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APPLIED PHYSICS A-MATERIALS SCIENCE & PROCESSING · 2026 ·Vol. 132 ·期 8 ·710 · IF 3

Investigation of BTZ@OSA-GelMA-BCP composite bone scaffold

Guo Lin,Shi Zhitian,Zhan Jifan,Qu Lanfeng,Tan Jiawei,Yan Tingting

Large-scale bone defects resulting from trauma, infection, aging, tumors, and other diseases present significant clinical challenges. Current treatment modalities primarily involve surgical intervention, chemotherapy, and radiotherapy. However, conventional bone repair materials exhibit limitations in addressing tumor-associated defects, including inadequate drug loading capacity, uncontrolled release kinetics, and insufficient mechanical adaptability. To address these deficiencies in existing bone repair materials, we developed a novel composite bone scaffold utilizing a biphasic calcium phosphate (BCP) osteoconductive matrix. This matrix was integrated with polyacrylamide-modified gelatin (GelMA) hydrogel to enhance mechanical strength and oxidized sodium alginate (OSA) hydrogel containing pH-sensitive acylhydrazone bonds. The incorporation of the hydrogels significantly increased the compressive strength of the composite scaffold from 1.920 MPa to 2.515 MPa. Furthermore, the scaffold was physically adsorbed with the anti-tumor drug bortezomib (BTZ), demonstrating sustained release under simulated physiological conditions (pH 7.4). Notably, the release rate accelerated under acidic conditions that mimic the tumor microenvironment (pH 5.4 and 6.8).

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Gels · 2026 ·Vol. 12 ·期 9 ·833 · IF 6.4

Siloxane-Reinforced GelMA/Methacrylated Chitosan Hydrogels for DLP Printing

Yufan Zhang,Jing Wang,Bo Liu,Xueqin Zhang,Yunxuan Weng

Photocrosslinked gelatin methacryloyl/methacrylated chitosan (GelMA/CSMA) hydrogels are attractive for biomedical applications but are limited by insufficient mechanical strength. Here, γ-methacryloxypropyltrimethoxysilane (MPTS) was prehydrolyzed and condensed to generate siloxane species retaining polymerizable methacrylate groups, which were subsequently incorporated into the GelMA/CSMA network as a reinforcing phase. The effects of MPTS precursor concentration (2–5%w/v) and prehydrolysis time (12–48 h) on the morphology, viscoelasticity, compressive behavior, cytocompatibility, and DLP printability of the resulting GCM hydrogels were systematically investigated. FTIR confirmed methoxy-group consumption while retaining C=C functionality. SEM showed that increasing MPTS precursor concentration increased the apparent abundance of granular features, whereas prolonged prehydrolysis produced larger structures. XRD indicated a predominantly amorphous MPTS-derived phase. GCM-48 h-5% achieved a storage modulus of 23.5 kPa, compressive modulus of 0.682 MPa, and maximum compressive stress of 1.081 MPa, corresponding to 7.4-, 16.9-, and 4.0-fold increases over the GelMA/CSMA control, respectively. The hydrogels exhibited favorable L929 cytocompatibility and retained DLP printability under 405 nm irradiation. These findings demonstrate that regulating MPTS precursor concentration and prehydrolysis time provides a simple route to mechanically reinforce DLP-printable GelMA/CSMA hydrogels without directly incorporating preformed silica particles.

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Biofabrication · 2025 ·Vol. 17 ·期 4 ·045002 · IF 8

3D bioprinted GelMA/collagen hydrogel for corneal stroma regeneration

Yingni Xu,Wenfang Liu,Qi Zhao,Xiaoyan Feng,Zhibiao Li,Yongrui Huang,Jia Liu,Yuehai Peng,Wenjing Song,Li Ren

