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Comprehensive Summary: Due to the immunosuppressive tumor microenvironment (TME), T cells are usually inactivated and tend to differentiate into regulatory T cells (Tregs) in the tumor tissues, which seriously hinders the anti‐tumor efficiency of immunotherapy. In this study, an immune‐stimulating polypeptide hydrogel conjugated with an indoleamine‐2,3‐dioxygenase (IDO) inhibitor, 1‐methyl‐D‐tryptophan (D1MT), through a glutathione (GSH)‐responsive spacer was developed as an immunotherapy platform capable of regulating the TME. A combined immunotherapy system was further constructed through encapsulating doxorubicin (Dox) and immune checkpoint blocking antibody targeting programmed cell death protein 1 (aPD‐1) in the hydrogel. Dox released from the hydrogel could cause the immunogenic cell death (ICD) of tumor cells and induce the maturation of antigen presenting cells (APCs). After intratumoral injection, the multiple agent‐loaded hydrogel elicited effective anti‐tumor immunity in mice bearing B16F10 melanoma. Moreover, compared with the control hydrogel without D1MT, the immune‐stimulating hydrogel showed better efficiency in improving the immunosuppressive TME with increased number of activated T cells and reduced number of Tregs. Therefore, the immune‐stimulating hydrogel has great potential as a stimuli‐responsive platform for regulating suppressive TME and enhanced anti‐tumor chemo‐immunotherapy. [ABSTRACT FROM AUTHOR]

Bacterial infections are common during skin wound healing, which can interrupt the healing process, delay wound healing and seriously affect the quality of life. Long‐term antibiotic treatment may lead to the development of drug resistance. Traditional bandages, sponges, films, and textiles are commonly single‐functional, and usually fail to satisfy the complicated needs of wound healing process. In recent years, antibacterial hydrogel dressings have received extensive attention for treatment of infected and chronic wounds, which can serve as biocompatible, multifunctional platforms for both promoting tissue regeneration and inhibiting bacterial infection. Cationic polymers with inherent antibacterial properties have been used as the hydrogel backbone, and metal ions and metal nanoparticles can be loaded in the hydrogels to enhance the antibacterial effects. Besides, various drugs and bioactive factors have been incorporated to provide the hydrogel with anti‐inflammatory and antioxidant activities in complicated environment of chronic wound healing. Additionally, the tissue adhesion of hydrogel dressings can have advantages in fixing the dressings at wound sites and promoting the dressing‐tissue interactions. In this review, we focus on the designing strategies for tissue‐adhesive, antibacterial, naturally‐derived polymer hydrogels for treating infected and chronic wounds. The typical tissue adhesion mechanisms and antibacterial mechanisms of the hydrogel dressings are summarized. Finally, the prospects and challenges in the further development of multi‐functional hydrogels to treat infected and chronic wounds are proposed. [ABSTRACT FROM AUTHOR]

Dural defects and subsequent complications, including cerebrospinal fluid (CSF) leakage, are common in both spine surgery and neurosurgery, and existing clinical treatments are still unsatisfactory. In this study, a tissue-adhesive and low-swelling hydrogel sealant comprising gelatin and o -phthalaldehyde (OPA)-terminated 4-armed poly(ethylene glycol) (4aPEG-OPA) is developed via the OPA/amine condensation reaction. The hydrogel shows an adhesive strength of 79.9 ± 12.0 kPa on porcine casing and a burst pressure of 208.0 ± 38.0 cmH2O. The hydrogel exhibits a low swelling ratio at physiological conditions, avoiding nerve compression in the limited spinal and intracranial spaces. In rat and rabbit models of lumbar and cerebral dural defects, the 4aPEG-OPA/gelatin hydrogel achieves excellent performance in dural defect sealing and preventing CSF leakage. Moreover, local inflammation, epidural fibrosis and postoperative adhesion in the defect areas are markedly reduced. Thus, these findings establish the strong potential of the hydrogel sealant for the effective watertight closure of dural defects. [ABSTRACT FROM AUTHOR]

Surgical excision is the first choice for clinical cancer therapy. However, major challenges, such as postoperative tumor recurrence and unsatisfactory wound healing after surgery, remain. In this study, an adhesive hydrogel is developed as a multifunctional platform for antitumor chemoimmunotherapy and postoperative wound treatment. The hydrogel adheres firmly to diverse tissues and degrades within 4 weeks in vivo with good histocompatibility. The immune‐stimulating hydrogel ((DOX+R837@HN)@Gel) is fabricated by encapsulating doxorubicin (DOX) and imiquimod‐loaded HSA nanoparticles (R837@HNs) into the hydrogel. When combined with immune checkpoint blockade (ICB) therapy, intratumorally administering (DOX+R837@HN)@Gel exhibits markedly enhanced systemic antitumor efficacy and strengthened antitumor immunity. For tumor surgical resection, (DOX+R837@HN)@Gel can adhere to the wounds and effectively prevents tumor recurrence and achieves long‐term immune memory with ICB therapy. Moreover, the hydrogel achieves rapid hemostasis and promotes wound healing after treating surgical wound models. Therefore, this multifunctional hydrogel has great significance for clinical postsurgical cancer treatment. [ABSTRACT FROM AUTHOR]

Hydrogels are hydrophilic three‐dimensional networks containing a large amount of water, with physicochemical properties similar to extracellular matrix and controlled mechanical strength, making them ideal scaffolds for 3D cell culture and tissue engineering. However, the cross‐linked hydrogel network often restricts the migration of cells and the exchange of nutrients, which affects cell proliferation and the development of normal tissues. In recent years, hydrogels with pore‐channel structures have attracted significant attention, but these spatial structures are usually preconstructed before gelation, posing challenges in meeting the dynamic physiological conditions required during cell and tissue growth. Therefore, considerable efforts have been devoted to structurally regulate the scaffolds after gelation, so as to enhance the interactions between the scaffolds and cells for promoting the growth of cells and tissues. This review firstly outlines the preparation of hydrogel scaffolds with pore structure and the necessity of postgelation pore modulation. Two types of methods for postgelation pore modulation, including chemical degradation and physical dissolution, are then summarized. Finally, the potential application of such postgelation structural modulation in 3D cell culture and tissue engineering is discussed. [ABSTRACT FROM AUTHOR]