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Matter · 2024 · IF 17.3

A soft and fatigue-resistant material that mimics heart valves

Xi Chen,Fengkai Liu,Qifeng Yu,Meng Yang,Zhigang Suo,Jingda Tang

Bovine pericardium, a tissue commonly used to make artificial heart valves, fulfills two fundamental mechanical requirements: a low modulus to ensure opening and closing in cyclic pulsatile flow and a high fatigue threshold to prevent crack growth. The tissue consists of a soft matrix and crimped fibers. Inspired by this architecture, we develop a composite of a soft polymer matrix and a knitted fabric. When the stretch is small to modest, the knitted fabric is easily stretched, so that the composite is soft. When the stretch is large, the knitted fabric is stiff and strong, so that the composite resists fatigue crack growth. The mechanical behavior of the composite is comparable to that of bovine pericardium. The composite has an exceptionally long fatigue life, enduring 25 million cycles of pulsatile flow, two orders of magnitude longer than the polymer matrix. This soft and fatigue-resistant composite may find broad applications in biomedicine.

CAS / MDL: 106797-53-9
研究领域: 生物医学工程 · 材料科学
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CHINESE JOURNAL OF POLYMER SCIENCE · 2022 ·Vol. 41 ·期 1 ·51-66 · IF 3.815

A Biosurfactant-containing TSD Strategy to Modify Bovine Pericardial Bioprosthetic Valves for Anticalcification

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
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Journal of Materials Chemistry B · 2025 · IF 5.7

An oxidized chondroitin sulfate-crosslinked and CuCDs-loaded decellularized bovine pericardium with improved anti-coagulation, pro-endothelialization and anti-calcification properties for BHVs

Shubin Shi,Xu Wei,Xu Peng,Xinyun Pu,Shaoxiong Feng,Xi Gao,Xixun Yu

With the growth of the elderly people and the development of transcatheter aortic valve replacement (TAVR) technology, bioprosthetic heart valves (BHVs) originating from the decellularized bovine pericardium (DBP) have become a favourable option for severe valvular heart disease (VHD). However, currently, available commercial bioprosthetic heart valves prepared from glutaraldehyde (GA)-crosslinked xenografts have limited durability because of various factors, including severe cytotoxicity, inflammatory response, poor pro-endothelialization ability and calcification. Therefore, the development of valve materials with better performance is urgent. In this work, we first synthesized Cu-doped carbon dots (CuCDs) with excellent biocompatibility and high stability using sodium citrate, ethylenediamine and copper chloride. Subsequently, oxidized chondroitin sulfate (OCS) was used to crosslink the decellularized bovine pericardium to obtain OCS–BP followed by loading CuCDs onto the surface of this OCS-fixed BP sample through amide bonds formed by an EDC/NHS-catalyzed reaction between the functional groups on CuCDs and OCS–BP to prepare the BHV (CuCDs–OCS–BP) with specific properties. Relevant experiments conducted both in vivo and in vitro indicate that CuCDs–OCS–BP with good stability showed improved mechanical properties, compliance and flexibility, encouraging HUVEC-cytocompatibility, excellent anti-blood cell adhesion, antithrombogenic properties, anti-inflammatory and anti-calcification properties, and a good endothelialisation ability due to the catalytic generation of endogenous nitric oxide. Overall, CuCDs–OCS–BP is a promising material for BHVs.

研究领域: 生物医学工程 · 心血管材料科学 · 组织工程
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Frontiers in Bioengineering and Biotechnology · 2023 · IF 5.7

Free-aldehyde neutralized and oligohyaluronan loaded bovine pericardium with improved anti-calcification and endothelialization for bioprosthetic heart valves

