Viscoelastic Characterization and Modeling of Gelation Kinetics of Injectable In Situ Cross-Linkable Poly(lactide-co-ethylene oxide-co-fumarate) Hydrogels

Abstract

Cell transplantation by injection of biodegradable hydrogels is a recently developed strategy for the treatment of degenerated tissues. A cell carrier should be cytocompatible, have suitable working time and rheological properties for injection, and harden in situ to attain dimensional stability and the desired mechanical strength. Hydrophilic macromer/cross-linker polymerizing systems, due to the relatively high molecular weight of the macromer and its inability to cross the cell membrane, are very attractive as injectable cell carriers. The objective of this research was to determine the effects of cross-linker, initiator, and accelerator concentrations on the gelation kinetics and ultimate modulus of a biodegradable, in situ cross-linkable poly(lactide-co-ethylene oxide-co-fumarate) (PLEOF) macromer. The in situ polymerizing mixture consisted of PLEOF macromer, methylene bisacrylamide cross-linker, and a neutral redox initiation system of ammonium persulfate initiator and tetramethylethylenediamine accelerator. Measurement of the time evolution of the viscoelastic properties of the network during the sol-gel transition showed the important influence of each component on the gel time and stiffness of the hydrogels. A kinetic model was developed to predict the modulus as a function of composition. Model predictions were consistent with most of the experimental findings. The values of the storage and loss moduli at the gel point were found to be approximately equal for samples with equal PLEOF concentrations, resulting in a simple method to predict the gelation time based on the Winter--Chambon criterion, with the use of the proposed kinetic model. The results of this study can be coupled with component cytocompatibility measurements to predict the effect of composition on the viability of the cells encapsulated in the hydrogel matrix.

Introduction to cell–hydrogel mechanosensing

“…These characteristics are dependent on the percentage water content, porosity of the hydrogel and the polymer arrangement. Several studies have examined the viscoelastic properties of hydrogels [19,[155][156][157][158], although few have examined in detail the influence these properties have on cell behaviour. The viscoelastic characteristic of cell-seeded hydrogels can change over time owing to a combination of contraction [97], enzyme-associated degradation and extracellular matrix deposition [53,127].…”

The impact of damage accumulation on the kinetics of network strength recovery for a physical polymer gel subjected to shear deformation

“…13,[17][18][19][20] These methods typically use oscillation-based measurements to evaluate postdeformation strength recovery and are similar to the tests used to measure network gelation kinetics. 21,22 For "shear thinning" injectable materials, the material's storage modulus (G 0 ) is the critical parameter used to quantify selfhealing behavior because it describes the elastic character of Additional Supporting Information may be found in the online version of this article. is typically observed to increase over time to match its original value, which is thought to indicate full strength recovery or "healing" of the material.…”

Cytotoxicity of Paclitaxel in Biodegradable Self-Assembled Core-Shell Poly(Lactide-Co-Glycolide Ethylene Oxide Fumarate) Nanoparticles

“…ULMW PLA and PLGA were synthesized by ring opening polymerization of L-lactide (LA) and/or Glycolide (GL) monomers with DEG as the initiator and TOC as the polymerization catalyst as described (36)(37)(38). LA and GL monomers were dried under vacuum at 40°C for at least 12 h before the reaction.…”

“…In the next step, poly(lactide fumarate) (PLAF) or poly (lactide-co-glycolide fumarate) (PLGF) was synthesized by condensation polymerization of ULMW PLA or PLGA, respectively, with fumaryl chloride (FuCl) as described (36)(37)(38). Similarly, for the synthesis of poly(lactide-co-ethylene oxide fumarate) (PLEOF), ULMW PLA and PEG were reacted with FuCl.…”

“…The polymer sample was dissolved in deuterated chloroform (Aldrich, 99.8 atom% deuterated) at a concentration of 50 mg/ml and 1% v/v trimethylsilane (TMS; Aldrich) was used as the internal standard. The molecular weight distribution of the polymers was measured by GPC (38). Measurements were carried out with a Waters 717 Plus Autosampler GPC system (Waters, Milford, MA) connected to a model 616 HPLC pump, model 600S controller, and a model 410 refractive index detector.…”