Hydrogel Elastic Modulus Research Articles

Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated boneformation.

The effectiveness of stem-cell therapies has been hampered by cell death and limited control over fate1. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype2–4. Stem cell behavior can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials5–7, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel's elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel's elasticity regulated bone regeneration, with optimal bone formation at 60 kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem-cell behaviors in situ.

Influence of crosslinking on the stiffness and degradation of dermis‐derived hydrogels

Natural hydrogels have been investigated for three-dimensional tissue reconstruction and regeneration given their ability to emulate the structural complexity of multi-component extracellular matrices (ECM). Hydrogels rich in ECM can be extracted and assembled from soft tissues, retain a composition specific to the tissue source, and stimulate vascularized tissue formation. However, poor mechanical properties and rapid degradation hinder their performance in regenerative applications. This study investigates the effect of glutaraldehyde (GA) crosslinking on the mechanical properties, biological activity, and degradation of dermis-isolated ECM-rich hydrogels. Compression tests indicated that hydrogel elastic moduli and yield stress values increased significantly with GA exposure time. Lyophilization was shown to decrease yield stress values with respect to non-lyophilized gels. Crosslinked ECM, unlike non-crosslinked gels, was resistant to pepsin degradation in vitro. In a rodent subcutaneous implant model, crosslinking for 0.5 hours or longer drastically slowed degradation relative to controls. Inflammation was low and mature vascularized granulation tissue was observed in all gels, with an increase in vessel density at 1 week in crosslinked gels relative to controls. These results support the potential use of dermis-derived hydrogels as materials for tissue engineering applications and suggest that crosslinking can enhance mechanical properties and prolong hydrogel lifetime while promoting vascularized tissue formation.

Effective tuning of ligand incorporation and mechanical properties in visible light photopolymerized poly(ethylene glycol) diacrylate hydrogels dictates cell adhesion and proliferation

Cell behavior is guided by the complex interplay of matrix mechanical properties as well as soluble and immobilized biochemical signals. The development of synthetic scaffolds that incorporate key functionalities of the native extracellular matrix (ECM) for support of cell proliferation and tissue regeneration requires that stiffness and immobilized concentrations of ECM signals within these biomaterials be tuned and optimized prior to in vitro and in vivo studies. A detailed experimental sensitivity analysis was conducted to identify the key polymerization conditions that result in significant changes in both elastic modulus and immobilized YRGDS within visible light photopolymerized poly(ethylene glycol) diacrylate hydrogels. Among the polymerization conditions investigated, single as well as simultaneous variations in N-vinylpyrrolidinone and precursor concentrations of acryl-PEG3400-YRGDS resulted in a broad range of the hydrogel elastic modulus (81–1178 kPa) and YRGDS surface concentration (0.04–1.72 pmol cm−2). Increasing the YRGDS surface concentration enhanced fibroblast cell adhesion and proliferation for a given stiffness, while increases in the hydrogel elastic modulus caused decreases in cell adhesion and increases in proliferation. The identification of key polymerization conditions is critical for the tuning and optimization of biomaterial properties and the controlled study of cell–substrate interactions.

Hydrogel Reinforced by Short Albumin Fibers: Mechanical Characterization and Assessment of Biocompatibility

AbstractInjectable hydrogels represent biomaterials attractive for many biomedical applications. Here, a hybrid material composed of dextran‐crosslinked gelatin embedded with ≈100–1 000 µm long, electrospun bovine serum albumin fibers is described. Incorporation of fibers at weight fractions of 1–6% increases the hydrogel elastic modulus by up to ≈40% and decreases the gelation time by ≈20%. The addition of short fibers does not affect the injection of the pre‐gel solution throughout medical needles at moderate shear rates. Finally, viability of seeded fibroblasts confirms the biocompatibility of the composite scaffold. This hybrid represents a class of biomaterials that structurally mimics the ECMs of common tissues and that can be delivered by a minimal‐invasive approach.magnified image

Carboxymethyl derivative of scleroglucan: a novel thermosensitive hydrogel forming polysaccharide for drug delivery applications

A carboxymethyl derivative of scleroglucan (Scl-CM) with a derivatization degree of 65 +/- 5% was synthesized. The rheological behaviour of this novel polymer was studied and compared with that of the starting polymer. We observed that the charged moieties carried on the chains could prevent the triple helix formation of Scl. Scl-CM aqueous solutions behave like true polymer solutions up to 1% w/v, whereas above this concentration a weak gel behaviour was observed. CaCl(2) addition to aqueous Scl-CM solutions led to a physical gel formation; the hydrogel strength was related to polymer and CaCl(2) concentrations. Temperature sweeps, registered at 1 Hz on hydrogels differing in CaCl(2) concentration, evidenced a gel --> sol transition in the range of 30-40 degrees C, depending on the molar ratio between carboxylic groups and Ca(+2). In order to verify a possible use of these hydrogels as drug delivery systems, acyclovir was loaded into the network. Rheological analysis evidenced that the loaded drug can affect the hydrogel elastic modulus. The release of acyclovir in phosphate buffer was evaluated at different temperatures in order to assess the suitability of this novel drug delivery system in topical applications.

Structural and rheological properties of methacrylamide modified gelatin hydrogels.

Dynamic shear oscillation measurements at small strain were used to characterize the viscoelastic properties and related differences in the molecular structure of hydrogels based on gelatin methacrylamide. Gelatin was derivatized with methacrylamide side groups and was subsequently cross-linked by radical polymerization via photoinitiation. The light treatment of methacrylamide gelatin solutions resulted in the production of hydrogel films with high storage modulus (G'). Mechanical spectra and thermal scanning rheology of the obtained hydrogels are described. The temperature scan of the network below and above melting point of gelatin allowed us to identify the respective contributions of chemical and physical cross-linkage to the hydrogel elastic modulus. The results indicate that the rheological properties of the gelatin-based hydrogels can be controlled by the degree of substitution, polymer concentration, initiator concentration, and UV irradiation conditions.