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Regenerative Biomaterials · 2024 · IF 5.6

Amorphous curcumin-based hydrogels to reduce the incidence of Post-Surgical intrauterine adhesions

Zhang Wenya,He Yuxin,Chu Yun,Zhai Yuanxin,Qian Song,Wang Xinhui,Jiang Pengju,Cui Pengfei,Zhang Yin,Wang Jianhao

The incidence of intrauterine adhesions (IUA) was raised accompanied by the increasing utilization of intrauterine surgery. The postoperative physical barrier methods commonly used, such as balloons and other fillers, have limited effectiveness and may even cause further damage to the remaining endometrial tissue. Herein, we developed an injectable thermosensitive hydrogel using Pluronic F127/F68 as pharmaceutical excipients and curcumin as a natural active molecule. The hydrogel effectively addresses solubility and low bioavailability issues associated with curcumin. In vitro, drug release assays revealed that the amorphous curcumin hydrogel promotes dissolution and sustained release of curcumin. In vitro experiments reveal high biocompatibility of the hydrogel and its ability to enhance vascular formation while inhibiting the expression of fibrotic factor TGF-β1. To assess the effectiveness of preventing intrauterine adhesions, in vivo experiments were conducted using IUA rats and compared with a class III medical device, a new-crosslinked hyaluronic acid gel (NCHA). According to the study, curcumin hydrogel is more effective than the NCHA group in improving the regeneration of the endometrium, increasing the blood supply to the endometrium, and reducing the abnormal deposition of fibrin, thus preventing intrauterine adhesion more effectively. This study provides a promising strategy for treating and preventing IUA.

CAS / MDL: 67-68-5
研究领域: 药剂学 · 生物医学工程 · 妇科学
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Science Advances · 2024 ·Vol. 10 ·期 35 · IF 11.7

A temperature-responsive dual-hormone foam nanoengine improves rectal absorptivity of insulin-pramlintide for diabetes treatment

Shujun Feng,Yu Zhang,Chunyuan Hou,Yuta Liu,Yanfeng Gao,Yujun Song,Jun Luo

Despite the therapeutic benefits of insulin-pramlintide dual-hormone therapy in diabetes, its application potential has been limited due to a lack of efficient delivery routes. Here, we developed a temperature-responsive dual-hormone foam nanoengine (HormFoam) and combined it with a customized spraying device to further construct an in situ foam-generating system for improving the rectal bioavailability of dual-hormone therapy. To support rapid clinical translation, a continuous microfluidic preparation for HormFoam was proposed, including the power unit of perfluorocarbon nanodroplets and the pharmaceutical components Pluronic F127–functionalized liposomal insulin and pramlintide. We found that HormFoam could consistently generate foams to drive drugs forward after rectal administration, which enhanced intestinal distribution and mucosa absorption, leading to systemic codelivery of insulin-pramlintide. HormFoam reproduced the physiology of endocrine pancreas for glycemic control and induced body weight loss while reversing metabolic disorders in diabetic mice with good biosafety. Therefore, HormFoam represents a state-of-the-art dual-hormone regimen with the potential to address unmet needs in diabetes management.

CAS / MDL: 18883-66-4 11061-68-0
研究领域: 药学 · 生物医学工程 · 糖尿病研究 · 药物递送系统
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ACS Applied Materials & Interfaces · 2022 · IF 10.383

Injectable and Self-Healing Probiotics-Loaded Hydrogel for Promoting Superbacteria-Infected Wound Healing

Li Mei,Dongjie Zhang,Huarong Shao,Yuanping Hao,Ting Zhang,Weiping Zheng,Yanjing Ji,Peixue Ling,Yun Lu,Qihui Zhou

