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Endometriosis is a prevalent gynecological condition characterized by chronic pelvic pain, dysmenorrhea, and infertility, affecting ≈176 million women of reproductive age worldwide. Current treatments, including pharmacological and surgical interventions, are often associated with significant side effects and high recurrence rates. Consequently, there is an urgent need for innovative and safer therapeutic approaches. In this study, an injectable magnetic hydrogel nanosystem is developed designed for the dual‐purpose magnetothermal and anti‐inflammatory treatment of endometriosis. This hydrogel incorporates Fe3O4 nanoparticles alongside an anti‐inflammatory peptide. Upon magnetic activation, the Fe3O4 nanoparticles induce a localized hyperthermic response, raising the temperature of endometriotic lesions to 63.3 °C, effectively destroying endometriotic cells. Concurrently, the thermally responsive hydrogel facilitates the controlled release of the anti‐inflammatory peptide, thus modulating the inflammatory milieu. The biocompatibility and complete in vivo degradability of the hydrogel further enhance its therapeutic potential. The in vivo studies demonstrated that this injectable magnetic hydrogel system achieved a 90% reduction in the volume of endometriotic lesions and significantly decreased inflammatory markers, offering a promising non‐invasive treatment modality for endometriosis. By integrating precise lesion ablation with the modulation of the inflammatory microenvironment, this system represents a novel approach to the clinical management of endometriosis. [ABSTRACT FROM AUTHOR]

Surgical resection remains the mainstream treatment for malignant melanoma. However, challenges in wound healing and residual tumor metastasis pose significant hurdles, resulting in high recurrence rates in patients. Herein, a bioactive injectable hydrogel (BG‐Mngel) formed by crosslinking sodium alginate (SA) with manganese‐doped bioactive glass (BG‐Mn) is developed as a versatile platform for anti‐tumor immunotherapy and postoperative wound healing for melanoma. The incorporation of Mn2+ within bioactive glass (BG) can activate the cGAS‐STING immune pathway to elicit robust immune response for cancer immunotherapy. Furthermore, doping Mn2+ in BG endows system with excellent photothermal properties, hence facilitating STING activation and reversing the tumor immune‐suppressive microenvironment. BG exhibits favorable angiogenic capacity and tissue regenerative potential, and Mn2+ promotes cell migration in vitro. When combining BG‐Mngel with anti‐PD‐1 antibody (α‐PD‐1) for the treatment of malignant melanoma, it shows enhanced anti‐tumor immune response and long‐term immune memory response. Remarkably, BG‐Mngel can upregulate the expression of genes related to blood vessel formation and promote skin tissue regeneration when treating full‐thickness wounds. Overall, BG‐MnGel serves as an effective adjuvant therapy to regulate tumor metastasis and wound healing for malignant melanoma. [ABSTRACT FROM AUTHOR]

Abstract Endometriosis is a prevalent gynecological condition characterized by chronic pelvic pain, dysmenorrhea, and infertility, affecting ≈176 million women of reproductive age worldwide. Current treatments, including pharmacological and surgical interventions, are often associated with significant side effects and high recurrence rates. Consequently, there is an urgent need for innovative and safer therapeutic approaches. In this study, an injectable magnetic hydrogel nanosystem is developed designed for the dual‐purpose magnetothermal and anti‐inflammatory treatment of endometriosis. This hydrogel incorporates Fe3O4 nanoparticles alongside an anti‐inflammatory peptide. Upon magnetic activation, the Fe3O4 nanoparticles induce a localized hyperthermic response, raising the temperature of endometriotic lesions to 63.3 °C, effectively destroying endometriotic cells. Concurrently, the thermally responsive hydrogel facilitates the controlled release of the anti‐inflammatory peptide, thus modulating the inflammatory milieu. The biocompatibility and complete in vivo degradability of the hydrogel further enhance its therapeutic potential. The in vivo studies demonstrated that this injectable magnetic hydrogel system achieved a 90% reduction in the volume of endometriotic lesions and significantly decreased inflammatory markers, offering a promising non‐invasive treatment modality for endometriosis. By integrating precise lesion ablation with the modulation of the inflammatory microenvironment, this system represents a novel approach to the clinical management of endometriosis.

