Effect of the Addition of a Labile Gelatin Component on the Degradation and Solute Release Kinetics of a Stable PEG Hydrogel

Abstract

Characterization of the degradation mechanisms and resulting products of biodegradable materials is critical in understanding the behavior of the material including solute transport and biological response. Previous mathematical analyses of a semi-interpenetrating network (sIPN) containing both labile gelatin and a stable cross-linked poly(ethylene glycol) (PEG) network found that diffusion-based models alone were unable to explain the release kinetics of solutes from the system. In this study, degradation of the sIPN and its effect on solute release and swelling kinetics were investigated. The kinetics of the primary mode of degradation, gelatin dissolution, was dependent on temperature, preparation methods, PEGdA and gelatin concentration, and the weight ratio between the gelatin and PEG. The gelatin dissolution rate positively correlated with both matrix swelling and the release kinetics of high-molecular-weight model compound, FITC-dextran. Coupled with previous in vitro studies, the kinetics of sIPN degradation provided insights into the time-dependent changes in cellular response including adhesion and protein expression. These results provide a facile guide in material formulation to control the delivery of high-molecular-weight compounds with concomitant modulation of cellular behavior.

3D cell entrapment in crosslinked thiolated gelatin-poly(ethylene glycol) diacrylate hydrogels

“…All samples were run at 0.5 mL/min at 37 °C in a mobile phase consisting of 80% (v/v) 0.1 M NaNO 3 with 20% (v/v) acetonitrile. Chromatogram analysis was performed using PeakFit software (v4.12, SeaSolve Software, Inc.) to fit Gaussian peaks based on features within the chromatorgram [18,28]. The 1 H-NMR spectrum of Gel-PEG-Cys with D 2 O as solvent shows: δ1.3, d, 2Hs, -C H 2 SH; δ2.89, t, 1H, -C H CH 2 SH; δ3.65, m, -C H 2 - from PEG backbone; broad peaks composed of many overlapping small peaks at 1.7, 1.75, 1.92, 3.18, 4.19, and 4.2 ppm were characteristic gelatin peaks, consistent with previous findings [17].…”

“…Primary human monocyte adhesion and protein expression on sIPN surfaces was found to depend on bioactive ECM peptide and integrin identities [17]. Physically incorporated gelatin underwent rapid dissolution at physiological temperature such that more than 70% gelatin loss was observed within the first 48 h in vitro [18]. Thus, different gelatin crosslinking modalities may result in different matrix structures and different gelatin chain relaxation behaviors at physiological temperature, which may further affect bulk physicochemical matrix properties such as those controlling swelling, degradation and viscoelasticity.…”

Mesenchymal Stromal/Stem Cell and Minocycline-Loaded Hydrogels Inhibit the Growth of Staphylococcus aureus that Evades Immunomodulation of Blood-Derived Leukocytes

“…This hydrogel system has also shown to release loaded solutes with controlled kinetics depending on gelatin and PEG composition. For example, hydrogels simultaneously loaded with silver sulfadiazine and bupivacaine achieved antimicrobial efficacy on Staphylococcus aureus (SA) and methicillin-resistant SA while promoting cutaneous wound healing (14)(15)(16).…”

A Biosynthetic Scaffold that Facilitates Chondrocyte-Mediated Degradation and Promotes Articular Cartilage Extracellular Matrix Deposition

“…To assess enzymatic cleavage of the norbornene-functionalized gelatin, 0.2 wt% gelatin solutions with varying extents of functionalization (1:1, 0.5:1, 0.25:1 NB:gelatin amine molar ratios, or unmodified gelatin) were dissolved in 0.1 M sodium nitrate (Sigma Aldrich) and 0.1 M sodium dibasic phosphate (Sigma Aldrich), so that the resulting solution could be assessed using aqueous mobile phase gel permeation chromatography (GPC) as previously described [40]. The gelatin solutions were incubated with either 20 units/mL (~0.1 mg/mL) type II collagenase (Worthington Biochemical) or chondrocyte-conditioned media from cells cultured for 3 days.…”