Nanotechnology-Driven Therapeutic Interventions in Wound Healing: Potential Uses and Applications

Abstract

The chronic nature and associated complications of nonhealing wounds have led to the emergence of nanotechnology-based therapies that aim at facilitating the healing process and ultimately repairing the injured tissue. A number of engineered nanotechnologies have been proposed demonstrating unique properties and multiple functions that address specific problems associated with wound repair mechanisms. In this outlook, we highlight the most recently developed nanotechnology-based therapeutic agents and assess the viability and efficacy of each treatment, with emphasis on chronic cutaneous wounds. Herein we explore the unmet needs and future directions of current technologies, while discussing promising strategies that can advance the wound-healing field.

Figure 1

Phases of cutaneous wound healing depicting the cells and molecules responsible for the regaining of a healthy barrier.

Figure 2

Schematic representation of the nanotechnology-based therapies employed in wound healing.

Figure 3

(A) Diagrammatic representation of a custom-made electrospinning apparatus. (B) A representative scanning electron microscopy image of an electrospun scaffold with random fiber orientation, (C) with aligned fiber orientation, (D) with gridded fiber alignment, and (E) a tubular scaffold. Adapted with permission from ref (102). Copyright 2011 Acta Materialia Inc. Published by Elsevier Ltd.

Figure 4

(A) Schematic illustration of the nanoparticle-embedded electrospun nanofibers loaded with two growth factors VEGF and PDGF-BB for the wound healing and (B) representative macroscopic appearance of wound closure after treatment of rat wounds with control, 2:1 chitosan/PEO (CS/PEO) without growth factor, and 2:1 CS/PEO-NPs with nanoparticles and growth factors. Adapted with permission from ref (114). Copyright 2013 Acta Materialia Inc. Published by Elsevier Ltd.

Figure 5

Layer-by-layer (LbL) coating for sustained release of siRNA and reduction of MMP-9 expression. (A) Chemical structures of polymers used for the preparation of LbL coating. (B) Hierarchical structure of LbL films into a single coating. (C) Application of bandages on full-thickness excisional wounds on the backs of mice. (D) Digital imaging of wounds immediately following surgery (day 0) and after 7 or 14 d of treatment. Adapted with permission from ref (118). Copyright 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Figure 6

(A) Schematic illustration for the design of nanocarriers (Ac-G5 dendrimers complexed with sE-sel moiety) for stem cell coating. (B) Representative image of the “mono-arm”: Ac-G5-dendrimer-sE-sel, for bone marrow derived endothelial progenitor cell (EPC) coating; the adhesion moiety sE-sel interacts selectively with E-selectin ligand (CD44) expressed on inflamed luminal endothelial cells (EC) in wound tissues. (C) Bioluminescence imaging showing Ac-G5-dendrimer-sE-sel nanocarrier-coated Luciferase2⁺-MSC selectively homed to skin wound tissues but not other organs. (D, E) Healing of murine wound tissues (macroscopic images and wound-healing rate) upon systemic delivery of Ac-G5-sE-sel and Ac-G5-BSA nanocarrier-coated BMC. Adapted with permission from ref (135). Copyright 2016 PLOS.