Cell transplantation holds promise to provide regenerative therapy in treating malfunctioned organ/tissue in modern medicine. Once in the body, the cells, however, are hard to be kept normal or functional due to the harsh in vivo conditions—e.g. lack of nutrient supply and emergence of host reaction—at the transplantation site. The problem has in particular generated formidable hurdles in islet transplantation for treating diabetes: A large number of cells are needed to be placed into the body while islets randomly packed together could easily die from necrosis and fail to engraft and reverse the diabetes.
Recently, a research team led by Professor Ying Luo of the Department of Biomedical Engineering of Peking University in China developed a micropatterned scaffold through a special electrospinning process integrated with the micromolding technique. Nanoscale electrospun fibers based on a polyurethane material were deposited to bear ordered arrayed microwells in the diameter of a few hundreds of micrometers, resulting in scaffold materials with topographical features both on nano- and micro-scales. The scaffolds were used to template the islets or aggregates of mensenchymal stem cells (MSCs), so that hundreds of these microtissues were “knitted” in arrays onto the material. When transplanted in the epididymal fat pad in the mouse model with chemically induced type-1 diabetes (T1D), islets were found to engraft with vascularization and show the function to lower the sugar level to a normal value in the hosts. In transplanting MSCs, the micropatterned scaffolds were turned into a sealed isolation device that protected the micropatterned MSCs from the immune attack of the host; the transplantation reversed the diabetic condition in the rat model, likely through boosting the pancreas repair and islet regeneration.
“The scaffold is in a sense like an egg carton used for carrying and transporting whole eggs, ” commented the authors, “Except that the carton was composed of synthetic polymer fibers and created at a much smaller scale for holding and organizing tiny tissues capable of curing disease.” After dwelling in the microwells on the scaffold, these otherwise quite fragile microtissues were arranged with spatial order and kept apart to minimize the cell necrosis. Moreover, compared to many previously reported micropatterned hydrogel materials, the polyurethane nanofibers can offer not only superior mechanical strength but also suitable local mass transport properties: The nutrients were able to pass through the membranous scaffold to let the supported cells “breathe” normally through “tiny pores” in the membrane to survive.
Compacting the microtissues and endowing them with appropriate spatial patterns represents a critical step in generating cell-based “live” artificial organs. Assembling the microtissues such as islets through micropatterned scaffolds shows a paradigm to fabricate functional mini-organs for regenerative therapy. Although important questions remain regarding how to maximize the cell-loading capacity while ensuring ample oxygen/blood supply to the transplanted cells, scaffolds with engineered structures might pave the way for further developing cell-transplantation devices that could be scaled-up for use in human patients.
Left and middle: Electrospun scaffolds and micro-wells structure; the upper right: vascularized cell graft; the lower right: the stent-assembled islets survive in the body and function.