1. J Control Release. 2009 Jun 5;136(2):148-54. Epub 2009 Feb 20.

Fibrin hydrogels for non-viral vector delivery in vitro.

des Rieux A, Shikanov A, Shea LD.

Université Catholique de Louvain, Unité de Pharmacie Galénique Industrielle et
Officinale, Avenue E. Mounier 73, 1200 Brussels, Belgium.

Comment in:
    J Control Release. 2009 Jun 5;136(2):87.

Fibrin based hydrogels have been employed in vitro as a scaffold to promote
tissue formation and investigate underlying molecular mechanisms. These hydrogels
support a variety of cellular processes, and are being developed to enhance the
presentation of biological cues, or to tailor the biological cues for specific
tissues. The presentation of these cues could alternatively be enhanced through
gene delivery, which can be employed to induce the expression of tissue inductive
factors in the local environment. This report investigates gene delivery within
fibrin hydrogels for two in vitro models of tissue growth: i) cell encapsulation 
within and ii) cell seeding onto the hydrogel. Naked plasmid and lipoplexes can
be efficiently entrapped within the hydrogel, and after 1 day in solution more
than 70% of the entrapped DNA is retained within the gel, with a sustained
release observed for at least 19 days. Encapsulated lipoplexes did not aggregate 
and retain their original size. Transgene expression in vitro by delivery of
lipoplexes was a function of the fibrinogen and DNA concentration. For
encapsulated cells, all cells had intracellular plasmid and transgene expression 
persisted for at least 10 days, with maximal levels achieved at day 1. For cell
infiltration, expression levels were less than those observed for encapsulation, 
and expression increased throughout the culture period. The increasing expression
levels suggest that lipoplexes retain their activity after encapsulation;
however, interactions between fibrin and the lipoplexes likely limit
internalization. The inclusion of non-viral vectors into fibrin-based hydrogels
can be employed to induce transgene expression of encapsulated and infiltrating
cells, and may be employed with in vitro models of tissue growth to augment the
intrinsic bioactivity of fibrin.

PMCID: 2752208
PMID: 19232532 [PubMed - in process]