JOURNAL OF APPLIED POLYMER SCIENCE
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2026
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IF 3.1
Bincan Deng,Dingding Chen,Fernando López Lasaosa,Caimiao Zheng,Yiyan He,Chen Xuan,Yuwen Cui
Reliable viscosity prediction of methacrylated hyaluronic acid (HAMA)/methacrylated gelatin (GelMA) hybrid hydrogels is essential for reproducible multi-batch biofabrication, yet batch effect can severely impair the cross-batch generalization of data-driven models. We established two experimentally measured HAMA/GelMA viscosity datasets collected at different time periods and covering different formulation ranges to characterize batch-effect-induced distributional shifts and support same-batch, cross-batch, and out-of-distribution (OOD) evaluation. Baseline machine learning (ML) models achieved high same-batch predictive performance ( R 2 > 0.90) but degraded markedly under cross-batch conditions ( R 2 = 0.265–0.772). To address these challenges, we propose a physics-informed correction strategy integrating data- and model-level physical priors. A physics-informed data preprocessing (PIDP) strategy filters samples that violate the rheological priors that viscosity increases monotonically with polymer concentration and decreases with temperature. PIDP increased cross-batch R 2 from 0.713 to 0.892 and reduced RMSE by up to 38.8%. A physics-informed neural network (PINN) further improved physical plausibility of the predictions. Integrating PIDP-PINN strategy (IPPS) achieved the best overall performance ( R 2 = 0.898) and reduced OOD errors by 37.7%. The strategy enables more robust and physically consistent hydrogel viscosity prediction for practical biofabrication, providing a transferable route toward reliable modeling and intelligent design of soft polymer materials under realistic experimental variability.
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Scientific Reports
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2025
·Vol. 15
·期 1
·1-20
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IF 3.9
Wu Honghan,Huang Jun,Wu Hengpeng,Xu Weikang,Zhong Qian,Song Jiaxiang,Linghu Xitao,Gao Botao,Wa Qingde
Autologous and allogeneic bone grafting is currently the clinical gold standard for the treatment of bone defects; however, it is limited by the scarcity of autologous sources and the risk of secondary trauma, as well as the complications of disease transmission and immune rejection associated with allogeneic grafts. The clinical management of bone defects remains a significant challenge. In this study, we prepared a demineralized bone matrix/gelatin methacrylate composite hydrogel loaded with deferoxamine (GelMA/DBM/DFO) using a freeze-drying method and investigated its properties. Assessments using CCK-8, live-dead fluorescence staining, alkaline phosphatase staining, and Alizarin Red staining indicated that the GelMA/DBM/DFO composite hydrogel demonstrated superior biocompatibility and in vitro osteogenic differentiation capacity compared with the GelMA/DBM composite hydrogel. We established a cranial defect model in Sprague–Dawley (SD) rats and examined peripheral blood indices, micro-computed tomography (Micro-CT), hematoxylin and eosin (HE) staining, Masson’s trichrome staining, and immunohistochemical staining for bone morphogenetic protein-2 (BMP-2) and collagen type I (COL-1). Both hydrogels exhibited good biosafety and the GelMA/DBM/DFO hydrogel showed more effective repair of cranial defects in SD rats. This study provides a novel material for bone-defect repair.
