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MACROMOLECULAR BIOSCIENCE · 2023 ·Vol. 23 ·期 4 ·2200554 · IF 4.6

Injectable Polyzwitterionic Lubricant for Complete Prevention of Cardiac Adhesion

Yi Wang,Weijie Zhai,Hongyu Zhang,Shujie Cheng,Jinghua Li

After cardiac surgery, tissue damage to the heart may cause adhesion between heart and its surrounding tissues. Post-operative cardiac adhesion may lead to limited normal cardiac function, decreased quality of cardiac surgery, and increased risk of major bleeding during reoperation. Therefore, it is necessary to develop an effective anti-adhesion therapy to overcome cardiac adhesion. An injectable polyzwitterionic lubricant is developed to prevent adhesion between the heart and surrounding tissues and to maintain normal pumping function of the heart. This lubricant is evaluated in a rat heart adhesion model. Poly (2-methacryloyloxyethyl phosphorylcholine) (i.e., PMPC) polymers are successfully prepared via free radical polymerization of monomer MPC, and the optimal lubricating performance, biocompatibility both in vitro and in vivo is demonstrated. Besides, a rat heart adhesion model is conducted to evaluate the bio-functionality of lubricated PMPC. The results prove that PMPC is a promising lubricant for complete adhesion-prevention. The injectable polyzwitterionic lubricant shows excellent lubricating properties and biocompatibility and can effectively prevent cardiac adhesion.

CAS / MDL: 7727-54-0
研究领域: 生物材料 · 心血管外科 · 组织工程 · 生物医学工程
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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

Wet Tissue Interfacial Water Triggers Ultrafast In Situ Gelation of Sprayable Dry Powder for Postoperative Anti-Adhesion

Chaoyao Wen,Yihang Gong,Haoyan Chen,Yu Tian,Hui Yu,Xudan Xin,Le Wang,Chuyang Xiang,Yisheng Chen,Tianhua Xiao,Chengyun Ning,Xuebin Yang,Lei Zhou,Guoxin Tan

Postoperative adhesions complicate the majority of surgical procedures, imposing an excess medical burden. The segregation of injured tissue from healthy tissue is considered the optimal therapeutic strategy. However, achieving hemostasis while preventing adhesions in the immediate postoperative setting continues to pose a significant challenge. This paper presents the in situ formation of an asymmetrically adhesive hydrogel barrier via a sprayable dry powder (SDP) that enables interfacial water-induced, ultra-rapid gelation. Owing to SDP hydrophilicity and the interstitial spaces between particles, it can rapidly and efficiently absorb interfacial water, thereby facilitating smooth cross-linking between material functional groups and tissue functional groups. In addition, SDP becomes less adhesive after gelation as a layer of interfacial water forms on the surface of the SDP hydrogel, enhancing its anti-adhesion properties. Animal experiment outcomes demonstrate that SDP exhibits significant asymmetric adhesive properties before and after gelation, successfully preventing postoperative adhesions. As a result, SDP heralds a novel approach to the development of adhesives that can simultaneously mitigate adhesions and promptly arrest bleeding.

研究领域: 生物材料学 · 医学工程 · 外科手术
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JOURNAL OF CONTROLLED RELEASE · 2021 · IF 9.776

An oxidative stress-responsive electrospun polyester membrane capable of releasing anti-bacterial and anti-inflammatory agents for postoperative anti-adhesion

Jin Zhang,Chunsheng Xiao,Xi Zhang,Yandai Lin,Huanghao Yang,Yu Shrike Zhang,Jianxun Ding

ABSTRACT Peritendinous adhesion, secondary to the repair surgery of tendon rupture or injury, is one of the most common causes of reoperation, owing to the proliferation of fibrous tissue and excessive collagen synthesis caused by the residing inflammatory cells. In this study, a smart oxidative stress-responsive electrospun polyester membrane (EPM) was fabricated as both physical barrier and reservoir of curcumin/celecoxib (CUR/CEL) to prevent peritendinous adhesion. The multicomponent EPM was designed to release the encapsulated drugs in response to oxidative stress of the local microenvironment induced by inflammation. Specifically, sulfides in the EPM were able to react with reactive oxygen species (ROS) and become hydrophilic sulfoxide or sulfone to accelerate the release rate of drugs and regulate oxidative stress level in the inflammatory site intelligently. The oxidation-sensitive multicomponent EPM loaded with CUR and CEL was tested for anti-adhesion capacity in vitro and in vivo . An excellent ROS-sensitive degradation behavior and good cytocompatibility with cell viability of above 85% were presented with the fabricated EPM. The CUR- or CEL-loaded EPM possessed a better anti-adhesion ability compared with EPM without the drugs. Nevertheless, they were inferior to the EPM simultaneously loaded with both drugs, where the adhesion rate and fibrous adhesion number in the EPM+CUR/CEL group were close to extremely low values of about zero, demonstrating that CUR and CEL could synergistically prevent peritendinous adhesion. More interestingly, the multicomponent EPM was able to react with the local oxidative stress, leading to a smart and sustained behavior of releasing approximately 80% of the drug within 20 days. Overall, the smart multicomponent EPM offers a promising barrier strategy to prevent peritendinous adhesion.

