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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Enhanced enzyme-like DNAzyme@MOFs for non-enzymatic uric acid detection in interstitial fluid

Jiuhong Zhao,Wenjing Zhu,Yuxuan Mao,Guixia Ling,Peng Zhang

The increased uric acid (UA) level is closely related to many diseases. However, the detection of UA remains great challenges due to the pain of blood testing and the complexity of common methods. Therefore, the detection of UA is of great significance for public health. In this paper, a new method for UA detection is proposed. The swellable hydrogel microneedles (hydrogel MNs) can be used for minimally invasive extraction of skin interstitial fluid (ISF). The colorimetric detection of trace UA in ISF can be successfully achieved by virtue of DNAzyme@MOFs with enhanced peroxidase activity. This study provides a powerful tool for minimally invasive, painless, rapid and convenient detection of UA in clinical applications. This study not only avoids the use of expensive and unstable natural enzymes but also expands the applications of DNAzyme@MOFs in biomedical detection.

CAS / MDL: 54827-17-7
研究领域: 医学检测 · 生物化学 · 材料科学
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Scientific Reports · 2017 ·Vol. 7 ·期 1 ·1-10 · IF 4.259

Minimally Invasive Hemostatic Materials: Tackling a Dilemma of Fluidity and Adhesion by Photopolymerization in situ

Zhang Yun,Song Dandan,Huang Hong,Liang Zhiling,Liu Houhe,Huang Yugang,Zhong Cheng,Ye Guodong

Hemostasis in vivo is a key to success in minimally invasive surgery (MIS). However, solid hemostatic materials cannot pass through the sheath tube of the MIS apparatus, while liquid ones are restricted by their low adhesion, which leads to them peeling off of tissue. To tackle the dilemma of fluidity and adhesion, a formulation containing a multifunctional sucrose allyl ether (SAE) monomer and an alpha-hydroxyketone liquid photoinitiator (HMPP) was applied as a lead hemostatic material for MIS. Real-time infrared results showed that SAE initiated by HMPP can rapidly polymerize into a transparent crosslinking membrane. Quantum chemistry showed that this occurs via a free radical addition reaction mechanism. Thermodynamic properties, such as reaction driving force and enthalpy change, were similar to those for a corresponding small molecular analogue, allyl methyl ether (AME), but the addition rate was lower than that for AME. The CC50 values of SAE and HMPP were also obtained by cell experiments. A hemostasis experiment in vivo was performed by comparing the formulation with chitosan and a traditional Chinese medicine (Yunnan Baiyao powder). The result showed that the formulation had a competitive advantage for use in MIS.

研究领域: 生物医学工程 · 外科手术
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Drug Design Development and Therapy · 2019 · IF 3.208

Drug-release system of microchannel transport used in minimally invasive surgery for hemostasis

Hong Huang,Houhe Liu,Hua Zhou,Zhiling Liang,Dandan Song,Yun Zhang,Wanqiu Huang,Xiaotian Zhao,Bo Wu,Guodong Ye,Yugang Huang

Background Sucrose allyl ether (SAE) containing hemostatic drugs and a photoinitiator was established to treat mild postpartum hemorrhage or long-term continuous abnormal uterine bleeding in minimally invasive surgery (MIS) using a photopolymerization method.Methods and results Real-time infrared spectroscopy and rheological experiments showed that the SAE monomer with shear-thinning characteristics could polymerize rapidly into a transparent membrane. Cytotoxicity experiments in vitro showed that this system could elicit a long-term hemostatic effect. Tissue adhesion was also evaluated. The photo-stability of four delivered antifibrinolytic drugs (6-aminocaproic acid, ethylenediaminediacetic acid, tranexamic acid and p-(aminomethyl) benzoic acid) was tested by ultraviolet-photolysis experiments and illustrated by time-dependent density functional theory. Sustained-release experiments revealed that the formed film could be used as a drug carrier. Molecular docking and molecular dynamics were done to investigate the binding mechanism between hemostatic drugs as ligands and the human plasminogen kringle-1 (1HPK) as a target.Conclusion It has been suggested that SAE with tranexamic acid could be a drug-release system of microchannel transport used in MIS. This system could tackle the dilemma of fluidity and adhesion in MIS. The photo-stable tranexamic acid was the most suitable drug according to its satisfactory binding energy, good photo-stability, and sustained release.

