Cellular Response to Reagent‐Free Electron‐Irradiated Gelatin Hydrogels

Abstract

As a biomaterial, it is well established that gelatin exhibits low cytotoxicity and can promote cellular growth. However, to circumvent the potential toxicity of chemical crosslinkers, reagent-free crosslinking methods such as electron irradiation are highly desirable. While high energy irradiation has been shown to exhibit precise control over the degree of crosslinking, these hydrogels have not been thoroughly investigated for biocompatibility and degradability. Here, NIH 3T3 murine fibroblasts are seeded onto irradiated gelatin hydrogels to examine the hydrogel's influence on cellular viability and morphology. The average projected area of cells seeded onto the hydrogels increases with irradiation dose, which correlates with an increase in the hydrogel's shear modulus up to 10 kPa. Cells on these hydrogels are highly viable and exhibits normal cell cycles, particularly when compared to those grown on glutaraldehyde crosslinked gelatin hydrogels. However, proliferation is reduced on both types of crosslinked samples. To mimic the response of the hydrogels in physiological conditions, degradability is monitored in simulated body fluid to reveal strongly dose-dependent degradation times. Overall, given the low cytotoxicity, influence on cellular morphology and variability in degradation times of the electron irradiated gelatin hydrogels, there is significant potential for application in areas ranging from regenerative medicine to mechanobiology.

Magnetically responsive composites: electron beam assisted magnetic nanoparticle arrest in gelatin hydrogels for bioactuation

“…Parametrization has been taken from ref. 18, and the others are included in Tables 1 and 2 Dose (kGy) (DL/L 0 ) eqn (14) (%) (DL/L 0 ) eqn (10)…”

“…This approach constitutes a biocompatible procedure that also facilitates thermal stabilization and allows for tuning of mechanical properties to mimic, e.g., the desired extracellular matrix (ECM) properties. [9][10][11][12] Gelatin itself is an advantageous material as it is biopolymerderived and of very little complexity such that it exhibits less irregularities and is simple to handle. Compared to collagen of which it is a derivative, it also shows less antigenicity.…”

Micropatterning of reagent‐free, high energy crosslinked gelatin hydrogels for bioapplications

“…For 10 wt % gelatin, the storage modulus increased from 7 kPa to 11 kPa after irradiation with 40 kGy . Furthermore, doses on this order of magnitude result in sterilization of the samples and have exhibited good biocompatibility with NIH 3T3 fibroblasts …”

“…34 Furthermore, doses on this order of magnitude result in sterilization of the samples and have exhibited good biocompatibility with NIH 3T3 fibroblasts. 35 This present work establishes a method of transferring mm-sized grooves onto gelatin hydrogels by micromolding. As low mechanical strength hinders such microfabrication techniques, 25 crosslinking by electron irradiation was used to tune the mechanical properties and stabilize the patterned microstructures in ambient and physiological conditions.…”

Programing stimuli-responsiveness of gelatin with electron beams: basic effects and development of a hydration-controlled biocompatible demonstrator

“…glutaraldehyde 9 ), reagent-free methods are highly desirable in the areas of biomedical and pharmaceutical applications. High energy electron irradiation represents such a nontoxic crosslinking method for gelatin modifying its properties, such as thermal stability, structure and swelling while maintaining chemical structure 10 and biocompatibility 11 . In addition, even electron doses of just a few kGy are known to sterilize gelatin 12 , which makes it attractive for biomedical applications.…”