Porous EH and EH-PEG scaffolds as gene delivery vehicles to skeletal muscle

Erin E. Falco, Martha O. Wang, Joshua A. Thompson, Joshua M. Chetta, Diana M. Yoon, Erik Z. Li, Mangesh M. Kulkami, Sameer Shah, Abhay Pandit, J. Scott Roth, John P. Fisher

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Purpose: Synthetic biomaterials are widely used in an attempt to control the cellular behavior of regenerative tissues. This can be done by altering the chemical and physical properties of the polymeric scaffold to guide tissue repair. This paper addresses the use of a polymeric scaffold (EH network) made from the cyclic acetal monomer, 5-ethyl-5-(hydroxymethyl)-β,β- dimethyl-1,3-dioxane-2-ethanol diacrylate (EHD), as a release device for a therapeutic plasmid encoding for an insulin-like growth factor-1 green fluorescent protein fusion protein (IGF-1 GFP). Methods: Scaffolds were designed to have different porous architectures, and the impact of these architectures on plasmid release was determined. We hypothesized that IGF-1 could be delivered more effectively using a porous scaffold to allow for the release of IGF-1. Results: We showed that by altering the number of pores exposed to the surface of the network, faster plasmid loading and release were achieved. In addition, the IGF-1 GFP plasmids were found to be effective in producing IGF-1 and GFP within human skeletal muscle myoblast cell cultures. Conclusions: This work aims to show the utility of EH biomaterials for plasmid delivery for potentially localized skeletal muscle regeneration.

Original languageEnglish
Pages (from-to)1306-1316
Number of pages11
JournalPharmaceutical Research
Volume28
Issue number6
DOIs
StatePublished - Jun 2011

Bibliographical note

Funding Information:
This work was supported by the National Science Foundation through a CAREER Award to JPF (#0448684) as well as the Maryland NanoCenter and the NispLab. The NispLab is supported in part by the NSF and as a MRSEC Shared Experimental Facility. The authors would like to thank Dr. Sameer Shah for the Lipofectamine 2000 transfection reagent and Dr. Adam Hsieh for providing ampicillin, both whom are at the University of Maryland. We would also like to thank Chen-Yu Tsao, Chi-Wei Hung and Hsuan-Chen Wu from the lab of Dr. William Bentley at University of Maryland for their contributions.

Funding

This work was supported by the National Science Foundation through a CAREER Award to JPF (#0448684) as well as the Maryland NanoCenter and the NispLab. The NispLab is supported in part by the NSF and as a MRSEC Shared Experimental Facility. The authors would like to thank Dr. Sameer Shah for the Lipofectamine 2000 transfection reagent and Dr. Adam Hsieh for providing ampicillin, both whom are at the University of Maryland. We would also like to thank Chen-Yu Tsao, Chi-Wei Hung and Hsuan-Chen Wu from the lab of Dr. William Bentley at University of Maryland for their contributions.

FundersFunder number
University of Maryland, The Maryland NanoCenter
National Science Foundation (NSF)0448684
Materials Research Science and Engineering Center, Harvard University

    Keywords

    • IGF-1
    • cyclic acetal
    • gene therapy
    • synthetic meshes

    ASJC Scopus subject areas

    • Biotechnology
    • Molecular Medicine
    • Pharmacology
    • Pharmaceutical Science
    • Organic Chemistry
    • Pharmacology (medical)

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