Injectable alginate hydrogel for enhanced spatiotemporal control of lentivector delivery in murine skeletal muscle

Roberta S. Stilhano, Justin L. Madrigal, Kevin Wong, Priscilla A. Williams, Priscila K.M. Martin, Fabio S.M. Yamaguchi, Vivian Y. Samoto, Sang W. Han, Eduardo Silva

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Hydrogels are an especially appealing class of biomaterials for gene delivery vehicles as they can be introduced into the body with minimally invasive procedures and are often applied in tissue engineering and regenerative medicine strategies. In this study, we show for the first time the use of an injectable alginate hydrogel for controlled delivery of lentivectors in the skeletal muscle of murine hindlimb. We propose to alter the release rates of lentivectors through manipulation of the molecular weight distribution of alginate hydrogels. The release of lentivector was tested using two different ratios of low and high molecular weight (MW) alginate polymers (75/25 and 25/75 low/high MW). The interdependency of lentivector release rate and alginate degradation rate was assessed in vitro. Lentivector-loaded hydrogels maintained transduction potential for up to one week in vitro as demonstrated by the continual transduction of HEK-293T cells. Injection of lentivector-loaded hydrogel in vivo led to a sustained level of transgene expression for more than two months while minimizing the copies of lentivirus genome inserted into the genome of murine skeletal muscle cells. This strategy of spatiotemporal control of lentivector delivery from alginate hydrogels may provide a versatile tool to combine gene therapy and biomaterials for applications in regenerative medicine.

Original languageEnglish (US)
Pages (from-to)42-49
Number of pages8
JournalJournal of Controlled Release
Volume237
DOIs
StatePublished - Sep 10 2016

Fingerprint

Hydrogel
Hydrogels
Skeletal Muscle
Injections
Regenerative Medicine
Molecular Weight
Biocompatible Materials
Genome
Lentivirus
HEK293 Cells
Tissue Engineering
Hindlimb
Transgenes
Genetic Therapy
Muscle Cells
Polymers
alginic acid
Genes
In Vitro Techniques

Keywords

  • Biodegradable gels
  • Gene therapy
  • Regenerative medicine
  • Sustained gene delivery
  • Tissue engineering

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Injectable alginate hydrogel for enhanced spatiotemporal control of lentivector delivery in murine skeletal muscle. / Stilhano, Roberta S.; Madrigal, Justin L.; Wong, Kevin; Williams, Priscilla A.; Martin, Priscila K.M.; Yamaguchi, Fabio S.M.; Samoto, Vivian Y.; Han, Sang W.; Silva, Eduardo.

In: Journal of Controlled Release, Vol. 237, 10.09.2016, p. 42-49.

Research output: Contribution to journalArticle

Stilhano, RS, Madrigal, JL, Wong, K, Williams, PA, Martin, PKM, Yamaguchi, FSM, Samoto, VY, Han, SW & Silva, E 2016, 'Injectable alginate hydrogel for enhanced spatiotemporal control of lentivector delivery in murine skeletal muscle', Journal of Controlled Release, vol. 237, pp. 42-49. https://doi.org/10.1016/j.jconrel.2016.06.047
Stilhano, Roberta S. ; Madrigal, Justin L. ; Wong, Kevin ; Williams, Priscilla A. ; Martin, Priscila K.M. ; Yamaguchi, Fabio S.M. ; Samoto, Vivian Y. ; Han, Sang W. ; Silva, Eduardo. / Injectable alginate hydrogel for enhanced spatiotemporal control of lentivector delivery in murine skeletal muscle. In: Journal of Controlled Release. 2016 ; Vol. 237. pp. 42-49.
@article{b3ec406f5e284c968e32fcd605ab7fc4,
title = "Injectable alginate hydrogel for enhanced spatiotemporal control of lentivector delivery in murine skeletal muscle",
abstract = "Hydrogels are an especially appealing class of biomaterials for gene delivery vehicles as they can be introduced into the body with minimally invasive procedures and are often applied in tissue engineering and regenerative medicine strategies. In this study, we show for the first time the use of an injectable alginate hydrogel for controlled delivery of lentivectors in the skeletal muscle of murine hindlimb. We propose to alter the release rates of lentivectors through manipulation of the molecular weight distribution of alginate hydrogels. The release of lentivector was tested using two different ratios of low and high molecular weight (MW) alginate polymers (75/25 and 25/75 low/high MW). The interdependency of lentivector release rate and alginate degradation rate was assessed in vitro. Lentivector-loaded hydrogels maintained transduction potential for up to one week in vitro as demonstrated by the continual transduction of HEK-293T cells. Injection of lentivector-loaded hydrogel in vivo led to a sustained level of transgene expression for more than two months while minimizing the copies of lentivirus genome inserted into the genome of murine skeletal muscle cells. This strategy of spatiotemporal control of lentivector delivery from alginate hydrogels may provide a versatile tool to combine gene therapy and biomaterials for applications in regenerative medicine.",
keywords = "Biodegradable gels, Gene therapy, Regenerative medicine, Sustained gene delivery, Tissue engineering",
author = "Stilhano, {Roberta S.} and Madrigal, {Justin L.} and Kevin Wong and Williams, {Priscilla A.} and Martin, {Priscila K.M.} and Yamaguchi, {Fabio S.M.} and Samoto, {Vivian Y.} and Han, {Sang W.} and Eduardo Silva",
year = "2016",
month = "9",
day = "10",
doi = "10.1016/j.jconrel.2016.06.047",
language = "English (US)",
volume = "237",
pages = "42--49",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",

