Introduction: Renal failure is a devastating disease that requires dialysis and transplantation. Tissue engineering and regenerative medicine technologies have been developed to bring alternative therapies to patients with incurable diseases. Recently, 3D bioprinting technology has emerged as a powerful tool to fabricate tissue structures that mimic native tissue constructs in a precise and reproducible manner. However, one of the challenges in 3D bioprinting is finding an appropriate bioink that provides a tissue-specific microenvironment supporting cellular growth and maturation. Accordingly, decellularized extracellular matrix (dECM)-derived hydrogels have been proposed as bioinks for the cell-based bioprinting due to their capability to inherit the intrinsic cues from native ECM.
Methods: This study developed a photo-crosslinkable kidney ECM-derived bioink (KdECMMA) that could provide a kidney-specific microenvironment for renal tissue bioprinting. Porcine whole kidneys were decellularized through a perfusion method, dissolved in an acid solution, and chemically modified by methacrylation. This KdECMMA-based bioink was formulated and evaluated for rheological properties and printability for the printing process. Afterward, the bioprinted cell-laden constructs were implanted in the kidneys of nude rats for subsequent analysis.
Results: The photo-crosslinkable kidney-specific ECM bioink formulation, consisting of gelatin, HA, glycerol, and KdECMMA, was successfully developed for kidney tissue bioprinting. The bioink provided the desired printability and structural integrity. The bioprinted human kidney cells in the KdECMMA bioink were highly viable and matured over time. The 3D bioprinted human renal cell constructs implanted in the renal cortical region of nude rats showed newly formed tubular and glomerular-like structures at 1 and 2 months post-surgery. The bioprinted renal constructs exhibited the structural and functional characteristics of the native renal tissue.
Conclusions: We demonstrated the potential of the tissue-specific ECM-derived bioink for cell-based bioprinting that could enhance cellular maturation and eventually tissue formation. 3D bioprinting strategy with kidney-specific ECM bioink has excellent potential to bioengineer a functional renal tissue construct in future regenerative medicine applications.
Source of Funding: This study was supported by NIH/NIBIB (1P41EB023833).