CARBOHYDRATE POLYMERS
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2025
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IF 12.5
Bo Ma,Hailin Ma,Baixin Gu,Kangling Xu,Pei Cao,Xiaotong Wu,Tiantian Qi,Rou Wen,Tianze Sun,Junyu Su,Hanwen Cheng,Yujie Wang,Shiyan Liu,Yiyang Liu,Qiuan Xiang,Zhongyu Xu,Yuanchao Zhu,Jian Weng,Fei Yu
Persistent reactive oxygen species (ROS) stress, excessive inflammation, insufficient angiogenesis, and inadequate neurogenesis severely hinder peripheral nerve repair and remain inadequately addressed by current biomaterials. To overcome these challenges, we developed a multifunctional conduit system with a facile and efficient assembly process. Specifically, 4-amino-3-fluorophenylboronic acid (AFBA) functionalized hyaluronic acid (HP) was crosslinked with tannic acid (TA) through boronate ester bonds to obtain a dynamic hydrogel (HT), during which VEGF was encapsulated. Subsequently, HT was physically blended with NGF-encapsulated Gelatin Methacryloyl (GelMA) microspheres (MS). In the early stage of nerve injury, the ROS-rich inflammatory microenvironment triggered the oxidative cleavage of boronate ester bonds, resulting in rapid degradation of the HT hydrogel and the corresponding release of TA and VEGF. Subsequently, the released TA, enriched with phenolic hydroxyl groups, effectively continued to scavenge excessive ROS and promoted macrophage polarization toward the M2 phenotype, while VEGF facilitated early neovascularization at the injury site. Additionally, the UV-crosslinked MS ensured the sustained release of encapsulated NGF, thereby providing long-term neurotrophic support that enhanced Schwann cell activity and promoted axonal elongation. The in vivo application of the HT/MS hydrogel with chitin conduits demonstrated effective nerve regeneration across a 10-mm defect in rats.
研究领域:
生物材料
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组织工程
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神经科学
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高分子化学
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生物医学工程
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CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yufeng Ai,Jingting Wu,Wenfeng Li,Fancheng Xu,Jianxin Wu,Li Li,Kaiqiang Yang,Chenjiang He,Pengyan Zhu,Xueli Leng,Fang Dai,Li Song
In the aging society, bone defects significantly threaten human health. Therefore, several biomaterials have been developed to promote bone regeneration. However, previous studies have predominantly focused on optimizing the osteoinductive capacity of materials while neglecting vascular regeneration and immune responses elicited by biomaterials. The repair of bone defects is a complex biological process that involves not only bone resorption and formation, but also inflammation, immunity, and vascularization. The present study successfully encapsulated deferoxamine (DFO) into poly (lactic-co-glycolic acid) (PLGA) to form nanospheres for the sustained release of DFO, thereby simulating a hypoxic microenvironment. DFO-PLGA/Bioactive glass (BG)/Bone marrow mesenchymal stem cells (BMSCs) @GelMA (DBB@GelMA) exhibited excellent biocompatibility and osteoinductive properties in vitro. Furthermore, DBB@GelMA continuously releases DFO to promote vascular regeneration, M2 polarization of macrophages, and osteogenic differentiation of BMSCs. The finding from the experiment on SD rat calvarial defect repair further validated its exceptional immunoregulatory, angiogenic, and osteoinductive capabilities. In conclusion, this composite hydrogel offers a novel strategy for regulating the hypoxic microenvironment and holds promise for bone-defect repair.
研究领域:
生物材料学
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组织工程学
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再生医学
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ACS Omega
·
2019
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IF 2.584
Yangjie Shao,Dongqi You,Yiting Lou,Jianhua Li,Binbin Ying,Kui Cheng,Wenjian Weng,Huiming Wang,Mengfei Yu,Lingqing Dong
Naringin, a Chinese herbal medicine, has been demonstrated to concentration-dependently promote osteogenic differentiation of mesenchymal stem cells (MSCs). However, it remains a challenge to load naringin on coatings for osteogenesis and further control the release kinetics. Here, we demonstrated that the release behavior of naringin on rutile nanorod films could be controlled by either mixing naringin with gelatin methacryloyl (GelMA) before spinning onto the films or soaking the obtained GelMA-incorporated films with the naringin solution to achieve the distinct degradation-type release and diffusion-type release, respectively. We further revealed that the naringin-loaded coatings facilitated adhesion, proliferation and late differentiation, and mineralization of MSCs. Our findings provided a novel strategy to engineer the coatings with controlled release of naringin and emphasized the bioactivity of naringin for the osteogenic differentiation of MSCs.