Superbacteria-induced skin wound infections are huge health challenges, resulting in significant financial and medical costs due to notable morbidity and mortality worldwide. Probiotics are found in the skin and are effective in treating bacterial infection, moderating the microbial dysbiosis and inflammation induced by pathogens, regulating the immune system, as well as even promoting tissue repair. However, improving their colonization efficiency and viability remains a large obstacle for proper applications. Inspired by probiotic therapy and the natural extracellular matrix structure, hyaluronate-adipic dihydrazide/aldehyde-terminated Pluronic F127/fucoidan hydrogels loaded with Lactobacillus rhamnosus (HPF@L.rha) with unique (bio)physicochemical characteristics were developed through the dynamic Schiff-base reaction for superbacteria-infected trauma management. The developed HPF@L.rha exhibit a shortened gelation time, enhanced mechanical strength, and excellent self-healing and liquid-absorption abilities. Importantly, their anti-superbacteria (Pseudomonas aeruginosa) effect was greatly increased in a dose-dependent fashion. Additionally, in vitro evaluation shows that the prepared HPF@L.rha containing appropriate probiotic concentrations (less than 1 × 107 CFU/mL) possess satisfactory cytocompatibility and blood compatibility. Further, compared to the HPF hydrogel, in vivo the hydrogel combined with probiotics significantly inhibits P. aeruginosa infection and inflammation, promotes the formation of re-epithelialization and collagen, and thus accelerates full-thickness superbacteria-infected wound repair, which is comparable to commercial Prontosan gel formulation. This work suggests that the combination of biomimicking hydrogels and probiotic therapy displays the great potential to manage superbug-infected trauma.

研究领域: 生物医学工程 · 材料科学 · 微生物学 · 组织工程 · 药学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Stimulus-responsive nanomedicine mediated by metabolic intervention mechanisms to amplify redox anticancer therapy

Yongli Shen,Lin Wang,Binglong Ji,Xinlei Lu,Delong Zhao,Yujie Dai,Xuan Meng

Metabolic reprogramming and altered redox balance are two common hallmarks of cancer. Redox homeostasis is intricately intertwined with tumor energy metabolism, but the potential for metabolic intervention mechanisms to disrupt redox balance has been consistently underestimated. In this study, we present a stimulus-responsive nanocarrier (NC) designed to leverage metabolic intervention mechanisms to enhance redox-based anticancer therapy. These nanoparticles are composed of zeolitic imidazolate framework-90 (ZIF-90) as the ATP- and pH-responsive porous core, enveloped in an amphiphilic pluronic 407 (poloxamer F127) coating to ensure steric stabilization. Within the core of these hybrid NCs, we co-loaded active cargos 3-bromopyruvate (3-BrPA) and metformin (MET). Serving as a multifaceted inhibitor of both aerobic glycolysis and respiration, 3-BrPA impedes the activities of hexokinase II, leading to reduced glucose consumption and an increase in ROS levels. This synergistic effect, in conjunction with MET, results in a decrease in the levels of reducing substances, sensitizing 3-BrPA-induced apoptosis in cancer cells. At both the cellular and animal levels, these hybrid NCs have demonstrated superior anticancer activity by inhibiting metabolism and disrupting redox homeostasis. This study introduces a novel approach targeting the metabolism-redox interplay for tumor treatment, potentially broadening the scope of available antitumor strategies.

研究领域: 纳米技术 · 癌症生物学 · 药学 · 生物化学 · 治疗学
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Advanced Science · 2024 · IF 14.3

Harnessing Mechanical Stress with Viscoelastic Biomaterials for Periodontal Ligament Regeneration

Jiu-Jiu Zhang,Xuan Li,Yi Tian,Jie-Kang Zou,Dian Gan,Dao-Kun Deng,Chen Jiao,Yuan Yin,Bei-Min Tian,Rui-Xin Wu,Fa-Ming Chen,Xiao-Tao He

The viscoelasticity of mechanically sensitive tissues such as periodontal ligaments (PDLs) is key in maintaining mechanical homeostasis. Unfortunately, PDLs easily lose viscoelasticity (e.g., stress relaxation) during periodontitis or dental trauma, which disrupt cell–extracellular matrix (ECM) interactions and accelerates tissue damage. Here, Pluronic F127 diacrylate (F127DA) hydrogels with PDL-matched stress relaxation rates and high elastic moduli are developed. The hydrogel viscoelasticity is modulated without chemical cross-linking by controlling precursor concentrations. Under cytomechanical loading, F127DA hydrogels with fast relaxation rates significantly improved the fibrogenic differentiation potential of PDL stem cells (PDLSCs), while cells cultured on F127DA hydrogels with various stress relaxation rates exhibited similar fibrogenic differentiation potentials with limited cell spreading and traction forces under static conditions. Mechanically, faster-relaxing F127DA hydrogels leveraged cytomechanical loading to activate PDLSC mechanotransduction by upregulating integrin–focal adhesion kinase pathway and thus cytoskeletal rearrangement, reinforcing cell–ECM interactions. In vivo experiments confirm that faster-relaxing F127DA hydrogels significantly promoted PDL repair and reduced abnormal healing (e.g., root resorption and ankyloses) in delayed replantation of avulsed teeth. This study firstly investigated how matrix nonlinear viscoelasticity influences the fibrogenesis of PDLSCs under mechanical stimuli, and it reveals the underlying mechanobiology, which suggests novel strategies for PDL regeneration.

