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.
Highlights
Adipose tissue is a highly vascularized, metabolically active connective tissue that plays a crucial role in supporting normal human appearance, protecting organs, modulating pressure, providing insulation, and functioning as an endocrine regulator [1]
Prior to using the decellularized lung matrix (DLM), it was important for us to establish that all processing steps required to homogenize, breakup, and filter the adipose cells did not negatively affect the cellular viability, metabolism (Resazurin), and functionality
Once we determined perfusion culture resulted in enhanced metabolism over static conditions, we proceeded to use the DLM perfusion culture system to seed endothelial cells in co-culture with adipocytes towards a proof of concept fully vascularized adipose tissue construct
Summary
Adipose tissue is a highly vascularized, metabolically active connective tissue that plays a crucial role in supporting normal human appearance, protecting organs, modulating pressure, providing insulation, and functioning as an endocrine regulator [1]. The appearance and function of subcutaneous adipose tissue can be compromised by traumatic injury (i.e., motor vehicle accidents, burns), ablative procedures (i.e., mastectomy), or congenital malformations (Romberg’s disease, Poland syndrome) leading to contour abnormalities and exposure of vital organs [2,3]. Large subcutaneous defects are treated with autologous adipose grafts which result in donor-site morbidity and have limited applicability to patients with minimal body fat. Tissue-engineered adipose grafts using patient-derived cells hold promise in resolving these limitations. It remains challenging to engineer large-volume (>200 cm3 )
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