Development of Enzymatic-Resistant and Compliant Decellularized Extracellular Matrixes via Aliphatic Chain Modification for Bladder Tissue Engineering

ACS Appl Mater Interfaces. 2022 Aug 24;14(33):37301-37315. doi: 10.1021/acsami.2c06865. Epub 2022 Aug 10.

ABSTRACT

Here, we report the design and development of highly stretchable, compliant, and enzymatic-resistant transiently cross-linked decellularized extracellular matrixes (dECMs) (e.g., porcine small intestine submucosa/dSIS, urinary bladder matrix/dUBM, bovine pericardium/dBP, bovine dermis/dBD, and human dermis/dHD). Specifically, these dECMs were modified with long aliphatic chains (C9, C14, and C18). Upon modification, dECMs became significantly resistant to enzymatic degradation for extended periods, showed increased water contact angle (>20%-90%), and stretched >200% than their control counterparts. Modified dECMs are compliant, undergoing 100% elongation at only 0.3-0.5 MPa of applied tensile stress (∼10%-25% of their control counterparts), similar to the control bladder tissue. Furthermore, modified dECMs remain structurally stable at the physiological temperature with increased storage and loss modulus values but decreased tan δ values compared to their control counterparts. Although modification reduces cell adhesion, the gene expressions in polarized macrophages remain unchanged (e.g., TGFβ, CD163, and CD86), except for the modified bovine pericardium (dBP) where a significant decrease in TNFα gene expression is observed. When implanted in the rat subcutaneous model, modified dECMs degraded relatively slowly and did not cause significant fibrotic tissue formation. The numbers of pro-regenerative macrophages increased to several folds in a later time point of evaluation. Modified dECM also supported the bladder wall regeneration with formations of the urothelium, lamina propria, blood vessels, and muscle bundles and reduced the occurrence of calculi formation by 50% in a rat bladder augmentation model. We anticipate that the enhanced stretchability, compliance, and physiological stability of dECMs indicate their suitability for urologic tissue regeneration.

PMID:35948054 | DOI:10.1021/acsami.2c06865

A Novel Crosslinking Method for Improving the Anti-Calcification Ability and Extracellular Matrix Stability in Transcatheter Heart Valves

Front Bioeng Biotechnol. 2022 Jul 12;10:909771. doi: 10.3389/fbioe.2022.909771. eCollection 2022.

ABSTRACT

More than 200,000 patients with aortic diseases worldwide undergo surgical valve replacement each year, and transcatheter heart valves (THV) have been more widely used than ever before. However, THV made by the glutaraldehyde (Glut) crosslinking method has the disadvantage of being prone to calcification, which significantly reduces the durability of biomaterials. In this study, we applied a novel crosslinking method using ribose in THV for the first time, which can decrease calcification and increase the stability of the extracellular matrix (ECM). We incubated the bovine pericardium (BP) in ribose solution at 37°C by shaking for 12 days and confirmed that the structure of the BP was more compact than that of the Glut group. Moreover, the ribose method remarkably enhanced the biomechanical properties and provided reliable resistance to enzymatic degradation and satisfactory cellular compatibility in THV. When the BP was implanted subcutaneously in vivo, we demonstrated that ECM components were preserved more completely, especially in elastin, and the immune-inflammatory response was more moderate than that in the Glut treatment group. Finally, the ribose-cross-linked materials showed better anti-calcification potential and improved durability of THV than Glut-cross-linked materials.

PMID:35903798 | PMC:PMC9315440 | DOI:10.3389/fbioe.2022.909771

Modified subcostal arch xiphoid thoracoscopic expanded thymectomy for thymic carcinoma: a case report and review of literature

Thymic neoplasms are a relatively uncommon tumor, with the anterior mediastinum being the most common. Median sternotomy is the procedure of choice for the treatment of thymomas. With the advent of thoracoscop…  Read More

Minimally-invasive cardiac surgery: a bibliometric analysis of impact and force to identify key and facilitating advanced training

The number of citations an article receives is a marker of its scientific influence within a particular specialty. This bibliometric analysis intended to recognise the top 100 cited articles in minimally-invas…  Read More

Development of Antithrombogenic ECM-Based Nanocomposite Heart Valve Leaflets

ACS Appl Bio Mater. 2022 Aug 15;5(8):3883-3895. doi: 10.1021/acsabm.2c00423. Epub 2022 Jul 15.

