Journal article
Co-Release of Cells and Polymeric Nanoparticles from Sacrificial Microfibers Enhances Nonviral Gene Delivery Inside 3D Hydrogels
Tissue engineering. Part C, Methods, v 20(10), pp 798-805
01 Oct 2014
PMID: 24483329
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Hydrogels can promote desirable cellular phenotype by mimicking tissue-like stiffness or serving as a gene delivery depot. However, nonviral gene delivery inside three-dimensional (3D) hydrogels remains a great challenge, and increasing hydrogel stiffness generally results in further decrease in gene delivery efficiency. Here we report a method to enhance nonviral gene delivery efficiency inside 3D hydrogels across a broad range of stiffness using sacrificial microfibers for co-releasing cells and polymeric nanoparticles (NPs). We fabricated hydrolytically degradable alginate as sacrificial microfibers, and optimized the degradation profile of alginate by varying the degree of oxidization. Scanning electron microscopy confirmed degradation of alginate microfibers inside hydrogels, leaving behind microchannel-like structures within 3D hydrogels. Sacrificial microfibers also serve as a delivery vehicle for co-releasing encapsulated cells and NPs, allowing cell attachment and spreading within the microchannel surface upon microfiber degradation. To examine the effects of sacrificial microfibers on nonviral gene delivery inside 3D hydrogels, alginate microfibers containing human embryonic kidney 293 cells and polymeric NPs were encapsulated within 3D hydrogel scaffolds with varying stiffness (9, 58, and 197 kPa). Compared with cells encapsulated in bulk hydrogels, we observed up to 15-fold increase in gene delivery efficiency using sacrificial microfibers, and gene delivery efficiency increased as hydrogel stiffness increased. The platform reported herein provides a strategy for enhancing nonviral gene delivery inside 3D hydrogels across a broad range of stiffness, and may aid tissue regeneration by engaging both mechanotransduction and nonviral gene delivery.
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Details
- Title
- Co-Release of Cells and Polymeric Nanoparticles from Sacrificial Microfibers Enhances Nonviral Gene Delivery Inside 3D Hydrogels
- Creators
- Christopher M. Madl - Stanford UniversityMichael Keeney - Stanford UniversityXiaolan Li - Tsinghua UniversityLi-Hsin Han - Stanford UniversityFan Yang - Stanford University
- Publication Details
- Tissue engineering. Part C, Methods, v 20(10), pp 798-805
- Publisher
- Mary Ann Liebert, Inc
- Number of pages
- 8
- Grant note
- Stanford Bio-X Interdisciplinary Initiative grant Basil O'Connor Starter Scholar Research Award from March of Dimes Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Mechanical Engineering and Mechanics; Drexel University
- Web of Science ID
- WOS:000342562700004
- Scopus ID
- 2-s2.0-84911917821
- Other Identifier
- 991020100047704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell & Tissue Engineering
- Cell Biology
- Engineering, Biomedical
- Materials Science, Biomaterials