研究领域:
生物医学工程
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骨组织工程
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再生医学
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Journal of Materials Chemistry B
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2026
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IF 6.2
Lisha Jiang,Jiaqiao Liang,Tianyue Wu,Jianyang Shi,Chenggong Hu,Haibo Wang
Infected diabetic wounds, particularly those complicated by multidrug-resistant bacteria, pose a significant clinical challenge due to the limited efficacy of conventional debridement and antibiotic therapies. Photodynamic therapy (PDT) has emerged as a promising antimicrobial strategy.However, its therapeutic potential is severely hampered by the hypoxic microenvironment of diabetic wounds. This study aimed to develop a multifunctional nanozyme-integrated microneedle system (GM@MnFC) based on a "material design-delivery strategy-microenvironment modulation" therapeutic paradigm. MnFC nanoparticles were constructed through coordinationdriven self-assembly of Fmoc-L-leucine, Mn 2+ , and the photosensitizer chlorin e6. The incorporated Mn 2+ endowed the nanoparticles with intrinsic catalase-like activity. This enabled in situ oxygen generation from pathological hydrogen peroxide accumulated in diabetic wounds, thereby overcoming the oxygen dependency of PDT. Loading MnFC nanoparticles into dissolving gelatin methacryloyl microneedles achieved efficient deep tissue delivery to target bacteria residing in dermal layers. In vitro studies demonstrated that MnFC nanoparticles possessed excellent catalase-like activity and efficient singlet oxygen generation under 660-nm laser irradiation, exhibiting potent antibacterial efficacy against both Escherichia coli and methicillinresistant Staphylococcus aureus (MRSA). GM@MnFC microneedle treatment significantly accelerated wound closure, enhanced re-epithelialization and collagen deposition, and favorably regulated inflammatory cytokine expression in a diabetic mouse model of MRSA-infected wounds.Biosafety evaluations confirmed the excellent biocompatibility of this system. This study presents an innovative strategy exploiting pathological by-products of diabetic wounds to fuel antimicrobial therapy, thereby providing valuable insights for designing multifunctional nanomedicine platforms for chronic wound management.
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International Journal of Nanomedicine
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2023
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IF 8
Suyang Zheng,Dong Li,Qingbai Liu,Cheng Tang,Wenhao Hu,Shengshan Ma,Yan Xu,Yong Ma,Yang Guo,Bo Wei,Chuanlin Du,Liming Wang
Purpose This study aims to investigate the impact of enhancing subchondral bone repair on the efficacy of articular cartilage restoration, thereby achieving improved osteochondral regeneration outcomes.Methods In this study, we modified the surface of nano-hydroxyapatite (n-HAp) through alkylation reactions to prepare n-HApMA. Characterization techniques, including X-ray diffraction, infrared spectroscopy scanning, thermogravimetric analysis, particle size analysis, and electron microscopy, were employed to analyze n-HApMA. Bioinks were prepared using n-HApMA, high porosity GelMA hydrogel, and adipose tissue derived stromal cells (ADSCs). The rheological properties of the bioinks during photocuring were investigated using a rheometer. Based on these bioinks, a biphasic scaffold was constructed. The viability of cells within the scaffold was observed using live-dead cell staining, while the internal morphology was examined using scanning electron microscopy. The stiffness of the scaffold was evaluated through compression testing. Scaffolds were implanted into the osteochondral defects of New Zealand rabbit knees, and microCT was utilized to observe the subchondral bone repair. Hematoxylin and eosin (H&E) staining, Masson’s trichrome staining, and Safranin O/Fast Green staining were performed to assess the regeneration of subchondral bone and cartilage. Furthermore, immunohistochemical staining was employed to detect the expression of osteogenic and chondrogenic-related molecules.Results Scaffold characterization revealed that surface modification enables the uniform distribution of n-HApMA within the GelMA matrix. The incorporation of 5% n-HApMA notably enhanced the elastic modulus and stiffness of the 6% high-porosity GelMA in comparison to n-HAp. Moreover, in-vivo study showed that the homogeneous dispersion of n-HApMA on the GelMA matrix facilitated the osteogenic differentiation of adipose-derived stem cells (ADSCs) and promoted osteochondral tissue regeneration.Conclusion These findings suggest potential applications of the n-HApMA/GelMA composite in the field of tissue engineering and regenerative medicine.