CAS / MDL: 9004-07-3 9004-06-2
研究领域: 生物医学工程 · 药理学 · 组织工程
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ACS Omega · 2018 · IF 0

Porous Polylactide Film Plus Atorvastatin-Loaded Thermogel as an Efficient Device for Peritoneal Adhesion Prevention

Jiannan Li,Xiangru Feng,Jian Shi,Tongjun Liu,Jianxun Ding

Peritoneal adhesion is a common postoperative complication that causes many kinds of organ dysfunctions. It can be minimized by the integration of physical isolation and pharmaceutical treatment. However, the gas permeability of traditional medical devices for adhesion prevention is not satisfactory, which increases the risk of infection and inflammation, thus facilitating the formation of peritoneal adhesion. In this study, a device of porous polylactide (PLA) film plus atorvastatin (ATV)-loaded thermogel was developed for peritoneal adhesion prevention. PLA film acted as a physical barrier to prevent the connection of fibrin bridges between the injured tissues and nearby normal organs. Simultaneously, ATV was released to achieve the antifibrin deposition and anti-inflammatory effect. The porous properties of PLA film and thermogel increased the gas permeability and further inhibited the inflammatory responses. The in vivo study demonstrated that the porous PLA film with ATV-loaded thermogel possessed excellent anti-inflammation ability and satisfactory antiadhesion capacity, indicating its great potential for clinical application.

CAS / MDL: 198904-31-3 9004-06-2
研究领域: 生物医学工程 · 药学 · 外科手术
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BIOMEDICAL MICRODEVICES · 2019 ·Vol. 21 ·期 4 ·1-11 · IF 2.327

20(S)-Ginsenoside Rg3-loaded electrospun membranes to prevent postoperative peritoneal adhesion

Qiu Renna,Li Jian,Sun Denghua,Li Hongjun,Qian Feng,Wang Lizhe

Postoperative peritoneal adhesions are one of the most common surgical complications. In this study, we developed a 20(S)-ginsenoside Rg3-loaded methoxy poly (ethylene glycol)-block-poly(L-lactide-co-glycolide) (mPEG- b -PLGA) electrospun membrane (PEM/Rg3) that could not only serve as a physical barrier, but also as a drug delivery system that releases 20(S)-ginsenoside Rg3 constantly to prevent postoperative peritoneal adhesions. The characteristics of PEM/Rg3, including scanning electron microscopy, water contact angle, and mechanical analyses, were assessed. Degradation and drug release assays of PEM/Rg3 were performed. The anti-adhesion efficacy of PEM/Rg3 was evaluated in an abdomen-cecum mouse model. The adhesion scores, adhesion areas, hematoxylin and eosin (H&E) staining, immunofluorescence, and western blotting were assessed. The 20(S)-ginsenoside Rg3 loaded mPEG- b -PLGA electrospun fibers were successfully fabricated. The fibers were smooth, with no obvious drug crystals. PEM/Rg3 membranes were biodegradable and could be degraded gradually to release 20(S)-Ginsenoside Rg3 constantly from the membranes. The animal study showed that PEM/Rg3 exhibited an excellent adhesion prevention ability when compared with the control group, the PEM group, and polylactic acid (PLA) commercial membrane (Surgiwrap™) group. Immunofluorescence and western blotting studies showed that PEM/Rg3 inhibited the expressions of interleukin 1 (IL-1), interleukin 6 (IL-6), and reactive oxygen species modulator-1 (ROMO1). The 20(S)-ginsenoside Rg3-loaded mPEG- b -PLGA electrospun membranes exhibited satisfactory anti-adhesion efficacy by inhibiting inflammatory responses and oxidative stress. This composite represents a promising strategy to prevent postoperative peritoneal adhesions.

