Engineering a 3D Vascularized Adipose Tissue Construct Using a Decellularized Lung Matrix

Abstract

Critically sized defects in subcutaneous white adipose tissue result in extensive disfigurement and dysfunction and remain a reconstructive challenge for surgeons; as larger defect sizes are correlated with higher rates of complications and failure due to insufficient vascularization following implantation. Our study demonstrates, for the first time, a method to engineer perfusable, pre-vascularized, high-density adipose grafts that combine patient-derived adipose cells with a decellularized lung matrix (DLM). The lung is one of the most vascularized organs with high flow, low resistance, and a large blood–alveolar interface separated by a thin basement membrane. For our work, the large volume capacity within the alveolar compartment was repurposed for high-density adipose cell filling, while the acellular vascular bed provided efficient graft perfusion throughout. Both adipocytes and hASCs were successfully delivered and remained in the alveolar space even after weeks of culture. While adipose-derived cells maintained their morphology and functionality in both static and perfusion DLM cultures, perfusion culture offered enhanced outcomes over static culture. Furthermore, we demonstrate that endothelial cells seamlessly integrate into the acellular vascular tree of the DLM with adipocytes. These results support that the DLM is a unique platform for creating vascularized adipose tissue grafts for large defect filling.

A three-dimensional human adipocyte model of fatty acid-induced obesity

“…Importantly, the cellulose scaffold maintains its integrity throughout long-term culture, thereby providing a porous environment and anchor points for the hydrogel-cell mixture to attach to, highlighting another merit of the paper scaffold-based approach. Our work is also in line with previous studies demonstrating that several different biomaterial scaffolds and extracellular matrices can be used for effective adipocyte differentiation in vitro [40][41][42][43]. Recently, trends in the development of self-assembled tissue cultures have sparked the creation of adipocyte spheroids cultures for the study of adipogenesis or adipocyte (dys)function [16,[44][45][46].…”

“…Our work is also in line with previous studies demonstrating that several different biomaterial scaffolds and extracellular matrices can be used for effective adipocyte differentiation in vitro. [42][43][44][45] Recently, trends in the development of self-assembled tissue cultures have sparked the creation of adipocyte spheroids cultures for the study of adipogenesis or adipocyte (dys)function. 16,[46][47][48] While these systems resemble physiologically relevant aspects of adipocyte biology, it is challenging to create specific tissue architectures using self-assembled aggregate cultures.…”

3D Lipogluing: Preliminary Results of a Novel Technique for Direct Three-dimensional Fat Grafting in Breast Reconstruction Surgery

“…However, further extensive studies [44][45][46] with longer follow-up periods are necessary to thoroughly evaluate the long-term safety and aesthetic outcomes. Additionally, exploring its potential application after conservative oncoplastic breast surgery, in cosmetic breast surgery, and in other fields of aesthetic surgery would contribute to a comprehensive understanding of its indications and benefits.…”

Biofabrication of vascularized adipose tissues and their biomedical applications

“…Although this is a promising approach for AT regeneration, it has several restrictions such as the fact that different lobe sizes may limit parallel studies or that time points are limited by the number of lung lobes. 143…”