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Advanced Healthcare Materials
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2023
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IF 10
Yu Qiu,Jun Tian,Siyi Kong,Yanping Feng,Yangyu Lu,Lefeng Su,Yanling Cai,Mengjie Li,Jiang Chang,Chen Yang,Xi Wei
Vital pulp therapy (VPT) is considered a conservative treatment for preserving pulp viability in caries-induced dental pulp infections. However, bacterial contamination negatively affects dentine-pulp complex repair. The common capping materials show limited antimicrobial effects against some microorganisms. To improve the VPT efficacy, capping materials with increased antibacterial properties and enhanced odontogenic and angiogenic activities are needed. Herein, a SrCuSi 4 O 10 /gelatin methacrylate(SC/Gel) composite hydrogel has been proposed for infected dental pulp treatment. SrCuSi 4 O 10 (SC) is a microscale bioceramic composed of assembled multilayered nanosheets that possesses good near-infrared photothermal conversion ability and multiple bioactivities due to sustained Sr 2+ , Cu 2+ , and SiO 3 2− ion release. It is shown that the SC/Gel composite hydrogel efficiently eliminates Streptococcus mutans and Lactobacillus casei and inhibits biofilm formation under photothermal heating, while the ion extract from SC promotes odontogenesis of rat dental pulp stem cells and angiogenesis of human umbilical vein endothelial cells. The as-designed therapeutic effect of SC/Gel composite hydrogel-mediated VPT has been proven in a rat dental pulp infection model and yielded improved dentine-pulp complex repair compared with the commercially used iRoot® BP Plus. This study suggests that the SC/Gel composite hydrogel is a potential pulp-capping material with improved effects on dentine−pulp complex repair in infected pulp.
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Small
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2022
·Vol. 18
·期 25
·2106357
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IF 15.153
Sili Yi,Qiong Liu,Zeyu Luo,Jacqueline Jialu He,Hui-Lin Ma,Wanlu Li,Di Wang,Cuiping Zhou,Carlos Ezio Garciamendez,Linxi Hou,Jin Zhang,Yu Shrike Zhang
It is well-known that tissue engineering scaffolds that feature highly interconnected and size-adjustable micropores are oftentimes desired to promote cellular viability, motility, and functions. Unfortunately, the ability of precise control over the microporous structures within bioinks in a cytocompatible manner for applications in 3D bioprinting is generally lacking, until a method of micropore-forming bioink based on gelatin methacryloyl (GelMA) was reported recently. This bioink took advantage of the unique aqueous two-phase emulsion (ATPE) system, where poly(ethylene oxide) (PEO) droplets are utilized as the porogen. Considering the limitations associated with this very initial demonstration, this article has furthered the understanding of the micropore-forming GelMA bioinks by conducting a systematic investigation into the additional GelMA types (porcine and fish, different methacryloyl-modification degrees) and porogen types (PEO, poly(vinyl alcohol), and dextran), as well as the effects of the porogen concentrations and molecular weights on the properties of the GelMA-based ATPE bioink system. This article exemplifies not only the significantly wider range of micropore sizes achievable and better emulsion stability, but also the improved suitability for both extrusion and digital light processing bioprinting with favorable cellular responses.
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Materials Science & Engineering C-Materials for Biological Applications
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2021
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IF 7.328
Zhenming Yang,Xuehong Ren,Yu Liu
Bacterial infections are the major challenges of wound treatment in current clinical applications. In this study, Three-dimensional (3D) antibacterial wound dressing has been fabricated via introducing N-halamine/TiO 2 to gelatin methacrylate and xanthan gum. The prepared 3D printed dressings showed ideal swelling ratio and excellent water uptake efficiency. TiO 2 nanoparticles were introduced by in-situ to improve the ultraviolet stability of N-halamines. The 3D printed GX2-TiO 2 -PSPH-Cl prepared dressings containing titanium dioxide retained 0.19% active chlorine after ultraviolet irradiation for 20 min, which was much higher than that of N-halamine dressings without the addition of TiO 2 . The 3D printed dressings showed good antibacterial activity, and 100% of Escherichia coli O157:H7 and Staphylococcus aureus were inactivated after 60 min of contact. Furthermore, the biofilm test indicated that the 3D antibacterial dressings were able to inhibit the formation of bacterial biofilm. The 3D printed dressings possess outstanding biocompatibility. Moreover, in vivo data demonstrated that the 3D printed dressings could significantly accelerate wound healing in a mouse model, indicating that the developed 3D printed dressings are ideal candidates for wound treatment.
