ACS Biomaterials Science & Engineering
·
2025
·
IF 5.5
Xinyun Pu,Xu Peng,Shubin Shi,Shaoxiong Feng,Xu Wei,Xi Gao,Xixun Yu
Valvular heart disease (VHD) poses a significant threat to human health, and the transcatheter heart valve replacement (THVR) is the best treatment for severe VHD. Currently, the glutaraldehyde cross-linked commercial bioprosthetic heart valves (BHVs) remain the first choice for THVR. However, the cross-linking by glutaraldehyde exhibits several drawbacks, including calcification, inflammatory reactions, and difficult endothelialization, which limits the longevity and applicability of BHVs. In this study, λ-carrageenan with anticoagulant function was modified by carboxymethylation into carboxymethyl λ-carrageenan (CM-λC); subsequently, CM-λC was used as a cross-linking agent to stabilize decellularized bovine pericardial tissue through amide bonds formed by a 1-(3-(Dimethylamino)propyl)-3-ethylcarbodiimide/N-Hydroxysuccinimide (EDC/NHS)-catalyzed reaction between the amino functional groups within pericardium and the carboxyl group located on CM-λC. Lastly, the inclusion complex (CD/Rutin) (formed by encapsulating the rutin molecule through the hydrophobic cavity of the mono-(6-ethylenediamine-6-deoxy)-β-cyclodextrin) was immobilized onto above BHVs materials (λCar-BP) through the amidation reaction. The treated sample exhibited mechanical properties and collagen stability similar to those of GA-BP, except for improved flexibility. Because of the presence of sulfonic acid groups and absence of aldehyde group as well as the Rutin release from CD/Rutin immobilized onto BHVs, the hemocompatibility, anti-inflammatory, HUVEC-cytocompatibility, and anticalcification properties, of the CM-λC-fixed BP modified with CD/Rutin was significantly better than that of GA-BP. In summary, this nonaldehyde-based natural polysaccharide cross-linking strategy utilizing the combination of CM-λC and CD/Rutin provides a novel solution to obtain BHVs with durable and stable anticoagulant, anticalcification, and anti-inflammatory properties, and has a wide range of potential applications in improving the various properties of BHVs.
研究领域:
医学材料学
·
心血管病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Jianming Zhao,Abudureheman Bahatibieke,Guodong Liu,Jinming Li,Junfei Li,Feilong Zhao,Bohao Yao,Yajie Xie,Yudong Zheng
Injury to cardiac valves is a major contributor to mortality associated with cardiovascular diseases. Artificial valves are preferred for their mimicry of natural valve efficiency in optimizing hemodynamics and minimizing associated complications. To endure the substantial pressures of the cardiovascular system, these valves require exceptional fatigue resistance, calcification resistance, and blood compatibility. To address these demands, we have designed and synthesized a silane uniformly integrated polyurea-polyurethane elastomer (PSCU). The PSCU features a highly responsive hydrogen bond network, conferred by the integration of oxygen-containing spirochemical rings and polyurethane urea segments, which forms orientation to prevent material fatigue damage. Concurrently, PSCU has almost no adverse effects on the blood due to the uniform integration of silane, and long-term use will not cause calcification. In vivo evaluations have confirmed PSCU’s exceptional biocompatibility and stability, with no observable tissue inflammation or material accumulation. Moreover, fluid dynamics studies have demonstrated PSCU’s superior mechanical attributes, maintaining effective unidirectional blood flow under a sustained 60 mmHg pressure gradient. This breakthrough material represents a significant advancement in the field of cardiovascular medicine, offering enhanced durability and reliability for artificial heart valves.
