Kidney regeneration with biomimetic vascular scaffolds based on vascular corrosion casts

Abstract

We have developed a biomimetic renal vascular scaffold based on a vascular corrosion casting technique. This study evaluated the feasibility of using this novel biomimetic scaffold for kidney regeneration in a rat kidney cortical defect model. Vascular corrosion casts were prepared from normal rat kidneys by perfusion with 10% polycaprolactone (PCL) solution, followed by tissue digestion. The corrosion PCL cast was coated with collagen, and PCL was removed from within the collagen coating, leaving only a hollow collagen-based biomimetic vascular scaffold. The fabricated scaffolds were pre-vascularized with MS1 endothelial cell coating, incorporated into 3D renal constructs, and subsequently implanted either with or without human renal cells in the renal cortex of nude rats. The implanted collagen-based vascular scaffold was easily identified and integrated into native kidney tissue. The biomimetic vascular scaffold coated with endothelial cells (MS1) showed significantly enhanced vascularization, as compared to the uncoated scaffold and hydrogel only groups (P < 0.001). Along with the improved vascularization effects, the MS1-coated scaffolds showed a significant renal cell infiltration from the neighboring host tissue, as compared to the other groups (P < 0.05). Moreover, addition of human renal cells to the MS1-coated scaffold resulted in further enhancement of vascularization and tubular structure regeneration within the implanted constructs. The biomimetic collagen vascular scaffolds coated with endothelial cells are able to enhance vascularization and facilitate the formation of renal tubules after 14 days when combined with human renal cells. This study shows the feasibility of bioengineering vascularized functional renal tissues for kidney regeneration. Statement of SignificanceVascularization is one of the major hurdles affecting the survival and integration of implanted three-dimensional tissue constructs in vivo. A novel, biomimetic, collagen-based vascular scaffold that is structurally identical to native kidney tissue was developed and tested. This biomimetic vascularized scaffold system facilitates the development of new vessels and renal cell viability in vivo when implanted in a partial renal defect. The use of this scaffold system could address the challenges associated with vascularization, and may be an ideal treatment strategy for partial augmentation of renal function in patients with chronic kidney disease.