Tissue-engineering approaches for subcutaneous cell delivery
Pancreatic islets are embedded within sub-millimetre rods and then seeded with endothelial cells. Mesenchymal stromal cells (MSC) can also be incorporated within the endothelialized modules. These modules are then subcutaneously injected, which self-assemble and become vascularized over time.
The subcutaneous space has been pursued as an alternative site for pancreatic islet transplantation because it is readily accessible and can support a large transplant volume; however, its avascular nature precludes its utility.
In this work, we demonstrated that modular tissue engineering could be adapted to deliver pancreatic islets into the subcutaneous space to return diabetic mice to normoglycemia by creating islet modules.
Using whole implant clearing (CLARITY), we showed that embedded islets became revascularized and integrated with the host’s vasculature, a feature not seen in other subcutaneous studies.
Furthermore, islet modules drove a a shift towards the pro-angiogenic M2-like macrophage (CD206+MHCII−) response, a feature of module-associated vascularization.
Read our 2017 publication in PNAS and book chapter for more details.
Islet modules with HUVEC vascularized and integrated with the host’s vasculature at day 21. Vessels are perfused with GSL-1 lectin conjugated to Alexa-555 (red), and cells have been stained with DAPI (blue).
Preparation of interpenetrating polymer network (IPN) hydrogel from a collagen-alginate blend. Microspheres were further coated with collagen in sodium citrate and seeded with endothelial cells.
In this study, we created an interpenetrating polymer network (IPN) hydrogel from a collagen-alginate blend and evaluated its use as microspheres in modular tissue engineering.
By combining the ionotropic gelation of alginate with collagen fibrillogenesis, we created a hydrogel that was stiffer and a greater resistance to enzymatic degradation relative to collagen alone.
IPN microspheres were rapidly generated using a coaxial air-flow technique.
Mesenchymal stromal cells were embedded within IPN microspheres and coated with endothelial cells to generate robust vasculature when transplanted into the subcutaneous space.
Perfusion studies confirmed that graft-associated vasculature was connected to the host vasculature - enabling IPN microspheres as a platform to deliver cells into the subcutaneous space.
For more details check out our 2017 publication in ACS Biomaterials Science & Engineering