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MATERIALS & DESIGN · 2025 · IF 7.9

NELL-1-loaded GelMA-fibrinogen crosslinked hydrogel maintains periosteum stability to promote stem cell enrichment and osteogenesis

Jingxia Chen,Jing Xu,Huixin Lv,Jiaxin Luo,Zhen Ci,Yangfan Pei,Yihan Wang,Xiuyu Liu,Sicong Ren,Sheng Chen,Siyu Chen,Ting Zhu,Jingjie Zhai,Yanmin Zhou

Jawbone defects pose significant challenges for oral implantation and restoration. Guided bone regeneration is the most common strategy for bone augmentation. However, inadequate efficiency of osteogenesis remains a persistent issue. Periosteum serves as a potential source of osteogenesis, but insufficient mesenchymal stem cells (MSCs) in periosteum often exist due to the lack of initial bone support. Inadequate blood supply near the submembranous osteogenic region also impedes the osteogenesis process. This paper proposes a dual cross-linked natural protein-derived hydrogel, GelMA-fibrinogen/NELL-1(GFN), which optimizes both physical and biological factors to stabilize the elevated maxillary sinus membrane (MSM) (an anatomical structure involved in osteogenesis in maxillary posterior dental region, resembling periosteum) and support the osteogenic space. The results showed stem cells derived from the membrane could migrate to GFN and exhibit robust proliferation capability. Under osteogenic induction, the adequately expanded MSM-derived MSCs enhanced osteogenic differentiation under the synergetic guidance of fibrinogen and Nell-1 through TGF-β/HIF-1α/β-catenin signaling pathway. In vivo experiments showed that GFN could promote bone formation with double-layered cortical bone structures in maxillary sinus region, which provides a new direction for construction of bone grafting materials.

CAS / MDL: 85073-19-4 96-33-3
研究领域: 生物材料 · 组织工程 · 再生医学 · 口腔种植学 · 干细胞生物学
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BIOMACROMOLECULES · 2025 · IF 5.4

Silk Fibroin Hydrospongel with Interconnected Porosity and Robust Adhesion for Rapid Hemostasis and Scarless Repair

Yajing Liu,Bo Zou,Zhenhao Teng,Litao Wang,Ning Zhang,Na Zhao,Xiaofeng Wang,Qian Li,Xiaomeng Li

Rapid hemorrhage control and effective tissue regeneration are essential for improving outcomes in trauma and surgical wound management. Adhesive hydrogels adapt to irregular wounds but lack sufficient interconnected macroporosity for effective cell infiltration and tissue remodeling. Herein, a macroporous silk fibroin methacryloyl (SilMA) hydrospongel was developed via a simple foaming strategy. The foamed hydrospongel exhibits gel-like behavior before cross-linking and can be further stabilized through in situ photo-cross-linking. The SilMA hydrospongel achieves rapid hemostasis by absorbing blood and enhancing platelet aggregation and clot formation. Beyond hemostatic performance, its interconnected porous structure facilitates cellular infiltration and supports tissue integration, while its conformability and adhesion ensure seamless conformity to irregular wounds. Furthermore, the hydrospongel reduces fibrosis and scar formation in cutaneous and cardiac wounds by modulating the immune microenvironment. Collectively, this study demonstrates the translational potential of the hydrospongel as a multifunctional system for hemostasis, tissue regeneration, and drug delivery.

研究领域: 生物医学工程 · 组织工程 · 伤口护理 · 生物材料 · 再生医学
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Applied Materials Today · 2025 · IF 6.9

Trehalose-toughened transparent hydrogel with fast-healing and anti-freezing capability for precision human motion detection

