Physiological Relevant 3D Biomanufacturing of Pluripotent Stem Cells for Regenerative Medicine

Abstract Purpose of Review Regenerative medicine is transforming modern healthcare by offering personalized approaches to the treatment of diseases and injuries. With rapid market growth and significant breakthroughs in cell and biomaterial technologies, the field is poised to reshape the future of medicine. This short review highlights emerging trends, and the critical roles of human induced pluripotent stem cells (hiPSCs) and 3D biomanufacturing in advancing regenerative solutions and challenges. Recent Findings Recent studies have shown that the potentials of hiPSCs have been significantly limited by current monolayer (2D) or 3D suspension technologies. hiPSCs require physiologically relevant 3D microenvironment to support their migration and signaling and interact with the 3D environment as well as between hiPSCs themselves, regulating and sustaining their proliferation and pluripotency, thereby enabling long-term maintenance, expansion, and differentiation. Summary hiPSCs play a significant role in regenerative medicine, including applications in drug development, disease modeling, and tissue regeneration. Synthetic peptide hydrogels (PepGel), such as PGmatrix, have demonstrated the ability to enable physiologically relevant 3D biomanufacturing of hiPSCs by supporting the maintenance and growth of hiPSCs in a biologically natural manner while preserving their pluripotent integrity for high performance somatic cells and organoids production. Advanced automation and AI aided processing have been aligned to traditional 2D culture and 3D suspension systems, which need to be adapted into physiologically relevant biomanufacturing of 3D hiPSC and their derived products.