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Materials Today Bio · 2024 · IF 8.7

Glucose-responsive, self-healing, wet adhesive and multi-biofunctional hydrogels for diabetic wound healing

Zhuo Huang,Min Wang,Langjie Chai,Hang Chen,Danyang Chen,Yulin Li,Hongtao Liu,You Wu,Xuxia Yang,Lu He,Longjian Xue,Yifeng Lei,Liang Guo

Diabetic wounds are serious clinical complications which manifest wet condition due to the mass exudate, along with disturbed regulation of inflammation, severe oxidative stress and repetitive bacterial infection. Existing treatments for diabetic wounds remain unsatisfactory due to the lack of ideal dressings that encompass mechanical performance, adherence to moist tissue surfaces, quick repair, and diverse therapeutic benefits. Herein, we fabricated a wet adhesive, self-healing, glucose-responsive drug releasing hydrogel with efficient antimicrobial and pro-healing properties for diabetic wound treatment. PAE hydrogel was constructed with poly(acrylic acid- co -acrylamide) (AA-Am) integrated with a dynamic E-F crosslinker, which consisted of epigallocatechin gallate (EGCG) and 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylboronic acid (AFPBA). Due to the dynamic crosslinking nature of boronate esters, abundant catechol groups and hydrogen bonding, PAE hydrogel demonstrated excellent mechanical properties with about 1000 % elongation, robust adhesion to moist tissues, fast self-healing, and absorption of biofluids of 10 times of its own weight. Importantly, PAE hydrogel exhibited sustained and glucose-responsive release of EGCG. Together, the bioactive PAE hydrogel had effective antibacterial, antioxidative, and anti-inflammatory properties in vitro , and accelerated diabetic wound healing in rats via reducing tissue-inflammatory response, enhancing angiogenesis, and reprogramming of macrophages. Overall, this versatile hydrogel provides a straightforward solution for the treatment of diabetic wound, and shows potential for other wound-related application scenarios.

研究领域: 生物材料学 · 医学工程 · 药剂学
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Advanced Healthcare Materials · 2023 ·Vol. 12 ·期 29 ·2302073 · IF 10

Bioactive Glasses-Based Nanozymes Composite Macroporous Cryogel with Antioxidative, Antibacterial, and Pro-Healing Properties for Diabetic Infected Wound Repair

Shuangli Zhu,Maocai Li,Zetao Wang,Qi Feng,Huichang Gao,Qingtao Li,Xiaofeng Chen,Xiaodong Cao

The treatment for diabetic ulcers still remains a big clinic challenge owing to the adverse repair microenvironment. Bioactive glasses (BGs) play an important role in the late stages of healing due to their ability to promote vascularization and collagen fiber deposition, but fail to improve infection and oxidative stress in the early stage.Therefore, it is critical to develop a material involved in regulating the whole healing phases. In this work, BGs-based nanozymes (MnO 2 @PDA-BGs) with antioxidation, antibacterial and pro-healing abilities are synthesized by the redox deposition of MnO 2 on mesoporous BGs. Afterward, cryogel with the interconnected macropore structure is fabricated by the polymerization of methacrylate anhydride gelatin (GelMA) at −20 °C. MnO 2 @PDA-BGs are loaded into the cryogel to obtain nanocomposite cryogel (MnO 2 @PDA-BGs/Gel) with multiple enzymes-like- activities to eliminate reactive oxygen species (ROS). Besides, MnO 2 @PDA-BGs/Gel has intensive peroxidase-like activity under acidic condition and near infrared photothermal responsiveness to achieve excellent antibacterial performance. Cells experiments demonstrate that MnO 2 @PDA-BGs/Gel recruits L929s and promotes their proliferation. Furthermore, MnO 2 @PDA-BGs/Gel eliminates intracellular overexpressed ROS and maintains the viability of L929s. Animal experiments confirm that MnO 2 @PDA-BGs/Gel promotes wound healing and avoided scarring by killing bacteria, reversing inflammation, promoting vascularization, and improving the deposition of collagen III.

