Integrated Bioactive Scaffold with Polydeoxyribonucleotide and Stem-Cell-Derived Extracellular Vesicles for Kidney Regeneration

Kidney tissue engineering and regeneration approaches offer great potential for chronic kidney disease treatment, but kidney tissue complexity imposes an additional challenge in applying regenerative medicine for renal tissue regeneration. In this study, a porous pneumatic microextrusion (PME) composite scaffold consisting of poly(lactic-co-glycolic acid) (PLGA, P), magnesium hydroxide (MH, M), and decellularized porcine kidney extracellular matrix (kECM, E) is functionalized with bioactive compounds, polydeoxyribonucleotide (PDRN), and tumour necrosis factor-α (TNF-α)/interferon-γ (IFN-γ)-primed mesenchymal stem-cell-derived extracellular vesicles (TI-EVs) to improve the regeneration and maintenance of a functional kidney tissue. The combination of PDRN and TI-EVs showed a significant synergistic effect in regenerative processes including cellular proliferation, angiogenesis, fibrosis, and inflammation. In addition, the PME/PDRN/TI-EV scaffold induced an effective glomerular regeneration and restoration of kidney function compared to the existing PME scaffold in a partial nephrectomy mouse model. Therefore, such an integrated bioactive scaffold that combines biochemical cues from PDRN and TI-EVs and biophysical cues from a porous PLGA scaffold containing MH and kECM can be used as an advanced tissue engineering platform for kidney tissue regeneration.