Characterizing a Biomedical Hydrogel Device

Abstract

E-Matrix™, a hydrogel principally composed of gelatin and dextran, common food ingredients, is being manufactured with an amino acid formulation and considered as a new medical device. The compound purportedly accelerates the rate of healing once injected beneath a wound. The improved healing is believed to be caused by shifting the healing process from a slower healing adult inflammatory tissue stage to a quicker healing fetal regenerative tissue stage. In addition, gelatin and dextran are anticipated to interact within the medical device to form a stable hydrogel. The objectives of this study were to rheologically characterize E-Matrix™, develop quality control protocols for evaluation of E-Matrix™ and gelatin, investigate the nature of the proposed relationship between gelatin and dextran, and examine rheological properties of E-Matrix™ components.

Rheological techniques using a StressTech Controlled Stress Rheometer (ReoLogica Instruments AB, Lund, Sweden) were used to characterize E-Matrix™, to establish physical properties, and to describe the material flow behavior. Differential scanning calorimetry (PerkinElmer DSC7) was used to determine melt points of E-Matrix™ and a 12% gelatin solution to compare thermal transition temperatures. Rheological protocols were developed for both E-Matrix™ and the principle ingredient in the material, a 12% gelatin solution. The protocols evaluate specific rheological properties to compare either gelatin lots or manufactured E-Matrix™ batches with established standards. Incorporation of the rheological protocols into a quality control procedure would be a valuable tool for accessing the acceptability of gelatin lots and newly manufactured E-Matrix™ batches. To further understand and characterize E-Matrix™, studies were performed to examine key physical components of the material. Specifically solutions of 12% gelatin, 17% gelatin, 5% dextran, 12% gelatin-5% dextran, and the gelatin-rich domain of E-Matrix™ were rheologically examined and compared to rheological properties of E-Matrix™. In addition the affect of ionic strength and salt valence was also examined through rheological analysis. To determine whether a protein-carbohydrate conjugation resulted from the Maillard reaction, a spectrophotometric technique was performed to determine the degree of covalent conjugation by measuring the change in free amino groups.

E-Matrix™ was rheologically characterized at 37°C and 50°C as having pseudoplastic and Newtonian material flow behaviors, respectively. Differential scanning calorimetry determined the calorimetric melt point of E-Matrix™ (23.9°C) and a 12% gelatin solution (26.0°C) to occur sooner than those determined rheologically (33.7°C) and (32.7°C), respectively. Rheological protocols were developed for quality control evaluation of E-Matrix™ and gelatin. The protocols can be used as a quality control tool by the manufacturer of E-Matrix™, Encelle, Inc. of Greenville, North Carolina. Rheological properties were evaluated for different components of E-Matrix™; individual components, salt type, and ionic strength concentration. Individual E-Matrix™ components were found to differ significantly in regard to rheological properties. However salt type; monovalent versus divalent, using NaCl and CaCl₂ was not found to create significant differences for the properties examined in this study, but ionic strength concentration was found to produce rheological properties of significant difference. In addition, according to spectrophotometry, a hypothesized chemical interaction between gelatin and dextran was not likely occurring.

By understanding the rheological properties of E-Matrix™, the nature of the protein and carbohydrate interaction, and the rheological properties of the E-Matrix™ components, the mechanisms behind the functionality of the wound healing accelerant can be more clearly understood and benefit the product producers through further formulation optimization.