研究领域: 材料科学 · 医学 · 生物工程
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

A multifunctional conductive organohydrogel as a flexible sensor for synchronous real-time monitoring of traumatic wounds and pro-healing process

Ranran Si,Yifan Wang,Yuchun Yang,Yang Wu,Miaofeng Wang,Bingnan Han

Ion-conductive hydrogels (ICHs) offer promising applications in the realm of flexible bioelectronics due to their attributes, such as transparency, flexibility, tissue adhesion, and self-healing. However, it remains a challenge to integrate excellent material properties and bio-properties into ICHs-based smart wearables for intricate biomedical applications. Herein, a multifunctional conductive C-CST/PMC organohydrogel with stretchability, anti-freezing, self-healing, antibacterial, antioxidant, and biocompatibility was synthesized by catechol-conjugated chitosan (C-CS), silk nanofibrils (SNFs), tannic acid (TA), MgCl 2 /CaCl 2 , and polyvinyl alcohol (PVA), with a binary solvent system composed of ethylene glycol (EG) and H 2 O. The C-CST/PMC exhibited excellent mechanical properties (175 kPa stress and 330 % strain), anti-freezing capacity, moisture retention, self-healing performance, and high conductivity (1.76 mS/cm at 25 °C and 1.43 mS/cm at –18 °C). Moreover, we have employed this organohydrogel as a flexible strain sensor for monitoring human movements, achieving a high sensitivity (gauge factor (GF) = 1.20 at 100 % strain) and glorious fatigue resistance (>1000 cycles). Furthermore, the C-CST/PMC displayed good antibacterial, antioxidant, hemo-, and cytocompatibility. In vivo tests on diabetic rats have demonstrated that the C-CST/PMC organohydrogel effectively reduces inflammatory responses and promotes angiogenesis, consequently expediting wound healing. Notably, trials involving the use of this flexible sensor in a medical silicone bionic shoulder have indicated its potential as a wearable electronic device for real-time monitoring of human wound healing progress. Overall, this research contributes novel insights to the design and fabrication of multifunctional flexible sensors that synchronous pro-healing and real-time monitoring of traumatic skin.

研究领域: 生物医学工程 · 材料科学 · 创伤修复
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ACS Applied Nano Materials · 2024 · IF 5.3

pH-Responsive Medical Dressing Based on Zinc Sulfide Nanoparticle/Silk Fibroin Composite Fibers

Yueyue Yang,Guojin Liu,Yang Tang,Yuqi Xu,Teng Ma,Wanbin Ma,Hailin Zhu,Jianyong Chen,Caihong Lei,Yin Wang

Wound dressings play a crucial role in wound treatment. Silk fibroin fiber membranes prepared via electrostatic spinning have generated medical wound dressings, exhibiting good biocompatibility with hemostatic, antimicrobial, and pro-healing properties. A pH-responsive ZnS/SF composite fiber membrane was prepared by loading zinc sulfide (ZnS) nanoparticles into a silk fibroin fiber membrane via in situ polymer matrix growth. The composite fiber membranes produced under the optimized conditions were successfully loaded with nanoscale ZnS particles. They had a dense reticular structure and high-water absorption with good biocompatibility and hemostatic properties. Upon exposure to an acidic microenvironment at the wound site, ZnS reacted with H+, giving a sustained release of hydrogen sulfide (H2S) and zinc ions (Zn2+), possessing strong bactericidal activity and pro-cell migration effects, facilitating angiogenesis. The composite fiber film is effective in helping to further promote wound healing when it is used as a wound dressing. This pH-responsive multifunctional ZnS/SF composite fiber membrane has potential applications in medical wound dressings.

