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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Immunomodulatory hydrogel patches loaded with curcumin and tannic acid assembled nanoparticles for radioactive dermatitis repair and radioprotection

Ruoyuan Huang,Wenjie Sun,Wenzhao Li,Rui Hu,Rui Meng,Zheng Peng,Rongbo Yang,Tianyu Huang,Jinhui Du,Luoran Shang,Congying Xie

Radiation dermatitis, as a major side effect of radiotherapy, is a form of skin injury linked to the production of reactive oxygen species (ROS). Development of functional patches with excellent ROS scavenging ability and biosafety is crucial for radioactive dermatitis repair. Herein, we present a nanohybrid hydrogel patch composed with natural-derived substances. The patch possesses dual functionalities of chemically scavenging ROS and physically absorbing radiation, thereby alleviating radiation damage. Curcumin@tannic acid (Cur@TA) nanoparticles are synthesized through spontaneous coordination of TA and iron ions (Fe 3+ ), enabling the encapsulation of Cur. The nanoparticles are then loaded into methacrylate gelatin (GelMA) hydrogel patches, which endow the hydrogel with tissue adhesion as well as photothermal properties. Simultaneously, the patch exhibits powerful ROS scavenging capability and promotes M2 polarization of macrophages. Additionally, the high-water content of the GelMA hydrogel enables physical absorption of low-energy X-rays, providing radiation shielding. Based on these characteristics, we have demonstrated the augmented therapeutic efficacy of the hydrogel patch loaded with Cur@TA nanoparticles in the mouse model of radiation dermatitis. Our findings introduce a novel therapeutic approach for radiation protection and treatment, with potential clinical applications.

研究领域: 生物医学工程 · 纳米技术 · 放射肿瘤学 · 药学 · 材料科学
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Materials Today · 2024 · IF 21.1

Hypoxia-triggered exosome-mimetics accelerate vascularized osteogenesis

Zhenyu Zhong,Yan Li,Zeyu Sun,Xiaodan Wu,Jiaqi Li,Shangtong Jiang,Yifan Wang,Jianglin Wang,Yingying Du,Shengmin Zhang

Angiogenesis plays a pivotal role in tissue development and regeneration, but few safe and efficient pro-angiogenic factors are available for long-term clinical therapy. Although stem cell-derived exosomes exhibit excellent biocompatibility and considerable pro-angiogenic capacity, their low yield extremely limits their clinical potential. Exosome-mimetics (EMs) employ similar features to exosomes and can be produced in a higher yield. In this study, the HY-EMs were produced to enhance in vitro and in vivo pro-angiogenic ability from hypoxia-preconditioned bone marrow mesenchymal stem cells (BMSCs) using a serial extrusion method. The yield of EMs was over 10 times greater than that of exosomes. Furthermore, compared with the EMs group, the tube number of human umbilical vein endothelial cells (HUVECs) in vitro doubled in the HY-EMs treated group, and the number of blood vessels increased by 186% in subcutaneously implanted scaffold with HY-EMs. More importantly, the HY-EMs effectively promoted vascularized osteogenesis in a critical-sized cranial defect model, with the new bone volume and vessel number in regenerated bone increased to 120% and 175%, respectively. Consequently, our current work provides a promising strategy to customize and mass-produce functional EMs for vascularized osteogenesis.

CAS / MDL: 85073-19-4
研究领域: 组织工程 · 再生医学 · 干细胞生物学 · 生物材料
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Nano Today · 2024 · IF 13.2

Hypoxia-responsive microgels act as an intra-articular lubricant and inflammatory inhibitor for osteoarthritis therapy

Zhaoyi Wang,Shun-Yu Yao,Yuxiang Zhang,Shifen Li,Tong Zhou,Shuqin Wang,Dong-Sheng Guo,Changyou Gao

