Bottom-up Biomaterial strategies for creating tailored stem cells in regenerative medicine

Biomaterial-assisted stem cell therapies hold immense promise for regenerative medicine, yet clinical translation remains challenging. This review focuses on recent advances and persistent limitations in applying induced pluripotent stem cells (iPSCs), endothelial colony-forming cells (ECFCs), multi...

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Main Authors: Brenda Cruz-Gonzalez, Ellie Johandes, Dominique Gramm, Donny Hanjaya-Putra
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Bioengineering and Biotechnology
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Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2025.1581292/full
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author Brenda Cruz-Gonzalez
Ellie Johandes
Dominique Gramm
Donny Hanjaya-Putra
Donny Hanjaya-Putra
Donny Hanjaya-Putra
Donny Hanjaya-Putra
author_facet Brenda Cruz-Gonzalez
Ellie Johandes
Dominique Gramm
Donny Hanjaya-Putra
Donny Hanjaya-Putra
Donny Hanjaya-Putra
Donny Hanjaya-Putra
author_sort Brenda Cruz-Gonzalez
collection DOAJ
description Biomaterial-assisted stem cell therapies hold immense promise for regenerative medicine, yet clinical translation remains challenging. This review focuses on recent advances and persistent limitations in applying induced pluripotent stem cells (iPSCs), endothelial colony-forming cells (ECFCs), multipotent mesenchymal stromal cells (MSCs), and embryonic stem cells (ESCs) within engineered microenvironments. We introduce a novel “bottom-up” approach to biomaterial design. This approach focuses first on understanding the fundamental biological properties and microenvironmental needs of stem cells, then engineering cell-instructive biomaterials to support them. Unlike conventional methods that adapt cells to pre-existing materials, this strategy prioritizes designing biomaterials from the molecular level upward to address key challenges, including differentiation variability, incomplete matching of iPSCs to somatic counterparts, functional maturity of derived cells, and survival of ECFCs/MSCs in therapeutic niches. By replicating lineage-specific mechanical, chemical, and spatial cues, these tailored biomaterials enhance differentiation fidelity, reprogramming efficiency, and functional integration. This paradigm shift from passive scaffolds to dynamic, cell-instructive platforms bridges critical gaps between laboratory success and clinical translation, offering a transformative roadmap for regenerative medicine and tissue engineering.
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spelling doaj-art-ef50af177ebc493d9499209d9013f7362025-08-20T01:52:18ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852025-05-011310.3389/fbioe.2025.15812921581292Bottom-up Biomaterial strategies for creating tailored stem cells in regenerative medicineBrenda Cruz-Gonzalez0Ellie Johandes1Dominique Gramm2Donny Hanjaya-Putra3Donny Hanjaya-Putra4Donny Hanjaya-Putra5Donny Hanjaya-Putra6Department of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN, United StatesDepartment of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN, United StatesDepartment of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN, United StatesDepartment of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN, United StatesHarper Cancer Research Institute, University of Notre Dame, Notre Dame, IN, United StatesDepartment of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN, United StatesCenter for Stem Cells and Regenerative Medicine, University of Notre Dame, Notre Dame, IN, United StatesBiomaterial-assisted stem cell therapies hold immense promise for regenerative medicine, yet clinical translation remains challenging. This review focuses on recent advances and persistent limitations in applying induced pluripotent stem cells (iPSCs), endothelial colony-forming cells (ECFCs), multipotent mesenchymal stromal cells (MSCs), and embryonic stem cells (ESCs) within engineered microenvironments. We introduce a novel “bottom-up” approach to biomaterial design. This approach focuses first on understanding the fundamental biological properties and microenvironmental needs of stem cells, then engineering cell-instructive biomaterials to support them. Unlike conventional methods that adapt cells to pre-existing materials, this strategy prioritizes designing biomaterials from the molecular level upward to address key challenges, including differentiation variability, incomplete matching of iPSCs to somatic counterparts, functional maturity of derived cells, and survival of ECFCs/MSCs in therapeutic niches. By replicating lineage-specific mechanical, chemical, and spatial cues, these tailored biomaterials enhance differentiation fidelity, reprogramming efficiency, and functional integration. This paradigm shift from passive scaffolds to dynamic, cell-instructive platforms bridges critical gaps between laboratory success and clinical translation, offering a transformative roadmap for regenerative medicine and tissue engineering.https://www.frontiersin.org/articles/10.3389/fbioe.2025.1581292/fullbiomaterials3D printingstem cellstissue engineeringsdisease modelingdrug screening
spellingShingle Brenda Cruz-Gonzalez
Ellie Johandes
Dominique Gramm
Donny Hanjaya-Putra
Donny Hanjaya-Putra
Donny Hanjaya-Putra
Donny Hanjaya-Putra
Bottom-up Biomaterial strategies for creating tailored stem cells in regenerative medicine
Frontiers in Bioengineering and Biotechnology
biomaterials
3D printing
stem cells
tissue engineerings
disease modeling
drug screening
title Bottom-up Biomaterial strategies for creating tailored stem cells in regenerative medicine
title_full Bottom-up Biomaterial strategies for creating tailored stem cells in regenerative medicine
title_fullStr Bottom-up Biomaterial strategies for creating tailored stem cells in regenerative medicine
title_full_unstemmed Bottom-up Biomaterial strategies for creating tailored stem cells in regenerative medicine
title_short Bottom-up Biomaterial strategies for creating tailored stem cells in regenerative medicine
title_sort bottom up biomaterial strategies for creating tailored stem cells in regenerative medicine
topic biomaterials
3D printing
stem cells
tissue engineerings
disease modeling
drug screening
url https://www.frontiersin.org/articles/10.3389/fbioe.2025.1581292/full
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