Improved calcification resistance and biocompatibility of tissue patch grafted with sulfonated PEO or heparin after glutaraldehyde fixation

Abstract

A novel chemical modification of biological tissues was developed aimed at improving biocompatibility and calcification resistance. This method involved the additional grafting of sulfonated PEO (PEO-SO(3)) or heparin after conventional glutaraldehyde (GA) fixation of bovine pericardium (BP). The amino groups of PEO-SO(3) or heparin were utilized to react to the GA residues to block them. The PEO-SO(3) or heparin grafted tissues demonstrated a slightly higher shrinkage temperature and tensile strength, but greater resistance to collagenase digestion, than GA treated ones. These results suggest that modified tissues have improved durability due to the grafting and filling effect of PEO-SO(3) or heparin in addition to the GA cross-linking. At the direct contact cytotoxicity test in vitro, PEO-SO(3) or heparin grafted tissue was shown to be nontoxic, while relatively significant cytotoxicity was observed for the GA treated tissues, possibly due to the release of GA. From the in vivo calcification study, calcium contents deposited on the modified tissues were much less than those on GA treated tissues. Such a decreased calcification might be explained by the decrease of residual GA groups during the additional treatment, and the space-filling effect and the nonadhesive property and/or the blood compatibility of PEO-SO(3) or heparin grafted covalently. The newly modified tissue patch was observed to show improved pathological assessibility including less inflammation and tissue reactions. This simple modification method may be useful for calcification-resistant and blood-compatible tissue patches for cardiovascular implants.

Vascular patches tissue-engineered with autologous bone marrow-derived cells and decellularized tissue matrices

“…These vascular patches have shown good mechanical properties and in vivo durability. However, these patches have potential shortcomings of thrombus formation and calcium deposition due to blood and tissue incompatibility [4]. Moreover, these patches are susceptible to infection for their life span and need the ability to grow.…”

Effects of periodate and chondroitin 4-sulfate on proteoglycan stabilization of ostrich pericardium. Inhibition of calcification in subcutaneous implants in rats

“…This effect is not easily explained taking into account that GAGs present a high negative charge density due to the sulfate groups. However, it is interesting that other negatively charged compounds, as heparin or sulfated poly(ethylene oxide), when coupled to biological materials, also induce calcification resistance [29][30][31]. GA treatment has been shown to remove, at least partially, PGs from pericardium [1], generating voids and cavities that may potentially trap foreign particles that may lead to nucleation centers for calcification.…”

A Review of the Biocompatibility of Implantable Devices: Current Challenges to Overcome Foreign Body Response

“…146,147 Since some surfactants such as sodium dodecyl sulfate reduce mineralization, these are used in commercial products, such as commercial porcine valves. 148,149 To prevent calcification induced by glutaraldehyde, chemical modification of the device surface has been investigated [e.g., using hyaluronic acid, 152 sulfonated poly(ethylene oxide) and heparin, 151,152 protamine, 153,154 bovine pericardium, [155][156][157] and l-arginine 156,157 ].…”