The microvascular network plays an important role in providing nutrients to the injured tissue and exchanging various metabolites. However, how to achieve efficient penetration of the injured tissue is an important bottleneck restricting the reconstruction of microvascular network. Herein, the hydrogel precursor solution can efficiently penetrate the damaged tissue area, and ultrasound triggers the release of thrombin from liposomes in the solution to hydrolyze fibrinogen, forming a fibrin solid hydrogel network in situ with calcium ions and transglutaminase as catalysts, effectively solving the penetration impedance bottleneck of damaged tissues and ultimately significantly promoting the formation of microvascular networks within tissues. First, the fibrinogen complex solution is effectively permeated into the injured tissue. Second, ultrasound triggered the release of calcium ions and thrombin, activates transglutaminase, and hydrolyzes fibrinogen. Third, fibrin monomers are catalyzed to form fibrin hydrogels in situ in the damaged tissue area. In vitro studies have shown that the fibrinogen complex solution effectively penetrated the artificial bone tissue within 15 s after ultrasonic triggering, and formed a hydrogel after continuous triggering for 30 s. Overall, this innovative strategy effectively solved the problem of penetration resistance of ultrasound‐triggered hydrogels in the injured tissues, and finally activates in situ microvascular networks regeneration. [ABSTRACT FROM AUTHOR]

An ideal hydrogel for stem cell therapy would be injectable and efficiently promote stem cell proliferation and differentiation in body. Herein, an injectable, single‐component hydrogel with hyaluronic acid (HA) modified with phenylboronic acid (PBA) and spermidine (SM) is introduced. The resulting HAps (HA‐PBA‐SM) hydrogel is based on the reversible crosslinking between the diol and the ionized PBA, which is stabilized by the SM. It has a shear‐thinning property, enabling its injection through a syringe to form a stable hydrogel inside the body. In addition, HAps hydrogel undergoes a post‐injection "self‐curing," which stiffens the hydrogel over time. This property allows the HAps hydrogel to meet the physical requirements for stem cell therapy in rigid tissues, such as bone, while maintaining injectability. The hydrogel enabled favorable proliferation of human mesenchymal stem cells (hMSCs) and promoted their differentiation and mineralization. After the injection of hMSCs‐containing HAps into a rat femoral defect model, efficient osteogenic differentiation of hMSCs and bone regeneration is observed. The study demonstrates that simple cationic modification of PBA‐based hydrogel enabled efficient gelation with shear‐thinning and self‐curing properties, and it would be highly useful for stem cell therapy and in vivo bone regeneration. [ABSTRACT FROM AUTHOR]

Abstract Surgical resection remains the mainstream treatment for malignant melanoma. However, challenges in wound healing and residual tumor metastasis pose significant hurdles, resulting in high recurrence rates in patients. Herein, a bioactive injectable hydrogel (BG‐Mngel) formed by crosslinking sodium alginate (SA) with manganese‐doped bioactive glass (BG‐Mn) is developed as a versatile platform for anti‐tumor immunotherapy and postoperative wound healing for melanoma. The incorporation of Mn2+ within bioactive glass (BG) can activate the cGAS‐STING immune pathway to elicit robust immune response for cancer immunotherapy. Furthermore, doping Mn2+ in BG endows system with excellent photothermal properties, hence facilitating STING activation and reversing the tumor immune‐suppressive microenvironment. BG exhibits favorable angiogenic capacity and tissue regenerative potential, and Mn2+ promotes cell migration in vitro. When combining BG‐Mngel with anti‐PD‐1 antibody (α‐PD‐1) for the treatment of malignant melanoma, it shows enhanced anti‐tumor immune response and long‐term immune memory response. Remarkably, BG‐Mngel can upregulate the expression of genes related to blood vessel formation and promote skin tissue regeneration when treating full‐thickness wounds. Overall, BG‐MnGel serves as an effective adjuvant therapy to regulate tumor metastasis and wound healing for malignant melanoma.

Reactive oxygen species (ROS) have been recognized as prevalent contributors to the development of inner retinal injuries including optic neuropathies such as glaucoma, non‐arteritic anterior ischemic optic neuropathy, traumatic optic neuropathy, and Leber hereditary optic neuropathy, among others. This underscores the pivotal significance of oxidative stress in the damage inflicted upon retinal tissue. To combat ROS‐related challenges, this study focuses on creating an injectable and tissue‐adhesive hydrogel with tailored antioxidant properties for retinal applications. GelCA, a gelatin‐modified hydrogel with photo‐crosslinkable and injectable properties, is developed. To enhance its antioxidant capabilities, curcumin‐loaded polydopamine nanoparticles (Cur@PDA NPs) are incorporated into the GelCA matrix, resulting in a multifunctional nanocomposite hydrogel referred to as Cur@PDA@GelCA. This hydrogel exhibits excellent biocompatibility in both in vitro and in vivo assessments, along with enhanced tissue adhesion facilitated by NPs in an in vivo model. Importantly, Cur@PDA@GelCA demonstrates the potential to mitigate oxidative stress when administered via intravitreal injection in retinal injury models such as the optic nerve crush model. These findings underscore its promise in advancing retinal tissue engineering and providing an innovative strategy for acute neuroprotection in the context of inner retinal injuries. [ABSTRACT FROM AUTHOR]