The reduced oxygen concentration is a distinctive feature of osteoarthritic (OA) cartilage, whereas the mechanical friction also contributes to the inflammatory hypoxia microenvironment of OA. Herein, novel hypoxia-responsive methylprednisolone (MP) delivery microgels combining the capability of reactive oxygen species (ROS)-depletion and lubrication were constructed for regulating the microenvironment of OA. Methacrylate-modified sulfonated azocalix[4] arene (MACA) loaded with MP, the copolymers consisting of bioinspired lubricant 2-methacryloxyethyl phosphorylcholine (MPC), and polyethylene glycol-modified ROS-responsive poly(thioketal) (PEG-4PTK) were crosslinked together to construct the microgels. The zwitterionic MPC offered a lubrication effect, while the ROS-elimination was contributed by the PTK segments and the phenol groups in MACA. The microgels responsively released cargos in inflammatory environment and decreased inflammation by inhibiting the production of ROS and regulating the expression of inflammatory cytokines, and showed the lowest hypoxia-inducible factor-1α (HIF-1α) positive area and presented more deposition of glycosaminoglycans and collagen II with a smoother and integrated cartilage structure in therapy of OA in rats in vivo .

研究领域: 药学 · 生物医学工程 · 骨科
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JOURNAL OF CONTROLLED RELEASE · 2024 · IF 10.5

Hyperglycemia-responsive nitric oxide-releasing biohybrid cryogels with cascade enzyme catalysis for enhanced healing of infected diabetic wounds

Jiajun Hu,Kairui Duan,Yueming Zhao,Hangbin Xv,Xinxin Ge,Mian Lin,Hu Zhu,Dingze Chen,Hui Deng,Bae Hoon Lee

Diabetic wound infections are a frequent complication for diabetic patients, and conventional treatment for combating diabetic wound infections relies on antibiotics. However, the misuse and overuse of antibiotics have led to the emergence of drug-resistant bacteria, making these infections challenging to treat. Thus, there is an urgent need for alternative strategies to effectively manage diabetic wound infections. Herein, we have developed a hyperglycemia-responsive antibacterial cryogel system that can generate and release hydrogen peroxide (H 2 O 2 ) and nitric oxide (NO). This system involves incorporating glucose oxidase (GO) and L-Arginine (L-Arg: A) into hyaluronic acid aldehyde methacryloyl (HAAMA: H) and gelatin methacryloyl (GelMA: G) hybrid cryogels (GOA@HG). HAAMA facilitated higher loading and longer stability of L-Arg and GO via a Schiff base reaction. In vitro studies demonstrate that GOA@HG cryogels exhibited outstanding breathability, effective exudate management, and excellent hemostasis capabilities. Moreover, this system could consume excess glucose in diabetic wounds and efficiently eliminate bacteria through the cascaded release of H 2 O 2 and NO without causing antibiotic resistance. In vivo studies further reveal that GOA@HG cryogels significantly enhanced the healing of infected diabetic wounds by inhibiting bacterial growth, accelerating blood vessel formation, and promoting collagen deposition. Overall, GOA@HG cryogels displayed remarkable wound dressing properties and synergistic antimicrobial effects owing to glucose-responsive H 2 O 2 and NO release, which could serve as a highly efficient therapeutic strategy for treating infected diabetic wounds.

研究领域: 生物材料学 · 医学工程 · 药剂学
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Bioactive Materials · 2024 · IF 18

Protocol for engineering bone organoids from mesenchymal stem cells

Jian Wang,Dongyang Zhou,Ruiyang Li,Shihao Sheng,Guangfeng Li,Yue Sun,Peng Wang,Yulin Mo,Han Liu,Xiao Chen,Zhen Geng,Qin Zhang,Yingying Jing,Long Bai,Ke Xu,Jiacan Su

Bone organoids are emerging as powerful tools for studying bone development and related diseases. However, the simplified design of current methods somewhat limits their application potential, as these methods produce single-tissue organoids that fail to replicate the bone microarchitecture or achieve effective mineralization. To address this issue, we propose a three-dimensional (3D) construction strategy for generating mineralized bone structures using bone marrow-derived mesenchymal stem cells (BMSCs). By mixing BMSCs with hydrogel to create a bone matrix-mimicking bioink and employing projection-based light-curing 3D printing technology, we constructed 3D-printed structures, which were then implanted subcutaneously into nude mice, away from the native bone microenvironment. Even without external stimulation, these implants spontaneously formed mineralized bone domains. With long-term culture, these structures gradually matured into fully differentiated bone tissue, completing both mineralization and vascularization. This in vivo bone organoid model offers a novel platform for studying bone development, exploring congenital diseases, testing drugs, and developing therapeutic applications.