研究领域:
生物材料学
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细胞生物学
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组织工程学
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Materials Science & Engineering C-Materials for Biological Applications
·
2021
·
IF 7.328
Zongxi Wu,Shang Xie,Yifan Kang,Xiaofeng Shan,Qing Li,Zhigang Cai
Peripheral nerve injury can cause various degrees of damage to the morphological structure and physiological function of the peripheral nerve. At present, compared with “gold standard” autologous nerve transplantation, tissue engineering has certain potential for regeneration and growth; however, achieving oriented guidance is still a challenge. In this study, we used 3D bioprinting to construct a nerve scaffold of RSC96 cells wrapped in sodium alginate/gelatin methacrylate (GelMA)/bacterial nanocellulose (BNC) hydrogel. The 5% sodium alginate+5% GelMA+0.3% BNC group had the thinnest lines among all groups after printing, indicating that the inherent shape of the scaffold could be maintained after adding BNC. Physical and chemical property testing (Fourier transform infrared, rheometer, conductivity, and compression modulus) showed that the 5% alginate+5% GelMA+0.3% BNC group had better mechanical and rheological properties. Live/dead cell staining showed that no mass cell death was observed on days 1, 3, 5, and 7 after printing. In the 5% alginate+5% GelMA group, the cells grew and formed linear connections in the scaffold. This phenomenon was more obvious in the 5% alginate+5% GelMA+0.3% BNC group. In the 5% alginate+5% GelMA+0.3% BNC group, S-100β immunofluorescence staining and cytoskeleton staining showed oriented growth. Polymerase chain reaction (PCR) array results showed that mRNA levels of related neurofactors ASCL1, POU3F3, NEUROG1, DLL1, NOTCH1 and ERBB2 in the 5%GelMA+0.3%BNC group were higher than those of other groups. Four weeks after implantation in nude mice, RSC96 cells grew and proliferated well, blood vessels grew, and S-100β immunofluorescence was positive. These results indicate that a 3D-bioprinted sodium alginate/GelMA/BNC composite scaffold can improve cell-oriented growth, adhesion and the expression of related factors. This 3D-bioprinted composite scaffold has good biocompatibility and is expected to become a new type of scaffold material in the field of neural tissue engineering.
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Materials Today Bio
·
2025
·
IF 10.2
Yongbin Wang,Han Zhang,Zhili Xu,Weihang Zhu,Sheng Chang,Jiahao Wei,Shuqing Chen,Yong Liu,Weiqing Kong,Jianwei Guo
Large bone defects present significant clinical challenges due to limitations of current treatments including immune rejection, infection, and poor osteoinductive capacity. This study developed a novel biomimetic piezoelectric scaffold system combining 3D-printed potassium sodium niobate/nano-hydroxyapatite/polylactic acid (KNN/nHA/PLA) scaffolds with icariin-loaded gelatin methacryloyl hydrogel (ICA@G/NHP) to synergistically promote bone regeneration and immunomodulation. The composite scaffolds demonstrated excellent mechanical properties and stable piezoelectric output under ultrasonic activation. In vitro studies revealed that ultrasonic stimulation was essential for activating piezoelectric effects, significantly enhancing osteogenic differentiation of bone marrow mesenchymal stem cells through upregulation of ALP, RUNX2, and COL1 expression. The incorporated icariin effectively promoted endothelial cell migration and induced M2 macrophage polarization via C-type lectin receptor signaling pathway, creating a pro-regenerative immune microenvironment. In vivo validation using rat cranial and rabbit femoral condyle defect models demonstrated superior bone regeneration with enhanced bone mineral density, bone volume fraction, and mature trabecular architecture compared to controls. Immunofluorescence analysis confirmed sustained M2 macrophage dominance and suppressed inflammatory responses. RNA sequencing identified PI3K/Akt as the central mechanotransduction pathway mediating scaffold effects. This integrated platform addresses dual challenges of osteogenesis and immune regulation, offering a promising therapeutic strategy for critical-sized bone defect repair through ultrasound-activated piezoelectric stimulation combined with targeted immunomodulation.
