Researchers at Boston University are the first to have succeeded in engineering vascularized fat tissue that grows or shrinks when given the appropriate physiological signal. The new work is an important step towards making large, centimetre-sized samples of adipose tissue for regenerative medicine applications.
“We are particularly excited about our technique because it will allow us to make whole tissue rather than just its vascular components,” says Joe Tien, who led this research effort.
Repairing soft tissue damage
Soft tissue damaged, for example, by injury or when a tumour is removed, often needs to be reconstructed. The main way to do this today is to transfer fatty tissue from another part of the body to the damaged site, but this technique is far from ideal. Being able to engineer stable and functional adipose tissue that can then be grafted directly onto the area of interest would be better, explains Tien.
This tissue needs to be perfused with certain nutrients and hormones immediately after being grafted, however, if it is to survive and maintain its volume, he adds. Most research in this field has so far focused on engineering vascularized fatty tissue and then providing it with a combination of angiogenic and adipogenic growth factors, suspended endothelial cells and adipocytes, and/or adipocyte progenitors, together with an appropriate scaffold. This process usually takes several weeks and can produce a poorly organized microvascular network containing small-diameter microvessels that are difficult to access for further perfusion.
Continued perfusion now possible
Tien’s team has now managed to engineer small-sized samples of adipose tissue that contain perfusable microvessels. The researchers achieved their feat by building on previous work to vascularize microfluidic collagen scaffolds.
“The idea is very simple: we use a thin needle to create a channel (which serves as a template for cell growth) in the scaffold and then vascularize the scaffold through the channel,” Tien tells Physics World. “The important feature is that we can constantly perfuse the scaffold with nutrients and lipoactive hormones such as insulin and epinephrine. In the current work, the scaffold contains suspensions of (3T3-L1) adipocytes in type I collagen.
“When we flow vascular cells into the channel, these cells spontaneously rearrange themselves into a thin vessel. Once the vessel forms, the vascular cells stop growing.
“The lipoactive hormones we then perfuse into the construct primarily affect the adipocytes. When we perfuse the fat cells with insulin and epinephrine, they diffuse across the vessel wall and are taken up by the adipocytes, just as they would in vivo.”
Insulin causes fat cell accumulation and epinephrine fat cell loss, he says, so making the construct grow or shrink, respectively.
Cellular building blocks create life-like constructs
“Fat-on-a-chip”
“Our design could serve as a building block for making larger-sized tissues that might then be transplanted to repair a damaged soft tissue site,” he explains. “The tissue could also be used as a ‘fat-on-a-chip’ microphysiological system to model vessel-adipocyte interactions. It might thus even be used to model complex adipose-rich tissues, such as those in breast tumours.”
To scale up the constructs into clinically implantable ‘flaps’, Tien says that they need to be modified to contain only human cells, such as primary human adipocytes or adipose-derived stem cells. “They will also require a branching vascular network that can support large tissues, and perfusion at the pressures experienced by arteries.”
The research is detailed in Biofabrication 10.1088/1758-5090/aae5fe.