研究领域: 组织工程 · 再生医学 · 干细胞生物学 · 骨骼发育 · 药物测试
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Promotion and monitor wound healing by anthocyanin enhanced light curing ε-poly-l-lysine hydrogel encapsulated Cu-MOF

Xiawei Zhao,Rui Liu,Tiantian Tang,Zihao Liu,Xiaozhi Liu,Kai Yu,Ye Zhang,Hao Wang

Drug-resistant bacterial infections and biofilm formation have long posed significant challenges to public health, particularly in the context of chronic wound healing. In this study, the CuHspMOF were derived from copper and hesperitin (Hsp). The photocurable Epsilon-poly-l-lysine (EPLMA) and blueberry anthocyanin (BA) were synthesized through free radical polymerization. The multifunctional EB@CuHsp hydrogel exhibits excellent photothermal effect. One of the key features of the EB@CuHsp hydrogel is its ability to monitor the healing environment through color changes in response to variations in pH. This property allows for real-time assessment of the wound’s pH levels, reflecting the body fluid’s pH range during the healing process (pH 5–9). The hydrogel components work synergistically to facilitate wound healing. The EPLMA, with its positively charged, could captures bacteria and enable copper ions to eradicate bacteria at lower concentrations. This dual action leads to the creation of an optimal healing environment conducive to wound healing. During the inflammatory phase, BA and Hsp could collaborate to combat inflammation, which transited from the inflammatory stage to the proliferative phase soon. Continuous release of BA and Cu 2+ , coupled with thermotherapy, significantly enhances epithelial and blood vessel regeneration, thereby expediting the healing of chronic wounds. Overall, this multifunctional composite hydrogel holds great promise for promoting the regeneration of infected wound tissue, making it a potential candidate for chronic wound dressings.

研究领域: 生物医学工程 · 材料科学 · 药剂学 · 伤口护理 · 纳米技术 · 生物材料
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Tunable and fast-cured hyaluronic acid hydrogel inspired on catechol architecture for enhanced adhesion property

Fan Yang,Yunlu Chen,Wentao Zhang,Shaochun Gu,Zhenjie Liu,Maohu Chen,Leidan Chen,Feng Chen,Huicong Zhang,Yude Ding,Yanshan Liu,Jinyi Chen,Linhong Wang

Hyaluronic acid-based hydrogels have been broadly used in medical applications due to their remarkable properties such as biocompatibility, biodegradability, super hydroscopicity, non-immunogenic effect, etc. However, the inherent weak and hydrophilic polysaccharide structure of pure hyaluronic acid (HA) hydrogels has limited their potential use in muco-adhesiveness, wound dressing, and 3D printing. In this research, we developed in-situ forming of catechol-modified HA hydrogels with improved mechanical properties involving blue-light curing crosslinking reaction. The effect of catechol structure on the physicochemical properties of HA hydrogels was evaluated by varying the content (0–40 %). The as-synthesized hydrogel demonstrated rapid prototyping, excellent wetting adhesiveness, and good biocompatibility. Furthermore, an optimized hydrogel precursor solution was used as a blue light-cured bio-ink with high efficiency and good precision and successfully prototyped a microstructure that mimicked the human hepatic lobule by using DLP 3D printing method. This catechol-modified HA hydrogel with tunable physicochemical and rapid prototyping properties has excellent potential in biomedical engineering.

研究领域: 生物医学工程 · 材料科学 · 组织工程 · 药物递送
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Antioxidants · 2024 ·Vol. 13 ·期 7 ·857 · IF 6

Thermal-Responsive Antibacterial Hydrogel with Photothermal Therapy and Improving Wound Microenvironment for Promote Healing

