Self-Healing Hyaluronic Acid Nanocomposite Hydrogels with Platelet-Rich Plasma Impregnated for Skin Regeneration

Abstract

The development of natural hydrogels with sufficient strength and self-healing capacity to accelerate skin wound healing is still challenging. Herein, a hyaluronic acid nanocomposite hydrogel was developed based on aldehyde-modified sodium hyaluronate (AHA), hydrazide-modified sodium hyaluronate (ADA), and aldehyde-modified cellulose nanocrystals (oxi-CNC). This hydrogel was formed in situ using dynamic acylhydrazone bonds via a double-barreled syringe. This hydrogel exhibited improved strength and excellent self-healing ability. Furthermore, platelet-rich plasma (PRP) can be loaded in the hyaluronic acid nanocomposite hydrogels (ADAC) via imine bonds formed between amino groups on PRP (e.g., fibrinogen) and aldehyde groups on AHA or oxi-CNC to promote skin wound healing synergistically. As expected, ADAC hydrogel could protect and release PRP sustainably. In animal experiments, ADAC@PRP hydrogel significantly promoted full-thickness skin wound healing through enhancing the formation of granulation tissue, facilitating collagen deposition, and accelerating re-epithelialization and neovascularization. This self-healing nanocomposite hydrogel with PRP loading appears to be a promising candidate for wound therapy.

Recent advances of the nanocomposite hydrogel as a local drug delivery for diabetic ulcers

“…However, most of the platelet-rich plasma used in the clinic is liquid, which cannot be fixed in the local area, and the growth factors in platelet-rich plasma is released too fast to maintain the long-term effective concentration. Recently, it has been reported that the plasma-rich gel is an effective carrier to protect platelet growth (Li et al, 2022a).…”

“…However, most of the platelet-rich plasma used in the clinic is liquid, which cannot be fixed in the local area, and the growth factors in platelet-rich plasma is released too fast to maintain the long-term effective concentration. Recently, it has been reported that the plasma-rich gel is an effective carrier to protect platelet growth ( Li et al, 2022a ). In vivo studies showed that the hydrogel significantly promotes the healing of full-thickness skin wounds by enhancing granulation tissue formation, promoting collagen deposition and accelerating re-epithelialisation and neovascularisation.…”

“…In particular, nanocomposite hydrogels are advantageous, because they can be loaded with small-molecule drugs, biomacromolecules, inorganic nanoparticles and other active substances that enhance the biological activity of nanocomposite hydrogels and further expand their application to wound management ( Alvarez et al, 2014 ; Wu et al, 2019 ; Yang et al, 2021 ; Massironi et al, 2022 ; Rao et al, 2022 ). When a nanocomposite hydrogel is used as drug delivery system carrier, it can reach the lesion through active or passive transport, which is suitable for drug delivery to the skin, oral mucosa, eye and some gastrointestinal mucosa ( Sapino et al, 2019 ; Wróblewska et al, 2020 ; Cheng et al, 2021 ; Li et al, 2022a ). Compared with other types of nano carriers, nanocomposite hydrogels are similar to natural extracellular matrices, with good water dispersion and are easier to penetrate human skin, achieve the locally sustained and on demand release of drugs and form a physical barrier to create a clean and moist healing environment for the repair of diabetic ulcer ( Lou et al, 2021 ; Girija et al, 2022 ).…”

Supramolecular Hydrogel Dressing: Effect of Lignin on the Self-Healing, Antibacterial, Antioxidant, and Biological Activity Improvement

“…The supramolecular interaction is a general term for a class of intermolecular interactions . The supramolecular interactions mainly include hydrophobic interactions, − host–guest interactions, hydrogen bonds, crystallization, electrostatic interactions, and multiple intermolecular interactions. − These interactions exist between molecules, oligomers, or polymer chains. Compared to traditional chemical cross-linking hydrogels, the supramolecular hydrogel with self-healing properties has extremely outstanding advantages in the clinical wound management field.…”

Preparation and Properties of Double-Crosslinked Hydroxyapatite Composite Hydrogels

“…Natural polymer hydrogels with good biocompatibility and biodegradation can support cell adhesion, proliferation, and differentiation on its surface or inside. Thus, they are often used in the field of tissue engineering, for example, in cartilage repair and skin dressing [ 3 , 4 , 5 , 6 ]. However, their applications were hindered due to most natural polymers’ poor strength and toughness.…”