研究领域: 生物材料学 · 医学工程 · 组织工程
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Multifunctional coaxial gelatin/polylactic acid three-dimensional nanofibrous scaffolds for diabetic wounds

Xin Chen,Jingwen Wu,Tong Zhang,Hanfeng Li,Ruiying Zhang,Weipeng Lu,Yanchuan Guo

Diabetes, characterized by hyperglycemia, poses a significant threat to human health. Diabetic wounds exhibit heightened levels of excessive reactive oxygen species (ROS), bacterial infection, hypoxia, and substantial exudate. These factors accelerate the inflammatory phase and impede wound healing, often leading to chronicity. Inadequate wound healing is a common chronic complication of diabetes. In this study, we fabricated three-dimensional (3D) curcumin@(manganese dioxide (MnO 2 )@(gelatin/polylactic acid (PLA)@ε-polylysine (ε-pl))) (GPPMC) nanofibrous scaffolds dressing using coaxial electrospinning, homogenization, freeze-drying, glutaraldehyde crosslinking, and impregnation techniques. The presented gelatin-based 3D nanofibrous dressing demonstrated superior water absorption capacity, hemostatic proficiency, enhanced cell adhesion and tissue infiltration compared to two-dimensional (2D) counterparts. It also exhibited exceptional compressibility, biocompatibility, prolonged curcumin and ε-pl drug release, as well as scavenging capabilities against ROS, antibacterial efficacy and oxygen generation in vitro. Additionally, this dressing exhibited remarkable wound healing efficacy and anti-inflammatory in vivo. These findings suggested that the developed multifunctional gelatin-based 3D nanofibrous scaffold is a promising candidate for the treatment of diabetic wounds.

研究领域: 生物医学工程 · 材料科学 · 糖尿病研究
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Frontiers in Bioengineering and Biotechnology · 2023 · IF 5.7

Microneedle patches containing mesoporous polydopamine nanoparticles loaded with triamcinolone acetonide for the treatment of oral mucositis

Qu Xiaoying,Guo Xiaoli,Zhu Tingting,Zhang Zhe,Wang Wanchun,Hao Yuanping

Oral mucositis (OM) is the most common disease of the oral mucosa, which affects people’s daily production and life. Triamcinolone ointment is the common clinical drug for OM treatment. However, the hydrophobic properties of triamcinolone acetonide (TA) and the complex microenvironment of the oral cavity led to its low bioavailability and unstable therapeutic effects on ulcer wounds. Herein, dissolving microneedle patches (MNs) composed of mesoporous polydopamine nanoparticles (MPDA) loaded with TA (TA@MPDA), sodium hyaluronic acid (HA), and Bletilla striata polysaccharide (BSP) are prepared as the transmucosal delivery system. The prepared TA@MPDA-HA/BSP MNs exhibit well-arranged microarrays, high mechanical strength and fast solubility (<3 min) properties. In addition, the hybrid structure improves the biocompatibility of TA@MPDA and expedites oral ulcer healing in the SD rat model through the synergistic anti-inflammatory and pro-healing effects of microneedle ingredients (hormones, MPDA and Chinese herbs extracts), with 90% less amount of TA compared with Ning Zhi Zhu®. TA@MPDA-HA/BSP MNs are shown to be their great potential as novel ulcer dressings for OM management.

研究领域: 药学 · 纳米技术 · 药物递送系统 · 口腔健康 · 生物医学工程
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

An injectable, self-healable, antibacterial, and pro-healing oxidized pullulan polysaccharide/carboxymethyl chitosan hydrogel for early protection of open abdominal wounds

Yeying Zhao,Ruojing Li,Yangyang Liu,Lei Song,Zhao Gao,Ze Li,Xingang Peng,Peige Wang