Linjie Huang,Jingwen Deng,Yina Su,Xueqi Hu,Yichao Zhang,Shanni Hong,Xiahui Lin

Skin damage is one of the most prevalent human injuries, which affects the health of human beings. However, skin damage is often accompanied by bacterial infection and wound microenvironment changes, causing damage to normal cells and inhibiting wound healing. Herein, we designed a thermal-responsive antibacterial hydrogel (GAG hydrogel) loaded with catalase (CAT)-like Au@Pt@MgSiO3nanoparticles (APM NPs) and gentamicin (GM) to promote wound healing. The GAG hydrogel was used in a photothermal therapy (PTT)/antibiotic combination to kill bacteria, reduce the use of antibiotics, improve the wound microenvironment, promote cell proliferation, and accelerate wound healing. Under near-infrared laser irradiation, APM NPs in the hydrogel generated local hyperthermia to kill bacteria. Meanwhile, the generated heat led to a change in the hydrogel’s morphology, enabling it to release GM and APM NPs to prevent the overuse of antibiotics. Subsequently, the CAT-like ability of the APM NPs decreased the oxidative stress caused by hydrogen peroxide (H2O2), thus remodeling the wound microenvironment. Then, the weakly acidic microenvironment of the wound caused the decomposition of the APM NPs and the release of magnesium ions (Mg2+), promoting the growth and migration of cells for wound healing. Therefore, the studied thermal-responsive antibacterial (GAG) hydrogel has potential in the field of wound healing.

研究领域: 材料科学 · 生物医学工程 · 纳米技术 · 药学 · 伤口护理
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CERAMICS INTERNATIONAL · 2024 · IF 5.1

Study on performance regulation of electro-mechanical properties 3D printed BaTiO3/HA porous structure composite ceramic

Xin Zhao,Jimin Chen,Yong Zeng

BaTiO 3 /Ca 10 (PO 4 ) 6 (OH) 2 composite ceramic is an outstanding representative of piezoelectric biomaterials, with excellent biocompatibility and piezoelectric effect, and has potential applications in the field of bone tissue repair. In this work, vat photopolymerization 3D printing technology was used to fabricate triply periodic minimal surface structure BaTiO 3 /Ca 10 (PO 4 ) 6 (OH) 2 composite ceramic bone tissue scaffolds with different pore sizes and porosity, and their mechanical and electrical properties were studied. First, the ceramic slurry configuration process was optimized to obtain a ceramic slurry with high solid content (45 vol%) and excellent rheological properties. Then the effect of sintering temperature on microstructure, relative density, mechanical properties, and electrical properties is discussed. The results show that when sintering at 1300 °C, the BaTiO 3 /Ca 10 (PO 4 ) 6 (OH) 2 composite ceramic has the highest relative density (99.18 %), the highest compressive strength (44 MPa), large relative dielectric constant (379–389), and low dielectric loss. The polarization electric field strength of the BaTiO 3 /Ca 10 (PO 4 ) 6 (OH) 2 composite ceramic was set to 15 kV/cm through the test of the hysteresis loop. Finally, based on multi-physics coupled finite element simulation, the effects of different porosity and different pore sizes on stress distribution and piezoelectric potential were analyzed, and the relationship between them was explored through experiments. The results show that as the porosity increases and the pore size decreases, the mechanical properties of the scaffold decrease significantly, and its compressive strength ranges between 1.67 and 4.26 MPa; as the porosity increases and the pore size increases, the piezoelectric coefficient ( d 33 ) of the scaffold showed a decreasing trend, and its d 33 ranged between 2 and 9 pC/N. The mechanical and electrical properties of the scaffold meet the performance requirements of cancellous bone. In summary, this work provides a strategy for the application of customized BaTiO 3 /Ca 10 (PO 4 ) 6 (OH) 2 composite ceramic scaffolds in new-generation orthopedic implants.

CAS / MDL: 13048-33-4 85073-19-4
研究领域: 生物材料学 · 骨科医学 · 材料科学
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CARBOHYDRATE POLYMERS · 2025 · IF 12.5

Stimuli-responsive hydrogels composed of modified cellulose nanocrystal and gelatin with oriented channels for guiding axonal myelination

