Formulation of Hydrogels

Applications / Formulation of Hydrogels

Hydrogels have been widely used in the biomedical field for developing bioengineered tissues and novel treatments such as wound dressings and drug delivery systems. They are composed of over 90% water and crosslinked polymeric chains and exhibit a pronounced viscoelastic behavior. The precise evaluation and control of their viscoelastic properties are often critical in terms of functionality and efficacy. When hydrogels are used as 3D cell culture environments, their viscoelasticity plays an important role in the cell differentiation, proliferation and remodeling. Similarly, mastering the gel formation kinetics and its final viscoelasticity is crucial for manufacturing processes such as biocasting, 3D bioprinting and electrospinning. Similarly, hydrogels degradation plays an important role in applications such as drug release and tissue engineering.
Hydrogel Viscoelasticity

ElastoSens™ Bio offers an extensive testing platform to formulate, compare, qualify and control the viscoelasticity of hydrogels used in multiple applications such as tissue engineering, 3D bioprinting, drug delivery and hemostatic applications. As the test is non-destructive and the gel is contained in a detachable sample holder, you can follow both short (crosslinking kinetics) and long-term (slow degradation or remodeling) evolutions of the same gel sample. In addition, the system has been designed to allow the application of specific external conditions: the sample can be tested in real time under controlled temperature, UV light and atmospheric inert gases, and exposed to physiological solutions.

Hydrogel results
In this example, the evolution of the shear elastic modulus of chitosan gels is measured using the ElastoSens™ Bio during the gel formation and the enzymatic (papain digestion solution) degradation phases. It clearly appears how the enzymes are affecting the gel formation compared to the control sample with no digestion solution.
The precise evaluation of hydrogels viscoelasticity can accelerate their formulation and the optimization of their functionality. Combined with the power of Soft Matter Analytics™, the ElastoSens™ Bio offers an unprecedented development and control platform for scientists and engineers creating hydrogel-based biosystems or devices.
ElastoSens Bio Tablet

Related Application Notes

Hydrogels are biomaterials that are widely studied in the biomedical field. They are used, for example, to produce contact lenses and wound dressings, for drug release systems, or as scaffolds for tissue engineering. The design of such hydrogels is often multidimensional since multiple parameters related to their chemical composition and physical properties affect how they are going to behave in vivo.

Alginate is a polysaccharide present as a structural component of algae and a capsular component of soil bacteria. The polysaccharide is typically obtained from brown seaweed and used in many industries such as medical, pharmaceutical, food, textile due to its viscosifying, gelling and stabilizing properties.

The field of regenerative medicine comprises different strategies to replace or restore diseased and damaged tissues and organs. It includes tissue-engineered products that rely on the combination of biomaterials, cells and inductive biomolecules to promote tissue and organ regeneration.

All cells in the human body are exposed to mechanical forces which regulate cell function and tissue development, and each cell type is specifically adapted to the mechanical properties of the tissue it resides in. The matrix properties of human tissues can also change with disease and in turn facilitate its progression.

Gelatin and hyaluronic acid (HA) are biomaterials widely used in the biomedical research field. HA is the most abundant glycosaminoglycan in the body and is an important component of several tissues. HA contributes to tissue hydrodynamics, movement and proliferation of cells, and participates in a number of cell surface receptor interactions.

Cellularized hydrogels have been widely investigated for producing in vitro models of tissues such as skin, blood vessels, bone, etc. These models can be a valuable alternative to animal models used in trials for studying physio/pathological processes and for testing new drugs and medical devices.

Related Scientific Articles

This study introduces two novel smart polymer 3D-printable interpenetrating polymer network (IPN) hydrogel biomaterials for potential applications in traumatic brain injury (TBI). These IPN biomaterials show favorable chemical, mechanical, and morphological properties and can potentially assist in the restoration of neurological function and neural tissue regeneration. The scaffolds were prepared using collagen, elastin, and gelatin methacryloyl, and were crosslinked with Irgacure or Irgacure and Genipin. The biomaterials exhibited thermal stability, amorphous nature, and maintained the peptide secondary structure. With a stiffness suitable for softer tissue engineering applications, the IPN biomaterials resemble the native rat cortex. They supported the growth of PC12 cells and showed antimicrobial properties. However, it was observed that the full IPN was more brittle than the semi IPN, which was contradictory to previous literature findings. Overall, this research contributes to the development of potential biomaterials for TBI applications and 3D printing, paving the way for patient-specific scaffolds in neural treatments.

