assisted liposuction (UAL) device versus ASCs obtained via standard suction-assisted lipoaspiration were evaluated. ASC yield and viability, and expression of most osteogenic, adipogenic, and key regenerative genes were equivalent between the two methods. Cells harvested via UAL showed comparable abilities to enhance cutaneous regeneration and appear suitable for cell therapy and tissue engineering applications.