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

Abstract

Hydrogel-based nonviral gene delivery constitutes a powerful strategy in various regenerative medicine scenarios, as those concerning the treatment of musculoskeletal, cardiovascular, or neural tissues disorders as well as wound healing. By a minimally invasive administration, these systems can provide a spatially and temporarily defined supply of specific gene sequences into the target tissue cells that are overexpressing or silencing the original gene, which can promote natural repairing mechanisms to achieve the desired effect. In the present work, we provide an overview of the most avant-garde approaches using various hydrogels systems for controlled delivery of therapeutic nucleic acid molecules in different regenerative medicine approaches.

Recent Advances in Cardiac Tissue Engineering for the Management of Myocardium Infarction

“…There is mounting evidence that changes in ECM mechanical properties significantly impact on cell structure and function. Excessive collagen-I deposition/crosslinking orchestrated by activated fibroblasts during fibrosis and tumor growth, in particular, is thought to have a role in aberrant mechano-sensing and atypical cell behaviors [129].…”

MiRNAs and Muscle Regeneration: Therapeutic Targets in Duchenne Muscular Dystrophy

“…There is a great variety of hydrogels depending on their chemical nature. In this regard, either natural-based hydrogels, such alginate, cellulose, chitosan, collagen, dextran, fibrin, pullulan gelatin, and hyaluronic acid, or synthetic hydrogels, as polyethylene-glycol (PEG), poly(N-isopropylacrylamide) (PNIPAm), polyurethane or poly(organophosphazene) have been studied as delivery systems of therapeutic nucleic acids molecules, including microRNAs, in various tissue engineering approaches (reviewed in [179]). Although the controlled delivery of naked microRNAs from hydrogels enhances their local and sustained delivery [180], combination of nanoparticles, as vectors for microRNA delivery, and hydrogels, as delivery media, have shown a strong therapeutic efficacy in the context of heart muscle [181].…”

Scaffold-Mediated Gene Delivery for Osteochondral Repair

“…Other factors include the bone-specific Cbfa-1/runt-related transcription factor 2 (RUNX2) [29] that modulates osteoblast differentiation with endochondral and membranous ossification, and osterix (OSX) that is required for bone maintenance in synergism with RUNX2 [30]. More recently, the use of messenger ribonucleic acids (mRNAs) for these various factors has been evoked as tools for therapy, being potentially amenable to scaffold-mediated delivery in particular for strategies that aim at initiating osteochondral repair [31][32][33][34]. Figure 2 presents an overview of the pathways targeted by these various candidates.…”

“…A variety of biomaterials have been employed in osteochondral tissue engineering, including hydrogels [34,82], solid scaffolds [85], and hybrid scaffolds [76]. Each are made of either natural cell-compatible materials or of synthetic compounds with more controllable properties as mono-or multiphasic systems (Table 2).…”