Advanced biomanufacturing of scalable, perfusable, pre-vascularized adipose tissues

Carnegie Mellon University, Pittsburgh PA

Investigators

Abstract

Adipose/fat tissue is a dynamic endocrine organ that acts as a major site of energy storage, shock absorption, and a crucial regulator of metabolism, glucose, temperature, and hormonal processes. Accordingly, engineering adipose tissues is of critical importance for understanding physiology and pathology (such as obesity and diabetes), and for repairing body surface defects that can result from traumatic injury and invasive surgical procedures. While tissue engineering has been explored for these purposes, approaches have met limited success due to diffusion constraints, and insufficient adipose cell density and stability compared to the native tissue. This project aims to address these engineering challenges by delivering an innovative technology for manufacturing high-density, large human adipose tissues with integrated, perfusable vascular systems. The educational impact of this project will be achieved through integrating research-related demonstrations with existing biomedical engineering courses and facilitating opportunities to enhance the representation of underrepresented minorities in research. The goal of this project is to integrate adipose and vascular tissue engineering using a decellularized lung matrix (DLM) and offer a transformative solution for engineering perfusable, vascularized, high-density adipose tissue models. The lung is one of the most highly vascularized organs with high flow, low resistance, and a large blood-alveolar interface separated by a very thin basement membrane (<1 µm). The DLM offers the following unique advantages for adipose tissue engineering: (1) its large volume alveolar compartment can accommodate high-density adipose cell filling; (2) it offers a preserved, acellular vascular bed allowing efficient tissue perfusion and vascular cell seeding; (3) the alveolar compartment shields buoyant and fragile adipocytes from harmful high shear stresses by confining high flow rates to the vascular bed where they are required for proper endothelial functionality; and (4) it is scalable and can be adapted for critically sized defects using scaffold materials derived from large donor sources (example: pigs). Specific project tasks will: (1) engineer scalable, pre-vascularized adipose tissues; and (2) model adipose-vascular-extracellular matrix interactions during hyperglycemia. This model will facilitate the acquisition of basic knowledge on adipose physiology as well as provide a tissue-engineering platform for repairing critically sized (>200 mL) subcutaneous tissue defects. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.