Qianwen Zhang,Weiqing Zheng,Lingqin Cai,Jia Wan,Yongzhi Liang

Conductive hydrogels have garnered extensive attention in flexible sensing technologies due to their unique combination of mechanical compliance and electrical conductivity. However, conventional systems face a critical limitation that the inability to synergistically integrate optical transparency, balanced mechanical/electrical properties, fast self-recovery, and anti-freezing property, thereby constraining their advanced applications. This study explores a facile “one-step” strategy to engineer a poly (acrylic acid)-Zr 4+ /trehalose hydrogel, where biologically derived trehalose serves dual roles as both a cryoprotectant (enabling -45 °C operability) and mechanical toughener. The Zr 4+ -enabled ionic coordination network simultaneously establishes a stiff structured matrix, yielding multifunctionality such as high transparency (up to 92 %), robust mechanical performance (2.86 MPa tensile strength, 1542 % strain, 11.2 MJ/m 3 toughness), high ionic conductivity (32.1 mS/cm), and rapid autonomous recovery (99.6 % efficiency within 10 min). Notably, we developed an innovative ultrafast healing mechanism achieving 79.2 % healing efficiency in just 1 min, overcoming the time-dependent limitations of conventional dynamic networks, ensuring durability under cyclic mechanical stress. This systemic integration of previously incompatible properties positions the hydrogel as a candidate for multifunctional flexible sensors, particularly in extreme environments where traditional systems fail. Its high ionic conductivity and subzero resilience enable reliable sensing in extreme environments, while sensitive strain/pressure detection ensures precise monitoring of subtle motions. The synergy between anti-freezing capability of trehalose and dynamic network of zirconium addresses critical challenges in wearable sensors, combining durability, environmental adaptability, and signal fidelity.

研究领域: 生物材料 · 柔性电子 · 生物医学工程 · 可穿戴传感器 · 高分子化学 · 力学-电学耦合材料
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Journal of Materials Chemistry B · 2025 · IF 5.7

Sustained copper-releasing adhesive hydrogel patch promotes optimized scarless tongue wound healing via antioxidative, angiogenic and antifibrotic synergy

Yutang Ding,Kun Tang,Yuheng Zhang,Linxin Yang,Binjing Zhang,Xin Zhang,Jian Wang

Tongue injuries are among the most common acute soft tissue injuries encountered in oral clinical practice. Suturing, as the conventional treatment, often leads to tissue distortion and tension-induced collagen over-deposition, resulting in scarring and restricted tongue mobility. Sutures are also prone to microbial accumulation and provoke inflammation as foreign bodies. In this study, a hydrogel patch specifically designed for the tongue’s moist, frequently moving, and richly vascularized environment was developed for better healing of tongue injuries. Briefly, a chitosan-polyacrylic acid-tannic acid hydrogel matrix is loaded with Cu-MOF to form the CPTCu hydrogel, ensuring stable binding and controlled release of copper, while maintaining mechanical compliance with tongue tissue for continuous protection. The CPTCu hydrogel exhibited excellent biocompatibility, achieving free radical scavenging rate of 73.6% and bactericidal rate of over 99.5%. Compared with suturing, CPTCu hydrogel significantly reduced collagen volume by 35.9% and enhanced angiogenesis by 103.2%, as well as effectively promoted regeneration of local muscle fibers in a rat tongue wound model. These results demonstrate that CPTCu hydrogel is a promising candidate for optimized scarless tongue healing.

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ACS Applied Materials & Interfaces · 2026 · IF 7.8

Multifunctional ZIF-91-Based GelMA Hydrogel Microneedles Patch with Antibacterial and Anti-Inflammatory Effects for Diabetic Wound Healing

Meng Yuan,Rui Yin,Kun Liu,Tao Jiang,Xiaofan Yang,Xiang Xu,Pengjuan Nie,Shuoyuan Liu,Honglian Dai,Zhenbing Chen

Diabetic wound healing is a global biomedical challenge. Bacterial infection and microenvironmental modulation are major factors in the refractory healing of diabetic wounds. Conventional therapeutic approaches are often hindered by limitations, such as inadequate drug penetration, the rise of antimicrobial resistance, and restricted depth of drug delivery. Nanomedicine is emerging as a prospective drug delivery and anti-infective therapeutic approach in the field of wound management. Herein, all-trans retinoic acid (ATRA) was loaded into a zeolite imidazolate framework-91 salt+ (ZIF-91 salt+). A gelatin methacryloyl (GelMA) hydrogel microneedles (MNs) patch based on this multifunctional ZIFs (denoted as GelMA-ZIF-91 salt+@ATRA MNs patch) was developed, which makes transdermal drug delivery and combinatory treatment for diabetic wound healing feasible. Significantly, ATRA-containing ZIF-91 salt+ provides nanocomposites with anti-inflammatory activity through their modulation of macrophage polarization. Crucially, the prepared ZIF-91 salt+ showed efficient antibacterial activity against Staphylococcus aureus and Escherichia coli in vitro. Therapeutic effects of the GelMA-ZIF-91 salt+@ATRA MNs patch were verified in a diabetic mouse model with full-thickness cutaneous wounds. A unique MNs patch with antimicrobial, angiogenesis-inducing, and anti-inflammatory properties was designed in accordance with the physiological characteristics of wounds. Collectively, the designed MNs patch based on this multifunctional ZIF-91 salt+ provides new insights into diabetic wound therapy.

CAS / MDL: 760-93-0 85073-19-4
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2026 · IF 8.7

Double network crosslinked antibacterial and antioxidant cellulose-based hydrogel capable of healing wound for protecting open abdomen

Qingchuan Li,Sicheng Li,Ze Li,Weizhen Li,Guiwen Qu,Kang Chen,Luqiao Huang,Rui Ma,Liting Deng,Shuanghong Yang,Yitian Teng,Jinjian Huang,Xiuwen Wu,Yinghai Xie

Open abdomen (OA) is a life-saving surgical intervention commonly performed in patients with severe pancreatitis, intra-abdominal infection, or major trauma. However, abdominal exposure after OA inevitably leads to continuous fluid and heat loss, making temporary abdominal closure (TAC) indispensable in these cases. Conventional materials, such as polypropylene (PP) mesh, can prevent abdominal wall retraction. However, they may cause intestinal abrasions, which can lead to enteroatmospheric fistulas. Thus, the development of wound dressings that combine structural support and bioactivity is highly important. In this study, we developed a multifunctional composite hydrogel by combining gelatin methacryloyl (GelMA) with TEMPO-oxidized cellulose nanofibers (TC) and further crosslinking with zinc ions (Zn 2+ ) coordination to form Zn-TC-GelMA (Zn-TCG). The Zn-TCG hydrogel exhibited tunable mechanical properties, excellent injectability, and sustained Zn 2+ release. It exhibited good hemocompatibility, suppressed reactive oxygen species (ROS) accumulation, and inhibited bacterial proliferation. In vitro, Zn-TCG significantly enhanced fibroblast migration and HUVEC tube formation. In vivo, it markedly accelerated re-epithelization, collagen deposition, and angiogenesis compared to the control treated with GelMA and PP mesh. Mechanistic studies confirmed the activation of the MAPK/ERK signaling pathway and upregulation of epidermal differentiation markers (Krt10, Loricrin, and Tgm1). RNA-seq further revealed enrichment in keratinization and immune-related pathways. In conclusion, the Zn-TCG hydrogel represents a promising strategy for temporary abdominal closure and wound management.

CAS / MDL: 85073-19-4
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CHEMICAL ENGINEERING JOURNAL · 2026 · IF 12.5

A morphology-adaptive in situ assembled microporous annealed particle scaffold for localized exosome delivery in spinal cord injury therapy

Bo Li,Kaixuan Ma,Tao Yuan,Haoran Wu,Yiming Huo,Haojue Wang,Xiao Xu,Yang Liu,Lei Yang,Kai Chen

Repairing spinal cord injury (SCI) remains hindered by two major unmet challenges: the inability to precisely reconstruct irregular lesion cavities, where tissue contraction and collapse disrupt anatomical continuity, and the lack of effective platforms for stable and localized delivery of fragile therapeutics such as exosomes, whose rapid clearance severely limits efficacy. Addressing these bottlenecks requires biomaterials that can simultaneously rebuild three-dimensional structure and orchestrate a pro-regenerative microenvironment. Here, we present a morphology-adaptive injectable microporous annealed particle scaffold (MS) for localized and long-term release of human umbilical cord MSC-derived exosomes (hucMSC-Exo). GelMA/SFMA microspheres were fabricated via solvent-free microfluidic electrospraying combined with liquid nitrogen-assisted cryo-processing, preserving exosome bioactivity. This “disassemble-and-reassemble” approach enables minimally invasive injection of microspheres into irregular lesion cavities, followed by body temperature-induced annealing and in situ photocuring to form a mechanically stable, interconnected three-dimensional scaffold, which supports cell infiltration, nutrient diffusion, and sustained exosome release. In vivo , MS@Exo suppressed inflammation and scar formation, enhanced angiogenesis, and promoted neuronal survival, axonal regeneration, and myelination, ultimately achieving superior functional recovery over MS or Exo alone, demonstrating a clear synergistic effect. Transcriptomic profiling further revealed that MS@Exo reprogrammed gene expression by downregulating extracellular matrix- and collagen-related pathways while upregulating neuronal, synaptic, and ion channel signaling networks, thereby shifting the repair process from an inflammatory-proliferative phase toward a differentiation-remodeling phase. Collectively, MS@Exo acts as an intelligent multifunctional scaffold that couples advanced fabrication with exosome-based therapy to overcome fundamental limitations in SCI repair, offering a broadly applicable strategy for reconstructing irregular tissue defects in regenerative medicine.

CAS / MDL: 85073-19-4 9000-70-8
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BIOMATERIALS · 2026 · IF 13.6

Engineered exosomes mediated siNox4 delivery loaded polyzwitterionic hydrogel with electrophysiologic conductivity for synergistic treatment of spinal cord injury via suppressing neuronal ferroptosis.

Chenyu Wu,Yueman Tang,Zhichen Jiang,Chenglong Hong,Qi Yang,Zhouwei Wu,Jiangwei Zhu,Kaijie Guo,Jiang Liu,Si Yu Zheng,Lei Guo,Hui Xu,Wenfei Ni,Xiangyang Wang,Sunren Sheng,Jian Xiao,Chenggui Wang

CAS / MDL: 110-26-9 85073-19-4
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Small · 2026 · IF 11.8

Multidimensional Oriented Piezoelectric Conduits for Peripheral Nerve Defect Regeneration

Tong Qi,Xiao Wang,Lina Wu,Min Han,Changchun Zhou,Bo Wu,Xuan Pei,Chengqi He

Peripheral nerve regeneration and functional recovery hold immense clinical significance, as they are critical for reinnervating the motor and sensory functions of organs. In this study, piezoelectric nerve guidance conduits (NGCs) with multidimensional oriented structures and zinc oxide (ZnO) nanoparticles were developed for this purpose, fabricated via a combination of digital light processing (DLP) 3D printing and directional freezing technologies. The therapeutic efficacy of the NGCs was evaluated in a rat model of sciatic nerve defect, with continuous monitoring of neuromorphological and functional recovery metrics. Results indicated that the oriented structure of the NGCs and the piezoelectrically generated electric field significantly promoted both morphological regeneration and functional restoration of peripheral nerves, achieving repair effects comparable to the gold-standard autologous nerve transplantation. This work presents a promising strategy for the clinical treatment of peripheral nerve defects.

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Biomaterials Science · 2026 · IF 5.7

ROS-Responsive Antioxidant Hydrogel with Immunomodulatory Activity for Promoting Diabetic Wound Healing

Yurao Liu,Qianqian Yang,Ling Zhang,Qiyue Lu,Yuhang Li,Haisong Zhang,Chunfang Zhang,Pingli Wu

The accumulation of reactive oxygen species (ROS) in the microenvironment of diabetic wounds can trigger oxidative stress and hinder wound healing. This study developed a novel ROS-responsive antioxidant hydrogel relying on boronated ester bond. GMOP/TA hydrogel is constructed using methacrylic acid modified gelatin (GelMA) and phenylboronic acid modified oxidized hyaluronic acid (OHA-PBA) as the crosslinking framework, with tannic acid (TA) loaded as the active antioxidant component. GelMA and OHA-PBA crosslink through covalent bond and Schiff base, and the reversible properties of their imine and boronate ester groups enables responsive TA release under high ROS conditions. GMOP/TA hydrogel exhibits suitale mechanical properties, excellent biocompatibity and ROS-responsive antioxidant capabilities. In vivo evaluation results show that this hydrogel can effectively alleviates oxidative stress, accelerating cell migration, proliferation, and angiogenesis. Transcriptome sequencing analysis further revealed that its pro-healing effects is mechanistically associated with key signaling pathways, especially through PI3K-AKT, PPAR signaling pathway to facilitate cell proliferation and suppress inflammation. Overall, the hydrogel provides a straightforward but effective platform for chronic diabetic wound healing.

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Advanced Healthcare Materials · 2026 · IF 9.6

Engineered 3D Printing Bilayer Scaffold with Spatiotemporal Release of Drug for Synergistic Osteochondral Regeneration

Xueling Yin,Wanting Xia,Meng Zhang,Xiaoyu Yang,Wei Yu,Huimin Fan,Xiaona Wu,Ruikai Zhu,Ye Ren,Zhihong Zhu

Osteoarthritis (OA) is characterized by the disruption of chondro-bone homeostasis, where progressive cartilage degeneration and aberrant bone remodeling exacerbate joint dysfunction. Restoring this imbalance remains a critical challenge in OA treatment. Here, a 3D-printed bilayer scaffold with spatiotemporal release is presented, which integrates an alendronate sodium-triphenylphosphine (ALN-TPP)-loaded polyacrylic acid/methacrylated flaxseed gum (PAA/FGMA) cartilage layer and an ALN-TPP-loaded PAA/vinyl-modified montmorillonite (vinyl-MMT) bone layer. Specifically, FGMA establishes a biomimetic microenvironment that supports the migration and proliferation of chondrocytes. vinyl-MMT improves the mechanical strength of the scaffold, providing structural support for bone regeneration. Crucially, the differential degradation kinetics of the scaffolds orchestrate a temporal release of the ALN-TPP. The faster-degrading upper layer ensures rapid initial release of ALN-TPP, which specifically targets dysfunctional mitochondrial metabolism characteristic of OA, reduces oxidative stress, and inhibits the expression of matrix-degrading enzymes during the early critical phase. Simultaneously, the slower-degrading lower layer provides a sustained release profile. ALN-TPP promotes osteogenesis by stimulating osteoblast differentiation, which effectively reverses abnormal bone remodeling in osteoarthritis. In a rabbit model with osteochondral defects, the bilayer scaffold facilitates effective formation of hyaline-like cartilage and achieves subchondral bone reconstruction. This work establishes a multifunctional therapeutic platform that can advance the repair of osteochondral defects.

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Materials Today Bio · 2026 · IF 10.2

3D-Printed PRP-Infused Double-Network Hydrogels Orchestrate Inflammation Resolution and Vascular Regeneration in Infected Wounds

Danlei Xing,Zhiyuan Hu,Yue Tao,Hang Xia,Juanjuan Li,Guoqing Xia,Le Qiu,Jie Shan,Xiaojun Zha,Xu-Lin Chen

Bacterial infection and excessive inflammation critically impede wound healing, necessitating the development of multifunctional bioactive materials. Herein, we report a biodegradable composite hydrogel (PPG) fabricated via projection-based 3D biophotocuring, comprising an interpenetrating double-network of gelatin methacryloyl (GelMA) and poly-L-lysine methacryloyl (PLMA), embedded with platelet-rich plasma (PRP). The resulting hydrogel exhibits potent antibacterial activity and robust inhibition of biofilm formation, alongside integrated anti-inflammatory and pro-angiogenic functions. In vitro, incorporating PRP promotes the migratory and proliferative activity of human skin fibroblasts and facilitated macrophage polarization toward the M2 phenotype. In vivo , PPG accelerates wound closure in bacteria-infected models by facilitating re-epithelialization, collagen remodeling, and neovascularization, as evidenced by sustained α-SMA and elevated CD31 expression. Mechanistically, PPG activates the PI3K/AKT/eNOS signaling axis, further supporting angiogenesis and extracellular matrix deposition. RNA-seq validation showed that PPG upregulated DEFB4 and SPRR2F, promoting wound healing and modulating inflammation. Collectively, this work presents a 3D-printed, bioactive hydrogel platform with synchronized antibacterial, immunomodulatory, and pro-regenerative properties, offering strong translational potential for treating infected wounds.

CAS / MDL: 85073-19-4
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