Stem cell microencapsulation maintains stemness in inflammatory microenvironment

Abstract

Maintaining the stemness of the transplanted stem cell spheroids in an inflammatory microenvironment is challenging but important in regenerative medicine. Direct delivery of stem cells to repair periodontal defects may yield suboptimal effects due to the complexity of the periodontal inflammatory environment. Herein, stem cell spheroid is encapsulated by interfacial assembly of metal-phenolic network (MPN) nanofilm to form a stem cell microsphere capsule. Specifically, periodontal ligament stem cells (PDLSCs) spheroid was coated with Fe^III/tannic acid coordination network to obtain spheroid@[Fe^III-TA] microcapsules. The formed biodegradable MPN biointerface acted as a cytoprotective barrier and exhibited antioxidative, antibacterial and anti-inflammatory activities, effectively remodeling the inflammatory microenvironment and maintaining the stemness of PDLSCs. The stem cell microencapsulation proposed in this study can be applied to multiple stem cells with various functional metal ion/polyphenol coordination, providing a simple yet efficient delivery strategy for stem cell stemness maintenance in an inflammatory environment toward a better therapeutic outcome.

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Funding

National Natural Science Foundation of China (National Science Foundation of China)(81873716, 82170964, 82100977, 82001042)

Shandong Province Key Research and Development Program (No. 2021ZDSYS18), Shandong Province Major Scientific and Technical Innovation Project (No. 2021SFGC0502), the Construction Engineering Special Fund of “Taishan Scholars” of Shandong Province (No. ts20190975), Collaborative Innovation Center of Technology and Equipment for Biological Diagnosis and Therapy in Universities of Shandong, Rongxiang Regenerative Medicine Foundation of Shandong University (No. 2019SDRX-14), and the Fundamental Research Funds of Shandong University.

China Postdoctoral Science Foundation(2021M691930)

The Youth Scientific Research Funds of School of Stomatology, Shandong University (2020QNJJ03), the Opening Research Fund from Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University (2022LHM-KFKT004)

Collaborative Innovation Center of Technology and Equipment for Biological Diagnosis and Therapy in Universities of Shandong, Rongxiang Regenerative Medicine Foundation of Shandong University (2019SDRX-15), the Taishan Scholars Program of Shandong Province (tsqn201909180) and Qilu Young Scholar Foundation of Shandong University.