Blindness caused by corneal stroma disease affects millions worldwide, the regeneration of corneal stroma has always been a challenge due to its sophisticated curvature structure and keratocyte-fibroblast transformation. In this study, we developed and optimized a series of gelatin methacrylate/collagen-based bioinks to fabricate convex corneal implants via 3D printing techniques. A novel method was proposed to enhance collagen solubility in neutral solutions by combining 2,3-epoxypropyltrimethylammonium chloride with high-molecular-weight type I collagen, with simulations suggesting that the mechanism primarily involved electrostatic interactions. To evaluate whether keratocytes respond to a convex microenvironment and to verify the effectiveness of the proposed printing strategy for corneal stromal regeneration, particularly in mitigating corneal fibrosis, we fabricated topological structures of both flat and convex corneas. These structures were systematically analyzed for their influence on keratocyte-to-fibroblast transformation and keratocyte phenotype maintenance. Morphological observations, along with gene and protein expression analyses, demonstrated that the convex architecture provided an optimal microenvironment for preserving the keratocyte phenotype. Moreover, in vivo transplantation revealed the convex cornea effectively suppressed corneal fibrosis compared to the flat cornea. These findings suggest that convex cornea holds promise as a potential translational approach for treating corneal stroma regeneration.

CAS / MDL: 7647-01-0
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MATERIALS SCIENCE FORUM · 2020 · IF 0

GelMa Microbubbles Prepared in Microfluidics as Suitable Cell Carriers

Fu Liang Jiang,Hong Bo Zhang,Wen Jun Zhang

Microfluidics has great control over the size and uniformity of microspheres, which has been widely used in fabrication of different types of microspheres such as core-shell microbubbles. Gelatin Methacrylate (GelMa) as a biodegradable material that is closely resemble to native extracellular matrix (ECM). Photocrosslinked GelMa microspheres have gained numerous concerns in biomedical applications especially in three-dimensional cell culture and tissue engineering. In this article, we presented a suitable core-shell cell carrier based on biocompatible GelMa microbubbles. Highly monodispersed microbubbles were fabricated using a non-planar flow focusing microfluidic device. Both intact and collapsed microbubbles morphology were characterized through scanning electron microscopy (SEM), where clear hollow structures were found resulting from the gas core collapsing during the manipulation process. Furthermore, human umbilical vein endothelial cells (HUVEC) were seeded in the existence of microbubbles. Cells adhesion, migration and proliferation were observed in one week. It was notable that cells maintained high level of cell viability throughout the experiment. GelMa microbubble surface was also covered with cells, which became a facile carrier for cell culturing and targeted cell delivery.

研究领域: 生物医学工程 · 材料科学 · 细胞生物学
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Materials · 2020 ·Vol. 13 ·期 17 ·3735 · IF 3.057

A GelMA-PEGDA-nHA Composite Hydrogel for Bone Tissue Engineering

Yihu Wang,Xiaofeng Cao,Ming Ma,Weipeng Lu,Bing Zhang,Yanchuan Guo

A new gelatin methacrylamine (GelMA)-poly (ethylene glycol) diacrylate (PEGDA)-nano hydroxyapatite (nHA) composite hydrogel scaffold was developed using UV photo-crosslinking technology. The Ca2+from nHA can form a [HO]Ca2+[OH] bridging structure with the hydroxyl group in GelMA, thereby enhancing the stability. Compared with GelMA-PEGDA hydrogel, the addition of nHA can control the mechanical properties of the composite hydrogel and reduce the degradation rate. In vitro cell culture showed that osteoblast can adhere and proliferate on the surface of the hydrogel, indicating that the GelMA-PEGDA-nHA hydrogel had good cell viability and biocompatibility. Furthermore, GelMA-PEGDA-nHA has excellent injectability and rapid prototyping properties and is a promising 3D printed bone repair scaffold material.Keywords:hydrogel;GelMA;nHA;photo-crosslinking

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Nano Life · 2021 · IF 0

4D Printing of Self-Folding Hydrogel Tubes for Potential Tissue Engineering Applications