Open abdomen (OA) is an effective method for treating critical abdominal conditions such as severe abdominal infections. The temporary abdominal closure (TAC) technique is often used to temporarily restore the physiological environment of the abdominal cavity and maintain the homeostatic balance of the abdominal cavity. However, most of the common TAC materials available today lack bio-responsiveness, tend to abrade the intestinal canal, and lead to delayed tissue healing of the wound. Hydrogels could mimic the extracellular matrix and have shown significant potential in life science fields such as tissue regeneration, wound repair, and controlled drug release. In this study, a composite hydrogel scaffold was constructed by the Schiff base reaction of oxidized pullulan polysaccharide with carboxymethyl chitosan. The hydrogel exhibited excellent self-healing, cellular biocompatibility, and antibacterial and anti-inflammatory abilities, and in experiments it reduced secondary damage caused by friction between tissue and patch, thereby preventing serious complications such as intestinal fistula, promoted M1–M2 polarization of macrophages, reduced the inflammatory response, regulated the inflammatory microenvironment in vivo, promoted angiogenesis and granulation tissue regeneration, and accelerated wound healing. Therefore, our hydrogel provides a new strategy for material-assisted wound protection during OA and has potential clinical applications.

研究领域: 生物材料 · 伤口愈合 · 组织工程 · 生物医学工程
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Endogenous stimulation-driven Janus mesh with antibacterial, anti-adhesive and prohealing performances for hernia repair

Liwei Sun,Xu Zhang,Jiteng Zhang,Xinmeng Li,Jie Zhao,Rujian Jiang,Lingjie Song,Shifang Luan

Hernia incidence remains a high level worldwide as witnessed by the fact that more than 20 million hernias are estimated to be repaired each year. Mesh-based hernioplasty allowing wound defects to close more easily and low recurrence rate is considered as the gold standard option for hernia repair. However, clinical polypropylene mesh (PPM) is still lack of effective treatments for the unavoidable bacterial infection, postoperative adhesion and foreign body reaction. Herein, a stimulus-responsive gel was constructed on the PPM by a simple photo-initiated polymerization. The homogeneous gel-modified mesh could spontaneously transform to a Janus mesh locally under endogenous stimulations evoked from inflammatory response or bacterial infection, and demonstrate asymmetric performances. One side of the Janus mesh facing the abdominal viscera could maintain intact gel structures and form a hydration layer to hinder the stick of proteins and cells, while the other side adjacent to the hernia defect site where bacteria prefer to colonize would accelerate degradation due to bacterial growth and release the bactericidal agent for combating the bacterial infection. The in vivo experiments’ results demonstrated that no adhesions were detectable on the Janus mesh treated group on the 14th day and the level of inflammatory response in histological evaluation was lower as compared to the commercial PPM. Overall, the endogenous stimulation-driven Janus gel network in abdominal wall wound provides a new approach for soft tissue repair biomaterials.

研究领域: 生物医学工程 · 材料科学 · 组织工程 · 外科材料 · 伤口愈合
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Frontiers in Bioengineering and Biotechnology · 2022 · IF 6.064

3D-printed Sr2ZnSi2O7 scaffold facilitates vascularized bone regeneration through macrophage immunomodulation

Hao Pan,Li Deng,Lingwei Huang,Qi Zhang,Jing Yu,Yueyue Huang,Lei Chen,Jiang Chang

Biomaterial-based bone grafts are emerged as an effective strategy for the treatment of large bone defects, especially for the scaffolds with enhanced osteogenic and angiogenic bioactivities. However, most studies focused on the direct interactions between scaffolds and bone-related cells such as osteoblasts and endothelial cells, and ignored the effects of material-triggered immunomodulation and the subsequent immune-regulated bone regeneration process. In this study, we developed a silicate bioceramic (Sr 2 ZnSi 2 O 7 , SZS) scaffold with well-defined pore structures using a three-dimensional (3D) printing technique. The prepared scaffolds were biodegradable, and the released bioactive ions were beneficial for immunomodulation, which stimulated macrophages to release more pro-healing cytokines and less pro-inflammatory cytokines. The obtained scaffold/macrophage conditioned medium further promoted the proliferation and osteogenic differentiation of a murine preosteoblast cell line (MC3T3-E1), as well as the angiogenic activity of human umbilical vein endothelial cells (HUVECs). Moreover, the in vivo experiments of critical-sized calvarial defects in rats revealed that the 3D printed SZS scaffolds could facilitate more vascularized bone regeneration than the 3D printed β-tricalcium phosphate (β-TCP, a typical clinically used bioceramic) scaffolds, suggesting that the 3D-printed SZS scaffolds hold the potential as implantable biomaterials with favorable osteoimmunomodulation for bone repair.