This study presents a novel 3D bioprinting strategy using a microfluidic printhead to fabricate hydrogel fibrous structures of gelatin methacryloyl (GelMA) with precise control over polymer concentration. The printhead utilizes a coaxial core-sheath flow and a photo-crosslinking system to enable in situ cross-linking of GelMA and the formation of hydrogel filaments. Computational modeling was employed to optimize process parameters and understand the diffusive and fluid dynamic behavior of the coaxial flow. The cytocompatibility of the system was demonstrated by bioprinting cell-laden bioinks containing U87-MG cells. This pipeline, integrating computational modeling with bioprinting, has the potential to be applied to various photo-cross-linkable bioinks for the generation of living tissues with customizable material and cellular characteristics.

Hydrogels are extensively used for tissue engineering and regenerative medicine. Their mechanical properties determine not only their function but also cell response (i.e. proliferation and differentiation of stem cells) and their degradation kinetics is particularly important to predict scaffold resorption, new tissue formation and integration after implantation. Non-destructive methods are needed to screen and follow long-term evolution of rheological properties. In this work, we demonstrate the potential of a new non-destructive instrument, ElastoSens™ Bio2 (Rheolution Inc., Montréal, QC), that measures in real-time and without contact the evolution of rheological properties of chitosan hydrogels during network formation and degradation during exposure to human lysozyme.

Hydrogels are extensively used for tissue engineering, cell therapy or controlled release of bioactive factors. Non-destructive techniques that can follow their viscoelastic properties during polymerization, remodeling and degradation are needed, since these properties are determinant for their in vivo efficiency. In this work, we proposed the Viscoelastic Testing of Bi-Layered Materials (VeTBiM) as a new method for nondestructive and contact-less mechanical characterization of soft materials. The VeTBiM method measures the dynamic displacement response of a material, to a low amplitude vibration in order to characterize its viscoelastic properties. We validated VeTBiM by comparing data obtained on various agar and chitosan hydrogels with data from rotational rheometry, and compression tests. We then investigated its potential to follow the mechanical properties of chitosan hydrogels during gelation and in the presence of papain and lysozyme that induce fast or slow enzymatic degradation. Thanks to this nondestructive and contactless approach, samples can be removed from the instrument and stored in different conditions between measurements. VeTBiM is well adapted to follow biomaterials alone or with cells, over long periods of time. This new method will help in the fine-tuning of the mechanical properties of biomaterials used for cell therapy and tissue engineering.

Chitosan (CH) hydrogels with remarkable mechanical properties and rapid gelation rate were recently synthesized by combining sodium hydrogen carbonate (SHC) with another weak base, such as beta-glycerophosphate (BGP). To improve their biological responses, in the present study, chondroitin sulfate (CS) was added to these CH hydrogels. Hydrogel characteristics in terms of pH and osmolarity, as well as rheological, mechanical, morphological and swelling properties, were studied in the absence and presence of CS. Effect of CS addition on cytocompatibility of hydrogels was also assessed by evaluating the viability and metabolic activity of encapsulated L929 fibroblasts. New CH hydrogels containing CS were thermosensitive and injectable with pH and osmolality close to physiological levels and enhanced swelling capacity. Encapsulated cells were able to maintain their viability and proliferative capacity up to 7 days and CS addition improved the viability of the cells, particularly in serum-free conditions. Addition of CS showed a reducing and dose-dependent effect on the mechanical strength of the hydrogels after complete gelation. This work provides evidence that CH-CS hydrogels prepared with a combination of SHC and BGP as a gelling agent have a promising potential to be used as thermosensitive, injectable and biocompatible matrices with tunable mechanical properties for cell therapy applications.

In this study, we fabricated and characterized a smart shear-thinning hydrogel composed of gelatin and laponite for localized drug delivery. We added chitosan (Chi) and poly N-isopropylacrylamide-co-Acrylic acid (PNIPAM) particles to the shear-thinning gel to render it pH-responsive. The effects of total solid weight and the percentage of laponite in a solid mass on the rheological behavior and mechanical properties were investigated to obtain the optimum formulation. The nanocomposite gel and particles were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), zeta potential, and dynamic light scattering techniques. Finally, release related experiment including degradability, swelling and Rhodamine B (Rd) release at various pH were performed. The results suggest that incorporation of silicate nanoplatelets in the gelatin led to the formation of the tunable porous composite, with a microstructure that was affected by introducing particles. Besides, the optimum formulation possessed shear-thinning properties with modified rheological and mechanical properties which preserved its mechanical properties while incubated in physiological conditions. The release related experiments showed that the shear-thinning materials offer pH-sensitive behavior so that the highest swelling ratio, degradation rate, and Rd release were obtained at pH 9.18. Therefore, this nanocomposite gel can be potentially used to develop pH-sensitive systems.


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