研究领域:
生物材料学
·
心血管医学
·
高分子化学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Bio Materials
·
2021
·
IF 0
Renqi Guo,Ying Zhou,Siju Liu,Chuang Li,Cuifen Lu,Guichun Yang,Junqi Nie,Feiyi Wang,Nian-Guo Dong,Jiawei Shi
Calcification of bioprosthetics is a primary challenge in the field of artificial heart valves and a main reason for biological heart valve prostheses failure. Recent advances in nanomaterial science have promoted the development of polymers with advantageous properties that are likely suitable for artificial heart valves. In this work, we developed a nanocomposite polymeric biomaterial POSS–PEG (polyhedral oligomeric silsesquioxane-polyethylene glycol) hybrid hydrogel, which not only has improved mechanical and surface properties but also excellent biocompatibility. The results of atomic force microscopy and in vivo animal experiments indicated that the content of POSS in the PEG matrix plays an important role on the surface and contributes to its biological properties, compared to the decellularized porcine aortic valve scaffold. Additionally, this modification leads to enhanced protection of the hydrogel from thrombosis. Furthermore, the introduction of POSS nanoparticles also gives the hydrogel a better calcification resistance efficacy, which was confirmed through in vitro tests and animal experiments. These findings indicate that POSS–PEG hybrid hydrogel is a potential material for functional heart valve prosthetics, and the use of POSS nanocomposites in artificial valves may offer potential long-term performance and durability advantages.
研究领域:
生物医学工程
·
心血管医学
·
材料科学
✓ 已验证
DOI
PubMed
Materials Today Bio
·
2025
·
IF 10.2
Xiaobo Yu,Jingli Ding,Yingjie He,Shunbo Wei,Xing Chen,Qiujie Luo,Yuqing Zhang,Chen Qian,Jiahui Wang,Mengjie Hu,Xiang Zhang,Cuifen Lu,Jinping Liu,Jianliang Zhou
Valvular heart disease (VHD) poses a thorny problem in cardiovascular diseases. The most effective treatment for VHD is heart valve replacement. Biological heart valve (BHV) is more favored than mechanical heart valve due to the maturity of transcatheter heart valve replacement (THVR) and the absence of the need for lifelong anticoagulant use. However, traditional commercial BHV suffers degeneration within 10 to 15 years because of calcification caused by the cross-linking reagent, glutaraldehyde. Considering the remarkable properties of POSS, PEG, and the star-like eight-arm structure, we fabricated POSS-PEG-PP, which is a decellularized porcine pericardium (DPP) crosslinked by a star-like eight-arm cross-linker octafunctionalized POSS of benzaldehyde-terminated polyethylene glycol (POSS-PEG-CHO) based on the Schiff's base reaction. POSS-PEG-PP exhibits more intense fiber arrangement and better mechanical properties than GLUT-PP (glutaraldehyde crosslinked DPP). The results also show that the cytocompatibility, endothelialization, and hemocompatibility of POSS-PEG-PP are outstanding in vitro. Subsequently, in vivo assessments demonstrate that POSS-PEG-PP has anti-inflammatory and anti-calcification abilities. Furthermore, RNA sequencing analysis of subcutaneous implants suggests that the intervention of AMPK and IL-17 signaling pathways plays an important role in the inflammatory and immune responses regulation of POSS-PEG-PP. Therefore, POSS-PEG-PP is an excellent substitute material for BHVs and is expected to be clinically transformed.
研究领域:
心血管疾病
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生物材料科学
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组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Cheng Hu,Rifang Luo,Yunbing Wang
In recent years, valvular heart disease has become a serious disease threatening human life and is a major cause of death worldwide. However, the glutaraldehyde (GLU)-treated biological heart valves (BHVs) fail to meet all requirements of clinical application due to disadvantages such as valve thrombus, cytotoxicity, endothelialization difficulty, immune response, and calcification. Encouragingly, there are a large number of carboxyls as well as a few amino groups on the surface of GLU-treated BHVs that can be modified to enhance biocompatibility. Inspired by natural biological systems, we report a novel approach in which the heart valve was cross-linked with erythrocyte membrane biomimetic drug-loaded nanoparticles. Such modified heart valves not only preserved the structural integrity, stability, and mechanical properties of the GLU-treated BHVs but also greatly improved anti-coagulation, anti-inflammation, anti-calcification, and endothelialization. The in vitro results demonstrated that the modified heart valves had long-term anti-coagulation properties and enhanced endothelialization processes. The modified heart valves also showed good biocompatibility, including blood and cell biocompatibility. Most importantly, the modified heart valves reduced the TNF-α levels and increased IL-10 compared to GLU-treated BHVs. In vivo animal experiments also confirmed that the modified heart valves had an ultrastrong resistance to calcification after implantation in rats for 120 days. The mechanism of anti-calcification in vivo was mainly due to the controlled release of anti-inflammatory drugs that reduced the inflammatory response after valve implantation. In summary, this therapeutic approach based on BHVs cross-linking with erythrocyte membrane biomimetic nanoparticles sparks a novel design for valvular heart disease therapy.