Yu-Dong Zhao,Jia-Hui Lai,Min Wang

In recent years, 4D printing has gained increasing attention in the tissue engineering field since this advanced manufacturing platform can create stimulus-responsive structures, which can change their shapes, functions, and/or properties when appropriate external stimulus/stimuli is/are applied. A number of hydrogels with swellable/shrinkable abilities have been explored for 4D printing to fabricate different shape-morphing structures for tissue engineering. Among them, gelatin methacryloyl (GelMA) has been 4D printed, which can self-fold into microtubular structures. Currently, the self-folding ability of 4D printed GelMA hydrogels is mainly based on the different cross-linking degrees (which control and govern the swelling degrees) across the thickness of hydrogels. However, this strategy alone can only form self-folding GelMA tubes with diameters at the micrometer level and cannot create self-folding GelMA tubes with diameters at the millimeter level, which is mainly due to the insufficient internal force generated in 4D printed GelMA hydrogels when they are exposed to water. To overcome this limitation, this study has investigated a new strategy to fabricate self-folding GelMA tubes with large diameters at the millimeter level for tissue engineering applications. The new strategy introduced a cross-linking degree gradient across the GelMA plane in addition to its thickness by printing a second layer of strips on the first 4D printed GelMA film. In the aqueous environment, under the current fabrication condition, such bilayer GelMA hydrogels could self-fold into tubes of larger diameters up to 6 mm. The in vitro release behavior of heparin incorporated into the 4D printed GelMA was also studied. It was shown that heparin release could be controlled by the GelMA concentration and heparin content in 4D printed GelMA. The 4D printed GelMA hydrogels with the improved self-folding ability and controlled release of a drug are promising for targeted tissue engineering applications.

研究领域: 生物医学工程 · 材料科学 · 组织工程
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Biomaterials Advances · 2025 · IF 6

Angiogenesis-osteogenesis coupling lithium-loaded bioglass/GelMA hydrogel for bone regeneration

Zerui Wu,Bingzhen Zhan,Shuo Feng,Qiaoqiao Ma,Gaoran Ge,Peixin Liu,Zhihang Xiao,Heng Xie,Kai Chen,Dechun Geng,Xiaobin Guo,Guochun Zha,Shujun Lv,Ye Gu

Background Glucocorticoids are among the most common causes of nontraumatic osteonecrosis of the femoral head among young people. Bone grafting and core decompression are mainly used to treat glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) clinically. However, the results are usually not as satisfactory as expected. Herein, we report a functional hydrogel used to promote bone repair in GIONFH. Compared with traditional therapy, because of the adipogenic differentiation of mesenchymal stem cells in the ONFH region, the inhibition of fat infiltration better promotes bone remodeling. Given that hydrogels can serve as ideal carriers for continuous drug release to improve the efficiency of treatment and application in vivo, we encapsulated lithium-modified bioglass (M-Li) in a methacryloyl gelatin (GelMA) to construct a lithium-loaded bioglass hydrogel (GM/M-Li). Methods GM/M-Li hydrogel was synthesized and characterized, and co-cultured with BMSCs, HUVECs, and 3T3-L1 cells, and the lithium concentration was selected after evaluating the biotoxicity and verifying the functions of osteogenesis, angiogenesis, and inhibition of adipogenesis. In addition, New Zealand rabbits were used to establish femoral head necrosis model, and the therapeutic effect was evaluated by establishing bone tunnels through medullary core decompression, and injecting hydrogel into the necrotic bone tissues after removing them. Comparisons between multiple groups were analyzed by one-way or two-way ANOVA. Results GM/M-Li hydrogel exhibited a suitable compressive modulus of 4 kPa, and satisfactory biocompatibility, supporting cell proliferation in an adequate microenvironment. Additionally, the synthesized lithium-loaded bioglass, featuring a nanoscale size of 217 ± 3.2 nm, possessed high specific surface area, excellent intracellular effects, and efficient carrier properties. The sustained release of Li + and Si 4+ was observed to last over 35 days, significantly enhanced the proliferation and migration of bone marrow mesenchymal stem cells and human umbilical vein endothelial cells and promoted osteogenesis and angiogenesis both in vitro and in vivo. In vivo, micro-CT analysis at 12 weeks revealed that bone mineral density (BMD) of GM/M-Li group was significantly increased by 50 %, while trabecular separation (Tb.Sp) decreased by 20 %, compared to the model group. Histological and immunofluorescence staining were as well confirmed enhanced osteogenesis and angiogenesis. Conclusion Considering the limited therapeutic options for early femoral head necrosis, in order to enhance the efficacy of the treatment and to prevent subchondral osteoradionecrosis collapse of the femoral head, we designed GM/M-Li hydrogels to verify the biocompatibility and the ability of osteogenensis, angiogenesis and fatty infiltration both in vitro and in vivo. In general, GM/M-Li hydrogels provided an appropriate microenvironment for orchestrating ONFH bone regeneration. Therefore, our research presents a promising regenerative platform to improve the ONFH microenvironment and accelerate bone remodeling. Take-home message This study presented a novel multi-functional regenerative strategy that simultaneously targeted osteogenesis, angiogenesis, and adipogenesis, using lithium-integrated bioactive hydrogel, offering a comprehensive and promising therapeutic platform beyond conventional bone grafts.

