Bone defects represent a prevalent and significant challenge in clinical practice. Given the inflammatory microenvironment at injury sites and the requirement for endogenous cell and tissue infiltration, there is an urgent need for an ideal biomaterial that can modulate inflammation and promote bone regeneration. We developed an innovative injectable hydrogel (CH@PUE&MSN) designed for immunomodulation and bone regeneration through in situ self-assembly, incorporating puerarin and chitosan with mesoporous silica nanoparticles. In vitro experiments demonstrated that this multifunctional injectable hydrogel promotes tissue cell regeneration, reduces inflammation, inhibits osteoclast formation, induces the migration and differentiation of bone marrow mesenchymal stem cells, and facilitates bone regeneration. Furthermore, we conducted an extensive in vivo evaluation using a bone defect model, employing advanced imaging and histological analyses. Our findings indicate that this multifunctional injectable hydrogel is a promising bioactive material for bone regeneration and presents a novel strategy for the clinical management of bone defects.

One of the main illnesses that put people’s health in jeopardy is myocardial infarction (MI). After MI, damaged or dead cells set off an initial inflammatory response that thins the ventricle wall and degrades the extracellular matrix. At the same time, the ischemia and hypoxic conditions resulting from MI lead to significant capillary obstruction and rupture, impairing cardiac function and reducing blood flow to the heart. Therefore, attenuating the initial inflammatory response and promoting angiogenesis are very important for the treatment of MI. Here, to reduce inflammation and promote angiogenesis in infarcted area, we report a new kind of injectable hydrogel composed of puerarin and chitosan via in situ self-assembly with simultaneous delivery of mesoporous silica nanoparticles (CHP@Si) for myocardial repair. On the one hand, puerarin degraded from CHP@Si hydrogel modulated the inflammatory response via inhibiting M1-type polarization of macrophages and expression of pro-inflammatory factors. On the other hand, silica ions and puerarin released from CHP@Si hydrogel showed synergistic activity to improve the cell viability, migration and angiogenic gene expression of HUVECs in both conventional and oxygen/glucose-deprived environments. It suggests that this multifunctional injectable CHP@Si hydrogel with good biocompatibility may be an appropriate candidate as a bioactive material for myocardial repair post-MI.

Melanoma is one of the highly malignant tumors whose incidence and fatality rates have been increased year by year. However, in addition to early surgical resection, there still lacks specific targeted drugs and treatment strategies. In this study, it was discovered that hinokiflavone (HF) encapsulated in zeolitic imidazolate framework-8 (ZIF-8) exhibited a superior anti-melanoma effect in vitro and in vivo. HF was encapsulated in ZIF-8 through a one-step synthesis method, and polyethylene glycol (PEG-2000) was used to optimize the size and dispersion of the drug-loaded complex (PEG/ZIF-8@HF). The results show that the prepared PEG/ZIF-8@HF has a high encapsulation efficiency (92.12%) and can achieve selective drug release in an acidic microenvironment. The results of in vitro anti-melanoma experiments indicate that PEG/ZIF-8@HF shows up-regulation of reactive oxygen species (ROS) levels and can restrain the migration and invasion of B16F10 cells. Moreover, in vivo animal experiments further confirm that PEG/ZIF-8@HF shows anti-tumor effect by up-regulating the pro-apoptotic proteins caspase-3 and caspase-8, and down-regulating the migration-promoting invasion protein MMP-9. This study developed a safe and effective oral administration of HF based on the high-efficiency delivery ZIF-8 system, which provides an effective treatment strategy for melanoma.

Chronic diabetic wounds affect millions and often fail to heal due to infection, inflammation, and poor angiogenesis, leading to high rates of amputation. Current treatments offer limited control over the wound microenvironment. Here, this work develops GPP@ZnBG hydrogels that can respond to elevated glucose and oxidative stress in diabetic wounds to release therapeutic ions in a self-pH–regulated and sequential manner. At an early stage, this hydrogel initiates a release of zinc ions under alkaline conditions, providing antibacterial activity while avoiding toxicity from excessive dosing. During the late stage, the hydrogel degrades, and it steadily releases zinc, calcium, and silicate ions that support angiogenesis, reduce inflammation, and promote tissue repair. In diabetic mice, GPP@ZnBG hydrogels improve neovascularization and enhance collagen deposition, leading to enhanced wound closure. Single-cell RNA sequencing results indicate that the hydrogel modulates fibroblast behavior, specifically fine-tuning NF-κB signaling to reduce detrimental inflammation and promote wound repair. A pilot clinical study demonstrates that topical GPP@ZnBG application showed a 94.57% relative reduction in a wound surface area within 4 weeks, with no adverse events reported. These findings establish a self-pH–driven ion delivery strategy that targets both infection and tissue regeneration, offering a promising therapeutic platform for chronic diabetic wound care.

Background: Patients with diabetic wounds often experience challenges in the repair process, owing to increased concentration of glucose and reactive oxygen species (ROS). In addition, high glucose levels usually result in bacterial infections, which in turn worsen wound healing. This study aims to develop a multifunctional hydrogel with integrated antibacterial activity, ROS scavenging, and glucose-responsive properties to accelerate healing of infected diabetic wounds. Methods: A Zn ion-incorporated injected hydrogel was prepared using 4-carboxyphenylboronic acid-modified gelatine, tannic acid, and zinc ions. The spectra were detected using a Fourier transform infrared spectrometer and surface morphologies of hydrogels were obtained using a scanning electron microscopy. The release behavior of Zn ions was investigated using an inductively coupled plasma mass spectrometry instrument. To evaluate the antimicrobial properties of the GPT and GPT@Zn hydrogels, strains of Escherichia coli and Staphylococcus aureus were utilized. Cytocompatibility was evaluated using mouse fibroblasts (L929 cells) and human umbilical vein endothelial cells (HUVECs). Finally, diabetic wound models were constructed in rats to evaluate the effects of hydrogels on wound healing. Results: The results show that the hydrogels are injectable and have self-healing properties. Moreover, borate ester bonds are formed in the hydrogels, which are responsive to H2O2 and glucose and can eliminate them. At the same time, zinc ions were released, giving the hydrogels good antibacterial efficacy, with antibacterial rates of 99.7% and 99.9% against S. aureus and E. coli, respectively. Furthermore, the hydrogels demonstrated good cell compatibility with L929 cells and HUVECs and increased the gene expression of VEGF, COL I, and COL III because of the addition of zinc ions. Based on the ROS, glucose scavenging capacity, and biological functions of zinc ions, the hydrogels advanced the recovery of S. aureus-contaminated whole skin wounds in diabetic rats. Conclusions: This study provides a novel treatment strategy for diabetic wound healing by constructing Zn ion-incorporated injected hydrogels with reactive oxygen species and glucose-scavenging capacity.