研究领域:
生物医学工程
·
心血管病学
·
药剂学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Kunpeng Liu,Mingyu Li,Fanjun Zhang,Yanan Wang,Chong Chen,Yuan Wei,Li Yang,Rifang Luo,Yunbing Wang
Glutaraldehyde cross-linked pericardium (GLUT), mostly used in Bioprosthetic heart valves (BHVs) clinically, still has problems of valve thrombus, cytotoxicity, and calcification. Although many new crosslinking approaches have been explored to obtain certain biological achievements, their clinical applications are still some way off, which might be ascribed to the limitations of preservation and sterilization. In this study, a novel post-crosslinking of GLUT was developed using a zwitterionic copolymer. The copolymer imitating the molecular structure of phospholipids was composed of the copolymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC), N-(3-Aminopropyl) methacrylamide hydrochloride (APMA), and Lauryl methacrylate (LMA). With the introduction of primary amines, the zwitterionic copolymer could be effectively utilized in the post-crosslinking of GLUT. Meanwhile, the anticoagulation properties of valve leaflets could be adjusted by combining aminated zwitterionic copolymers with different molecular weights. The valve leaflets modified with aminated zwitterionic copolymer not only maintained original mechanical property and structural integrity, but also significantly improved the long-term anti-coagulation and stability in vitro and ex vivo. The subcutaneous implantation confirmed that the modified leaflets possessed great resistance to calcification along with reduced inflammatory response. Besides, the modified leaflets could be further stored in glutaraldehyde solution (a storage formula for commercial valves) and still retained great anti-coagulant and anti-calcification properties. The study demonstrated a better clinical potential of the modified leaflets via the post-crosslinking of glutaraldehyde treated leaflets with the aminated zwitterionic copolymer.
研究领域:
生物医学工程
·
心血管材料科学
✓ 已验证
DOI
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Mengyue Hu,Shubin Shi,Xu Peng,Xinyun Pu,Xixun Yu
ABSTRACT Currently, glutaraldehyde (GA)-crosslinked bioprosthetic heart valves (BHVs) still do not guarantee good biocompatibility and long-term effective durability for clinical application due to their subacute thrombus, inflammation, calcification, tearing and limited durability. In this study, double-modified xanthan gum (oxidized/vinylated xanthan gum (O 2 CXG)) was acquired from xanthan gum for subsequent double crosslinking and modification platform construction. Sulfonic acid groups with anticoagulant properties were also introduced through the free radical polymerization of vinyl sulfonate (VS) and vinyl on O 2 CXG. Taking advantage of the drug-loading function of xanthan gum, the treated pericardium was further loaded with inflammation-triggered dual drug-loaded nanogel (heparin (Hep) and atorvastatin (Ator)). Mechanical properties of O 2 CXG-crosslinked porcine pericardium (O 2 CXG-PP) were significantly improved via the first network formed by Schiff base bonds and the second C-C bonds network. Due to the presence of sulfonic acid groups as well as the dual drug release from nanogels under the stimulation of H 2 O 2 , the hemocompatibility, anti-inflammatory, pro-endothelialization and anti-calcification properties of the crosslinked pericardium modified with nanogels loaded with Hep and Ator (O 2 CXG+VS+(Hep+Ator) nanogel-PP) was significantly better than that of GA-crosslinked PP (GA-PP). The collaborative strategy of double crosslinking and sequential release of anticoagulant/endothelium-promoting drugs triggered by inflammation could effectively meet the requirement of enhanced multiple performance and long-term durability of bioprosthetic heart valves and provide a valuable pattern for multi-functionalization of blood contacting materials. Statement of significance Currently, glutaraldehyde-crosslinked bioprosthetic heart valves (BHVs) are subject to subacute thrombus, inflammation, calcification and tearing, which would not guarantee good biocompatibility and long-term effective durability. We developed a cooperative strategy of double crosslinking and surface modification in which double-modified xanthan gum plays a cornerstone. The mechanical properties of this BHV were significantly improved via the first network formed by Schiff base bonds and the second C-C bonds network. Inflammation-triggered combination delivery of heparin and atorvastatin has been demonstrated to enhance anticoagulation, anti-inflammatory and pro-endothelialization of BHVs by utilizing local inflammatory response. The collaborative strategy could effectively meet the requirement of enhanced multiple performance and long-term durability of BHVs and provide a valuable pattern for the multi-functionalization of blood-contacting materials.
