Green Regenerative Hydrogel Wound Dressing Functionalized by Natural Drug‐Food Homologous Small Molecule Self‐Assembled Nanospheres

Abstract

The goal of regenerative wound healing dressings is to restore tissue function back to normal physiological activity and accelerate skin tissue regeneration at wound sites. The optimal strategy to achieve this purpose requires a balance between material functionality, degradation, safety, and tissue regrowth. Herein, for the first time, an ultrasonic-triggered irreversible tending to equilibrium self-assembly and ionic cross-linking codriven strategy is proposed for producing multifunctional cinnamaldehyde-tannic acid-zinc acetate nanospheres (CA-TA-ZA NSs), realizing the fusion of hydrophilic and hydrophobic drug-food small molecules. Moreover, a novel "all-in-one" chitosan (CS)-based hydrogel functionalized by introducing drug-food small molecules self-assembled CA-TA-ZA NSs to the 3D network structures of CS is designed, integrating excellent antibacterial, antioxidant, anti-inflammatory and reducing oxidative stress damage abilities. Additionally, the multifunctional CS-based hydrogel can realize rapid in situ gelation at wound sites and completely cover the irregular wounds. All of these superiorities enable the CS-based hydrogel to clean the wound microenvironment, induce skin tissue remodeling, promote blood vessel repair and hair follicle regeneration, restore the immune system back to normal physiological activity, and accelerate wound healing. Therefore, this study offers a new perspective for the design of advanced functional materials with great application potential in the biomedical field.

Supramolecular assemblies based on natural small molecules: Union would be effective

“…Vesicular self-assemblies of NSMs are expected to mimic cellular membranes for delivering drugs better and catalyze nano-reactions as microreactors more efficiently [ 77 , 78 ]. The gels naturally formed by self-assembled NSMs, especially glycoside, can be redesigned as bioadhesive patch in place of handsewn closure of gastrointestinal defects or medical dressing to enhance tendon or wound healing [ 3 , [152] , [153] , [154] ]. Compared to synthetic substrates, natural hydrogels may be better suited to simulate the internal environment for 3D cell culture and organogenesis [ 155 , 156 ].…”

“…A large number of supramolecular assemblies based on them were constructed with a realization of the translation of one-dimensional carbohydrate polymers into various kinds of tunable, multifunctional, renewable and bioactive materials for application in optical components, drug delivery systems, regenerative medicine and tissue engineering. However, most of these macromolecular polymers without biofunctional modifications could only act as vehicles and carriers with insufficient bioactivities [ 3 ]. On the other hand, more and more synthetic and NSMs exhibiting intrinsic self-assembly properties have also attracted much attention.…”

Bioactive hydrogels based on polysaccharides and peptides for soft tissue wound management

“…Benefit from the strong hygroscopicity and abundant internal space, chitosan-based hydrogels can also absorb contaminants from wound effusion. Further antimicrobial-enhanced chemical modification (such as quaternary ammonium, 30,35,[37][38][39][40][41][42][43] alkylate [44][45][46] and antibacterial peptide 41,47 ) and physical encapsulation (such as antibiotics, 31,32,45,47 polydopamine, 38,42,48 graphene oxide, 30,38,49 carbon nanotubes 50 and other nanomaterials 37,42,45,48,51 ) methods are also favorable.…”

Biomaterials to promote vascularization in tissue engineering organs and ischemic fibrotic diseases

“…For example, spirulina can release oxygen (Figure 2H) 57 under laser irradiation; NOX powder can deliver dissolved oxygen to the wound site; 25 oxygen microsphere oxygen‐release microsphere can maintain oxygen release for at least 2 weeks; 26 manganese dioxide (MnO 2 ) nanosheets can induce the decomposition of endogenous ROS (H 2 O 2 ) into oxygen (O 2 ) 27 . Proanthocyanidin B2, 28 cinnamaldehyde, 29 tannic acid, 30 polydopamine nanoparticles, 31 epigallocatechin gallate (EGCG), 32 and hydrogel dressings have significant free radical scavenging and antioxidant properties, which can remove ROS produced in hypoxic wounds and inhibit excessive inflammation and promote wound angiogenesis.…”