Microgels produced using microfluidic on-chip polymer blending for controlled released of VEGF encoding lentivectors

Justin L. Madrigal, Shonit N. Sharma, Kevin T. Campbell, Roberta S. Stilhano, Rik Gijsbers, Eduardo Silva

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Alginate hydrogels are widely used as delivery vehicles due to their ability to encapsulate and release a wide range of cargos in a gentle and biocompatible manner. The release of encapsulated therapeutic cargos can be promoted or stunted by adjusting the hydrogel physiochemical properties. However, the release from such systems is often skewed towards burst-release or lengthy retention. To address this, we hypothesized that the overall magnitude of burst release could be adjusted by combining microgels with distinct properties and release behavior. Microgel suspensions were generated using a process we have termed on-chip polymer blending to yield composite suspensions of a range of microgel formulations. In this manner, we studied how alginate percentage and degradation relate to the release of lentivectors. Whereas changes in alginate percentage had a minimal impact on lentivector release, microgel degradation led to a 3-fold increase, and near complete release, over 10 days. Furthermore, by controlling the amount of degradable alginate present within microgels the relative rate of release can be adjusted. A degradable formulation of microgels was used to deliver VEGF-encoding lentivectors in the chick chorioallantoic membrane assay and yielded a proangiogenic response in comparison to the same lentivectors delivered in suspension. The utility of blended microgel suspensions may provide an especially appealing platform for the delivery of lentivectors or similarly sized therapeutics. Statement of Significance: Genetic therapeutics hold considerable potential for the treatment of diseases and disorders including ischemic cardiovascular diseases. To realize this potential, genetic vectors must be precisely and efficiently delivered to targeted regions of the body. However, conventional methods of delivery do not provide sufficient spatial and temporal control. Here, we demonstrate how alginate microgels provide a basis for developing systems for controlled genetic vector release. We adjust the physiochemical properties of alginate for quicker or slower release, and we demonstrate how combining distinct formulations of microgels can tune the release of the overall composite microgel suspension. These composite suspensions are generated using a straightforward and powerful application of droplet microfluidics which allows for the real-time generation of a composite suspension.

Original languageEnglish (US)
Pages (from-to)265-276
Number of pages12
JournalActa Biomaterialia
Volume69
DOIs
StatePublished - Mar 15 2018

Fingerprint

Microfluidics
Alginate
Vascular Endothelial Growth Factor A
Suspensions
Polymers
Composite materials
Genetic Vectors
Hydrogels
Degradation
Chorioallantoic Membrane
Body Regions
Hydrogel
Assays
alginic acid
Cardiovascular Diseases
Therapeutics
Membranes

Keywords

  • Alginate hydrogels
  • Controlled delivery
  • Microgels
  • Regenerative medicine
  • Sustained gene delivery
  • Therapeutic angiogenesis

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

Cite this

Microgels produced using microfluidic on-chip polymer blending for controlled released of VEGF encoding lentivectors. / Madrigal, Justin L.; Sharma, Shonit N.; Campbell, Kevin T.; Stilhano, Roberta S.; Gijsbers, Rik; Silva, Eduardo.

In: Acta Biomaterialia, Vol. 69, 15.03.2018, p. 265-276.

Research output: Contribution to journalArticle

Madrigal, Justin L. ; Sharma, Shonit N. ; Campbell, Kevin T. ; Stilhano, Roberta S. ; Gijsbers, Rik ; Silva, Eduardo. / Microgels produced using microfluidic on-chip polymer blending for controlled released of VEGF encoding lentivectors. In: Acta Biomaterialia. 2018 ; Vol. 69. pp. 265-276.
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