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Review
. 2022 Oct 19;14(10):2235.
doi: 10.3390/pharmaceutics14102235.

Recent Progress on Hyaluronan-Based Products for Wound Healing Applications

Affiliations
Review

Recent Progress on Hyaluronan-Based Products for Wound Healing Applications

Kuncham Sudhakar et al. Pharmaceutics. .

Abstract

Hyaluronic acid (HA) based nanocomposites are considered excellent for improving wound healing. HA is biocompatible, biodegradable, non-toxic, biologically active, has hemostatic ability, and resists bacterial adhesion. HA-based nanocomposites promote wound healing in four different sequential phases hemostasis, inflammation, proliferation, and maturation. The unique biological characteristics of HA enable it to serve as a drug, an antibacterial agent, and a growth factor, which combine to accelerate the healing process. In this review, we focus on the use of HA-based nanocomposites for wound healing applications and we describe the importance of HA for the wound healing process in each sequential phase, such as hemostasis, inflammation, proliferation, and maturation. Metal nanoparticles (MNPs) or metal oxide nanoparticles (MO-NPs) loaded with HA nanocomposite are used for wound healing applications. Insights into important antibacterial mechanisms are described in HA nanocomposites. Furthermore, we explain antibiotics loaded with HA nanocomposite and its combination with the MNPs/MO-NPs used for wound healing applications. In addition, HA derivatives are discussed and used in combination with the other polymers of the composite for the wound healing process, as is the role of the polymer in wound healing applications. Finally, HA-based nanocomposites used for clinical trials in animal models are presented for wound healing applications.

Keywords: antibacterial activity; antibiotic drugs; hyaluronic acid; metal/metal oxide nanoparticles; wound healing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The influence of HA at wound sites during the hemostasis, inflammation, proliferation, and remodeling phases of wound healing, Copyright 2017, ACS publication [36].
Figure 2
Figure 2
Possible antibacterial mechanism for a metal−based HA composite drug Copyright 2017, Elsevier [64].
Figure 3
Figure 3
Summary of the AgNPs formation to words bacterial killing for wound healing. Copyright 2017, Elsevier [70].
Figure 4
Figure 4
A(a) Cytotoxicity of at 24 and 72 h A(b) L929 Cell morphologies control and thermosensitive hydrogels for 1 day. DAPI stained nuclei (blue) and actin filaments stained with phalloidin−TRIC (green). Copyright 2019, Elsevier [71]. B(a) MRSA strain and B(b) drug resistance survival rates against E. coli under UV-light irradiation. SEM images for (c) MRSA and (d) drug resistance for E. coli after various treatments under UV-light irradiation (1) PBS (2) AgNO3 (3) PCN−224−HA and (4) PCN-224−Ag−HA. Copyright 2019, John Wiley and Sons [75].
Figure 5
Figure 5
(A) Preparation of antibacterial HA-SF/ZnO fibers with core-shell structure and applied for wound healing. Copy right 2020, John Wiley and Sons [106]. (B) Formation of HA and HA-ZnO hydrogels, (C). SEM images ZnO hydrogels. (D). Hemolysis and antibacterial activity of hydrogels Figure (BD) Copyright 2019, Elsevier [113]. (B) HA and HA-ZnO hydrogels B(a) formation of mechanism B(b) BDDE crosslinked hydrogels, B(c) ZnO nanoparticles, and (d) digital photographic hydrogels. (C) SEM images of C(aa-2) HA, C(bb-2) HA-ZnO-0.05, C(cc-2) HA-ZnO-0.1. (D) Hydrogels treated with pig whole blood, D(a) photographic images of blood clot formed, D(b) hemolysis (%) of different hydrogels (inset photographic images showing hemolysis), D(c) antibacterial activity of hydrogels against E. coli and S. aureus
Figure 6
Figure 6
HA combined with different drugs; release at wound sites, bacteria mortality, and skin regeneration. Copyright 2017, Elsevier [116].
Figure 7
Figure 7
(A) TEM and SEM images of MDR bacteria treated with HA-nanosystem. Copy right 2019, American Chemical Society [123]. (B) (a) Preparation of the HA-DA/rGO hydrogel (b) HA-DA polymer formation for rGO@PDA, (c) HA-DA/rGO self-healable hydrogel applied in wound healing applications. Copy right 2019, John Wiley and Sons [124]. (A) TEM (a) and SEM (b) images of MDR bacteria treated with NIR, Ru@HA-MoS2 + NIR, AA@Ru@HA-MoS2, and AA@Ru@HA-MoS2 + NIR for 2 h respectively [123].
Figure 8
Figure 8
Summarizes HA/polymers structure and significant properties in the wound healing process.

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