ACS Biomaterials Science & Engineering
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2025
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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
·
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
ACS Applied Bio Materials
·
2025
·
IF 4.7
Yang Yang,Jingjing Zhang,Fei Kong,Yunyang Zhang,Jian Ge,Jingwu Song,Changyu Shao,Haoran Li,Yunjiu Ren,Chengyao Ni,Xianghui Kong,Yiming Ni,Xiangdong Kong,Ruibo Zhao
In the absence of effective therapeutics, valve replacement remains the sole intervention for severe calcific aortic valve disease (CAVD), which impacts 26% of adults aged 65 and even 50% of adults aged 85. Pericardium-based bioprosthetic heart valves benefit from marginating anticoagulation. Still, they face recalcification due to residual aldehydes and inadequate elastin stabilization from the glutaraldehyde cross-linking process, posing a significant clinical challenge. Herein, we propose a biprotein stabilized pericardium material (CHPP) that involves both collagen and elastin cross-linked by procyanidins (PC) with the assistance of 3,4-hydroxyphenylpropionic acid (HPA), which conferred improved stability to pericardium even under enzymatic attack, increasing biocompatibility and minimizing platelet absorption, and taken together significantly contributed to resisting calcification. Further, in vivo studies demonstrated the preservation of the structure of CHPP, and more importantly, CHPP can prevent surrounding tissue infiltration and immune responses, reducing the infiltration of macrophages and T cells, along with their cascading inflammatory processes and establishing an immune-privileged microenvironment that further enhances its anticalcification capacity. These advancements offer an enhancing approach using procyanidins to significantly stabilize biprotein components within the pericardium, thereby creating immune tolerance against calcification and providing an alternative for robust generation of valve materials.
研究领域:
生物医学工程
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心血管医学
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生物材料
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组织工程
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免疫调节
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Hongxia Pu,Tao Yu,Yao Xiong,Canyu Wang,Zhizhuo Zhou,Gaocan Li,Yunbing Wang
Valvular heart disease (VHD) is a leading global health concern, contributing to significant mortality rates and imposing substantial economic burdens annually. To date, numerous bioprosthetic heart valves (BHVs) based on decellularized extracellular matrix (dECM) have been engineered as prosthetic solutions for the treatment of VHD. However, the irreversible deterioration of BHVs, driven by thrombosis, inflammatory responses, and calcification, represents a persistent and unresolved clinical concern. Moreover, the simultaneous optimization of multiple properties through a single technological approach presents a formidable challenge for BHVs. Herin, a dual regulation strategy based on functional hydrogel encapsulated with self-regulating bioreactors has been proposed to develop functional BHV materials, which involve nanoparticle-coated architectures with the intrinsic feedback mechanism. Specifically, a self-feedback thrombin-responsive peptide nanoparticle delivery system encapsulated with anticoagulant apixaban (Thr NPs) has been employed. Meanwhile, with the nanoparticles as bridging agents, the functional hydrogel coatings can be formed to provide passive defense against biofouling, while the three-dimensional network structures serve as the high-capacity reservoir for drug delivery. The excellent biocompatibility, superior anticoagulation, reduced calcification, and minimal inflammation are demonstrated for the developed BHV materials by a series of investigations in vitro and in vivo . Notably, the carotid artery implantation and endo-covered stent model are established to further confirm the blood compatibility and the enhancement of endothelialization of the developed BHV materials after implantation. It is expected that this dual regulation strategy might provide a good reference for the self-feedback biomedical material design and the application of blood-contact materials.
研究领域:
生物医学工程
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心血管材料
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再生医学
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药物递送系统
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生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）