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Advanced Healthcare Materials
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2024
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IF 10
Haonan Xiu,Kaili Yang,Li Dong,Haohua Lai,Zhangyu Zhu,Dongdong Jiang,Junwei Yan,Chen Shi,Shaowei Pan,Zhaowei Yin,Lihui Yuwen,Bin Liang
Managing fracture infections is a significant challenge in trauma orthopedics, given the limited self-healing capacity of fractures and the difficulty in eradicating infections. In this study, Cu 2 MoS 4 nanoparticles (CMSs) with are prepared enzyme-like activity and both pH and near-infrared (NIR) light responsiveness. These CMSs are combined with methacrylated gelatin (GelMA) to synthesize CMSs hydrogels (CMSs@Gel) with antimicrobial and bone tissue repair-promoting capabilities. In vitro and in vivo experiments, the CMSs@Gel demonstrated good biocompatibility; peroxidase-like (POD), oxidase-like (OXD), and catalase-like (CAT) activities; excellent photothermal conversion efficiency; and immunomodulatory capacity. Furthermore, the CMSs@Gel exhibited slow degradation, enabling it to exert different pH-responsive enzyme activities and modulate the production of reactive oxygen species (ROS) and the polarization of macrophages throughout the treatment process. Notably, these effects are significantly enhanced under near-infrared (NIR) light. Additionally, under NIR irradiation, the CMSs@Gel maintained the fracture environment at a mild temperature (40–42 °C), promoting osteogenesis and angiogenesis. In summary, the CMSs@Gel enhances bactericidal activity during fracture infection and effectively promotes fracture healing after infection control, providing long-term therapeutic effects. This study offers a robust theoretical basis for the staged and long-term treatment of fracture infections in the future.
研究领域:
生物医学工程
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材料科学
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骨科
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组织工程
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光热治疗
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抗菌技术
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骨再生
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Guangxin Shen,Botao Gao,Jiayi Guo,Weikang Xu,Guangfu Chen,Shuai Huang,Zhiwen Zeng,Xiaodong Zhao
Due to the limited ability to self-repair, the regeneration of bone critical-sized defects (CSD) is a significant challenge. Bone tissue engineering scaffolds are considered promising candidates for CSD repair, but low cell infiltration efficiency and a lack of nutrients greatly restrict bone regeneration abilities. Herein, we developed a dynamic culturing of large biomimetic bone scaffolds, PCL/GelMA@cells that combining 3D printed polycaprolactone (PCL) multi-channel cylinder with gelatin methacryloyl (GelMA) encapsulated with bone marrow mesenchymal stem cells (BMSCs) and rat aortic endothelial cells (RAECs). A cell dynamic culture system was fabricated to simulate the dynamic microenvironment. Compared to static culturing, dynamic culturing proved to enhance the nutrient exchange within the large scaffold to promote the cells infiltration, growth, proliferation and induce osteogenic and angiogenic differentiation. Furthermore, a rat cranial CSD (D = 10 mm) repair model verified the accelerated vascular ingrowth and new bone formation with the implantation of dynamic culturing of PCL/GelMA@cells scaffold (∼10 times higher than Blank group), indicating the great potential of dynamical culturing of scaffolds for bone repair. In summary, the results highlight the significant advantages of the dynamical culturing of cell-loaded scaffolds for bone regeneration, offering a promising strategy for addressing critical size bone defects.