}

TY - JOUR

T1 - Injectable alginate hydrogel for enhanced spatiotemporal control of lentivector delivery in murine skeletal muscle

AU - Stilhano, Roberta S.

AU - Madrigal, Justin L.

AU - Wong, Kevin

AU - Williams, Priscilla A.

AU - Martin, Priscila K.M.

AU - Yamaguchi, Fabio S.M.

AU - Samoto, Vivian Y.

AU - Han, Sang W.

AU - Silva, Eduardo

PY - 2016/9/10

Y1 - 2016/9/10

N2 - Hydrogels are an especially appealing class of biomaterials for gene delivery vehicles as they can be introduced into the body with minimally invasive procedures and are often applied in tissue engineering and regenerative medicine strategies. In this study, we show for the first time the use of an injectable alginate hydrogel for controlled delivery of lentivectors in the skeletal muscle of murine hindlimb. We propose to alter the release rates of lentivectors through manipulation of the molecular weight distribution of alginate hydrogels. The release of lentivector was tested using two different ratios of low and high molecular weight (MW) alginate polymers (75/25 and 25/75 low/high MW). The interdependency of lentivector release rate and alginate degradation rate was assessed in vitro. Lentivector-loaded hydrogels maintained transduction potential for up to one week in vitro as demonstrated by the continual transduction of HEK-293T cells. Injection of lentivector-loaded hydrogel in vivo led to a sustained level of transgene expression for more than two months while minimizing the copies of lentivirus genome inserted into the genome of murine skeletal muscle cells. This strategy of spatiotemporal control of lentivector delivery from alginate hydrogels may provide a versatile tool to combine gene therapy and biomaterials for applications in regenerative medicine.

AB - Hydrogels are an especially appealing class of biomaterials for gene delivery vehicles as they can be introduced into the body with minimally invasive procedures and are often applied in tissue engineering and regenerative medicine strategies. In this study, we show for the first time the use of an injectable alginate hydrogel for controlled delivery of lentivectors in the skeletal muscle of murine hindlimb. We propose to alter the release rates of lentivectors through manipulation of the molecular weight distribution of alginate hydrogels. The release of lentivector was tested using two different ratios of low and high molecular weight (MW) alginate polymers (75/25 and 25/75 low/high MW). The interdependency of lentivector release rate and alginate degradation rate was assessed in vitro. Lentivector-loaded hydrogels maintained transduction potential for up to one week in vitro as demonstrated by the continual transduction of HEK-293T cells. Injection of lentivector-loaded hydrogel in vivo led to a sustained level of transgene expression for more than two months while minimizing the copies of lentivirus genome inserted into the genome of murine skeletal muscle cells. This strategy of spatiotemporal control of lentivector delivery from alginate hydrogels may provide a versatile tool to combine gene therapy and biomaterials for applications in regenerative medicine.

KW - Biodegradable gels

KW - Gene therapy

KW - Regenerative medicine

KW - Sustained gene delivery

KW - Tissue engineering

UR - http://www.scopus.com/inward/record.url?scp=84979055370&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979055370&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2016.06.047

DO - 10.1016/j.jconrel.2016.06.047

M3 - Article

VL - 237

SP - 42

EP - 49

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -