It’s All in the Delivery: Designing Hydrogels for Cell and Non-viral Gene Therapies

Abstract

Hydrogels provide a regenerative medicine platform with their ability to create an environment that supports transplanted or endogenous infiltrating cells and enables these cells to restore or replace the function of tissues lost to disease or trauma. Furthermore, these systems have been employed as delivery vehicles for therapeutic genes, which can direct and/or enhance the function of the transplanted or endogenous cells. Herein, we review recent advances in the development of hydrogels for cell and non-viral gene delivery through understanding the design parameters, including both physical and biological components, on promoting transgene expression, cell engraftment, and ultimately cell function. Furthermore, this review identifies emerging opportunities for combining cell and gene delivery approaches to overcome challenges to the field.

Self‐healing injectable gelatin hydrogels for localized therapeutic cell delivery

“…Hydrogels are comprised of hydrophilic macromolecular polymeric networks of natural, synthetic, or mixed origin that retain a high water content while preserving their 3D structural integrity (Hoffman, ). Over the past many decades, these materials have been extensively employed in a variety of biomedical applications including for the delivery of therapeutic agents (Badeau, Comerford, Arakawa, Shadish, & DeForest, ; Badeau & DeForest, ; Hoare & Kohane, ; Youngblood, Truong, Segura, & Shea, ); to support 3D cell culture and dynamically direct cell fate (Caliari & Burdick, ; DeForest & Anseth, ; Healy, Rezania, & Stile, ; Shadish, Benuska, & DeForest, ; Tibbitt & Anseth, ); as scaffolds for tissue engineering and regenerative medicine (Drury & Mooney, ; Ifkovits & Burdick, ; Khademhosseini & Langer, ; Nicodemus & Bryant, ); and as components in biomedical devices, bioadhesives, and biosealants (Annabi, Yue, Tamayol, & Khademhosseini, ; Caló & Khutoryanskiy, ; Ghobril & Grinstaff, ). This growing list of applications stems directly from the materials' ability to be formulated in manners that are biocompatible, support nutrient diffusion, and offer tunable physiochemistry that mimics critical aspects of the native extracellular matrix (ECM; Seliktar, ).…”

New Developments in Medical Applications of Hybrid Hydrogels Containing Natural Polymers

“…Due to its biocompatibility and well-established safety profiles, hydrogels fabricated using collagen have been employed as delivery vehicles for therapeutic genes, which can direct and/or enhance the function of the transplanted or endogenous cells [398].…”

Hydrogel-Based Localized Nonviral Gene Delivery in Regenerative Medicine Approaches—An Overview

“…Nonviral systems involve the complexation of NA molecules with positively charged gene carriers like polycations (polyplexes), cationic or ionizable lipids, and lipid-like molecules (lipoplexes) to promote their uptake in the cells [3]. Despite their biosafety as compared with viral counterparts, gene transfer via nonviral systems is precluded by some obstacles associated to the vector itself (fast degradation, short half-life, serum neutralization, instability in physiological fluids, and aggregation tendency) as well as its internalization and cell trafficking mechanisms of the NA molecule to initiate the expression of the transgene [3,[13][14][15]. Unlike to pDNA, mRNA does not need to enter in the cell nucleus to be functional, requiring only the translational machinery in the cytosol for expression of its protein product [16].…”