Adipose tissue engineering for soft tissue regeneration

Abstract

Current treatment modalities for soft tissue defects caused by various pathologies and trauma include autologous grafting and commercially available fillers. However, these treatment methods present a number of challenges and limitations, such as donor-site morbidity and volume loss over time. As such, improved therapeutic modalities need to be developed. Tissue engineering techniques offer novel solutions to these problems through development of bioactive tissue constructs that can regenerate adipose tissue in both structure and function. Recently, a number of studies have been designed to explore various methods to engineer human adipose tissue. This review will focus on these developments in the area of adipose tissue engineering for soft tissue replacement. The physiology of adipose tissue and current surgical therapies used to replace lost tissue volume, specifically in breast tissue, are introduced, and current biomaterials, cell sources, and tissue culture strategies are discussed. We discuss future areas of study in adipose tissue engineering.

FIG. 1.

Regulation of adipogenesis by canonical Wnt signaling cascade. In the presence of Wnt signaling, adipogenesis is inhibited through β-catenin-mediated expression of Wnt target genes. Wnt pathway antagonists, including frizzled-related proteins (sFRPs), Wnt inhibitory factor (WIF-1), and Cerberus and Dickkopfs (Dkk), inhibit Wnt signaling and subsequently stimulate adipogenesis.

FIG. 2.

Schematic of adipose tissue outcome measures. Current adipose tissue engineering strategies examine various aspects of the following adipose tissue outcomes. Adipogenic differentiation is initiated upon inhibition of both Wnt and Hedgehog (Hh) signaling. Peroxisome-proliferator-activated receptor-gamma (PPARγ) and CCAAT/enhancer binding protein alpha (C/EBPα) are key transcriptional regulators that promote expression of adipogenic genes such as glycerol-3-phosphate dehydrogenase (GPDH), glucose transporter-4 (Glut4), fatty acid binding protein-4 (FABP4), and acyl-CoA synthetase (ACS). Triglyceride (TG) synthesis subsequently occurs, causing mature adipokines to be secreted (leptin and adiponectin) and extracellular matrix (ECM) production. TG breakdown, or lipolysis, is mediated by two key lipases (adipose triglyceride lipase [ATGL] and hormone sensing lipase [HSL]), producing glycerol and fatty acids.