研究领域: 生物医学工程 · 组织工程 · 再生医学 · 骨科 · 药物递送系统
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Gels · 2026 ·Vol. 12 ·期 7 ·635 · IF 6.4

Drug Delivery and Visual Monitoring of Nd(ATA)-GelMA Composite Hydrogels

Tongyu Qiu,Fengyuan Bian,Tong Meng,Wei Zhou,Weijie Zhang,Ming Ma,Yihu Wang,Bing Zhang

In this study, taking NdCl3and 2-amino-1,4-benzenedicarboxylic acid (H2ATA) as raw materials, a novel lanthanide metal–organic framework, Nd(ATA), was synthesized by the coprecipitation method. After loading antibiotic levofloxacin (LEV), Nd(ATA) was combined with GelMA hydrogel to prepare a drug-loaded composite hydrogel, LEV@Nd(ATA)-Gel, which can emit near-infrared fluorescence under excitation at 808 nm and possesses improved mechanical properties compared to pure GelMA hydrogel. LEV@Nd(ATA)-Gel exhibited high bactericidal activity and low cytotoxicity, with cell viability increased by 35% compared to the control group. The release rate of the loaded LEV was found increasing with the pH decreasing from 7 to 3, and demonstrated a potential responsiveness to wound microenvironment. Furthermore, drug delivery studies revealed a significant correlation with the fluorescence intensity of the composite hydrogel and the drug release behavior, and the extent of drug release was quantitatively captured by an in vitro imaging technology. This study successfully integrated the drug release with fluorescent signal of carrier, providing a highly sensitive and visualizable strategy for the development of internal wound adhesive.

CAS / MDL: 760-93-0
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2026 · IF 5.4

Patterned AgNWs-GelMA Conductive Hydrogels Enabled by Chemical Welding for Flexible Biosensing

Xuemei Liu,Kexin Guo,Zhaoxin Chen,Qile Miao,Xiaoming Zhang,Jieling Li,Qi Li,Sen Liang,Yafeng Jing,Yiming Niu,Tong Liu,Hong Li,Anhe Wang,Shuo Bai

Conductive hydrogels, owing to their flexibility, high biocompatibility, tissue-mimetic properties, and electrical responsiveness, hold broad application prospects in fields such as flexible biosensing, wearable electronics, and health monitoring. However, constructing continuous and stable conductive pathways while maintaining biocompatibility and mechanical stability remains a key challenge in the design of such materials. In this study, we combined template casting with a chemical welding strategy to fabricate patterned AgNWs-GelMA conductive hydrogels. The results indicate that chemical welding effectively improves the connection quality at AgNWs intersections, increasing the electrical conductivity of the samples by at least 67% under identical conditions. Furthermore, the conductive hydrogel exhibited good biocompatibility. Flexible sensors constructed from this material generated stable electrical responses to external stimuli, such as pressure and joint motion. Under a constant cyclic pressure of 0.2   N, the sensors exhibited a rapid total response and recovery time of 200 ms, demonstrating their potential for flexible biosensing applications, particularly under conditions of small deformation. Download: Download high-res image (202KB) Download: Download full-size image

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Biomaterials Science · 2024 · IF 5.8

Alginate/GelMA microparticles via oil-free interface shearing for untethered magnetic microbots

Shiyu Wu,Yang Zhou,Juan Wei,Zicheng Da,Wenquan Chen,Xiaoxia Shu,Tingting Luo,Yuping Duan,Runhuai Yang,Chengbiao Ding,Guangli Liu

