Jing Zhang

Following an injury at the implantation position, blood-material interactions form a fibrin architecture, which serves as the initial activator of foreign body response (FBR). However, there is limited knowledge regarding how the topography of fibrin architectures regulates macrophage behavior in mitigating FBR. Mechanical cues of the microenvironment have been reported to shape immune cell functions. Here, we investigated macrophage mechanobiology at the organelle level by constructing heterogeneous fibrin networks. Based on findings in vivo, we demonstrated that adhesion-mediated differentiation of mitochondrial function modulated macrophage polarization. The finite activation of integrin signaling upregulated transglutaminase 2 (Tgm2) in a trans-manner, augments PGC1α-mediated mitochondrial biogenesis. Our study highlighted the previously overlooked spatial structures of host proteins adsorbed on material surfaces, advocating for a paradigm shift in material design strategies, from focusing solely on physical properties to considering the modification of host proteins.

Diabetic wound healing remains clinically challenging due to persistent oxidative stress and dysregulated inflammation caused by the pathological microenvironment, particularly excessive reactive oxygen species (ROS). A near‐infrared (NIR)‐responsive multifunctional microneedle system (Res@ZIF‐67/Ce _0.1 Mn _0.9 ‐MMON, RZCM) integrating antioxidant, antibacterial, and angiogenic functionalities is developed. The microneedle substrate incorporates Ce _0.1 Mn _0.9 ‐MMON nanoparticles that synergistically exert antibacterial effects through peroxidase‐mimetic activity and NIR‐induced photothermal hyperthermia, while concurrently mimicking superoxide dismutase and catalase activities to scavenge ROS and alleviate hypoxia. The microneedle tips encapsulate pH‐responsive Res@ZIF‐67 nanoparticles that release cobalt ions (Co ²⁺ ) and resveratrol in acidic environments, cooperatively stabilizing hypoxia‐inducible factor 1α (HIF‐1α) under normoxic conditions to promote angiogenesis. In vivo evaluations demonstrate that RZCM accelerates diabetic wound healing through coordinated mechanisms: photothermal bacterial eradication, ROS scavenging (85.7% reduction), macrophage M2 polarization (2.3 fold increase), HIF‐1α‐mediated neovascularization (2.1 fold higher CD31 density), and enhanced collagen remodeling (78.4% increased collagen I/III ratio). This multifunctional system achieves complete epithelialization within 14 days, outperforming conventional treatments. By integrating multi‐enzyme mimetic nanomaterials with microenvironment‐responsive drug delivery, RZCM establishes a novel therapeutic paradigm for chronic wound management, demonstrating significant translational potential for diabetic wound care through synergistic regulation of oxidative, inflammatory, and angiogenic pathways.

A sandwich-structured zwitterionic hydrogel coating with anti-swelling, antithrombotic, and antibacterial properties was developed for medical catheters to enhance clinical safety and efficacy.

Anti‐peritoneal adhesions (PA) are very important after abdominal surgery for that PA often leads to other medical problems and imposes a huge financial burden on the national healthcare system. In this work, a “Janus” zwitterionic hydrogel patch where one side can adhere firmly to the tissue, while the other side has anti‐fouling properties and has little interaction with the surrounding tissue has been developed. The “Janus” hydrogel patch is prepared by in situ formation of a bonding polymer layer poly(acrylic‐co‐N‐hydroxysuccinimide acrylate) on one side of zwitterionic hydrogel. The mechanical, swelling, adhesion, biodegradability and biocompatibility tests are performed to study the function of “Janus” hydrogel patch to prevent wound adhesion and rapid repair. It is found that the adhesive side of the hydrogel patch has stable adhesion to tissues, avoiding the slippage faced by many commercial anti‐adhesion gels in the body. The other zwitterionic side can resist proteins and fibroblasts and prevent external interactions or adhesion with other tissues. This convenient and effective method provides a new idea for the design of postoperative anti‐adhesion materials and broadens the application of hydrogels in the biomedical field.

Cancer has become a highly prevalent disease and poses serious threats to human health. Conventional cancer treatments still face high risks of recurrence. Training the immune system to recognize and eliminate tumors via external stimulation, such as vaccines, emerges as a promising approach for cancer prevention and treatment. However, injectable vaccines may have limited immune activation, causing difficulties in maintaining long-term immune surveillance of tumorigenesis by tumor-specific cytotoxic T cells. Here, degradable zwitterionic cryogels were prepared using the cryogelation technique. The cryogenic preparation maintained the biological activities of tumor antigens and immune adjuvants loaded in the cryogels. The macroporous structure endowed the injectability of cryogels into the body via conventional syringes. In the presence of proteases, the cryogels degraded, allowing sustained release of antigens and adjuvants, ensuring continued dendritic cell (DC) recruitment and antigen presentation to maturing tumor-specific cytotoxic T cells. In vivo experiments demonstrated that the cryogel cancer vaccines elicited robust immune activation and effectively modulated tumor microenvironments. The combination with photothermal therapy significantly inhibited tumor growth, showing great potential for preventing postoperative recurrence. Additionally, the zwitterionic cryogels were biocompatible without obvious toxicities during degradation. The cryogels could serve as effective vaccine platforms to prevent cancer recurrence after surgery.

The increasing complexity and difficulty of surgical procedures have led to a rise in medical errors within clinical settings in recent years. Gastrointestinal diseases, in particular, present significant medical challenges and impose substantial economic burdens, underscoring the urgent need for experiential, high-fidelity gastrointestinal surgical training tools. This study leverages patient-specific computed tomography (CT) and magnetic resonance imaging (MRI) data, combined with 3D printed manufacturing, to develop hydrogel organ models with tunable performance and tissue-mimicking softness. These properties are achieved by regulating the freeze-thaw cycles, cross-linking agents, and the concentration of incorporated antibacterial nanoparticles in DN hydrogels. Through the application of indirect 3D printing and the "sacrificial material method", we successfully fabricate organ tissues such as the stomach, intestines, and blood vessels with high precision. In ex vivo surgical training demonstrations, these tissue-like soft hydrogels provide an effective platform for preoperative simulation and surgical training in digestive surgery, accommodating various surgical procedures and accurately simulating intraoperative bleeding. The development of advanced bionic organ models with specific and tunable characteristics based on DN hydrogels is poised to significantly advance surgical training, medical device testing, and the reform of medical education.