研究领域:
生物医学工程
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再生医学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Shengmiao Wang,Yang Song,Yupu Yang,Xiaohong Wang,Jing Lan,Zheqin Dong
Gelatin-based hydrogels are promising for bone tissue engineering due to their inherent biocompatibility and bioactivity, yet developing scaffolds that simultaneously achieve mechanical robustness, osteoinductivity, and structural precision remains a major challenge. Here, we report a high-strength GelMA-PVI-Zn hydrogel constructed through a double-crosslinked (DC) network of gelatin methacryloyl (GelMA), poly(1-vinylimidazole) (PVI), and Zinc ions. Dynamic PVI-Zn coordination bonds act as sacrificial interactions to dissipate energy, endowing the hydrogel with exceptional mechanical performance, including a tensile modulus of 11.72 ± 0.33 MPa (81.8-fold higher than single-network controls) and a fracture strength of 2.50 ± 0.12 MPa (44.0-fold increase). Importantly, the coordination network preserves the rapid photocrosslinking kinetics of GelMA, ensuring compatibility with digital light processing (DLP) 3D printing for the fabrication of complex, high-fidelity scaffolds. Moreover, sustained Zn 2+ release from the network promoted stem cell osteogenic differentiation in vitro and markedly enhanced bone regeneration in vivo. This work presents a robust and versatile hydrogel platform that integrates high mechanical strength, osteoinductivity, and printability, offering strong translational potential for the treatment of critical-sized bone defects.
研究领域:
生物材料
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组织工程
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生物医学工程
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再生医学
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3D打印
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MATERIALS & DESIGN
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2025
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IF 7.9
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.
研究领域:
生物材料
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组织工程
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再生医学
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口腔种植学
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干细胞生物学
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Materials Today Bio
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2026
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IF 11
Hengxi Li,Xinyuan Luo,Yan Cao,Hongyan Jiang,Zhiying Guo,Yiwei Zhu,Leyu Zhang,Zixin Li,Jinglin Li,Haiying Wu,Ping Li
Traumatic brain injury (TBI) remains a major cause of severe disability, and its secondary injury remains a key focus of interventional research. Cannabidiol (CBD) has neuroprotective potential, but conventional systemic administration still has limitations. In this study, we fabricated an in situ -implantable cannabidiol-loaded gelatin methacryloyl (GelMA) sponge (GM-CBD) with short-term cytocompatibility and hemocompatibility and no detectable in vivo abnormalities. Under a non-equivalent dosing regimen, GM-CBD and intraperitoneally injected CBD (10 mg/kg) showed distinct concentration–distribution profiles: in the GM-CBD group, CBD continuously accumulated in the perilesional cortex over 48 h, whereas serum CBD remained persistently low. In a rat Feeney model of TBI, combined behavioral and neuropathological evaluation identified a single sponge loaded with a nominal 15 μg CBD as the working dose. At this dose, GM-CBD reduced neurological deficit scores, altered locomotor and exploratory behaviors in TBI rats, and attenuated neuronal injury and apoptosis. GM-CBD concurrently upregulated tight junction proteins and CD31 + endothelial cell expression, downregulated GFAP⁺ astrocyte proliferation, and altered AQP4 distribution, thereby improving blood–brain barrier integrity and alleviating post-traumatic cerebral edema. Furthermore, GM-CBD decreased IL-6, IL-1β, and TNF-α levels, increased IL-10, and inhibited microglial activation, suggesting attenuated acute neuroinflammation after TBI. Transcriptomic sequencing further showed that GM-CBD-associated differentially expressed genes were mainly involved in immune, stress, and inflammatory responses, with significant enrichment of the NF-κB, PI3K-Akt, and TNF signaling pathways. In summary, GM-CBD provides an in situ sustained-release strategy that exerts neuroprotection by attenuating post-traumatic cerebral edema and neuroinflammation. Download: Download high-res image (412KB) Download: Download full-size image
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