Stem Cells, Biofabrication and Genetic Engineering in Tissue Engineering: A Narrative Review

Abstract

Tissue engineering harnesses stem cell biology, biomaterials, microfluidics, and genetic engineering to fabricate functional tissues for regenerative medicine, disease modeling, and drug discovery. Advances in induced pluripotent stem cells (iPSCs), organoids, organ-on-a-chip systems, three-dimensional (3D) bioprinting, and genome editing have not yet translated into clinical application, which remains limited by persistent challenges in vascularization and functional maturation. This narrative review examines the applications and limitations of these four platforms and asks whether they address the same or different barriers to forming physiologically relevant tissue constructs. Organoids achieve unmatched cellular self-organization but cannot direct formation of their own vasculature; organ-on-a-chip systems provide engineer-defined perfusion and mechanical cues but offer limited cellular diversity; 3D bioprinting affords direct control over macroscale geometry and vascular channel placement but does not ensure post-print functional maturation; and CRISPR-based genetic engineering offers programmable control over cell-intrinsic molecular behavior but is constrained by off-target effects and understudied long-term safety. Each technology therefore resolves only part of the challenge, but combining these platforms may offer system-level advantages unavailable to any single approach. This review proposes a conceptual framework in which iPSC-derived organoids, CRISPR-edited cells, 3D-bioprinted scaffolds, and organ-on-a-chip perfusion are integrated in sequence, motivated by recent proof-of-concept work demonstrating perfusable vascular networks self-assembling around organoids on a microfluidic chip. This framework is presented as testable hypotheses rather than a validated pipeline; realizing it will require shared, quantitative standards for reporting vascularization and maturation outcomes across platforms.