CAS / MDL: 75-05-8 67-56-1
研究领域: 医学 · 药学
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Advanced Science · 2021 ·Vol. 9 ·期 2 ·2102405 · IF 16.806

Raman Nanotags-Guided Intraoperative Sentinel Lymph Nodes Precise Location with Minimal Invasion

Binge Deng,Yaohui Wang,Yifan Wu,Wenjin Yin,Jinsong Lu,Jian Ye

The accurate positioning of sentinel lymph node (SLN) by tracers during surgery is an important prerequisite for SLN biopsy. A major problem of traditional tracers in SLN biopsy is the short surgery window due to the fast diffusion of tracers through the lymphatics, resulting in a misjudgment between SLN and second echelon lymph node (2 nd LN). Here, a nontoxic Raman nanoparticle tracer, termed gap-enhanced Raman tags (GERTs), for the accurate intraoperative positioning of SLNs with a sufficient surgical time window is designed. In white New Zealand rabbit models, GERTs enable precise identification of SLNs within 10 min, as well as provide the surgeon with a more than 4 h time window to differentiate SLN and 2 nd LN. In addition, the ultrahigh sensitivity of GERTs (detection limit is 0.5 × 10 −12 m ) allows detection of labeled SLNs before surgery, thereby providing preoperative positioning information for minimally invasive surgery. Comprehensive biosafety evaluations carried out in the context of the Food and Drug Administration and International Standard Organization demonstrate no significant toxicity of GERTs, which supports a promising clinical translation opportunity of GERTs for precise SLN identification in breast cancer.

CAS / MDL: 9003-39-8
研究领域: 肿瘤学 · 生物医学工程 · 外科手术
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Frontiers in Neurology · 2022 · IF 4.086

Minimally Invasive Surgery for ICH Evacuation Combined With Deferoxamine Treatment Increased Perihematomal Claudin-5 and ZO-1 Expression Levels and Decreased BBB Permeability in Rabbits

Ren Siying,Han Shanshan,Wang Likun,Huang Yuanxin,Wu Jing,Wu Guofeng

Objective: To investigate the role of minimally invasive surgery (MIS) in intracerebral hemorrhage (ICH) evacuation combined with deferoxamine (DFX) treatment on perihematomal tight junction protein (claudin-5 and ZO-1) expression levels and blood-brain barrier (BBB) permeability in rabbits.Methods: We randomly assigned 65 male rabbits (weight: 1.9–2.6 kg) to a normal control group (NC group, 13 rabbits), hemorrhage model group (HM group, 13), DFX treatment group (DFX group, 13 rabbits), MIS group (MIS group, 13 rabbits), or MIS combined with DFX treatment group (MIS + DFX group, 13 rabbits). ICH was established in all of the groups except the NC group. MIS was performed to evacuate the hematoma 6 h after the ICH model was created in the MIS and MIS + DFX groups. The DFX and MIS + DFX groups were treated with DFX (100 mg/kg, dissolved in 2 mL of 0.9% saline solution, administered intramuscularly) at 2 h, and then every 12 h for 7 d. The same dose of 0.9% saline solution was administered to the NC, HM, and MIS groups at the same time points. Sixty-five rabbits were divided into 5 groups, and 13 rabbits in each group. Neurological deficit (i.e., Purdy's score) was recorded in all rabbits before euthanasia (N total = 65). In each group, 2 rabbits were used for iron concentration measurement (N total = 10), 2 rabbits were used for brain water content measurement (N total = 10), 3 rabbits were used for BBB permeability measurement (N total = 15), 3 rabbits were used for claudin-5, ZO-1 expression detection by Western Blotting (N total = 15), and 3 rabbits were used for claudin-5, ZO-1 mRNA detection by real-time PCR (N total = 15). On day 7, the rabbits were sacrificed and the perihematomal brain tissue was harvested to test the iron concentration, brain water content (BWC), tight junction proteins (claudin-5 and ZO-1) expression, and BBB permeability.Results: Purdy's score, iron concentration, and BWC were lower in the MIS and MIS + DFX groups compared to the HM and DFX groups. The MIS + DFX group showed a significant decrease in these indicators. The use of MIS to evacuate the hematoma led to increased expression levels of claudin-5 and ZO-1, as well as decreased BBB permeability. The MIS + DFX group exhibited a remarkable increase in claudin-5 and ZO-1 expression levels and a significant decrease in BBB permeability.Conclusions: MIS combined with DFX treatment could increase the expression levels of perihematomal tight junction proteins (claudin-5 and ZO-1) expression, reduce BBB permeability, and improve the neurological function. MIS combined with DFX treatment may also prevent secondary brain damage following ICH.

