Immunocompatibility and non-thrombogenicity of gelatin-based hydrogels.

Immunocompatibility and non-thrombogenicity are important requirements for biomedical applications such as vascular grafts. Here, gelatin-based hydrogels formed by reaction of porcine gelatin with increasing amounts of lysine diisocyanate ethyl ester were investigated in vitro in this regard. In addition, potential adverse effects of the hydrogels were determined using the "Hen's egg test on chorioallantoic membrane" (HET-CAM) test and a mouse model.The study revealed that the hydrogels were immunocompatible, since complement activation was absent and a substantial induction of reactive oxygen species generating monocytes and neutrophils could not be observed in whole human blood. The density as well as the activation state of adherent thrombocytes was comparable to medical grade polydimethylsiloxane, which was used as reference material. The HET-CAM test confirmed the compatibility of the hydrogels with vessel functionality since no bleedings, thrombotic events, or vessel destructions were observed. Only for the samples synthesized with the highest LDI amount the number of growing blood vessels in the CAM was comparable to controls and significantly higher than for the softer materials. Implantation into mice showed the absence of adverse or toxic effects in spleen, liver, or kidney, and only a mild lymphocytic activation in the form of a follicular hyperplasia in draining lymph nodes (slightly increased after the implantation of the material prepared with the lowest LDI content). These results imply that candidate materials prepared with mid to high amounts of LDI are suitable for the coating of the blood contacting surface of cardiovascular implants.

Influence of physically crosslinked gelatins on the vasculature in the avian chorioallantoic membrane.

Gelatins functionalized with desaminotyrosine (DAT) or desaminotyrosyl tyrosine (DATT) form physically crosslinked hydrogels, due to the interactions between the introduced aromatic moieties and gelatin triple helices, whose extent depends on the thermal treatment of the material. The G-modulus of these hydrogels can be tailored to the range of the natural extracellular matrix by adjusting the degree of crosslinking. While these gelatin-based materials have been shown to be not angiogenic, the aim of the study was to evaluate whether these biomaterials influence the regulation of blood vessels when positioned on the chorionallantoic membrane (CAM) of fertilized eggs. The results clearly indicate that the DAT-functionalized gelatin led to an increase of the diameter of the blood vessels in the CAM, which at the same time is probably associated with an increased blood flow in these CAM vessels. The vessel diameters of the four groups (DAT-functionalized gelatin, DATT-functionalized gelatin, plain gelatin, control group without gelatin, each n = 10) differed significantly (p < 0.0001). Vessels in the CAM exposed to the DAT-functionalized gelatin showed with 36.4 µm ± 3.4 µm the largest mean diameters compared to the mean diameters of the samples exposed to DATT gelatin (16.0 µm ± 0.8 µm; p < 0.05) and the plain gelatin (21.2 µm ± 1.0 µm; p < 0.05), which both did not differ significantly from the vessels of the control group. The biocompatibility of the materials in vitro motivates the exploration of their application as matrix in local drug-release systems with short half-life times (one hour up to several days).

A NiTi alloy-based cuff for external banding valvuloplasty: a six-week follow-up study in pigs.

OBJECTIVE: The study aimed to test a Nitinol(®)-based vein cuff model for external banding valvuloplasty. METHOD: In 12 adult minipigs, the vena jugularis externa was covered for 42 days by a cuff with an inner diameter adapted to the outer vein diameter in supine position. By changing from supine into prone position hypostatically vein dilation was induced to simulate varicose vein dilation. Cuff position and the inner diameter of the vein lumen under the cuff were examined by computer tomography scanning. Also, histological analysis of the vein wall within the cuff was performed. RESULTS: The preset tubular shape of the cuff and the cuff position did not change in both prone and supine position, but due to fibrosis the luminal vein diameter within the cuff was decreased (P < 0.01) already after 21 days. CONCLUSION: A foreign body response resulted in a fibrous capsule covering the cuff which might limit cuff functionality.