**9. Gene (RNAi and siRNA) delivery by nanotherapeutic agents for wound repair**

It is a well-known fact that miRNAs can be critical regulators of wound repair [177], but the miRNAs involved and their specific role in wound healing remains unclear. Recently, a new method for the identification of functional miRNAs, which get elevated during skin injury, has been described. This group has identified miR-223 as a new potential therapeutic target influencing acute inflammation in wounds that are *S. aureus* infected [178].

RNAi therapy has been used to specifically silence gene expression of overexpressed targets in chronic wounds [179]. NP-based approach has been implemented to protect the effector molecule in siRNA from degradation *via* intracellular RNases leading to targeted delivery [180]. Of late, gold NP conjugates with spherical nucleic acid (SNA) have also been employed for efficient *in vivo* siRNA delivery [181]. The importance of SNA nanotechnology lies in its ability to cross the epidermal barrier, thereby permitting its use in topical therapeutics (**Figures 2** and **3**). Nevertheless, a pertinent demand for more efficacious and refined novel RNAi-based therapeutics for tissue repair. Such products should overcome the drawbacks of presently available materials in use and provide for better retention, bioavailability, effectiveness, safety, and selective targeting [180].

A combination of gene therapy and tissue engineering commonly called as geneactivated matrix therapy has come to the fore as a method to enhance or knockdown a specific target gene playing a role in bone, cartilage, or skin regeneration [182]. The major advantage of this approach is the higher stability of DNA in comparison to the

*Nanotechnological Interventions and Mechanistic Insights into Wound-Healing Events DOI: http://dx.doi.org/10.5772/intechopen.106481*

growth factor therapy [182, 183]. However, the major flaw of this technique is the need for repeated injections of colloidal and naked DNA to the wound site and the short-term and inconsistent gene expression [183]. To overcome these issues, nucleic acids have been impregnated into electrospun nanofibrous meshes to increase tissue regeneration and to decrease scarring [183]. More recently, polyester scaffolds have been used for the management of cutaneous wounds [179, 184]. Furthermore, electrospun scaffolds having a mixture of PLA and PCL were employed for the delivery of plasmid that encodes keratinocytes' growth factor [184].
