Self‐Healing and Injectable Hydrogel for Matching Skin Flap Regeneration

Abstract

The fabrication of highly biocompatible hydrogels with multiple unique healing abilities for the whole healing process, for example, multifunctional hydrogels with injectable, degradation, antibacterial, antihypoxic, and wound healing–promoting properties that match the dynamic healing process of skin flap regeneration, is currently a research challenge. Here, a multifunctional and dynamic coordinative polyethylene glycol (PEG) hydrogel with mangiferin liposomes (MF‐Lip@PEG) is developed for clinical applications through Ag–S coordination of four‐arm‐PEG‐SH and Ag+. Compared to MF‐PEG, MF‐Lip@PEG exhibits self‐healing properties, lower swelling percentages, and a longer endurance period. Moreover, the hydrogel exhibits excellent drug dispersibility and release characteristics for slow and persistent drug delivery. In vitro studies show that the hydrogel is biocompatible and nontoxic to cells, and exerts an outstanding neovascularization‐promoting effect. The MF‐Lip@PEG also exhibits a strong cytoprotective effect against hypoxia‐induced apoptosis through regulation of the Bax/Bcl‐2/caspase‐3 pathway. In a random skin flap animal model, the MF‐Lip@PEG is injectable and convenient to deliver into the skin flap, providing excellent anti‐inflammation, anti‐infection, and proneovascularization effects and significantly reducing the skin flap necrosis rate. In general, the MF‐Lip@PEG possesses outstanding multifunctionality for the dynamic healing process of skin flap regeneration.

A Biomimetic 3D‐Self‐Forming Approach for Microvascular Scaffolds

“…In the random flap model in rats, necrosis usually occurred at the distal end of the flap due to lack of blood supply. [ 7,37 ] To validate the MHT‐based microvessel scaffold established in this study, MHTs with diameter from 100–40 µm were implanted under the distal end of the flap, promoting the extension of new vessels from the adjacent area to the distal end of the flap via bridging effect of the scaffold, as illustrated in the Figure 1. From the transformation point of view, this operation converted a random flap into an axial one.…”

“…The reduced inflammation caused by implantation of MHTs is crucial when compared to other tissue engineering therapies, such as electrospun membranes and injectable scaffolds. [ 6,7,37,38 ]…”

Bioinspired Adhesive and Antibacterial Microneedles for Versatile Transdermal Drug Delivery

“…This poor adhesion ability seriously limits many practical applications of the hydrogel MNs, especially for the parts with high mobility and a large range of motion, such as joints. Besides, the biocompatible property of hydrogel MNs makes them extremely likely to be infected with bacteria [12][13][14][15], which not only causes inconvenience to the storage and usage but also increases the risk of skin infection. Therefore, hydrogel MNs with improved adhesion and antibacterial ability for drug delivery is highly desired.…”

Injectable Hydrogel-Based Nanocomposites for Cardiovascular Diseases

“…Recently, the utilization of injectable hydrogel-based DDSs has attracted considerable attention in many medicine fields, including chemotherapeutics (Norouzi et al, 2016), tissue engineering and regenerative medicine such as cartilage and spinal cord (Macaya and Spector, 2012). Injectable hydrogel has mechanical properties to closely match the targeting organ, and can also be loaded with cellular and a cellular therapeutics to modulate the wound environment and enhance regeneration (Frith et al, 2013;Seo et al, 2017;Cipriani et al, 2018;Mao et al, 2019). In the past years, hydrogels have been paid considerable attention as potential candidates for restoration of ischemia myocardial, in particular, those stem from natural extracellular matrix (ECM) components (e.g., collagen, fibronectin, as well as glycosaminoglycans) could favor greatly endothelial cells adhesion and their transformation to microvessels in vitro (Moon et al, 2010) attributing to their high water content and structural similarity to the natural ECM (Peppas et al, 2006;Seliktar, 2012).…”