Bottlebrush inspired injectable hydrogel for rapid prevention of postoperative and recurrent adhesion.

Postsurgical adhesion is a common clinic disease induced by surgical trauma, accompanying serious subsequent complications. Current non-surgical approaches of drugs treatment and biomaterial barrier administration only show limited prevention effects and couldn't effectively promote peritoneum repair. Herein, inspired by bottlebrush, a novel self-fused, antifouling, and injectable hydrogel is fabricated by the free-radical polymerization in aqueous solution between the methacrylate hyaluronic acid (HA-GMA) and N-(2-hydroxypropyl) methacrylamide (HPMA) monomer without any chemical crosslinkers, termed as H-HPMA hydrogel. The H-HPMA hydrogel can be tuned to perform excellent self-fused properties and suitable abdominal metabolism time. Intriguingly, the introduction of the ultra-hydrophilic HPMA chains to the H-HPMA hydrogel affords an unprecedented antifouling capability. The HPMA chains establish a dense hydrated layer that rapidly prevents the postsurgical adhesions and recurrent adhesions after adhesiolysis in vivo. The H-HPMA hydrogel can repair the peritoneal wound of the rat model within 5 days. Furthermore, an underlying mechanism study reveals that the H-HPMA hydrogel significantly regulated the mesothelial-to-mesenchymal transition (MMT) process dominated by the TGF-ß-Smad2/3 signal pathway. Thus, we developed a simple, effective, and available approach to rapidly promote peritoneum regeneration and prevent peritoneal adhesion and adhesion recurrence after adhesiolysis, offering novel design ideas for developing biomaterials to prevent peritoneal adhesion.

Reactive Oxygen Species-Responsive Polyether Micelle Nanomaterials for Targeted Treatment of Ulcerative Colitis.

As one of the most challenging inflammatory diseases, the incidence of ulcerative colitis (UC) is increasing year by year, but the existing therapeutic drugs are not effective and lack of targeting. Nanomaterials are expected to become promising delivery system due to their good targeting effects. Here, we designed a nanomaterial sensitive to reactive oxygen species, which can be used to treat IBD, especially UC. It is a self-assembled polyether micelle that can be oxidized at the inflammation site where the concentration of reactive oxygen increases, and effectively release the encapsulated budesonide (Bud). Experiments have proved that for DSS-induced colitis, the synthetic drug-loaded nanoparticles have excellent therapeutic effects, can effectively repair intestinal barrier, and significantly improve the damaged colon tissue. At the same time, it has a beneficial regulatory effect on inflammatory factors. Molecular mechanism studies have shown that it achieves its therapeutic effects by activating the peroxisome proliferators-activated receptors-γ (PPAR-γ) pathway and inhibiting the nuclear factor (NF)-κB pathway. This study proves that oral nano-micelles have an important impact on improving the efficacy of UC treatment drugs and have far-reaching significance for the targeted treatment of gastrointestinal diseases.

An Ultrasoft Self-Fused Supramolecular Polymer Hydrogel for Completely Preventing Postoperative Tissue Adhesion.

The intermolecular H-bonding density heavily influences the gelation and rheological behavior of hydrogen-bonded supramolecular polymer hydrogels, thus offering a delicate pathway to tailor their physicochemical properties for meeting a specific biomedical application. Herein, one methylene spacer between two amides in the side chain of N-acryloyl glycinamide (NAGA) is introduced to generate a variant monomer, N-acryloyl alaninamide (NAAA). Polymerization of NAAA in aqueous solution affords an unprecedented ultrasoft and highly swollen supramolecular polymer hydrogel due to weakened H-bonds caused by an extra methylene spacer, which is verified by variable-temperature Fourier transform infrared (FTIR) spectroscopy and simulation calculation. Intriguingly, poly(N-acryloyl alaninamide) (PNAAA) hydrogel can be tuned to form a transient network with a self-fused and excellent antifouling capability that results from the weakened dual amide H-bonding interactions and enhanced water-amide H-bonding interactions. This self-fused PNAAA hydrogel can completely inhibit postoperative abdominal adhesion and recurrent adhesion after adhesiolysis in vivo. This transient hydrogel network allows for its disintegration and excretion from the body. The molecular mechanism studies reveal the signal pathway of PNAAA hydrogel in inhibiting inflammatory response and regulating fibrinolytic system balance. This self-fused, antifouling ultrasoft supramolecular hydrogel is promising as a barrier biomaterial for completely preventing postoperative tissue adhesion.

Hyaluronic acid/lysozyme self-assembled coacervate to promote cutaneous wound healing.

Traditional hydrogel dressings are limited in practical applications due to the complexity of the preparation and low biocompatibility. So, there is an urgent need to design wound dressing with simple preparation method, higher biocompatibility, and superior therapeutic effect. Additionally, using a polysaccharide/protein mixture system is an attractive method to prepare the gel. In this study, a simple mixture of hyaluronic acid/lysozyme (HL) was used to obtain the HL coacervate gel. HL coacervate has suitable viscoelasticity and excellent adhesion on the skin tissue. We demonstrated its highly efficient self-healing property to overcome fracture or deformation. HL coacervate showed a significant effect on promoting wound healing in a full-thickness skin defect model. Compared to the commercial 3M dressing, it has faster epithelial tissue regeneration and stronger collagen deposition. In addition, cytotoxicity and organ toxicity tests indicated its high safety. In summary, HL coacervate has broad clinical application prospects as a wound dressing material.