Treating the most widespread complication of diabetes: diabetic wounds poses a significant clinical obstacle due to the intricate nature of wound healing in individuals with diabetes. Here a novel approach is proposed using easily applicable injectable gelatin/metal/tea polyphenol double nanonetworks, which effectively remodel the wound microenvironment and accelerates the healing process. The gelatin(Gel) crosslink with metal ions (Zr4+) through the amino acids, imparting advantageous mechanical properties like self‐healing, injectability, and adhesion. The nanonetwork's biological functions are further enhanced by incorporating the tea polyphenol metal nanonetwork through in situ doping of the epigallocatechin gallate (EGCG) with great antibacterial, self‐healing, antioxidant, and anticancer capabilities. The in vitro and in vivo tests show that this double nanonetworks hydrogel exhibits faster cell migration and favorable anti‐inflammatory and antioxidant properties and can greatly reshape the microenvironment of diabetic wounds and accelerate the wound healing rate. In addition, this hydrogel is completely degraded after subcutaneous injection for 7 days, with nondetectable cytotoxicity in H&E staining of major mice organs and the serum level of liver function indicators. Considering the above‐mentioned merits of this hydrogel, it is believed that the injectable gelatin/metal/tea polyphenol double nanonetworks have broad biomedical potential, especially in diabetic wound repair and tissue engineering. [ABSTRACT FROM AUTHOR]

Abstract The microvascular network plays an important role in providing nutrients to the injured tissue and exchanging various metabolites. However, how to achieve efficient penetration of the injured tissue is an important bottleneck restricting the reconstruction of microvascular network. Herein, the hydrogel precursor solution can efficiently penetrate the damaged tissue area, and ultrasound triggers the release of thrombin from liposomes in the solution to hydrolyze fibrinogen, forming a fibrin solid hydrogel network in situ with calcium ions and transglutaminase as catalysts, effectively solving the penetration impedance bottleneck of damaged tissues and ultimately significantly promoting the formation of microvascular networks within tissues. First, the fibrinogen complex solution is effectively permeated into the injured tissue. Second, ultrasound triggered the release of calcium ions and thrombin, activates transglutaminase, and hydrolyzes fibrinogen. Third, fibrin monomers are catalyzed to form fibrin hydrogels in situ in the damaged tissue area. In vitro studies have shown that the fibrinogen complex solution effectively penetrated the artificial bone tissue within 15 s after ultrasonic triggering, and formed a hydrogel after continuous triggering for 30 s. Overall, this innovative strategy effectively solved the problem of penetration resistance of ultrasound‐triggered hydrogels in the injured tissues, and finally activates in situ microvascular networks regeneration.

Abstract An ideal hydrogel for stem cell therapy would be injectable and efficiently promote stem cell proliferation and differentiation in body. Herein, an injectable, single‐component hydrogel with hyaluronic acid (HA) modified with phenylboronic acid (PBA) and spermidine (SM) is introduced. The resulting HAps (HA‐PBA‐SM) hydrogel is based on the reversible crosslinking between the diol and the ionized PBA, which is stabilized by the SM. It has a shear‐thinning property, enabling its injection through a syringe to form a stable hydrogel inside the body. In addition, HAps hydrogel undergoes a post‐injection “self‐curing,” which stiffens the hydrogel over time. This property allows the HAps hydrogel to meet the physical requirements for stem cell therapy in rigid tissues, such as bone, while maintaining injectability. The hydrogel enabled favorable proliferation of human mesenchymal stem cells (hMSCs) and promoted their differentiation and mineralization. After the injection of hMSCs‐containing HAps into a rat femoral defect model, efficient osteogenic differentiation of hMSCs and bone regeneration is observed. The study demonstrates that simple cationic modification of PBA‐based hydrogel enabled efficient gelation with shear‐thinning and self‐curing properties, and it would be highly useful for stem cell therapy and in vivo bone regeneration.