研究领域:
生物医学工程
·
材料科学
·
心血管医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Yuqing Zhang,Hai Hu,Yaoxi Zhu,Jie Xiao,Chenghao Li,Chen Qian,Xiaobo Yu,Jinping Zhao,Xing Chen,Jinping Liu,Jianliang Zhou
Valve replacement is the most effective means of treating heart valve diseases, and transcatheter heart valve replacement (THVR) is the hottest field at present. However, the durability of the commercial bioprosthetic valves has always been the limiting factor restricting the development of interventional valve technology. The chronic inflammatory reaction, calcification, and difficulty in endothelialization after the implantation of a glutaraldehyde cross-linked porcine aortic valve or bovine pericardium often led to valve degeneration. Improving the biocompatibility of valve materials and inducing endothelialization to promote in situ regeneration can extend the service life of valve materials. Herein, inspired by the hardening process of butterfly wings, this study proposed a dopamine–metal–phenol strategy to modify decellularized porcine pericardium (DPP). This is a strategy to make dopamine (DA) coordinate trivalent metal chromium ions (Cr(III)) with antiplatelets (PLTs) and anti-inflammatory properties, and then cross-link it with tea polyphenols (TP) to generate a valve scaffold that is mechanically comparable to glutaraldehyde-cross-linked scaffolds but avoids the cytotoxicity of aldehyde and presents better biocompatibility, hemocompatibility, anticalcification, and anti-inflammatory response properties.
研究领域:
生物医学工程
·
心血管病学
✓ 已验证
DOI
高影响因子
COMPOSITES PART B-ENGINEERING
·
2025
·
IF 14.2
Kaiyang Huang,Cheng Zheng,Xueyu Huang,Bangquan Wei,Lepeng Chen,Gaocan Li,Li Yang,Yunbing Wang
Glutaraldehyde cross-linked bioprosthetic heart valves (BHVs) have been widely used in clinical practice for its superior hemodynamic properties and significantly reduced requirement on anticoagulant therapy. However, the lifespan and biocompatibility of BHVs remain limited due to thrombus accumulation, poor endothelialization, inflammation, and progressive calcification. In this study, we introduced heparin-like fucoidan and recombinant humanized type III collagen (rhCol III) into glutaraldehyde cross-linked BHVs (GLUT) through photoinduced polymerization, thereby preparing an integrated hydrogel functionalized BHV (Fu-rhCol III). This multifunctional hydrogel formed a biocompatible barrier, providing robust protection for internal valve fibers and exhibiting strong resistance to platelet adhesion and thrombus formation in vitro. The Fu-rhCol III effectively reduced the cytotoxicity of GLUT, accelerating the endothelialization process. Fu-rhCol III maintained the structural stability and mechanical properties brought by glutaraldehyde cross-linking. This composite hydrogel demonstrated the significant suppression of acute inflammatory responses and satisfactory anti-calcification effect in subcutaneous implantation test. 60-day implantation results indicated that calcium deposition of Fu-rhCol III decreased by 96% compared with GLUT. In summary, this integrated hydrogel modification provides a promising strategy for future design of BHVs.