Shuqin Xu,Xiaoli Tang,Maosen Wang,Zhuqun Wang,Rui Zhan,Jinghua Chen

Myelination is modulated by neuron-glial communication, which is an essential physiological process during nerve regeneration. However, available scaffold for myelination of oriented axons is still challenging and lack of sufficient attention in neural tissue engineering. Here, we fabricate an extracellular matrix-mimic hydrogel (GB-SH), which was composed of cellulose nanocrystal grafted with sulfated hyperbranched polyglycerols (SHC) and 3-aminophenylboronic acid modified GelMA (GMPB) for stimuli-responsive release of sodium Danshensu (DSS). SHC with a “lubricative coating” maintained the crystalline core with a uniform size and 17.27 % of sulfation degree. GMPB having a grafting ratio of 14.94 % displayed a glucose-responsive release of dye. GB-SH hydrogels displaying oriented microchannels with controllable pore sizes were constructed by combining directional freeze-casting and photo-crosslinking strategies, which performed improved strengths, high water contents and slow degradation. It also exhibited stimulus (glucose, pH, H 2 O 2 ) triggered release of DSS. In vitro studies revealed that DSS loaded GB-SH enhanced the cellular viability, proliferation and orientation on fibroblast and oligodendrocyte precursor cells (OPCs). This scaffold induced OPCs differentiated into matured oligodendrocytes, which myelinated the extensive axons of hippocampal neurons successfully. The multi-functional hydrogel is a promising platform for studying myelination in vitro and a potential neural transplant in treating traumatic nerve injury.

研究领域: 神经组织工程 · 生物材料科学
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JOURNAL OF CONTROLLED RELEASE · 2026 · IF 12.4

An injectable biomimetic blood clot system for spatiotemporally programmed vascularized osteogenesis

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

Critical-sized bone defects pose a significant clinical challenge, with inadequate blood supply being a major factor impairing bone healing. In the initial stage of bone healing, the blood clot acts as a “natural glue,” serving not only as a scaffold for stem cell growth but also providing a reservoir of cytokines and growth factors that regulate and reconstruct the osteogenic microenvironment. In this study, we hierarchically integrated platelet concentrates with distinct functions into an injectable thermosensitive hydrogel, constructing a “biomimetic blood clot” system. First, leukocyte-platelet-rich fibrin (L-PRF) lyophilized powder, which promotes the osteogenic differentiation of periosteum-derived mesenchymal stem cells (PMSCs), was incorporated into methacrylated gelatin hydrogel microspheres (GM) to form GM L-PRF . Subsequently, advanced platelet-rich fibrin (A-PRF) lyophilized powder, which enhances the angiogenic differentiation of lamina propria-derived mesenchymal stem cells (LMSCs), was blended into a hydrogel precursor composed of chitosan (CS), polygalacturonic acid (PgA), β-glycerophosphate (β-GP), and GM L-PRF . This yielded a thermosensitive hydrogel, designated CSPgA A-PRF GM L-PRF (CP A G L ), which exhibits favorable mechanical properties at 37 °C and enables the programmed release of growth factors from both A-PRF and L-PRF. The CP A G L hydrogel could induce the differential differentiation of distinct types of MSCs. It facilitates vascularized bone regeneration by activating the JAK2-STAT3/HIF-1α and the TGF-β/Wnt signaling pathway, thereby effectively initiating the coupled an gio -osteogenic process. In summary, the biomimetic blood clot system CSPgA A-PRF GM L-PRF represents a potential injectable biomaterial strategy for bone defect repair.

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TALANTA · 2026 · IF 6.7

Fluorimetric detection of leucine aminopeptidase based on copper-initiated cascade amplification

Yu Liu,Qizheng Bi,Xiaoning Chu,Zhihao Dang,Junmin Hui,Zhuo Liu,Congkui Tian

The detection of leucine aminopeptidase (LAP) activity is essential for diagnosing liver cancer and liver injury. This study presents a novel fluorescence-based method designed for the sensitive detection of LAP through cascade catalytic reactions. Leucine-histidine (LeH) was synthesized using histidine and leucine as substrates for LAP. Notably, histidine (His) effectively inhibited the Cu 2+ -catalyzed oxidation of o-phenylenediamine (OPD) to fluorescent 2,3-diaminophenazine (oxOPD), resulting in a diminished fluorescence signal. Given that LAP hydrolyzes LeH to release His, which subsequently inhibits the Cu 2+ -OPD system, LAP activity can be quantitatively assessed by measuring fluorescence changes during the hydrolysis process. The exceptional performance of the Cu 2+ -OPD system in quantifying His allowed for highly sensitive LAP detection, achieving a detection limit as low as 0.05 U/L. Furthermore, the strategy was successfully implemented to evaluate LAP activity in cells.

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