Multifunctional hydrogels based on chitosan, hyaluronic acid and other biological macromolecules for the treatment of inflammatory bowel disease: A review.

Responsive multifunctional hydrogels emulating the infected chronic wounds healing cascade for skin repair.

Structurally dynamic self-healable hydrogel cooperatively inhibits intestinal inflammation and promotes mucosal repair for enhanced ulcerative colitis treatment.

The cardiac fibrosis caused by excessive deposition of collagen and the fibro‐inflammatory cascade reaction severely impedes the cardiac regenerative efficiency after myocardial infarction (MI) so that the onefold treating target is far from satisfying therapeutic efficacy. Herein, a yes‐associated protein (YAP)‐suppressive nanodrug‐crosslinked self‐immunoregulatory polysaccharide injectable hydrogel is fabricated for the first time. To this end, cationic liposomes loading YAP inhibitor verteporfin (Lipo‐VP) is prepared and coated with oxidized fucoidan (OFu), a unique anti‐inflammation polysaccharide, to form anti‐fibrotic and immunoregulatory nanodrug (OFu‐Lipo‐VP). The coated fucoidan itself acts as a reactive oxygen species (ROS) scavenger and inflammation regulator, thus facilitating angiogenesis function by eliciting endogenous vascular endothelial growth factor secretion of macrophages. Then an injectable hydrogel (termed as OFu‐Lipo‐VP‐PGA) is formed through addition reaction between the aldehyde groups of OFu‐Lipo‐VP and the thiol groups of thiol‐modified poly(γ‐glutamic acid) (PGA‐SH), where the thiol groups can also aid in eliminating ROS. The acute MI models are established and the infarcted male rats are treated with this injectable OFu‐Lipo‐VP‐PGA hydrogel after MI. The outcomes at 28 days post‐surgery indicate efficient restoration of cardiac functions and attenuation of cardiac fibrosis. This study opens up a new possibility for MI treatment with immunoregulatory and antifibrotic injectable polysaccharide‐based hydrogel.

YAP‐Suppressive Nanodrug Crosslinked Self‐Immunoregulatory Polysaccharide Injectable Hydrogel for Attenuating Cardiac Fibrosis to Treat Myocardial Infarction

Repurposing clinically approved drugs to construct novel nanomedicines is currently a very attractive therapeutic approach. Selective enrichment of anti-inflammatory drugs and reactive oxygen species (ROS) scavenging at the region of inflammation by stimuli-responsive oral nanomedicine is an effective strategy for the treatment of inflammatory bowel disease (IBD). This study reports a novel nanomedicine, which is based on the excellent drug loading and free radical scavenging ability of mesoporous polydopamine nanoparticles (MPDA NPs). By initiating polyacrylic acid（PAA）polymerization on its surface, a "core-shell" structure nano-carrier with pH response is constructed. Then, under alkaline conditions, using the π-π stacking and hydrophobic interaction between the anti-inflammatory drug sulfasalazine (SAP) and MPDA, the nanomedicines (PAA@MPDA-SAP NPs) loaded efficiently (928 μ g mg-1) of SAP was successfully formed. Our results reveal that PAA@MPDA-SAP NPs can pass through the upper digestive tract smoothly and finally accumulate in the inflamed colon. Through the synergistic effect of anti-inflammation and antioxidation, it can effectively reduce the expression of pro-inflammatory factors and enhance the intestinal mucosal barrier, and finally significantly alleviate the symptoms of colitis in mice. Furthermore, we confirmed that PAA@MPDA-SAP NPs have good biocompatibility and anti-inflammatory repair ability under inflammation induction through human colonic organoids. In summary, this work provides a theoretical basis for the development of nanomedicines for IBD therapy. 

A mesoporous polydopamine-derived nanomedicine for targeted and synergistic treatment of inflammatory bowel disease by pH-Responsive drug release and ROS scavenging.

A KPV-binding double-network hydrogel restores gut mucosal barrier in an inflamed colon.

Inflammatory bowel diseases (IBDs) treatments have shifted from small-molecular therapeutics to the oncoming biologics. The first-line biologics against the moderate-to-severe IBDs are mainly involved in antibodies against integrins, cytokines and cell adhesion molecules. Besides, other biologics including growth factors, antioxidative enzyme, anti-inflammatory peptides, nucleic acids, stem cells and probiotics have also been explored at preclinical or clinical studies. Biologics with variety of origins have their unique potentials in attenuating immune inflammation or gut mucosa healing. Great advances in use of biologics for IBDs treatments have been archived in recent years. But delivering issues for biologic have also been confronted due to their liable nature. In this review, we will focus on biologics for IBDs treatments in the recent publications; summarize the current landscapes of biologics and their promise to control disease progress. Alternatively, the confronted challenges for delivering biologics will also be analyzed. To combat these drawbacks, some new delivering strategies are provided: firstly, designing the functional materials with high affinity toward biologics; secondly, the delivering vehicle systems to encapsulate the liable biologics; thirdly, the topical adhering delivery systems as enema. To our knowledge, this review is the first study to summarize the updated usage of the oncoming biologics for IBDs, their confronted challenges in term of delivery and the potential combating strategies. 

From the updated landscape of the emerging biologics for IBDs treatment to the new delivery systems.

In situ polyphenol-adhesive hydrogel enhanced the noncarcinogenic repairing of KGF on the gut epithelial barrier on TNBS-induced colitis rats.

Montmorillonite (MMT), a layered aluminosilicate, has a mucosal nutrient effect and restores the gut barriers integrity. However, orally administrating MMT is not effective to combat the reactive oxygen species (ROS) and alleviate the acute inflammatory relapse for colitis patients. Herein, polydopamine-doped montmorillonite micro-sheets (PDA/MMT) have been developed as a therapeutic platform for colitis treatment. SEM and EDS analysis showed that dopamine monomer (DA) was easily polymerized in alkaline condition and polydopamine (PDA) was uniformly cladded on the surface of MMT micro-sheets. The depositing amount of PDA was reaching to 2.06 ​± ​0.08%. Moreover, in vitro fluorescence probes experiments showed that PDA/MMT presented the broad spectra of scavenging various ROS sources including •OH, •O2−, and H2O2. Meanwhile, the intracellular ROS of Rosup/H2O2 treated Caco-2 ​cell was also effectively scavenged by PDA/MMT, which resulted in the obvious improvement of the cell viability under oxidative stress. Moreover, most of orally administrated PDA/MMT was transited to the gut and form a protective film on the diseased colon. PDA/MMT exhibited the obvious therapeutic effect on DSS-induced ulcerative colitis mouse. Importantly, the gut mucosa of colitis mouse was well restored after PDA/MMT treatment. Moreover, the colonic inflammation was significantly alleviated and the goblet cells were obliviously recovered. The therapeutic mechanism of PDA/MMT was highly associated with inhibiting oxidative stress. Collectively, PDA/MMT micro-sheets as a therapeutic platform may provide a promising therapeutic strategy for UC treatment. 

https://doi.org/10.1016/j.mtbio.2023.100654

Polydopamine-cladded montmorillonite micro-sheets as therapeutic platform repair the gut mucosal barrier of murine colitis through inhibiting oxidative stress

Enhancing damping capacity and mechanical properties of aluminum matrix composites by the synergistic strengthening of SiC particles and carbon fibers

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