CAS / MDL: 75-12-7
研究领域: 神经科学 · 医学
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Science Advances · 2024 ·Vol. 10 ·期 5 · IF 11.7

tPA-anchored nanorobots for in vivo arterial recanalization at submillimeter-scale segments

Ben Wang,Qinglong Wang,Kai Fung Chan,Zhipeng Ning,Qianqian Wang,Fengtong Ji,Haojin Yang,Shuai Jiang,Zifeng Zhang,Bonaventure Yiu Ming Ip,Ho Ko,Jacqueline Pui Wah Chung,Ming Qiu,Jianguo Han,Philip Wai Yan Chiu,Joseph Jao Yiu Sung,Shiwei Du,Thomas Wai Hong Leung,Simon Chun Ho Yu,Li Zhang

Micro/nanorobots provide a promising approach for intravascular therapy with high precision. However, blood vessel is a highly complex system, and performing interventional therapy in those submillimeter segments remains challenging. While micro/nanorobots can enter submillimeter segments, they may still comprise nonbiodegradable parts, posing a considerable challenge for post-use removal. Here, we developed a retrievable magnetic colloidal microswarm, composed of tPA-anchored Fe3O4@mSiO2 nanorobots (tPA-nbots), to archive tPA-mediated thrombolysis under balloon catheter-assisted magnetic actuation with x-ray fluoroscopy imaging system (CMAFIS). By deploying tPA-nbot transcatheter to the vicinity of the thrombus, the tPA-nbot microswarms were magnetically actuated to the blood clot at the submillimeter vessels with high precision. After thrombolysis, the tPA-nbots can be retrieved via the CMAFIS, as demonstrated in ex vivo organ of human placenta and in vivo carotid artery of rabbit. The proposed colloidal microswarm provides a promising robotic tool with high spatial precision for enhanced thrombolysis with low side effects.

研究领域: 医学工程 · 生物材料 · 介入治疗
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Advanced Composites and Hybrid Materials · 2025 ·Vol. 8 ·期 3 ·1-21 · IF 21.8

A novel composite meniscus scaffold with shape memory and adhesive properties alleviates knee cartilage degeneration through minimally invasive and sutureless approach

Yan Wenqiang,Tian Feng,Zhao Lingyu,Wang Pengyi,Zhang Manwen,Gao Zeyuan,Huang Wei,Ao Yingfang,Yu Ran

Three-dimensionally (3D) printed engineered meniscus scaffolds offer a promising therapeutic strategy for post-meniscectomy defects. Nevertheless, existing scaffolds face critical limitations impeding clinical implementation. Primarily, the transplantation procedure necessitates larger incisions in skin and joint capsules due to insufficient scaffold deformability. This invasive approach risks iatrogenic tissue damage, prolongs recovery timelines, and compromises aesthetic outcomes. Secondly, conventional fixation methods involving sutures to peripheral meniscal remnants or capsular tissues introduce dual complications: mechanical perforation of scaffolds reduces structural integrity and accelerates degradation, while the demanding technical requirements for suture placement increase surgical complexity. To address these challenges, we engineered a composite meniscus scaffold featuring an elastomeric skeleton fabricated via digital light processing (DLP) 3D printing integrated with a hydrogel matrix. This biomimetic design recapitulates the native meniscus architecture comprising an aqueous extracellular matrix reinforced by collagen fibrils. The composite scaffold demonstrates three critical functional attributes: 1) biomechanical properties approximating native meniscus tissue, 2) exceptional shape recovery capabilities facilitating trans-arthroscopic delivery through minimally invasive portals, and 3) strong interfacial adhesion enabling suture-free fixation via covalent bonding to host tissues. In vivo evaluation using a rabbit meniscectomy model confirmed the scaffold’s chondroprotective efficacy. Notably, preclinical validation in an ex vivo ovine knee under arthroscopic guidance demonstrated successful scaffold deployment through subcentimeter incisions with stable adhesion to residual meniscal tissue. This innovative design eliminates suture-related complications while reducing surgical invasiveness, thereby presenting a clinically translatable solution for irreparable meniscal injuries.