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Acta Biomaterialia
·
2026
·
IF 10.4
Wenfang Liu,Zhuhao Tan,Sulei Lv,Wentai Guo,Qi Zhao,Baolei Huang,Yiping Liu,Yingni Xu,Wenjing Song,Li Ren
Keratoconus (KC), a progressive corneal ectasia characterized by central thinning, elevated curvature, and compromised biomechanical integrity, presents considerable therapeutic challenges. Existing clinical interventions exhibit limited efficacy in delaying disease progression or restoring native corneal structure. We report a concave corneal stromal scaffold (CCSS) featuring a unique concave structure, fabricated based on multi-crosslinked gelatin methacryloyl and β-cyclodextrin aldehyde hydrogels and specifically designed for intrastromal implantation. In vitro characterization confirmed that the optimized gelatin methacryloyl-based hydrogel possesses high optical transparency (>90%), suitable mechanical properties, and favorable cytocompatibility. Based on finite element model analysis of stress disparities between normal cornea and KC, a concave scaffold was fabricated to prevent KC progression. In vivo rabbit models of KC resulted in increased central corneal thickness in the Sc region (scaffold center), while a specially designed incremental topology in the peripheral Sp region (scaffold periphery) contributed to significant reduction in corneal curvature. The CCSS also promoted epithelial remodeling and substantially improved biomechanical properties, exhibiting notable restorative capacity. Importantly, animal studies experimentally validated finite element model predictions that the concave topology of the CCSS effectively redistributes stress, attenuating central stress concentration and reducing apical displacement. Moreover, the scaffold demonstrated sustained structural integrity over extended periods, thereby delaying KC progression and potentially diminishing the necessity for corneal transplantation. The design principles of the CCSS may inform future therapeutic strategies for stromal corneal disorders. Statement of significance Keratoconus (KC) as a progressive corneal ectasia characterized by structural disintegration and biomechanical weakening, for which current clinical interventions often fail to halt disease progression without biomechanical mismatch. While biomaterial-based strategies offer promise, conventional flat scaffolds cannot replicate the native stress distribution of the cornea. Here, we report a concave corneal stromal scaffold (CCSS)fabricated from a multi-crosslinked GelMA hydrogel. By synergizing material reinforcement with topological design, the CCSS actively redistributes intraocular stress from the thinned apex to the peripheral stroma, a mechanism predicted by finite element modeling and validated in vivo . Our findings provide a transformative paradigm for treating stromal corneal disorders by integrating structural restoration with biomechanical normalization, potentially reducing the reliance on corneal transplantation. Download: Download high-res image (249KB) Download: Download full-size image
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JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·1-18
·
IF 12.6
Zhang Yifan,Zhou Ziyi,Liu Na,Wang Jing,Guo Qingxia,You Yong,Mao Kaiping,Wang Yuanfei,Zhang Weina,Wu Tong
Excessive scarring can impede the normal skin movement, resulting in decreased body flexibility and functional abnormalities. These issues, in turn, impact patients’ daily lives and comfort. To prevent the pathological healing of infected wounds, this study developed a composite hydrogel microneedle that possesses stable mechanical properties and favorable biocompatibility. The microneedles, composed of gelatin methacryloyl hydrogels, were integrated with curcumin-loaded PLGA microparticles to promote wound healing and allow the controlled release of curcumin within a suitable timeframe, thereby minimizing the formation of hypertrophic scars. Zinc oxide nanoparticles were integrated into the base layer of the microneedle, forming a physical barrier and exhibiting significant antibacterial activity against both Staphylococcus aureus and Escherichia coli . Due to the unique structural and functional design, we demonstrated that this class of microneedles could accelerate the healing of infected wounds and downregulate the expression of α-SMA and collagen I in scar fibroblasts, thereby showing potential to inhibit scar formation. In vivo investigations further validated the effective repair of infected wounds in rat skin and demonstrated the inhibition of pathological scars using hypertrophic scar models in rabbit ears. Altogether, these materials exhibit promising potential to provide a new option for preventing pathological scarring in the treatment of infected wounds.
