Wake Forest Institute for Regenerative Medicine (WFIRM) researchers have show the feasibility of bioengineering vascularized functional renal tissues for kidney regeneration, developing a partial augmentation strategy that may be a more feasible and practical approach than creating whole organs.
The use of this scaffold system address the challenges associate with vascularization and may be an ideal treatment strategy for augmentation of renal function in patients with chronic kidney disease, said James Yoo, M.D., Ph.D., lead author and professor of regenerative medicine at WFIRM. Vascularization continues to be one of the major hurdles affecting the survival and integration of implant 3-D tissue constructs.
Current therapies for end
The limitations of current therapies for end stage renal disease led WFIRM researchers to explore the development of renal 3-D constructs with the goal of improving, restoring, or replacing partial or total renal function. A universal challenge in engineering large solid organs is the need for vascularization,” said Anthony Atala, M.D., a co-author of the paper and director of WFIRM.
Kidneys depend on complex 3-D vascular networks for tissue survival and renal function; but the intricate nature of the renal vasculature makes replication difficult. In order to treat chronic kidney disease; so the WFIRM researchers knew they need to address the feasibility of applying their vascular scaffold in the context of partial renal implantation.
Using polycaprolactone (PCL) solution and collagen as the casting and scaffold materials, respectively, the scientists essentially made molds using donor kidneys as templates; so creating hollow scaffolds that were culture in renal growth medium before implantation into the preclinical model. The level of neovascularization, survival of implant human renal cells; also renal structure formation was evaluate.
3D branching architecture
The renal vascular scaffold show a 3-D branching architecture; so with visible hollow channels that were interconnect and continuous. These branching structures were able to allow perfusion; so similar to native blood vessels. The researchers show that the vascular scaffolds integrate with the host vessels and support renal cell viability.
“The biomimetic vascular scaffold coated with endothelial cells; which show significantly enhance vascularization, as compare to the uncoated scaffold and hydrogel only groups,” Yoo said. “Along with the improved vascularization effects; so the endothelial cell coat scaffolds show a significant renal cell infiltration; hence from the neighboring host tissue, as compare to the other groups.”
The results are promising and support continue exploration of this method; so to further evaluate renal function of the implant constructs; also address limitations such as improving systemic renal function. Overall, they are very please with the outcomes thus far,” Atala said. “Further work is necessary to establish a reliable and reproducible system for clinical translation.