Polyplex-Loaded Hydrogels for Local Gene Delivery to Human Dermal Fibroblasts

Abstract

Impaired cutaneous healing, leading to chronic wounds, affects between 2 and 6% of the total population in most developed countries and it places a substantial burden on healthcare budgets. Current treatments involving antibiotic dressings and mechanical debridement are often not effective, causing severe pain, emotional distress and social isolation in patients for years or even decades, ultimately resulting in limb amputation. Alternatively, gene therapy (such as mRNA therapies) emerges as a viable option to promote wound healing through modulation of gene expression. However, protecting the genetic cargo from degradation and efficient transfection into primary cells remain significant challenges in the push to clinical translation. Another limiting aspect of current therapies is the lack of sustained release of drugs to match the therapeutic window. Herein, we have developed an injectable, biodegradable and biocompatible hydrogelbased wound dressing that delivers pBAE nanoparticles in a sustained manner over a range of therapeutic windows. We also demonstrate that pBAE nanoparticles, successfully used in previous in vivo studies, protect the mRNA load and efficiently transfect human dermal fibroblasts upon sustained release from the hydrogel wound dressing. This prototype wound dressing technology can enable the development of novel gene therapies for the treatment of chronic wounds.

Hydrogels for Mucosal Drug Delivery

“…This study demonstrated the effective delivery of the ASON to the wounded tissue . Gene therapy can also be achieved by loading the hydrogel with nucleic acid-loaded nanoparticles (e.g., liposomes, polyplexes) as cargo to further enhance mucosal gene delivery …”

“…197 Gene therapy can also be achieved by loading the hydrogel with nucleic acidloaded nanoparticles (e.g., liposomes, polyplexes) as cargo to further enhance mucosal gene delivery. 198…”

Editorial: Special Issue on Advanced Biomedical Hydrogels

“…Hydrogels can also be effective at binding to and protecting encapsulated cargo. For example, Oliva, Borros, and co-workers report a hydrogel-based wound healing patch containing mRNA-encapsulated nanoparticles . The hydrogel protected the genetic cargo from degradation and improved transfection.…”

Gelatin-Based Electrospun Nanofibers Cross-Linked Using Horseradish Peroxidase for Plasmid DNA Delivery

“…Scaffolds, such as hydrogels [ 2 , 10 ] and nanofibers [ 11 , 12 , 13 , 14 ], with nucleic acids, could be used for gene delivery as an alternative method to eliminate the above issues. These systems are capable of direct and sustained delivery of nucleic acids to cells and tissues [ 10 ]. In addition, these scaffolds have other advantages.…”

“…Second, local delivery using these scaffolds promotes tissue regeneration by supporting cell adhesion, proliferation, and migration. Third, these scaffolds can protect nucleic acids from extracellular or acidic environments [ 10 , 16 ].…”