Electrospun-Fibrous-Architecture-Mediated Non-Viral Gene Therapy Drug Delivery in Regenerative Medicine

Abstract

Gene-based therapy represents the latest advancement in medical biotechnology. The principle behind this innovative approach is to introduce genetic material into specific cells and tissues to stimulate or inhibit key signaling pathways. Although enormous progress has been achieved in the field of gene-based therapy, challenges connected to some physiological impediments (e.g., low stability or the inability to pass the cell membrane and to transport to the desired intracellular compartments) still obstruct the exploitation of its full potential in clinical practices. The integration of gene delivery technologies with electrospun fibrous architectures represents a potent strategy that may tackle the problems of stability and local gene delivery, being capable to promote a controlled and proficient release and expression of therapeutic genes in the targeted cells, improving the therapeutic outcomes. This review aims to outline the impact of electrospun-fibrous-architecture-mediated gene therapy drug delivery, and it emphatically discusses the latest advancements in their formulation and the therapeutic outcomes of these systems in different fields of regenerative medicine, along with the main challenges faced towards the translation of promising academic results into tangible products with clinical application.

Therapeutic Agent-Loaded Fibrous Scaffolds for Biomedical Applications

“…The scaffolds were prepared by a microsol electrospinning method using recombinant IL-10 containing HA to encapsulate IL-10 in the core of the fiber. Along with electrospinning fabrication, additional IL-10 was immobilized on the fibers by plasma treatment [ 211 ], resulting in an initial burst release of IL-10 when the scaffolds were implanted in the wound. This core–shell structure releases IL-10 from the scaffold during the initial and subsequent phases of wound repair, resulting in scarless skin regeneration [ 210 ].…”

“…Despite their potential, fibrous scaffolds loaded with therapeutic agents have not yet been approved for primary use. To fully realize their clinical application, various factors, such as the potential toxicity of solvents, crosslinkers, or materials must be thoroughly assessed [ 211 , 260 ]. Regulatory guidelines should also be considered to develop a clinically usable scaffold in the future [ 211 , 261 ].…”

“…To fully realize their clinical application, various factors, such as the potential toxicity of solvents, crosslinkers, or materials must be thoroughly assessed [ 211 , 260 ]. Regulatory guidelines should also be considered to develop a clinically usable scaffold in the future [ 211 , 261 ]. Although pre-clinical studies have been conducted to clarify the therapeutic effects of fibrous scaffolds, the significant differences between humans and animals tested in these studies could lead to unexpected results during clinical trials [ 261 , 262 ].…”

“…Therefore, it is necessary to prepare humanized animal models to evaluate the therapeutic effects and biocompatibility of scaffolds for further clinical trials [ 264 , 265 ]. Along with the regulatory aspects and proper strategies to reveal pre-clinical data, mass production with the reproducibility of the scaffold must also be considered for clinical applications and market release [ 211 , 262 ]. One example of a commercialized fibrous scaffold is Biogide, a collagen membrane used for guided tissue regeneration in dentistry.…”

Emergence of Small Interfering RNA-Based Gene Drugs for Various Diseases

“…Gene therapy is one of the most advanced biotechnologies in medicine . Gene therapy is defined as the correction of defective/disease-causing gene/s by transferring genetic medicine such as DNA/RNA to a patient’s cells to deactivate, replace, or repair. , The first gene manipulation was attempted as early as 1989 when human DNA is modified by direct insertion of DNA into the nuclear genome .…”