CAS / MDL: 814-68-6 75-09-2
研究领域: 生物材料 · 组织工程 · 牙科科学 · 生物力学 · 再生医学
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ACS Applied Materials & Interfaces · 2020 · IF 8.758

Mechano-Responsive, Tough, and Antibacterial Zwitterionic Hydrogels with Controllable Drug Release for Wound Healing Applications

Kun Fang,Rong Wang,Hua Zhang,Linjie Zhou,Ting Xu,Ying Xiao,Yang Zhou,Guorong Gao,Jing Chen,Donglei Liu,Fanrong Ai,Jun Fu

Acute wounds subject to frequent deformations are difficult to be treated because the healing process was easily interfered by external mechanical forces. Traditional wound dressings have limited efficacy because of their poor mechanical properties and skin adhesiveness and difficulty in the delivery of therapeutic drugs effectively. As such, tough and skin-adhesive wound dressings with sustainable and stimuli-responsive drug release properties for treatment of those wounds are highly desirable. For this purpose, we have developed a mechano-responsive poly(sulfobetaine methacrylate) hydrogel which aims to control the delivery of antibiotic drug upon application of mechanical forces. Diacrylated Pluronic F127 micelles were used as a macro-cross-linker of the hydrogel and loaded with hydrophobic antimicrobial drugs. The micelle-cross-linked hydrogel has excellent mechanical properties, with the ultimate tensile strength and tensile strain of up to 112 kPa and 1420%, respectively, and compressive stress of up to 1.41 MPa. Adhesiveness of the hydrogel to the skin tissue was ∼6 kPa, and it did not decrease significantly after repetitive adhesion cycles. Protein adsorption on the hydrogel was significantly inhibited compared to that on commercial wound dressings. Because of the mechano-responsive deformation of micelles, the release of drug from the hydrogel could be precisely controlled by the extent and cycles of mechanical loading and unloading, endowing the hydrogel with superior antibacterial property against both Gram-positive and Gram-negative bacteria. In addition, drug penetration into the skin tissue was enhanced by mechanical stress applied to the hydrogel. The micelle-cross-linked zwitterionic hydrogel also showed good cell biocompatibility, negligible skin irritation, and healing capacity to acute skin wounds in mice. Such a tough mechano-responsive hydrogel holds great promise as wound dressings for acute wounds subjected to frequent movements.

研究领域: 材料科学 · 生物医学工程 · 药剂学 · 伤口护理
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Frontiers in Bioengineering and Biotechnology · 2023 · IF 5.7

A poly (glycerol-sebacate-acrylate) nanosphere enhanced injectable hydrogel for wound treatment

Luo Jiajia,Sun Fenglei,Rao Pinhua,Zhu Tonghe,Liu Yonghang,Du Juan,Chen Sihao,Jin Xiangyun,Jin Jiale,Chai Yi

Wound repair remains a huge clinical challenge, which can cause bleeding, infection, and patient death. In our current research, a bioactive, injectable, multifunctional composite hydrogel doped with nanospheres was prepared with antibacterial and angiogenesis-promoting functions for the treatment of wounds. Amino groups in ε-polylysine (ε-EPL) undergo dynamic Schiff base reaction cross-linking with oxidized hyaluronic acid (OHA), and F127 exhibits unique temperature sensitivity to form an injectable thermosensitive hydrogel (FHE10), which can form a hydrogel to cover the wound at body temperature. Nanospheres (PNs) prepared using poly (glyceryl-sebacate-acrylate) (PGSA) were loaded into hydrogels (FHE10) for promoting wound repair. The prepared FHE10 exhibited rapid gelation, good injectable abilities, and showed resistance to the flourish of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In vitro investigations showed that FHE10 had good hemocompatibility and cytocompatibility. FHE10@PNs exhibited good proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) and human foreskin fibroblasts (HFF-1). Furthermore, FHE10@PNs significantly promoted reepithelialization and collagen deposition as well as micro-vascularization compared with the use of FHE10 or PNs alone, thereby accelerating the repair of wounds. In general, this study demonstrated that the multifunctional injectable composite hydrogel showed great potential in wound treatment.