研究领域:
生物医学工程
·
心血管医学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2023
·
IF 7
Jiahao Chang,Liyin Yu,Jiao Lei,Xiaoli Liu,Chunxiao Li,Yali Zheng,Hong Chen
Bio-patches for the treatment of valvular disease have been evaluated in clinical trials. It has been shown that failure of these devices, occurring within a few years of implantation, may be due to cytotoxicity, immune response, calcification and thrombosis. Some of these effects may be due to the glutaraldehyde crosslinking process used in the preparation of the materials. A number of studies have focused on strategies to control calcification, while others have concentrated on the prevention of micro-thrombus formation. In the present work, we have introduced amino-terminated poly(ethylene glycol) (NH2–PEG–NH2) as an intermolecular bridge, which not only eliminates free aldehyde groups to prevent calcification, but also introduces sites for the attachment of anticoagulant molecules. Furthermore, PEG, itself a hydrophilic polymer with good biocompatibility, may effectively prevent protein adsorption in the early stages of blood contact leading to thrombus formation. After further covalent attachment of heparin, modified bovine pericardium (BP) showed strong anti-calcification (calcium content: 39.3 ± 3.1 μg mg−1) and anti-coagulation properties (partial thromboplastin time: >300 s). The biocompatibility and mechanical properties, important for clinical use, were also improved by modification. The strategy used in this work includes new ideas and technologies for the improvement of valve products used in the clinic.
研究领域:
生物医学工程
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组织工程
·
心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2025
·
IF 5.7
Yifeng Chen,Qijun Wu,Wenzhong Cao,Haonan He,Minmin Ding,Xianchi Zhou,Xinyi Li,Shaohua Jiang,Peng Zhang,Jian Ji
Valvular heart disease (VHD) is a leading cause of cardiovascular morbidity and mortality. Polymeric heart valves (PHVs) offer potential solutions for treating VHDs but are limited by issues like thrombosis, calcification, and inflammation. Surface modification with antifouling coatings has been explored to mitigate those complications, but these coatings often exhibit poor stability and mechanical mismatch with elastomer substrates. Here, we report a fiber-reinforced zwitterionic elastomer composite for PHVs that simultaneously achieves antifouling surfaces and robust mechanical properties. This approach generates zwitterionic surfaces in situ and incorporates orthogonally aligned electrospun fibers for mechanical reinforcement. The resulting composite integrates excellent anticoagulant and antifouling properties with anisotropic mechanics, mimicking the structure and function of natural heart valve leaflets. It maintained chemical and mechanical integrity during 60-day serum immersion and withstood 100 million cycles in accelerated fatigue testing. In vivo evaluation using a rat subcutaneous implantation model revealed remarkable anti-inflammatory and anti-calcification effects.
研究领域:
生物医学工程
·
心血管医学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2022
·Vol. 41
·期 1
·51-66
·
IF 3.815
Gao Cai-Yun,Wang Gang,Wang Lin,Wang Qun-Song,Wang Han-Cheng,Yu Lin,Liu Jian-Xiong,Ding Jian-Dong
Bioprosthetic heart valves (BHVs) are important for transcatheter valve replacement. Current commercial BHVs on the market are basically porcine or bovine pericardium (BP) crosslinked with glutaraldehyde (GA). Simply applying GA to BHVs can enhance mechanical stability, but cannot alleviate in vivo calcification. In this work, we developed a two-step decellularization (TSD) strategy to modify this biomacromolecular network, in which BP was post-treated, as the second step of decellularization, with a mild biosurfactant n -dodecyl- β -D-maltoside in a mixture of isopropanol and phosphate-buffered saline after the first step of traditional decellularization and GA cross-linking. The TSD-treated BP exhibited not only low cytotoxicity and excellent mechanical properties in vitro , but also low immune responses and significant anticalcification in vivo . After 60 days of subcutaneous implantation in the back of Wistar rats, the calcium content was, as quantified with an inductively coupled plasma optical emission spectrometer, only 1.1 µg/mg compared to 138.6 µg/mg in the control group without the post-treatment. In addition, collagen fibrils were observed with field emitting scanning electron microscopy (SEM), and the morphology and composition of the calcified sites resulting from in vivo biomineralization were studied with SEM with energy dispersive spectroscopy and also X-ray diffraction. This study proposes a facile yet effective anticalcification strategy for the modification of the bovine pericardial bioprosthetic heart valve, a natural biomacromolecular network.
研究领域:
医学材料学
·
心血管外科
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）