Abstract Reactive oxygen species (ROS) have been recognized as prevalent contributors to the development of inner retinal injuries including optic neuropathies such as glaucoma, non‐arteritic anterior ischemic optic neuropathy, traumatic optic neuropathy, and Leber hereditary optic neuropathy, among others. This underscores the pivotal significance of oxidative stress in the damage inflicted upon retinal tissue. To combat ROS‐related challenges, this study focuses on creating an injectable and tissue‐adhesive hydrogel with tailored antioxidant properties for retinal applications. GelCA, a gelatin‐modified hydrogel with photo‐crosslinkable and injectable properties, is developed. To enhance its antioxidant capabilities, curcumin‐loaded polydopamine nanoparticles (Cur@PDA NPs) are incorporated into the GelCA matrix, resulting in a multifunctional nanocomposite hydrogel referred to as Cur@PDA@GelCA. This hydrogel exhibits excellent biocompatibility in both in vitro and in vivo assessments, along with enhanced tissue adhesion facilitated by NPs in an in vivo model. Importantly, Cur@PDA@GelCA demonstrates the potential to mitigate oxidative stress when administered via intravitreal injection in retinal injury models such as the optic nerve crush model. These findings underscore its promise in advancing retinal tissue engineering and providing an innovative strategy for acute neuroprotection in the context of inner retinal injuries.

Abstract Treating the most widespread complication of diabetes: diabetic wounds poses a significant clinical obstacle due to the intricate nature of wound healing in individuals with diabetes. Here a novel approach is proposed using easily applicable injectable gelatin/metal/tea polyphenol double nanonetworks, which effectively remodel the wound microenvironment and accelerates the healing process. The gelatin(Gel) crosslink with metal ions (Zr4+) through the amino acids, imparting advantageous mechanical properties like self‐healing, injectability, and adhesion. The nanonetwork's biological functions are further enhanced by incorporating the tea polyphenol metal nanonetwork through in situ doping of the epigallocatechin gallate (EGCG) with great antibacterial, self‐healing, antioxidant, and anticancer capabilities. The in vitro and in vivo tests show that this double nanonetworks hydrogel exhibits faster cell migration and favorable anti‐inflammatory and antioxidant properties and can greatly reshape the microenvironment of diabetic wounds and accelerate the wound healing rate. In addition, this hydrogel is completely degraded after subcutaneous injection for 7 days, with nondetectable cytotoxicity in H&E staining of major mice organs and the serum level of liver function indicators. Considering the above‐mentioned merits of this hydrogel, it is believed that the injectable gelatin/metal/tea polyphenol double nanonetworks have broad biomedical potential, especially in diabetic wound repair and tissue engineering.

Modulating the inflammatory microenvironment can inhibit the process of inflammatory diseases (IDs). A tri‐cross‐linked inflammatory microenvironment‐responsive hydrogel with ideal mechanical properties achieves triggerable and sustained drug delivery and regulates the inflammatory microenvironment. Here, this study develops an inflammatory microenvironment‐responsive hydrogel (OD‐PP@SeNPs) composed of phenylboronic acid grafted polylysine (PP), oxidized dextran (OD), and selenium nanoparticles (SeNPs). The introduction of SeNPs as initiators and nano‐fillers into the hydrogel results in extra cross‐linking of the polymer network through hydrogen bonding. Based on Schiff base bonds, Phenylboronate ester bonds, and hydrogen bonds, a reactive oxygen species (ROS)/pH dual responsive hydrogel with a triple‐network is achieved. The hydrogel has injectable, self‐healing, adhesion, outstanding flexibility, suitable swelling capacity, optimal biodegradability, excellent stimuli‐responsive active substance release performance, and prominent biocompatibility. Most importantly, the hydrogel with ROS scavenging and pH‐regulating ability protects cells from oxidative stress and induces macrophages into M2 polarization to reduce inflammatory cytokines through PI3K/AKT/NF‐κB and MAPK pathways, exerting anti‐inflammatory effects and reshaping the inflammatory microenvironment, thereby effectively treating typical IDs, including S. aureus infected wound and rheumatoid arthritis in rats. In conclusion, this dynamically responsive injectable hydrogel with a triple‐network structure provides an effective strategy to treat IDs, holding great promise in clinical application. [ABSTRACT FROM AUTHOR]

