A synergistic strategy based on active hydroxymethyl amine compounds and fucoidan for bioprosthetic heart valves with enhancing anti-coagulation and anti-calcification properties.

With an aging population, the patients with valvular heart disease (VHD) are growing worldwide, and valve replacement is a primary choice for these patients with severe valvular disease. Among them, bioprosthetic heart valves (BHVs), especially BHVs trough transcatheter aortic valve replacement, are widely accepted by patients on account of their good hemodynamics and biocompatibility. Commercial BHVs in clinic are prepared by glutaraldehyde cross-linked pericardial tissue with the risk of calcification and thrombotic complications. In the present study, a strategy combines improved hemocompatibility and anti-calcification properties for BHVs has been developed based on a novel non-glutaraldehyde BHV crosslinker hexakis(hydroxymethyl)melamine (HMM) and the anticoagulant fucoidan. Besides the similar mechanical properties and enhanced component stability compared to glutaraldehyde crosslinked PP (G-PP), the fucoidan modified HMM-crosslinked PPs (HMM-Fu-PPs) also exhibit significantly enhanced anticoagulation performance with a 72 % decrease in thrombus weight compared with G-PP in ex-vivo shunt assay, along with the superior biocompatibility, satisfactory anti-calcification properties confirmed by subcutaneous implantation. Owing to good comprehensive performance of these HMM-Fu-PPs, this simple and feasible strategy may offer a great potential for BHV fabrication in the future, and open a new avenue to explore more N-hydroxymethyl compound based crosslinker with excellent performance in the field of biomaterials.

A versatile modification strategy for functional non-glutaraldehyde cross-linked bioprosthetic heart valves with enhanced anticoagulant, anticalcification and endothelialization properties.

Valvular heart disease is a major threat to human health and transcatheter heart valve replacement (THVR) has emerged as the primary treatment option for severe heart valve disease. Bioprosthetic heart valves (BHVs) with superior hemodynamic performance and compressibility have become the first choice for THVR, and more BHVs have been requested for clinical use in recent years. However, several drawbacks remain for the commercial BHVs cross-linked by glutaraldehyde, including calcification, thrombin, poor biocompatibility and difficulty in endothelialization, which would further reduce the BHVs' lifetime. This study developed a dual-functional non-glutaraldehyde crosslinking reagent OX-VI, which can provide BHV materials with reactive double bonds (CC) for further bio-function modification in addition to the crosslinking function. BHV material PBAF@OX-PP was developed from OX-VI treated porcine pericardium (PP) after the polymerization with 4-vinylbenzene boronic acid and the subsequent modification of poly (vinyl alcohol) and fucoidan. Based on the functional anti-coagulation and endothelialization strategy and dual-functional crosslinking reagent, PBAF@OX-PP has better anti-coagulation and anti-calcification properties, higher biocompatibility, and improved endothelial cells proliferation when compared to Glut-treated PP, as well as the satisfactory mechanical properties and enhanced resistance effect to enzymatic degradation, making it a promising candidate in the clinical application of BHVs. STATEMENT OF SIGNIFICANCE: Transcatheter heart valve replacement (THVR) has become the main solution for severe valvular heart disease. However, bioprosthetic heart valves (BHVs) used in THVR exhibit fatal drawbacks such as calcification, thrombin and difficulty for endothelialization, which are due to the glutaraldehyde crosslinking, resulting in a limited lifetime to 10-15 years. A new non-glutaraldehyde cross-linker OX-VI has been designed, which can not only show great crosslinking ability but also offer the BHVs with reactive double bonds (CC) for further bio-function modification. Based on the dual-functional crosslinking reagent OX-VI, a versatile modification strategy was developed and the BHV material (PBAF@OX-PP) has been developed and shows significantly enhanced anticoagulant, anti-calcification and endothelialization properties, making it a promising candidate in the clinical application of BHVs.

A universal strategy for the construction of polymer brush hybrid non-glutaraldehyde heart valves with robust anti-biological contamination performance and improved endothelialization potential.