研究领域: 生物医学工程 · 再生医学 · 骨科
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

Hypoxia-Overcoming Breast-Conserving Treatment by Magnetothermodynamic Implant for a Localized Free-Radical Burst Combined with Hyperthermia

Jingsong Lu,Zhenhu Guo,Wensheng Xie,Yongjie Chi,Wanling Xu,Xiaoxiao Guo,Xiaohan Gao,Jielin Ye,Benhua Xu,Rong Zheng,Xiaodan Sun,Xiumei Wang,Shenglei Che,Jing Yu,Lingyun Zhao

For the purpose of improving the quality of life and minimizing the psychological morbidity of a mastectomy, breast-conserving treatment (BCT) has become the more preferable choice in breast cancer patients. Meanwhile, tumor hypoxia has been increasingly recognized as a major deleterious factor in cancer therapies. In the current study, a novel, effective, and noninvasive magnetothermodynamic strategy based on an oxygen-independent free-radical burst for hypoxia-overcoming BCT is proposed. Radical precursor (AIPH) and iron oxide nanoparticles (IONPs) are coincorporated within the alginate (ALG) hydrogel, which is formed in situ within the tumor tissue by leveraging the cross-linking effect induced by the local physiological Ca2+ with ALG solution. Inductive heating is mediated by IONPs under AMF exposure, and consequently, regardless of the tumor hypoxia condition, a local free-radical burst is achieved by thermal decomposition of AIPH via AMF responsivity. The combination of magnetic hyperthermia and oxygen-irrelevant free-radical production effectively enhances the in vitro cytotoxic effect and also remarkably inhibits tumor proliferation. This study provides a valuable protocol for an hypoxia-overcoming strategy and also an alternative formulation candidate for noninvasive BCT.

研究领域: 肿瘤学 · 生物医学工程 · 材料科学
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ANALYTICAL CHEMISTRY · 2021 · IF 6.986

Ultrasonic Sputter Desorption Mass Spectrometry Technique for Minimally Invasive Tissue Analysis

Xian Fu,Yu Wang,Bing Xia,Peiyu Shi,Yan Zhou

Minimally invasive techniques for in vivo tissue analysis are desired by life science and medical research. Herein, a new ionization interface coupled with ultrasonic sputter desorption (USD) was developed for in vitro and in vivo tissue analysis. Sample molecules were effectively sputtered out when the high-frequency ultrasonic probe touched the tissue. Then, the sputtered molecules were collected and ionized by a custom-made heated quartz tube and finally analyzed by mass spectrometry (MS) online. The sample pretreatment of the USD-MS technique was quite simple and required no other steps except for wetting the tissue surface with ethanol to assist molecular extraction. Experimental results demonstrated that the proposed method was suitable for the analysis of different morphologies of tissues (such as liver, brain, kidney, and lung) and performed well in the analysis of liver tumors and paracancerous tissues. Moreover, as the proposed method caused little damage to the tissues during analysis, rats and mice with orthotopic tumors still survived after the experiments. Overall, the newly developed USD-MS technique was an effective tool for minimally invasive tissue analysis and could be used as a new candidate method for in situ and real-time analysis of biological tissues in vitro and in vivo.

CAS / MDL: 34819-78-8
研究领域: 分析化学 · 生物医学工程 · 分子生物学
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CARBOHYDRATE POLYMERS · 2020 · IF 7.182

Nonswelling injectable chitosan hydrogel via UV crosslinking induced hydrophobic effect for minimally invasive tissue engineering

Haichang Ding,Baoqiang Li,Zonglin Liu,Gang Liu,Shouzhi Pu,Yujie Feng,Dechang Jia,Yu Zhou

Injectable chitosan hydrogels exhibit excellent biological properties for application in biomedical engineering, however most of these hydrogels have limited applicability because “Swelling” can induce volume expansion of conventional hydrogels implanted in the body damages the surrounding tissues. Here, we report a new “Nonswelling” pentenyl chitosan (PTL-CS) hydrogel via N‒acylation reaction to graft an UV crosslinkable short hydrophobic alkyl chain ( n ‒pentenyl groups). The incorporated pentenyl groups can be crosslinked by UV irradiation to form hydrophobic chains via combination termination, which generate strong hydrophobic effect to extrude the excess water in hydrogel, resulting in a “Nonswelling” state at biological temperature. Furthermore, the PTL-CS solution showed no cytotoxicity in vitro and minimally invasive treatment in vivo demonstrated the PTL-CS hydrogel no adverse effects in a rat model. The nonswelling injectable and UV crosslinkable chitosan hydrogel hold potential applications in smart biomaterials and biological engineering as well as providing a new natural hydrogel in minimally invasive tissue engineering..