CAS / MDL: 9004-06-2
研究领域: 药剂学 · 生物材料 · 手术并发症 · 药物递送系统 · 组织工程
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Science China-Chemistry · 2015 ·Vol. 58 ·期 7 ·1159-1168 · IF 1.695

A comparative study of preventing postoperative tendon adhesion using electrospun polyester membranes with different degradation kinetics

Song Zhiming,Shi Bo,Ding Jianxun,Zhuang Xiuli,Zhang Xiaonan,Fu Changfeng,Chen Xuesi

Complications arising from tendon injury include tendon sheath infection and peritendinous adhesion, in which tendon adhesion often leads to serious motor dysfunction. In this work, the electrospun membranes of poly( L -lactide) (PLA) and poly(ε-caprolactone) (PCL) with different degradation kinetics were used to investigate their efficacy for anti-adhesion toward Achilles tendon repair. Compared with the PCL membrane, the PLA sample showed a faster rate of degradation in 42 d, and all the degradation media (i.e., phosphate-buffered saline) maintained at a constant pH of around 7.4. Meanwhile, the superior biocompatibility of both the PLA and PCL membranes were proved by the in vitro cellular adhesion tests and in vivo histopathological assays. Simultaneously, the PLA membrane was more effective than the PCL sample in decreasing adhesion and promoting functional recovery. Furthermore, the experiment result was further confirmed by hematoxylin-eosin and Masson’s trichrome staining, and type I collagen immunohistochemical analysis. All results revealed that the model treated with the electrospun PLA membrane was obviously better with regard to both anti-adhesion and tendon repair than that in the PCL membrane group. Considering the results of degradation and adhesion prevention efficacy, the electrospun polyester membranes, especially the PLA one, would be applied with fascinating potential in clinical prevention of postoperative tendon adhesion.

CAS / MDL: 9004-07-3 9004-06-2
研究领域: 生物材料 · 组织工程 · 骨科手术 · 生物医学工程
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

A rapid crosslinking injectable polygalacturonic acid barrier modified with zwitterion bottlebrush for preventing postoperative adhesion

Jianchao Li,Zhenxv Wu,Zixue Jiao,Yu Wang,Zongliang Wang,Min Guo,Gang Li,Liqiang Wang,Peibiao Zhang

Postoperation adhesion, as a worldwide problem, are often accompanied by serious complications and cause severe pain to patients, and traditional medicines and commercial anti-adhesion barriers have limited protective effects. So, we designed a novel injective, antifouling and photo-crosslinked polygalacturonic acid (PGA) hydrogel barrier composed of PGA methacrylate (PGAMA) and 2-methacryloyloxyethyl phosphorylcholine (MPC) with excellent effect of covering the wound and preventing adhesion. The product termed, as PGAMA-MPC, enhanced hydration as expected with the introduction of abundant MPC, showing an obvious resistance to protein, cell, and microorganism. Simultaneously, as injectable medical materials, stable attachment to the wound and low invasiveness for tissue were provided by photo-crosslinking of PGAMA-MPC hydrogel during Minimally invasive surgery. In the rat model of cecal injury, the PGAMA-MPC hydrogel effectively prevented the postoperative peritoneal adhesion, showing an obvious protective effect within 7 d and the excellent ability to repair of cecum and abdominal wall after 14 d. Compared with the control group, the rats treated with PGAMA-MPC3 almost recovered to the level of the normal level. Furthermore, we found that PGAMA-MPC3 hydrogel significantly reduced the expression of inflammation and deposition of fibrin. The underlying mechanism of anti-adhesion was subsequently confirmed by analyzing the signaling pathway TGF-β1. The PGA-MPC3 hydrogel promoted fibrinolysis by blocking the activation of TGF-β1/Smad3 pathway. In conclusion, we developed an available polysaccharide hydrogel for rapid repair of peritoneum and prevention of postoperative adhesion, possessing an extensive application as medical materials.