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Biomaterials Advances
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2025
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IF 6
Huili Kang,Dong Zhang,Houming Zhou,Zhenhua Huang,Yina Xie,Fangping Chen,Changsheng Liu
Gelatin methacrylamide porous microcarriers (GelMA PMS) often fails to achieve complete interconnected pore structures and encounters local structural destruction, spherical distortion and limited cell proliferation rate. This study introduced an innovative dual ice crystal strategy, which enabled staged ice crystal growth before and after photo-crosslinking, along with the low-temperature gelation of GelMA. GelMA PMS with stable spherical structure and controllable interconnected pore structures (12 to 42 μm) were successfully fabricated. Various aspects of cell morphology, viability, proliferation and phenotypic markers were thoroughly investigated to assess the effects of different interconnected-pore structures of GelMA PMS on various cells. Results indicated that PMS60 (−60 °C) promoted bone marrow mesenchymal stem cells (BMSCs) adhesion ratio (91.69 %) and high proliferative activity. PMS196 (−196 °C) facilitated the adhesion and proliferation of human umbilical vein endothelial cells (HUVECs) and mouse renal tubular epithelial cells (mRTECs), as evidenced by amplification times of 7.47 and 8.17, respectively. It is worth mentioning that BMSCs cultured in PMS60 demonstrated a higher differentiation capacity and expression of phenotypic markers, with CD105/CD90 positive rates exceeding 99.54 %. Additionally, the stemness genes Nanog and Sox2 were upregulated by 2.48- and 2.31-fold, respectively. HUVECs in PMS196 exhibited enhanced the vascularization potential, forming well-organized capillary-like structures and more extensive interconnected tubular networks. Meanwhile, mRTECs in PMS196 showed a reduction in epithelial-mesenchymal transition (EMT), along with a significant downregulation of Vimentin/E-cadherin, which was reduced by 2.20-fold compared to cells cultured in Cytodex-3. Overall, the GelMA PMS fabricated in this study advances the development of cell therapy.
研究领域:
生物材料
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组织工程
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细胞治疗
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Materials Today Bio
·
2022
·
IF 10.761
Xiaojing Yuan,Zuoying Yuan,Yuanyuan Wang,Zhuo Wan,Xiaotong Wang,Shi Yu,Jianmin Han,Jianyong Huang,Chunyang Xiong,Lihong Ge,Qing Cai,Yuming Zhao
Dental pulp necrosis are serious pathologic entities that causes tooth nutrition deficiency and abnormal root development, while regeneration of functional pulp tissue is of paramount importance to regain tooth vitality. However, existing clinical treatments, which focus on replacing the necrotic pulp tissue with inactive filling materials, fail to restore pulp vitality and functions, thus resulting in a devitalized and weakened tooth. Currently, dental pulp regeneration via stem cell-based therapy for pulpless teeth has raised enormous attention to restore the functional pulp. Here, a novel design of injectable simvastatin (SIM) functionalized gelatin methacrylate (GelMA) cryogel microspheres (SMS) loaded with stem cells from human exfoliated deciduous teeth (SHEDs) was established to refine SHEDs biological behaviors and promote in vivo vascularized pulp-like tissue regeneration. In this system, SIM encapsulated poly (lactide- co -glycolide) (PLGA) nanoparticles were incorporated into GelMA cryogel microspheres via cryogelation and O 1 /W/O 2 emulsion method. SMS with sustained release of SIM promoted SHEDs adhesion, proliferation and exhibited cell protection properties during the injection process. Furthermore, SMS enhanced SHEDs odontogenic differentiation and angiogenic potential, and SHEDs loaded SMS (SHEDs/SMS) are beneficial for human umbilical vein endothelial cells (HUVECs) migration and angiogenesis, demonstrating their potential for use in promoting vascularized tissue regeneration. SHEDs/SMS complexes were injected into cleaned human tooth root segments for subcutaneous implantation in nude mice. Our results demonstrated that SHEDs/SMS could induce vessel-rich pulp-like tissue regeneration in vivo and that such an injectable nano-in-micro multistage system for the controlled delivery of bioactive reagents would be suitable for clinical application in endodontic regenerative dentistry.
研究领域:
牙科学
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组织工程
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再生医学
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干细胞生物学
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材料科学
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
·
2026
·Vol. 114
·期 4
·e70058
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IF 3
Zhengnan Zhao,Yingming Li,Yongwei Yin,Guoqing Li,Hong Wang
Diabetic chronic wounds are difficult to heal due to persistent inflammation, excessive oxidative stress, and high infection risk. Herein, a multifunctional GelMA-based microsphere co-loaded with silver ions and curcumin (GelMA-MS@Ag/Cur) was developed as an advanced wound dressing for diabetic wound repair. The porous GelMA microspheres enabled efficient encapsulation and sustained release of Ag + and curcumin while maintaining good biocompatibility and controlled degradation. GelMA-MS@Ag/Cur exhibited broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria and effectively reduced intracellular reactive oxygen species. The microspheres further promoted macrophage polarization toward the pro-regenerative M2 phenotype. Mechanistically, GelMA-MS@Ag/Cur regulated the KEAP1/Nrf2 signaling pathway and suppressed inflammation-induced ferroptosis by modulating ACSL4, SLC7A11, and GPX4 expression, thereby preserving cellular redox homeostasis. In a diabetic rat full-thickness wound model, GelMA-MS@Ag/Cur significantly accelerated wound closure, enhanced angiogenesis, collagen deposition, and tissue remodeling without observable systemic toxicity. This work provides a promising multifunctional strategy for diabetic chronic wound management.
