Cruz-Gonzalez Brenda, Johandes Ellie, Gramm Dominique, Hanjaya-Putra Donny
Department of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN, United States.
Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN, United States.
Front Bioeng Biotechnol. 2025 May 20;13:1581292. doi: 10.3389/fbioe.2025.1581292. eCollection 2025.
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.
生物材料辅助的干细胞疗法在再生医学领域具有巨大潜力，但临床转化仍面临挑战。本综述聚焦于在工程化微环境中应用诱导多能干细胞（iPSC）、内皮祖细胞（ECFC）、多能间充质基质细胞（MSC）和胚胎干细胞（ESC）的最新进展及持续存在的局限性。我们介绍了一种新型的生物材料设计“自下而上”方法。该方法首先着重于理解干细胞的基本生物学特性和微环境需求，然后构建具有细胞指导作用的生物材料来支持它们。与使细胞适应现有材料的传统方法不同，此策略优先从分子层面向上设计生物材料，以应对关键挑战，包括分化变异性、iPSC与体细胞对应物的不完全匹配、衍生细胞的功能成熟以及ECFC/MSC在治疗微环境中的存活。通过复制特定谱系的机械、化学和空间线索，这些定制的生物材料提高了分化保真度、重编程效率和功能整合。这种从被动支架到动态、具有细胞指导作用平台的范式转变弥合了实验室成功与临床转化之间的关键差距，并为再生医学和组织工程提供了一条变革性路线图。
