Protein-modified nanomaterials: emerging trends in skin wound healing

Abstract

Prolonged inflammation can impede wound healing, which is regulated by several proteins and cytokines, including IL-4, IL-10, IL-13, and TGF-β. Concentration-dependent effects of these molecules at the target site have been investigated by researchers to develop them as wound-healing agents by regulating signaling strength. Nanotechnology has provided a promising approach to achieve tissue-targeted delivery and increased effective concentration by developing protein-functionalized nanoparticles with growth factors (EGF, IGF, FGF, PDGF, TGF-β, TNF-α, and VEGF), antidiabetic wound-healing agents (insulin), and extracellular proteins (keratin, heparin, and silk fibroin). These molecules play critical roles in promoting cell proliferation, migration, ECM production, angiogenesis, and inflammation regulation. Therefore, protein-functionalized nanoparticles have emerged as a potential strategy for improving wound healing in delayed or impaired healing cases. This review summarizes the preparation and applications of these nanoparticles for normal or diabetic wound healing and highlights their potential to enhance wound healing.

Keywords: Antidiabetic agents; Growth factors; Nanoformulations; Proteins; Wound healing.

Fig. 1

The figure shows different proteins and growth factors widely used for making different types of nanoformulations for wound healing and skin regeneration activity

Fig. 2

The crystal structures of different proteins and growth factors along with their PDB IDs a insulin, b silk fibroin, c keratin, d collagen, and e heparin, f fibroblast growth factor (FGF), g keratinocyte growth factor (KGF), h vascular growth factor (VGF-B), i epidermal growth factor (EGF), and j platelets-derived growth factor (PDGF)

Fig. 3

The figure shows the signaling pathway followed by insulin and other growth factors for wound recovery. The generation of IFN-γ and TNF-α activated the STAT-1, IRF-3, and NF-kβ, which are responsible for the secretion of IL-10, IL-12, and other interleukins for the transition of pro-inflammatory cytokines to anti-inflammatory ones and promotes healing

Fig. 4

It shows the potential role and signaling pathway followed by silk fibroin in wound-healing activity by modulating inflammatory, proliferative, and remodeling phase of healing

Fig. 5

The figure demonstrates the signaling pathway followed by the keratin protein in wound healing. The three significant keratins, K6, K16, and K17, get secreted in response to injury and activate the keratinocytes, further promoting epidermal regeneration and wound healing

Fig. 6

The figure demonstrates the signaling pathway followed by the heparin protein in wound healing. Heparin promotes the secretion of different fibroblast growth factors responsible for re-epithelialization, migration, and differentiation of growth-promoting cells

Fig. 7

The figure provides information about the different techniques being followed for synthesizing the desired protein-functionalized nanoparticles and includes emulsification, desolvation, coacervation, and electrohydrojetting techniques

Fig. 8

SEM/TEM images of the different protein-loaded nanoformulations A Insulin-silk fibroin nanoparticles, B Insulin-PCL-Chitosan nanoparticles, C Insulin-PLGA nanoparticles, D Insulin-Ag nanoparticles, E Insulin-Chitosan nanoparticles, F Insulin-Cu Quantum clusters, G Insulin-Zinc quantum clusters, H Gelatin-AgNPs-PDGF-BB, I Keratin nanoparticles, J Collagen nanofibers, K Heparin nanofibers, L Fibroblast growth factor-CMCS nanoparticles, M bFGF-loaded chitosan nanoparticles, N VEGF-PLGA nanoparticles, O Vascular endothelial growth factor-loaded PLGA nanoparticles, P Keratin Growth factor-Au nanoparticles, Q KGF-loaded fibrin nanoparticles, R rh-EGF-loaded carboxymethyl chitosan nanoparticles, S rh-EGF-loaded solid lipid nanoparticles, T PDGF-BB nanoparticles [Adapted with permission from ACS, RSC, Elsevier, Taylor and Francis, Springer Nature, MDPI], all rights reserved