研究领域: 生物医学工程 · 材料科学 · 外科手术 · 药剂学
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ACS Biomaterials Science & Engineering · 2023 · IF 5.8

Degradable Temperature-Sensitive Hydrogel Loaded with Heparin Effectively Prevents Post-Operative Tissue Adhesions

Puxin Lang,Tiantian Liu,Shiqi Huang,Zhaojie Zhou,Mengxing Zhang,Yunzhu Lin,Qin He,Yuqin Yao,Zhenmi Liu,Ling Zhang

Tissue adhesions could occur following surgeries, and severe tissue adhesions can lead to serious complications. Medical hydrogels could be applied at surgical sites as a physical barrier to prevent tissue adhesion. For practical reasons, spreadable, degradable, and self-healable gels are highly demanded. To meet these requirements, we applied carboxymethyl chitosan (CMCS) to poloxamer-based hydrogels to generate low Poloxamer338 (P338) content gels displaying low viscosity at refrigerator temperature and improved mechanical strength at body temperature. Heparin, an effective adhesion inhibitor, was also added to construct P338/CMCS-heparin composite hydrogel (PCHgel). PCHgel presents as a flowable liquid below 20 °C and could rapidly transform into gel when spread on the surface of damaged tissue due to temperature change. The introduction of CMCS enabled hydrogels to form a stable self-healable barrier at injured positions and slowly release heparin during the wound healing period before being degraded after ∼14 days. Ultimately, PCHgel significantly reduced tissue adhesion in model rats and displayed higher efficiency than P338/CMCS gel without heparin. Its adhesion suppression mechanism was verified, and it also displayed good biosafety. Therefore, PCHgel showed good clinical transformation potential with high efficacy, good safety, and ease of use.

研究领域: 生物医学工程 · 材料科学 · 外科研究 · 药剂学
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Materials Today Bio · 2024 · IF 8.7

A Janus hydrogel that enables wet tissue adhesion and resists abdominal adhesions

Hanjie Shao,Junjie Deng,Zeping Xu,Jiujun Zhu,Wei Jian,Peiru Zhang,Xinhua Zhou,Xie Zhang,Hao She,Jingyun Ma,Xiang Wu,Hong Li

Hydrogels have indeed achieved significant advancements, yet their clinical translation has been hampered by their inherent limitations in wet adhesion properties. Furthermore, the design of adhesive hydrogels that can resist postoperative adhesions remains an intricate challenge. In this study, we introduce a Janus hydrogel (JGP) that offers a novel approach to address these challenges. The JGP hydrogel has two asymmetrical sides, consisting of an adhesion layer (AL) and an anti-adhesion layer (AAL). Specifically, the AL incorporates three key components: N-[tris(hydroxymethyl)methyl]acrylamide (THMA), acrylic acid (AAc), and the acrylic acid N-hydroxysuccinimide ester (AAc-NHS). By drying the AL, it has a rapid water absorption capability. The abundance of hydroxyl and carboxyl groups in the AL enables the formation of robust hydrogen bonds with tissues, thereby achieving superior adhesive properties. Additionally, the synergistic effect of THMA's tridentate hydrogen bonding and the covalent bonding formed by AAc-NHS with tissue ensures long-lasting wet adhesion. To realize the anti-adhesion function, one side of the AL was immersed in a solution of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), which undergoes crosslinking to form the AAL. A comprehensive series of tests have confirmed that the JGP hydrogel exhibits exceptional mechanical properties, efficient and enduring adhesion, excellent biocompatibility, and degradability. Moreover, it possesses remarkable hemostatic properties and robust anti-abdominal adhesion characteristics.

研究领域: 生物材料学 · 医学工程 · 组织工程
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Journal of Materials Chemistry B · 2016 ·Vol. 5 ·期 3 ·575-585 · IF 4.872

Poly(dopamine)-inspired surface functionalization of polypropylene tissue mesh for prevention of intra-peritoneal adhesion formation

Wanjun Hu,Shenglin Lu,Ying Ma,Pengfei Ren,Xiaoe Ma,Naizhen Zhou,Tianzhu Zhang,Zhenling Ji

Polypropylene (PP), as one of the most common prosthetic materials, has been widely used in intra-peritoneal repair. However, its adhesion to viscera has severely limited its application. Therefore it is critical to improve the PP surface with an anti-adhesion property. In this work, based on dopamine-inspired chemistry, virgin PP (V-PP) mesh was first pretreated with O2 plasma, subsequently dipped in dopamine aqueous solution for 24 h, and then chitosan (CS) was grafted onto it. Finally the anti-adhesion mesh (O-PP/PDA/CS) was obtained. The formation procedure of a PDA/CS ad-layer was characterized by water contact angle measurements, ATR-FTIR, SEM, and XPS. The results show that a PDA/CS ad-layer could be coated on the PP surface efficiently. NIH/3T3 cells were first cultured on O-PP/PDA/CS meshes to evaluate the availability of anti-adhesion and biocompatibility in vitro, and then the efficacy of the PDA/CS-coating as a barrier for reducing postsurgical adhesions was evaluated using a rat abdominal wall defect model. Compared with the V-PP group, NIH/3T3 cells exhibited higher viability in the O-PP/PDA/CS groups as evaluated by the CCK-8 method. In addition, NIH/3T3 cells grow into round-shapes on the O-PP/PDA/CS surface. This indicates that the modification strategy can facilely lead to excellent properties of anti-adhesion. In vivo tests further indicate that O-PP/PDA/CS meshes were effective in reducing adhesion formation.