研究领域: 生物医学工程 · 材料科学
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JOURNAL OF NANOBIOTECHNOLOGY · 2020 ·Vol. 18 ·期 1 ·1-15 · IF 6.518

The microneedles carrying cisplatin and IR820 to perform synergistic chemo-photodynamic therapy against breast cancer

Fu Ji-jun,Li Chu-wen,Liu Yang,Chen Ming-yue,Zhang Qiang,Yu Xi-yong,Wu Bo,Li Jie-xia,Du Ling-ran,Dang Yuan-ye,Wu Dan,Wei Min-yan,Lin Zhi-qiang,Lei Xue-ping

Backgrounds Surgical resection and adjunct chemotherapy or radio-therapy has been applied for the therapy of superficial malignant tumor in clinics. Whereas, there are still some problems limit its clinical use, such as severe pains and side effect. Thus, it is urgent need to develop effective, minimally invasive and low toxicity therapy stagey for superficial malignant tumor. Topical drug administration such as microneedle patches shows the advantages of reduced systemic toxicity and nimble application and, as a result, a great potential to treat superficial tumors. Methods In this study, microneedle (MN) patches were fabricated to deliver photosensitizer IR820 and chemotherapy agent cisplatin (CDDP) for synergistic chemo-photodynamic therapy against breast cancer. Results The MN could be completely inserted into the skin and the compounds carrying tips could be embedded within the target issue for locoregional cancer treatment. The photodynamic therapeutic effects can be precisely controlled and switched on and off on demand simply by adjusting laser. The used base material vinylpyrrolidone—vinyl acetate copolymer (PVPVA) is soluble in both ethanol and water, facilitating the load of both water-soluble and water-insoluble drugs. Conclusions Thus, the developed MN patch offers an effective, user-friendly, controllable and low-toxicity option for patients requiring long-term and repeated cancer treatments.

研究领域: 肿瘤学 · 药学 · 生物医学工程
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ACS Applied Polymer Materials · 2025 · IF 4.7

3D-Printed Thermally Activated Shape Memory PLA/TBC Composite Scaffold with Body-Compatible Temperature for Minimally Invasive Bone Repair

Yanjian Huang,Yufeng Mao,Hongfa Li,Enyu Wang,Huaming Mai,Wenjie Zhang,Jieming Wen,Hui You,Yu Long,Wang Guo,Bin Liu,Shan Wang

Shape memory polymers (SMPs) can transform between initial and programmed shapes under certain stimuli and have promising potential in developing shape-adaptative bone scaffolds to treat irregular bone defects in minimally invasive implantation. Polylactic acid (PLA) is a degradable, biocompatible polymer that has thermal-responsive shape memory properties; however, its high transition temperature (approximately 50–60 °C) limits clinical applicability. This study proposes to develop a shape memory PLA based composite bone scaffold that can be gently thermally driven under a moderate temperature near the body by adding tributyl citrate (TBC) and fabricated via FDM 3D printing. The 3D-printed PLA/TBC composite scaffolds showed ordered porous structures with an orthogonal periodic interconnection. The mechanical test showed that TBC significantly increased the toughness of the scaffolds while it decreased its strength and modulus. The thermal physical property test showed that the glass transition temperature was successfully reduced from 54.9 °C (pure PLA) to 40.2 °C (10% TBC), approaching body temperature through TBC’s plasticization mechanism where low-MW ester molecules increased PLA chain mobility, thereby enhancing their flexibility. The shape memory test showed the shape fixation rate of the PLA/TBC scaffold achieved 97.2% with 10% TBC, and it can transform from programmed shape to initial shape in 30 s with a shape recovery rate of 92.8% under a gentle thermal stimulation at 45 °C. Then, proof of concept of this scaffold for minimally invasive implantation of the irregular bone defect model was presented. Besides, other tests showed that the hydrophilicity and degradation performance of the scaffolds were improved with TBC. Meanwhile, TBC also promoted the biomineralization and cellular response of the scaffold. This study provides an insight for developing shape- and temperature-adaptive bone scaffolds for minimally invasive repair of irregular bone defects.

CAS / MDL: 77-94-1
研究领域: 生物材料学 · 医学工程 · 组织工程
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