Formulation Changes Affect Material Properties and Cell Behavior in HA-Based Hydrogels

Abstract

To develop and optimize new scaffold materials for tissue engineering applications, it is important to understand how changes to the scaffold affect the cells that will interact with that scaffold. In this study, we used a hyaluronic acid- (HA-) based hydrogel as a synthetic extracellular matrix, containing modified HA (CMHA-S), modified gelatin (Gtn-S), and a crosslinker (PEGda). By varying the concentrations of these components, we were able to change the gelation time, enzymatic degradation, and compressive modulus of the hydrogel. These changes also affected fibroblast spreading within the hydrogels and differentially affected the proliferation and metabolic activity of fibroblasts and mesenchymal stem cells (MSCs). In particular, PEGda concentration had the greatest influence on gelation time, compressive modulus, and cell spreading. MSCs appeared to require a longer period of adjustment to the new microenvironment of the hydrogels than fibroblasts. Fibroblasts were able to proliferate in all formulations over the course of two weeks, but MSCs did not. Metabolic activity changed for each cell type during the two weeks depending on the formulation. These results highlight the importance of determining the effect of matrix composition changes on a particular cell type of interest in order to optimize the formulation for a given application.

The Effects of a Crosslinked, Modified Hyaluronic Acid (xCMHA‐S) Gel on Equine Tendon Healing

“…Thiolated carboxymethyl hyaluronic acid (CMHA‐S) was synthesized as previously described . Thiol modification (3 × 10 −4 mmol/mg) was assessed using 5,5′‐dithio‐bis(2‐nitrobenzoic acid) (Ellman's reagent).…”

“…Thiolated carboxymethyl hyaluronic acid (CMHA-S) was synthesized as previously described. 25 Thiol modification (3 Â 10 À4 mmol/mg) was assessed using 5,5 0 -dithio-bis(2nitrobenzoic acid) (Ellman's reagent). Molecular weight (340 kDa) was assessed using gel permeation chromatography and dynamic light scattering.…”

The diverse roles of hydrogel mechanics in injectable stem cell transplantation

“…Similarly, hydrogels with intermediate elasticity were found to significantly increase the secretion of pro-angiogenic factors from adipose-derived stem cells [102]. Unfortunately, increasing hydrogel stiffness and crosslinking density often results in slower hydrogel degradation kinetics [85,103]. With a decrease in hydrogel degradation, there may be an associated decrease in the diffusion of secreted soluble factors, thus limiting the therapeutic benefit of transplanted stem cells [104].…”

In vitro evaluation of 3D bioprinted tri‐polymer network scaffolds for bone tissue regeneration

“…Additionally, the mechanical properties of the scaffolds must be appropriate to support cell proliferation and provide stability to counter cellular contractile forces imposed during migration throughout the matrix . Lawyer et al reported that the stiffness of the scaffolds greatly impacts the migration and proliferation abilities of the cells in the scaffold . Thus, it has been concluded that a synergistic effect exists between the biological and mechanical properties of the scaffold which plays a significant role in determining the physiological behavior of the encapsulated cells.…”

“…21,22 Lawyer et al reported that the stiffness of the scaffolds greatly impacts the migration and proliferation abilities of the cells in the scaffold. 23 Thus, it has been concluded that a synergistic effect exists between the biological and mechanical properties of the scaffold which plays a significant role in determining the physiological behavior of the encapsulated cells. These properties must be investigated and understood before the scaffold can be implemented in vivo.…”