ABSTRACT

Thrombogenicity, which is commonly encountered in artificial heart valves after replacement surgeries, causes valvular failure. Even life-long anticoagulant drug use may not be sufficient to prevent thrombogenicity. In this study, it was aimed to develop a heart valve construct with antithrombogenic properties and suitable mechanical strength by combining multiwalled carbon nanotubes within a decellularized bovine pericardium. In this context, the decellularization process was performed by using the combination of freeze-thawing and sodium dodecyl sulfate (SDS). Evaluation of decellularization efficiency was determined by histology (Hematoxylin and Eosin, DAPI and Masson’s Trichrome) and biochemical (DNA, sGAG and collagen) analyses. After the decellularization process of the bovine pericardium, composite pericardial tissues were prepared by incorporating -COOH-modified multiwalled carbon nanotubes (MWCNTs). Characterization of MWCNT incorporation was performed by ATR-FTIR, TGA, and mechanical analysis, while SEM and AFM were used for morphological evaluations. Thrombogenicity assessments were studied by platelet adhesion test, Calcein-AM staining, kinetic blood clotting, hemolysis, and cytotoxicity analyses. As a result of this study, the composite pericardial material revealed improved mechanical and thermal stability and hemocompatibility in comparison to decellularized pericardium, without toxicity. Approximately 100% success is achieved in preventing platelet adhesion. In addition, kinetic blood-coagulation analysis demonstrated a low rate and slow coagulation kinetics, while the hemolysis index was below the permissible limit for biomaterials.

PMID:35839464 | PMC:PMC9382671 | DOI:10.1021/acsabm.2c00423

Comparative study on Sichuan yak pericardium and Australian cattle pericardium

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2022 Jun 25;39(3):537-543. doi: 10.7507/1001-5515.202202044.

ABSTRACT

Currently, as the key raw material of artificial biological heart valve, bovine pericardium is mainly depend on import and has become a “bottleneck” challenge, greatly limiting the development of domestic biological heart valve. Therefore, the localization of bovine pericardium is extremely urgent. In this study, the pericardium of Sichuan yak was compared with that of Australian cattle in terms of fundamental properties and anti-calcification performance. The results demonstrated that the appearance and thickness of yak pericardium were more advantageous than the Australian one. Sichuan yak pericardium and Australian cattle pericardium had comparable performance in shrinkage temperature, mechanical test and anti-calcification test. This study preliminarily verifies the feasibility of substitution of Australian cattle pericardium by Sichuan yak pericardium and promotes the progression of bovine pericardium localization with data support.

PMID:35788523 | DOI:10.7507/1001-5515.202202044

Detection of HOCl-driven degradation of the pericardium scaffolds by label-free multiphoton fluorescence lifetime imaging

Sci Rep. 2022 Jun 20;12(1):10329. doi: 10.1038/s41598-022-14138-5.

ABSTRACT

Artificial biomaterials can significantly increase the rate of tissue regeneration. However, implantation of scaffolds leads not only to accelerated tissue healing but also to an immune response of the organism, which results in the degradation of the biomaterial. The synergy of the immune response and scaffold degradation processes largely determines the efficiency of tissue regeneration. Still, methods suitable for fast, accurate and non-invasive characterization of the degradation degree of biomaterial are highly demandable. Here we show the possibility of monitoring the degradation of decellularized bovine pericardium scaffolds under conditions mimicking the immune response and oxidation processes using multiphoton tomography combined with fluorescence lifetime imaging (MPT-FLIM). We found that the fluorescence lifetimes of genipin-induced cross-links in collagen and oxidation products of collagen are prominent markers of oxidative degradation of scaffolds. This was verified in model experiments, where the oxidation was induced with hypochlorous acid or by exposure to activated neutrophils. The fluorescence decay parameters also correlated with the changes of micromechanical properties of the scaffolds as assessed using atomic force microscopy (AFM). Our results suggest that FLIM can be used for quantitative assessments of the properties and degradation of the scaffolds essential for the wound healing processes in vivo.

PMID:35725581 | PMC:PMC9209456 | DOI:10.1038/s41598-022-14138-5

In-Vitro Endothelialization Assessment of Heparinized Bovine Pericardial Scaffold for Cardiovascular Application

Polymers (Basel). 2022 May 26;14(11):2156. doi: 10.3390/polym14112156.

ABSTRACT

(1) Background: Hemocompatibility is a critical challenge for tissue-derived biomaterial when directly contacting the bloodstream. In addition to surface modification with heparin, endothelialization of the grafted material is suggested to improve long-term clinical efficacy. This study aimed to evaluate the ability to endothelialize in vitro of heparinized bovine pericardial scaffolds. (2) Methods: bovine pericardial scaffolds were fabricated and heparinized using a layer-by-layer assembly technique. The heparinized scaffolds were characterized for heparin content, surface morphology, and blood compatibility. Liquid extraction of the samples was prepared for cytotoxicity testing on human endothelial cells. The in-vitro endothelialization was determined via human endothelial cell attachment and proliferation on the scaffold. (3) Results: The heparinized bovine pericardial scaffold exhibited a heparin coating within its microfiber network. The scaffold surface immobilized with heparin performed good anti-thrombosis and prevented platelet adherence. The proper cytotoxicity impact was observed for a freshly used heparinized sample. After 24 h washing in PBS 1X, the cell compatibility of the heparinized scaffolds was improved. In-vitro examination results exhibited human endothelial cell attachment and proliferation for 7 days of culture. (4) Conclusions: Our in-vitro analysis provided evidence for the scaffold’s ability to support endothelialization, which benefits long-term thromboresistance.

PMID:35683829 | PMC:PMC9182580 | DOI:10.3390/polym14112156