Journal article
Antiaging Metabolite‐Based Polymeric Microparticles for Intracellular Drug Delivery and Bone Regeneration
Small science, Vol.4(10), 2400201
10/06/2024
DOI: 10.1002/smsc.202400201
PMCID: PMC11460827
PMID: 39386061
Appears in UI Libraries Support Open Access
Abstract
α‐ketoglutarate (AKG), a key component of the tricarboxylic acid cycle, has attracted attention for its antiaging properties. In the recent study, it is indicated that locally delivered cell‐permeable AKG significantly promotes osteogenic differentiation and mouse bone regeneration. However, the cytotoxicity and rapid hydrolysis of the metabolite limit its application. In this study, novel AKG‐based polymeric microparticles (PAKG MPs) are synthesized for sustained release. In vitro data suggest that the chemical components, hydrophilicity, and size of the MPs can significantly affect their cytotoxicity and pro‐osteogenic activity. Excitingly, these biodegradable PAKG MPs are highly phagocytosable for nonphagocytic pre‐osteoblasts MC3T3‐E1 and primary bone marrow mesenchymal stem cells, significantly promoting their osteoblastic differentiation. RNA‐Sequencing (RNA‐Seq) data suggest that PAKG MPs strongly activate Wnt/β‐catenin and PI3K–Akt pathways for osteogenic differentiation. Moreover, PAKG enables poly(L‐lactic acid) and poly(lactic ‐co ‐glycolic acid) MPs (PLGA MPs) for efficient phagocytosis. In this data, it is indicated that PLGA–PAKG‐MPs‐mediated intracellular drug delivery can significantly promote stronger osteoblastic differentiation compared to PLGA‐MPs‐delivered phenamil. Notably, PAKG MPs significantly improve large bone regeneration in a mouse cranial bone defect model. Thus, the novel PAKG‐based MPs show great promise to improve osteogenic differentiation and bone regeneration and enable efficient intracellular drug delivery for broad regenerative medicine.
Details
- Title: Subtitle
- Antiaging Metabolite‐Based Polymeric Microparticles for Intracellular Drug Delivery and Bone Regeneration
- Creators
- Zhuozhi Wang - University of IowaJue Hu - University of IowaJeffrey S. Marschall - University of IowaLing Yang - University of IowaErliang Zeng - University of IowaShaoping Zhang - University of IowaHongli Sun - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Small science, Vol.4(10), 2400201
- DOI
- 10.1002/smsc.202400201
- PMID
- 39386061
- PMCID
- PMC11460827
- NLM abbreviation
- Small Sci
- ISSN
- 2688-4046
- eISSN
- 2688-4046
- Publisher
- Wiley
- Grant note
- National Institute of Dental & Craniofacial Research of the National Institutes of Health: R01DE029159
This work was supported by the startup funds from the Department of Oral and Maxillofacial Surgery at the University of Iowa College of Dentistry, the Mid-Career Faculty Scholar Award from the University of Iowa, and the National Institute of Dental & Craniofacial Research of the National Institutes of Health under the award number R01DE029159 (H.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors would like to acknowledge the use of the University of Iowa Central Microscopy Research Facility, a core resource supported by the University of Iowa Vice President for Research, and the Carver College of Medicine. The authors also would like to thank Dr. Aliasger Salem and the members of his lab for their technical support in equipment usage.
- Language
- English
- Electronic publication date
- 09/03/2024
- Date published
- 10/06/2024
- Academic Unit
- Preventive and Community Dentistry; Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Iowa Neuroscience Institute; Biostatistics; Craniofacial Anomalies Research Center; Oral and Maxillofacial Surgery; Fraternal Order of Eagles Diabetes Research Center; Dental Research; Periodontics
- Record Identifier
- 9984701658402771
Metrics
18 Record Views