CAS / MDL: 62-31-7
研究领域: 生物材料 · 医学工程 · 组织工程
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

A Single-Component Janus Zwitterionic Hydrogel Patch with a Bionic Microstructure for Postoperative Adhesion Prevention

Rui Liu,Zhongming Zhao,Qi Yang,Shuang Chen,Zhuojun Yan,Xiuqiang Li,Lei Liang,Bingyan Guo,Baoqun Wang,Hong Zhang,Fanglian Yao,Junjie Li

The development of anti-adhesion hydrogels for preventing postoperative adhesions is an ongoing challenge, particularly in achieving a balance between exceptional antifouling properties and effective in situ tissue retention. In this study, we propose a unique approach with the design of a single-component Janus zwitterionic hydrogel patch featuring a bionic microstructure. The Janus patches were prepared through free radical polymerization of sulfobetaine methacrylate with N, N′-methylenebis(2-propenamide) as the cross-linker. The incorporation of hexagonal facets separated by interconnecting grooves on one side imparts durable and reliable in situ retention capabilities to the Janus hydrogel patch when it is applied to traumatized tissues. The opposing flat surface exhibits outstanding resistance to bacteria, proteins, and cell adhesion, due to the superhydrophilicity and excellent antifouling characteristics of zwitterionic polymers. This dual functionality empowers the Janus hydrogel patch to mitigate adhesions between traumatized and surrounding tissues. The hexagonal and groove bionic microstructures facilitate rapid drainage, promoting swift contact with the tissue for increased adhesion strength, while independent hexagonal microfacets enhance the peeling energy. In an in vivo setting, Janus zwitterionic hydrogel patches with surface microstructures form mutually embedded structures with the cecum surface, minimizing the likelihood of slippage and detachment. Remarkably, in vivo experiments involving abdominal wall cecum injuries illustrate the Janus zwitterionic hydrogel patch’s superior anti-adhesion effectiveness compared to commercial controls. Thus, the Janus hydrogel patch, distinguished by its bionic microstructure surface, presents substantial potential in the biomedical field for averting postoperative adhesions.

CAS / MDL: 7727-54-0 110-26-9
研究领域: 生物医学工程 · 材料科学 · 组织工程 · 外科应用
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MATERIALS & DESIGN · 2022 · IF 9.417

Micro- and nano-environment dual-modulated anti-tendon adhesion barrier membranes

Qiang Zhang,Kui Ma,Chun-Hei Lam,Ho-Pan Bei,Yu Liu,Xing Yang,Xin Zhao

Despite promise in preventing peritendinous adhesion, electrospun membranes face many challenges related to their complex fabrication process, untargeted/uncontrolled drug delivery and consequently low therapeutical effect. Here, a micro-and nano-environment dual-modulated barrier membrane (MNBM) with on-demand gene delivery capability is presented. Our MNBM is developed by first preparing extracellular signal-regulated kinase-2 (ERK2) siRNA-loaded gelatin methacryloyl (GelMA) nanogels via facile nano-emulsification technique, then incorporating these nanogels into poly-L-lactic acid (PLLA) fibers via simple blending electrospinning. The GelMA nanogels offer a nano-niche for ERK2-siRNA encapsulation and allow for a nano-environment controlled siRNA release by readily tuning the GelMA concentrations during nano-emulsification, while the resultant MNBM can mediate a micro-environment controlled siRNA delivery in response to the matrix metalloproteinase-2 (MMP-2) enriched micro-environment at the tendon repair site. Such MNBM can not only biologically orchestrate fibroblast behaviors by silencing the target gene expression, but also physically shield the tendon from extrinsic cell/tissue invasion. This study provides a proof-of-concept of anti-adhesion barrier membrane as an intelligent gene delivery system to offer a spatiotemporal and biophysical dual control over tendon recovery according to disease state and ensure long-term therapeutic efficacy. We envision such MNBM represents a promising therapeutic platform with great efficacy to achieve adhesion-free tendon repair.

CAS / MDL: 920-66-1
研究领域: 生物医学工程 · 组织工程 · 基因治疗 · 材料科学
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