Microrobots hold broad application prospects in the field of precision medicine, such as intravenous drug injection, tumor resection, opening blood vessels and imaging during abdominal surgery. However, the rapid and controllable preparation of biocompatible hydrogel microparticles still poses challenges. This study proposes the one-step direct acquisition of biocompatible sodium alginate and gelatin methacrylate (GelMA) hydrogel microparticles using an oil-free aqueous solution, ensuring production with a controllable generation frequency. An adaptive interface shearing platform is established to fabricate alginate/GelMA microparticles using a mixture of the hydrogel, photoinitiator, and Fe3O4 nanoparticles (NPs). By adjusting the static magnetic field intensity (Bs), vibration frequency, and flow rate (Q) of the dispersed phase, the size and morphology of the hydrogel microparticles can be controlled. These hydrogel microparticle robots exhibit magnetic responsiveness, demonstrating precise rotating and rolling movements under the influence of an externally rotating magnetic field (RMF). Moreover, hydrogel microparticle robots with a specific critical frequency (Cf) can be customized by adjusting the Bs and the concentration of Fe3O4 NPs. The directional in situ untethered motion of the hydrogel microparticle robots can be successfully realized and accurately controlled in the climbing over obstacles and in vitro experiments of animals, respectively. This versatile and fully biodegradable microrobot has the potential to precisely control movement to bone tissue and the natural cavity of the human body, as well as drug delivery.

CAS / MDL: 9005-38-3
研究领域: 生物医学工程 · 材料科学 · 精准医学
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CRYOBIOLOGY · 2024 · IF 2.3

l-Proline and GelMA hydrogel complex:An efficient antifreeze system for cell cryopreservation

Xin Li,Yukun Cao,Chenxi Liu,Jia Tan,Xinli Zhou

Cryopreservation of biological samples is an important technology for expanding their applications in the biomedical field. However, the quality and functionality of samples after rewarming are limited by the toxicity of commonly used cryoprotectant agents (CPAs). Here, we developed a novel preservation system by combining the natural amino acid l -proline (L-Pro) with gelatin methacryloyl (GelMA) hydrogels. Compared with dimethyl sulfoxide (DMSO), L-Pro and GelMA demonstrated excellent biocompatibility when co-culturing with cells. Cryopreservation procedures were optimized using 3T3 as model cells. The results showed that rapid cooling was the most suitable cooling procedure for L-Pro and GelMA among the three cooling procedures. Co-culturing with cells for 3 h before cryopreservation, 6 % L-Pro +7 % GelMA had the highest survival rate, reaching up to 80 %. Differential Scanning Calorimetry (DSC) analysis showed that 6 % L-Pro + 7 % GelMA lowered the freezing point of the solution to −4.2 °C and increased the unfrozen water content to 20 %. To the best of our knowledge, this is the first report of cell cryopreservation using a combination of L-Pro and GelMA hydrogels, which provides a new strategy for improving cell cryopreservation.

CAS / MDL: 67-68-5 147-85-3
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ACS Biomaterials Science & Engineering · 2019 · IF 4.511

Coaxial Extrusion of Tubular Tissue Constructs Using a Gelatin/GelMA Blend Bioink

Ying Wang,Ranjith Kumar Kankala,Kai Zhu,Shi-Bin Wang,Yu Shrike Zhang,Ai-Zheng Chen

Gelatin methacryloyl (GelMA) hydrogels have been commonly used in fabricating cannular tissue constructs due to their excellent cytocompatibility, as well as amenity to migration and proliferation of encapsulated cells. Here, we present a simple yet efficient approach for fabricating hollow structures with gelatin-based hydrogels using a modified microfluidic-based biofabrication technology. Hollow microfibers were generated using a customized coaxial nozzle by soft templating against a polyvinyl alcohol solution core. Reversible thermo-cross-linking and irreversible photo-cross-linking were achieved successively through gelatin (Gel) mixed into the GelMA solution and by irradiating with UV light, resulting in stable and continuous generation of hollow structures. Furthermore, in vitro evaluations confirmed good proliferation of multiple cell types in the GelMA/Gel hollow microfibers. Together, we believe that this approach holds great potential in engineering cannular constructs for applications in regenerative medicine and tissue modeling.

CAS / MDL: 81-88-9 9002-93-1
研究领域: 生物医学工程 · 组织工程 · 再生医学 · 生物制造
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