研究领域: 生物医学工程 · 材料科学 · 组织工程 · 伤口愈合
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Advanced Healthcare Materials · 2023 · IF 10

A 4D Printed Adhesive, Thermo-Contractile, and Degradable Hydrogel for Diabetic Wound Healing

Zhe Lu,Jingjing Cui,Fukang Liu,Chen Liang,Shiwei Feng,Yongding Sun,Weizi Gao,Yunlong Guo,Biao Zhang,Wei Huang

Chronic wound healing remains a substantial clinical challenge. Current treatments are often either prohibitively expensive or insufficient in meeting the various requirements needed for effective diabetic wound healing. A 4D printing multifunctional hydrogel dressing is reported here, which aligns perfectly with wounds owning various complex shapes and depths, promoting both wound closure and tissue regeneration. The hydrogel is prepared via digital light process (DLP) 3D printing of the mixture containing N-isopropylacrylamide (NIPAm), curcumin-loaded Pluronic F127 micelles (Cur-PF127), and poly(ethylene glycol) diacrylate-dopamine (PEGDA575-Do), a degradable crosslinker. The use of PEGDA575-Do ensures tissue adhesion and degradability, and cur-PF127 serves as an antibacterial agent. Moreover, the thermo-responsive mainchains (i.e., polymerized NIPAm) enables the activation of wound contraction by body temperature. The features of the prepared hydrogel, including robust tissue adhesion, temperature-responsive contraction, effective hemostasis, spectral antibacterial, biocompatibility, biodegradability, and inflammation regulation, contribute to accelerating diabetic wound healing in Methicillin-resistant Staphylococcus aureus (MRSA)-infected full-thickness skin defect diabetic rat models and liver injury mouse models, highlighting the potential of this customizable, mechanobiological, and inflammation-regulatory dressing to expedite wound healing in various clinical settings.

CAS / MDL: 62-31-7
研究领域: 材料科学 · 生物医学工程 · 组织工程 · 伤口愈合
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Frontiers in Bioengineering and Biotechnology · 2023 · IF 5.7

Injectable FHE+BP composites hydrogel with enhanced regenerative capacity of tendon-bone interface for anterior cruciate ligament reconstruction

Eunshinae Cho,Yi Qiao,Changan Chen,Junjie Xu,Jiangyu Cai,Yamin Li,Jinzhong Zhao

Features of black phosphorous (BP) nano sheets such as enhancing mineralization and reducing cytotoxicity in bone regeneration field have been reported. Thermo-responsive FHE hydrogel (mainly composed of oxidized hyaluronic acid (OHA), poly-ε-L-lysine (ε-EPL) and F127) also showed a desired outcome in skin regeneration due to its stability and antibacterial benefits. This study investigated the application of BP-FHE hydrogel in anterior cruciate ligament reconstruction (ACLR) both in in vitro and in vivo , and addressed its effects on tendon and bone healing. This BP-FHE hydrogel is expected to bring the benefits of both components (thermo-sensitivity, induced osteogenesis and easy delivery) to optimize the clinical application of ACLR and enhance the recovery. Our in vitro results confirmed the potential role of BP-FHE via significantly increased rBMSC attachment, proliferation and osteogenic differentiation with ARS and PCR analysis. Moreover, In vivo results indicated that BP-FHE hydrogels can successfully optimize the recovery of ACLR through enhancing osteogenesis and improving the integration of tendon and bone interface. Further results of Biomechanical testing and Micro-CT analysis [bone tunnel area (mm2) and bone volume/total volume (%)] demonstrated that BP can indeed accelerate bone ingrowth. Additionally, histological staining (H&E, Masson and Safranin O/fast green) and immunohistochemical analysis (COL I, COL III and BMP-2) strongly supported the ability of BP to promote tendon-bone healing after ACLR in murine animal models.

研究领域: 组织工程 · 再生医学 · 骨科手术 · 生物材料科学
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