Sustained, localized transgene expression mediated from lentivirus‐loaded biodegradable polyester elastomers

Abstract

The study of biomaterials for gene delivery in tissue engineering and regenerative medicine is a growing area, necessitating the investigation of new biomaterials and gene delivery vectors. Poly(1,8-octanediol citrate) (POC) and poly(glycerol-sebacate) (PGS) are biodegradable, biocompatible elastomers that have tunable mechanical properties, surface characteristics, and degradation rate. The objective of this work was to investigate whether POC and PGS would support the immobilization and release of lentivirus to allow sustained and localized transgene expression. Porous biomaterials were prepared using salt as a porogen and in vitro and in vivo transgene expression from immobilized and released lentiviruses were assessed. Cells seeded onto biomaterials loaded with lentiviruses yielded titer-dependent transgene expression in vitro. Lentivirus activity on both biomaterials was maintained for at least 5 days. When implanted subcutaneously in rats, POC and PGS with immobilized lentivirus exhibited sustained and localized transgene expression for at least 5 weeks. This research demonstrates that lentivirus immobilization on POC and PGS is feasible and potentially useful for a variety of tissue engineering and regenerative medicine applications.

Citrate-Based Biomaterials and Their Applications in Regenerative Engineering

“…In addition to the delivery of nonviral vectors, POC has been investigated for use as a substrate to deliver genes via a lentivirus. To obtain sustained and localized transgene expression, a lentivirus was immobilized on porous POC scaffolds through the negative charges naturally present on the surface of POC (142). Cells seeded on lentivirus-loaded POC showed titer-dependent transgene expression with lentivirus activity up to 5 days in vitro and up to 5 weeks in vivo.…”

Sustained viral gene delivery from a micro-fibrous, elastomeric cardiac patch to the ischemic rat heart

“…3D porous scaffolds, as shown in this report, provide a structural and mechanical support that can maintain a space for tissue growth upon implantation, as the porosity supports cell infiltration throughout the scaffold. Lentivirus has been loaded onto microporous scaffolds processed from poly(lactide-co-glycolide) [72], and poly (1,8-octanediol citrate) and poly(glycerol-sebacate) [73] by simple absorption into the scaffolds. The high efficiency of the vector enables substantial transgene expression that persists for at least 4 weeks after being implanted subcutaneously into murine models, although rapid release occurred in vitro due to the low affinity of the virus to the scaffolds.…”

Polyglycerol Hyperbranched Polyesters: Synthesis, Properties and Pharmaceutical and Biomedical Applications

“…The rapid in vivo degradation of PGSeb is expected to limit the use of this device to short-term drug therapies. Jen et al investigated the immobilization and release of lentiviruses on PGSeb in the context of substrate-mediated gene delivery [170]. Finally, Lee and his colleagues reported the use of a PGSeb scaffold for the delivery of stromal cell-derived factor-1α (SDF-1α) embedded in a heparin/poly(ethylene argininyl aspartate diglyceride) coacervate [171].…”