Methods and devices for changing the flow rates of pH modifying fluids for controlling cross-linking rates of reactive components of biocompatible sealing compositions

Abstract

A method of making a biocompatible composition for sealing tissue includes mixing a first fluid having a first reactive component (e.g., an electrophile) and a second fluid having a second reactive component (e.g., a nucleophile) to form a mixture and expressing the mixture. During expression, a pH modifying fluid (e.g., NaOH) is added to the mixture at a rate that changes. In one embodiment, a higher ratio of the pH modifying fluid is added to the mixture during a first expressing stage and a lower ratio of said pH modifying fluid is added to the mixture during a second expressing stage. During the first expressing stage, a mixing ratio of the pH modifying fluid, the first fluid and the second fluid is 0.7-1.4:1:1. During the second expressing stage, the mixing ratio of the pH modifying fluid, the first fluid and the second fluid is 0.12-0.24:1:1.

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