研究领域: 生物材料 · 组织工程 · 免疫学 · 再生医学 · 骨科
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Advanced Healthcare Materials · 2021 ·Vol. 11 ·期 3 ·2102236 · IF 9.933

A Hierarchical-Structured Mineralized Nanofiber Scaffold with Osteoimmunomodulatory and Osteoinductive Functions for Enhanced Alveolar Bone Regeneration

Yang He,Mi Tian,Xilin Li,Jianwen Hou,Song Chen,Guang Yang,Xian Liu,Shaobing Zhou

Alveolar bone resorption is a major cause of teeth loss and jeopardizes the osseointegration of dental implants, greatly affecting patient's quality of life and health. It is still a great challenge to completely regenerate the alveolar bone defect through traditional guided bone regeneration (GBR) membranes due to their limited bioactivity and regeneration potential. Herein, a new hierarchical-structured mineralized nanofiber (HMF) scaffold, which is combined with both anisotropic and isotropic nanofibrous surface topography and the mineralized particles, is fabricated via a simple template-assisted electrospinning technology and in situ mineralization method. This HMF scaffold can not only directly induce osteogenic differentiation of bone mesenchymal stem cells (osteoinduction), but also stimulate macrophage toward pro-healing (M2) phenotype-polarization with an elevated secretion of the pro-healing cytokines, eventually enhancing the osteogenesis (osteoimmunomodulation). The results of in vivo rat alveolar bone defect repair experiments demonstrate that as compared with the combination of commercial Bio-Gide and Bio-Oss, the single HMF scaffold shows comparable or even superior bone repair effect, with better tissue-integration and more suitable degradation time and accompanied by a simplified operation.

CAS / MDL: 75-89-8
研究领域: 生物材料 · 组织工程 · 再生医学 · 口腔种植学 · 生物医学工程
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BIOMATERIALS · 2021 · IF 12.479

Aligned microfiber-induced macrophage polarization to guide schwann-cell-enabled peripheral nerve regeneration

Xianhao Dong,Siyang Liu,Yueyue Yang,Shan Gao,Wenlei Li,Jiasong Cao,Ye Wan,Ziqi Huang,Guanwei Fan,Quan Chen,Hongjun Wang,Meifeng Zhu,Deling Kong

Mechanistic understanding of the topological cues delivered by biomaterials in promotion of oriented tissue regeneration ( e.g ., peripheral nerve regrowth) remains largely elusive. Here, we engineered nerve conduits composed of oriented microfiber-bundle cores and randomly organized nanofiber sheaths to particularly interrogate the regulatory mechanism of microfiber orientation on promoted peripheral nerve regeneration . With comprehensive yet systematic analyses, we were able to elucidate the intricate cascade of biological responses associated with conduit-assisted nerve regrowth, i.e ., oriented microfibers facilitated macrophage recruitment and subsequent polarization toward a pro-healing phenotype, which in turn promoted Schwann cell (SC) migration, myelinization and axonal extension. Pronounced improvement of nerve regeneration in rat sciatic nerve injury was evidenced with enhanced electrophysiologic function, sciatic functional index and alleviated muscle atrophy 3 months post-implantation. The obtained results offer essential insights on the topological regulation of biomaterials in functional nerve tissue regeneration via immune modulation .

CAS / MDL: 920-66-1
研究领域: 生物材料 · 组织工程 · 神经科学 · 再生医学 · 免疫学
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