ArticleBioactive materials2026
Scalable synthetic peptide hydrogel enables self-organized luminal cavity architecture within hiPSC 3D colonies supporting functional hepatocyte differentiation.
Article in Bioactive materials, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Meniscus Tissue Engineering Scaffolds: Biomaterials, Biofabrication, and Translation.Polymers · 2026Review
- Xeno-Free Peptide-Functionalized Hydrogels Support hiPSC Encapsulation andbioRxiv : the preprint server for biology · 2026Article
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Authors and funding
15 authors.
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Abstract
Human induced pluripotent stem cells (hiPSCs) possess broad differentiation potential; however, efficient maturation into functional hepatocytes remains challenging, in part because conventional differentiation strategies rely on 2D culture or partially defined 3D systems that fail to recapitulate key developmental microenvironmental cues. Although 3D culture has been shown to promote hepatic specification and maturation, a fully defined platform that supports the entire differentiation process from hiPSCs in 3D has not been established. Here, we report a scalable synthetic peptide hydrogel (PepGel) platform that enables hiPSCs to self-organize into long-term, proliferative luminal cavity (LC) architectures within 3D colonies (LC-hiPSCs). These LC-hiPSCs exhibited markedly enhanced differentiation efficiency compared to hiPSC aggregates generated via scaffold-free suspension methods. Using a shear-thinning, self-healing hydrogel configuration optimized for suspension culture, we produced large quantities of LC-hiPSCs and directed their differentiation into PepGel-derived hiPSC-derived hepatocyte-like cells (PG-hiHs). PG-hiHs formed polarized, multi-luminal organoid-like structures and exhibited robust expression of hepatocyte-specific genes and proteins, high cytochrome P450 activity, and in vitro metabolic functions comparable to primary human hepatocytes (PHHs). Following live shipment and transplantation into immunocompromised mouse livers, PG-hiHs engrafted efficiently and maintained human-specific albumin and alpha-1 antitrypsin secretion at PHH-equivalent levels. Furthermore, both LC-hiPSCs and PG-hiHs retained viability, structural organization, and phenotype in complex 3D bioprinted constructs for at least 14 days. Together, this work establishes a fully defined, reproducible, and scalable 3D platform that supports the entire differentiation process, overcoming limitations in hiPSC-derived hepatic maturation and enables physiologically relevant hepatocyte-like tissues for disease modeling, regenerative medicine, and biofabrication.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.