DRI researchers are designing implantable devices
that can house and protect transplanted cells. These bioengineered “containers” hold many cells and, if necessary, can be retrieved and/or reloaded with more islets.
Mesh cylinder
In one approach, researchers implant a small, biocompatible mesh cylinder under the skin (subcutaneous) and allow a network of blood vessels to grow in and around the mesh.
Following adequate vascularization, islets are inserted into the cylinder and the “already established” blood vessels are able to immediately deliver oxygen and other vital nutrients.
In a recent study, DRI researchers tested this device in the mouse model and achieved comparable glucose control to that of traditional islet infusions.
Local drug delivery
The use of an implantable, bioengineered device provides additional opportunities to design strategies to protect islets from immune attack.
With funding provided by Converge, a biotechnology company formed in collaboration with DRI and the University of Miami, DRI scientists are working to develop a biohybrid device able to deliver local immunosuppression within the transplant environment.
Instead of using oral or infused drug therapy, which affects the entire body, the collaborative group is developing a system to provide low-dose drugs directly into a device containing the insulin producing islets.
The researchers are exploring the use of several drugs, including corticosteroids, a “soft drug” for local use, since it is specifically designed to deliver the desired therapy and then break down into a harmless substance.
This approach will test the ability to achieve long-term graft acceptance and transplantation tolerance with local, low dose immunosuppressive drugs. In addition, local drug delivery could eliminate many of the serious problems associated with current systemic therapies, including inflammation and infections.
Scaffolds
The tissue engineering team is also developing bioengineered “scaffolds”.
Similar to the scaffolding of a building where the framework provides the overall mechanical integrity and three-dimensional structure, tissue engineered scaffolds provide support and spatial distribution to the islets.
To replicate the islets’ natural environment within the native pancreas, researchers are using novel biomaterials to construct innovative scaffolds that will house the islets and enhance delivery of oxygen and other nutrients.
One strategy incorporates an oxygen binding compound into these scaffolds, resulting in significantly improved islet viability and glycemic control in study animals.
Testing New Sites
In addition to the subcutaneous implant sites, the DRI is testing other sites in the body, such as the omentum. This natural, apron-like covering of the abdomen is highly vascularized and may have biological properties that can enhance cell survival.
Investigators are creating a “pouch” in this tissue to house islets within scaffolds and/or other biocompatible devices.