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Biomaterials Science
·
2026
·
IF 6.1
Ruirui Ding,Zhe Wang,Yuwen Wang,Bo Du,Ruiping Duan,Xuemin Li,Lingrong Liu
Gelatin methacryloyl (GelMA) hydrogels are widely used in tissue engineering because of their excellent biocompatibility, yet their dense network structure restricts substance transport and limits cell proliferation. Although the introduction of macroporous structures can alleviate this problem, most existing studies are limited to qualitative descriptions of permeability, lacking a quantitative framework to characterize the substance transport efficiency in such hydrogel networks and to study their impact on cell proliferation. In this work, we fabricated a series of GelMA macroporous hydrogels with tunable pore sizes through liquid–liquid phase separation (LLPS) combined with photopolymerization. The influence of pore size on the permeability of model solutes with different molecular weights was systematically investigated. Based on the classical analytical solution of Fick's second law, a quantitative diffusion model was established to determine the effective diffusion coefficient (Deff) of each solute in hydrogels with varying pore structures. A power-law relationship between the normalized diffusion coefficient and pore size was further constructed. The results indicated that for the same solute, its relative diffusion capacity exhibits a nonlinear increase with increasing pore size, indicating that larger pores significantly enhance permeability. Among different solutes, macromolecular solutes displayed significantly higher sensitivity to pore size variations compared to small molecules. In vitro studies with bone marrow mesenchymal stem cells (BMSCs) suggest that enhanced permeability facilitates glucose uptake and ATP production, consistent with the observed vigorous cell proliferation. This study offers insights into the quantitative correlation between pore architecture, substance transport, and cellular responses, providing a theoretical basis for designing hydrogel scaffolds with optimized microenvironments.
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Advanced Science
·
2026
·
IF 14.1
Zhikang Li,Gengyu Han,Boqing Jia,Jijian Lu,Changxu Zhang,Bin Wang,Jiaxiang Wang,Kang Zhao,Muhammad Afzal Khan Qureshi,Lan Yu,Min Li,Guoxi Luo,Tong Wang,Qijing Lin,Weishi Li,Libo Zhao,Yumeng Xue
Gelatin methacryloyl (GelMA) hydrogels are promising for wearable tactile sensors due to their biocompatibility, tissue‐mimic softness and conductivity, yet restricted by mechanical property, structure damage, dehydration, and freezing during usage. Herein, a mechanically robust, self‐healable, moisturizing, cryotolerant and adhesive GelMA hydrogel is developed by incorporating polyvinyl alcohol, acrylic acid, sodium tetraborate, and glycerol into GelMA matrix via a photoinitiated polymerization process. This unique approach overcomes the chemical‐mechanical conflictions among different molecules, and contributes to remarkable stretchability (≥220%, 5.5‐fold higher), elasticity (≈91.9% recovery), autonomous self‐healing within wide temperature range (from ‐40°C to 25°C), adhesion (≥23.5 kPa), moisture retention (≥81% after 10 d) and anti‐freezing (‐55.4°C) properties, significantly outperforming previous GelMA. Based on this, an omni‐healable ionotronic pressure sensor is constructed, featuring high sensitivity within broad pressure range (0–25 kPa), rapid recovery time, long‐term stability (≈120 h), excellent durability and performance self‐repairing (≈100% sensing range recovery) under subzero temperature. Sensitively and consistently monitoring of various physiological signals under harsh conditions, such as multiple structure damages, long period (≥5 d) and subzero temperatures (≤‐38.2°C) highlights its prominent durability, lifetime and environmental‐stability, demonstrating great promise toward practical application. A mechanically robust, self‐healable, moisturizing, cryotolerant and adhesive GelMA hydrogel is developed by incorporating polyvinyl alcohol, acrylic acid, sodium tetraborate, and glycerol into GelMA matrix via a photoinitiated polymerization process. The hydrogel‐derived omni‐healable ionotronic pressure sensor can sensitively and consistently monitor various physiological signals under harsh conditions, demonstrating great promise toward practical application.
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