With the intensification of the aging population and the development of transcatheter heart valve replacement technology (THVR), clinical demand for bioprosthetic valves is increasing rapidly. However, commercial bioprosthetic heart valves (BHVs), mainly manufactured from glutaraldehyde cross-linked porcine or bovine pericardium, generally undergo degeneration within 10-15 years due to calcification, thrombosis and poor biocompatibility, which are closely related to glutaraldehyde cross-linking. In addition, endocarditis caused by post-implantation bacterial infection also accelerates the failure of BHVs. Herein, a functional cross-linking agent bromo bicyclic-oxazolidine (OX-Br) has been designed and synthesized to crosslink BHVs and construct a bio-functionalization scaffold for subsequent in-situ atom transfer radical polymerization (ATRP). The porcine pericardium cross-linked by OX-Br (OX-PP) exhibits better biocompatibility and anti-calcification property than the glutaraldehyde-treated porcine pericardium (Glut-PP) as well as comparable physical and structural stability to Glut-PP. Furthermore, the resistance to biological contamination especially bacterial infection of OX-PP along with anti-thrombus and endothelialization need to be enhanced to reduce the risk of implantation failure due to infection. Therefore, amphiphilic polymer brush is grafted to OX-PP through in-situ ATRP polymerization to prepare polymer brush hybrid BHV material SA@OX-PP. SA@OX-PP has been demonstrated to significantly resist biological contamination including plasma proteins, bacteria, platelets, thrombus and calcium, and facilitate the proliferation of endothelial cells, resulting in reduced risk of thrombosis, calcification and endocarditis. Altogether, the proposed crosslinking and functionalization strategy synergistically achieves the improvement of stability, endothelialization potential, anti-calcification and anti-biofouling performances for BHVs, which would resist the degeneration and prolong the lifespan of BHVs. The facile and practical strategy has great potential for clinical application in fabricating functional polymer hybrid BHVs or other tissue-based cardiac biomaterials. STATEMENT OF SIGNIFICANCE: Bioprosthetic heart valves (BHVs) are widely used in valve replacements for severe heart valve disease, and clinical demand is increasing year over year. Unfortunately, the commercial BHVs, mainly cross-linked by glutaraldehyde, can serve for only 10-15 years because of calcification, thrombus, biological contamination, and difficulties in endothelialization. Many studies have been conducted to explore non-glutaraldehyde crosslinkers, but few can meet high requirements in all aspects. A new crosslinker, OX-Br, has been developed for BHVs. It can not only crosslink BHVs but also serve as a reactive site for in-situ ATRP polymerization and construct a bio-functionalization platform for subsequent modification. The proposed crosslinking and functionalization strategy synergistically achieves the high requirements for stability, biocompability, endothelialization, anti-calcification, and anti-biofouling propeties of BHVs.

Impact of co-landfill proportion of bottom ash and municipal solid waste composition on the leachate characteristics during the acidogenesis phase.

Incineration has become an important municipal solid waste (MSW) treatment strategy, and generates a large amount of bottom ash (BA). Although some BA is reused, much BA and pretreatment residues from BA recycling are disposed in landfill. When BA and MSW are co-landfilled together, acid neutralization capacity and alkaline earth metal dissolution of BA, as well as different components of MSW may change environmental conditions within the landfill, so the degradation of organic matter and the physical and chemical properties of leachate would be affected. In this study, the effect of co-landfilled BA and MSW on the leachate characteristics during the hydrolysis and acidogenesis phase was studied using different BA/MSW ratios and MSW compositions. The results showed that the co-landfill system increased leachate pH, electric conductivity and alkalinity. For MSW with a high content of degradable components, the release and degradation of total organic carbon (TOC) and volatile fatty acids (VFA) from MSW were promoted when the BA ratio by wet weight was less than 50%, and the biodegradability of leachate was improved. When the BA ratio exceeded 50%, the degradation of organic matters was inhibited. For MSW with low content of degradable components, when the proportion of BA was less than 20%, the release and degradation of TOC and VFA from MSW were promoted and alkalinity increased. When the BA ratio exceeded 20%, the degradation of organic matters was inhibited. The 50% BA ratio could improve the bio-treatability of leachate indicated by the leachate pH and C/N ratio. However, BA inhibited the release of nitrogen (TN and NH4+-N) at all BA ratios and MSW compositions. At the same time, the addition of BA increased the risk of leachate collection system clogging due to the dissolution and re-precipitation of alkaline earth metals contained in BA.

Inhibition effects of high calcium concentration on anaerobic biological treatment of MSW leachate.

With the increasing use of municipal solid waste incineration (MSWI) and more stringent limits on landfilling of organic waste, more MSWI bottom ash is being landfilled, and the proportion of inorganic wastes in landfills is increasing, causing the increased Ca concentrations in landfill leachate. In this research, the inhibition effect of Ca concentration on the anaerobic treatment of landfill leachate was studied using a biochemical methane potential experiment. Slight inhibition of methane production occurred when the addition of Ca concentration was less than 2000 mg/L. When the addition of Ca concentration was between 6000 and 8000 mg/L, methane production was significantly reduced (to 29.4-34.8 % of that produced by the BLK reactor), and the lag phase was increased from 8.55 to 16.32 d. Moreover, when the dosage of Ca concentration increased from zero to 8000 mg/L, reductions in solution Ca concentration increased from 929 to 2611 mg/L, and the proportion of Ca in the residual sludge increased from 22.58 to 46.87 %. Based on the results, when the dosage of Ca concentration was less than 4000 mg/L, the formation of Ca precipitates on the surface of sludge appeared to prevent mass transfer and was the dominant reason for the reduction in methane production and sludge biomass. At higher Ca concentrations (6000-8000 mg/L), the severe inhibition of methane production appeared to be caused by the toxic effect of highly concentrated Ca on sludge as well as mass transfer blockage.