A Bioinspired Alginate-Gum Arabic Hydrogel with Micro-/Nanoscale Structures for Controlled Drug Release in Chronic Wound Healing

Abstract

Biopolymeric hydrogels have drawn increasing research interest in biomaterials due to their tunable physical and chemical properties for both creating bioactive cellular microenvironment and serving as sustainable therapeutic reagents. Inspired by a naturally occurring hydrogel secreted from the carnivorous Sundew plant for trapping insects, here we have developed a bioinspired hydrogel to deliver mitsugumin 53 (MG53), an important protein in cell membrane repair, for chronic wound healing. Both chemical compositions and micro-/nanomorphological properties inherent from the natural Sundew hydrogel were mimicked using sodium alginate and gum arabic with calcium ion-mediated cross-linking. On the basis of atomic force microscopy (AFM) force measurements, an optimal sticky hydrogel scaffold was obtained through orthogonal experimental design. Imaging and mechanical analysis showed the distinct correlation between structural morphology, adhesion characteristics, and mechanical properties of the Sundew-inspired hydrogel. Combined characterization and biochemistry techniques were utilized to uncover the underlying molecular composition involved in the interactions between hydrogel and protein. In vitro drug release experiments confirmed that the Sundew-inspired hydrogel had a biphasic-kinetics release, which can facilitate both fast delivery of MG53 for improving the reepithelization process of the wounds and sustained release of the protein for treating chronic wounds. In vivo experiments showed that the Sundew-inspired hydrogel encapsulating with rhMG53 could facilitate dermal wound healing in mouse model. Together, these studies confirmed that the Sundew-inspired hydrogel has both tunable micro-/nanostructures and physicochemical properties, which enable it as a delivery vehicle for chronic wounding healing. The research may provide a new way to develop biocompatible and tunable biomaterials for sustainable drug release to meet the needs of biological activities.

Natural product-based nanomedicines for wound healing purposes: therapeutic targets and drug delivery systems

“…Adhesive nanohydrogels possess the ability to bind to the injured tissues, and can successfully act as hemostat and provide a microenvironment to facilitate the proliferation, differentiation, and migration of cells. 117 As mentioned, curcumin as an active herbal compound suffers from the drawback of low water solubility and low bioavailability, which restrict its therapeutic applications. One promising method to overcome this drawback of curcumin and other hydrophobic compounds is to incorporate them in the aqueous nanostructures such as nanohydrogels.…”

Recent Progress of Polysaccharide‐Based Hydrogel Interfaces for Wound Healing and Tissue Engineering

“…These hydrogels are able to release the drug at the desired time under external stimulation in a specific site. The application in drug delivery of hydrogels is particularly beneficial in preventing drug degradation and avoiding some shortcomings such as poor water solubility or short‐life‐cycle at the interface . Hydrogels possess less side effects, efficient drug utilization, accurate drug targeting toward specific sites, and low cost in a drug delivery system …”

“…Oxidation or photo‐crosslinking strategies have been used to prepare hydrogels in drug delivery. Recently, Luc et al synthesized chemically crosslinked alginate hydrogels by reacting alginate modified by furan and bifunctional crosslinkers . The investigation of the ensuing hydrogels toward pH stimuli revealed a clear pH‐dependent swelling.…”

Recent Advances in Natural Gum-Based Biomaterials for Tissue Engineering and Regenerative Medicine: A Review

“…Further, in vivo analysis demonstrated enhanced dermal wound healing in the mouse model, where sundew-inspired hydrogels were encapsulated with rhMG53 cells. The schematic formation and mechanism of sundew-inspired adhesive hydrogel for controlled drug delivery and chronic wound healing is shown in Figure 5 [190]. used for Sundew mucilage; and (E) hydrogel forming by SA and ArG with Ca 2+ as crosslinking agent, characteristic of adhesive hydrogel by touching and pulling the hydrogel, porous network structure (AFM image), and the potential applications for drug delivery and wound healing.…”