Yuhong Liu,Chunyang Chen,Ting Lu,Sixi Liu,Zhongshi Wu,Zhenjie Tang

The number of patients with valvular heart disease is increasing yearly, and valve replacement is the most effective treatment, during which bioprosthetic heart valves (BHVs) are the most widely used. Commercial BHVs are mainly prepared with glutaraldehyde (Glut) cross-linked bovine pericardial or porcine aortic valves, but the residual free aldehyde groups in these tissues can cause calcification and cytotoxicity. Moreover, insufficient glycosaminoglycans (GAGs) in tissues can further reduce biocompatibility and durability. However, the anti-calcification performance and biocompatibility might be improved by blocking the free aldehyde groups and increasing the GAGs content in Glut-crosslinked tissues. In our study, adipic dihydrazide (ADH) was used to neutralize the residual free aldehyde groups in tissues and provide sites to blind with oligohyaluronan (OHA) to increase the content of GAGs in tissues. The modified bovine pericardium was evaluated for its content of residual aldehyde groups, the amount of OHA loaded, physical/chemical characteristics, biomechanical properties, biocompatibility, and in vivo anticalcification assay and endothelialization effects in juvenile Sprague-Dawley rats. The results showed that ADH could completely neutralize the free aldehyde groups in the Glut-crosslinked bovine pericardium, the amount of OHA loaded increased and the cytotoxicity was reduced. Moreover, the in vivo results also showed that the level of calcification and inflammatory response in the modified pericardial tissue was significantly reduced in a rat subcutaneous implantation model, and the results from the rat abdominal aorta vascular patch repair model further demonstrated the improved capability of the modified pericardial tissues for endothelialization. Furthermore, more α-SMA + smooth muscle cells and fewer CD68 + macrophages infiltrated in the neointima of the modified pericardial patch. In summary, blocking free-aldehydes and loading OHA improved the anti-calcification, anti-inflammation and endothelialization properties of Glut-crosslinked BHVs and in particularly, this modified strategy may be a promising candidate for the next-generation of BHVs.

研究领域: 生物医学工程 · 心血管医学 · 组织工程 · 生物材料
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Journal of Materials Chemistry B · 2024 · IF 6.1

Double Crosslinking decellularized bovine pericardium of Dialdehyde Chondroitin Sulfate and Zwitterionic Copolymer for Bioprosthetic Heart Valves with Enhanced Antithrombogenic, Anti-inflammatory and Anti-calcification Properties

Shubin Shi,Mengyue Hu,Xu Peng,Can Cheng,Shaoxiong Feng,Xinyun Pu,Xixun Yu

Due to the increasing aging population and the advancements in transcatheter aortic valve replacement (TAVR), the use of bioprosthetic heart valves (BHVs) in patients diagnosed with valvular disease has increased substantially. Commercially available glutaraldehyde (GA) cross-linked biological valves suffer from reduced durability due to a combination of factors, including the high cell toxicity of GA, subacute thrombus, inflammation and calcification. In this study, the oxidized chondroitin sulfate (OCS), a natural polysaccharide derivative, was used to replace GA to cross-link decellularized bovine pericardium (DBP), carrying out the first crosslinking of DBP to obtain OCS-BP. Subsequently, in situ the zwitterion radical copolymerization system was introduced to perform double cross-linking to obtain double crosslinked BHVs with biomimetic modification (P(APM/MPC)-OCS-BP). P(APM/MPC)-OCS-BP presented enhanced mechanical properties, collagen stability and enzymatic degradation resistance owing to double crosslinking. The ex vivo AV-shunt assay and coagulation factors test suggested that P(APM/MPC)-OCS-BP exhibited excellent anticoagulant and antithrombotic properties due to the introduction of P(APM/MPC). P(APM/MPC)-OCS-BP also showed good HUVECs-cytocompatibility due to the substantial reduction of its residual aldehyde group. The subcutaneous implantation also demonstrated that P(APM/MPC)-OCS-BP showed a weak inflammatory response due to the anti-inflammatory effect of OCS. Finally, in vivo and in vitro results revealed that P(APM/MPC)-OCS-BP exhibited an excellent anti-calcification property. In a word, this simply cooperative crosslinking strategy provides a novel solution to obtain BHVs with good mechanical properties, HUVECs-cytocompatibility, anti-coagulation, anti-inflammatory and anti-calcification. It might be a promising alternative to GA-fixed BP and exhibited a good prospect in the clinical applications.

研究领域: 心血管工程 · 生物材料科学 · 组织工程 · 医疗器械 · 生物医学工程
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