Abstract Modulating the inflammatory microenvironment can inhibit the process of inflammatory diseases (IDs). A tri‐cross‐linked inflammatory microenvironment‐responsive hydrogel with ideal mechanical properties achieves triggerable and sustained drug delivery and regulates the inflammatory microenvironment. Here, this study develops an inflammatory microenvironment‐responsive hydrogel (OD‐PP@SeNPs) composed of phenylboronic acid grafted polylysine (PP), oxidized dextran (OD), and selenium nanoparticles (SeNPs). The introduction of SeNPs as initiators and nano‐fillers into the hydrogel results in extra cross‐linking of the polymer network through hydrogen bonding. Based on Schiff base bonds, Phenylboronate ester bonds, and hydrogen bonds, a reactive oxygen species (ROS)/pH dual responsive hydrogel with a triple‐network is achieved. The hydrogel has injectable, self‐healing, adhesion, outstanding flexibility, suitable swelling capacity, optimal biodegradability, excellent stimuli‐responsive active substance release performance, and prominent biocompatibility. Most importantly, the hydrogel with ROS scavenging and pH‐regulating ability protects cells from oxidative stress and induces macrophages into M2 polarization to reduce inflammatory cytokines through PI3K/AKT/NF‐κB and MAPK pathways, exerting anti‐inflammatory effects and reshaping the inflammatory microenvironment, thereby effectively treating typical IDs, including S. aureus infected wound and rheumatoid arthritis in rats. In conclusion, this dynamically responsive injectable hydrogel with a triple‐network structure provides an effective strategy to treat IDs, holding great promise in clinical application.

Abstract Uveal melanoma (UM) is the most prevalent primary intraocular malignant tumor with a high lethal rate. Patients who undergo conventional enucleation treatments consistently suffer permanent blindness, facial defects, and mental disorders, therefore, novel therapeutic modalities are urgently required. Herein, an injectable and stimuli‐responsive drug delivery antibacterial hydrogel (CP@Au@DC_AC50) is constructed via a facile grinding method that is inspired by the preparation process of traditional Chinese medicine. The incorporation of gold nanorods can enhance the mechanical strength of the hydrogel and realize photothermal therapy (PTT) and thermosensitive gel‐sol transformation to release the gene‐targeted drug DC_AC50 on demand in response to low‐density near‐infrared (NIR) light. The orthotopic model of UM is built successfully and indicates the excellent efficiency of CP@Au@DC_AC50 in killing tumors without damage to normal tissue because of its synergistic mild temperature PTT and gene‐targeted therapy. Moreover, the eyeball infection model reveals the remarkable antibacterial properties of the hydrogel which can prevent endophthalmitis in the eyeball. There is negligible difference between the CP@Au@DC_AC50+NIR group and normal group. This NIR light‐triggered gene‐targeted therapy/PTT/antibacterial treatment pattern provides a promising strategy for building multifunctional therapeutic platform against intraocular tumors and exhibits great potential for the clinical treatment of UM.

Uveal melanoma (UM) is the most prevalent primary intraocular malignant tumor with a high lethal rate. Patients who undergo conventional enucleation treatments consistently suffer permanent blindness, facial defects, and mental disorders, therefore, novel therapeutic modalities are urgently required. Herein, an injectable and stimuli‐responsive drug delivery antibacterial hydrogel (CP@Au@DC_AC50) is constructed via a facile grinding method that is inspired by the preparation process of traditional Chinese medicine. The incorporation of gold nanorods can enhance the mechanical strength of the hydrogel and realize photothermal therapy (PTT) and thermosensitive gel‐sol transformation to release the gene‐targeted drug DC_AC50 on demand in response to low‐density near‐infrared (NIR) light. The orthotopic model of UM is built successfully and indicates the excellent efficiency of CP@Au@DC_AC50 in killing tumors without damage to normal tissue because of its synergistic mild temperature PTT and gene‐targeted therapy. Moreover, the eyeball infection model reveals the remarkable antibacterial properties of the hydrogel which can prevent endophthalmitis in the eyeball. There is negligible difference between the CP@Au@DC_AC50+NIR group and normal group. This NIR light‐triggered gene‐targeted therapy/PTT/antibacterial treatment pattern provides a promising strategy for building multifunctional therapeutic platform against intraocular tumors and exhibits great potential for the clinical treatment of UM. [ABSTRACT FROM AUTHOR]