Challenges in tissue engineering: are hydrogels the answer?

Carmen Piras

Gels are materials with several applications in everyday life. They can be defined as coherent systems composed of a liquid as the majority component, and a solid as the minority component. In these systems, the liquid is the dispersion medium, with the solid acting as the dispersed constituent. These materials can be classified in different ways depending upon their origin, composition, constitution and the kind of interactions that are responsible for the formation of the gel. One of the main classifications is based on the medium they encompass and, in this case, further subdivisions can be made, into organogels, hydrogels, xerogels and aerogels.

  • In organogels, organic solvents represent the disphydrogel-wound-care-fillerersion medium.
  • In hydrogels, water is the dispersion medium, making them highly absorbent and flexible materials. Due to these amongst many other properties, they can be used for several applications, such as drug delivery, tissue engineering, regenerative medicine, diagnostics and clinical practice.
  • Xerogels are formed after evaporation by drying with unhindered shrinkage of the solvent in a hydrogel or an organogel. The main properties of these gels are high porosity and enormous surface area. These characteristics make them suitable for various optical, acoustic and thermal applications.
  • Aerogels are highly porous, low-density materials with excellent insulation properties, formed by evaporation of the solvent in supercritical conditions. They are utilised for several applications in the field of cosmetics and insulation.

PROPERTIES AND APPLICATIONS OF HYDROGELS

id35162Despite being around for only a few decades, hydrogels are now a class of versatile materials that have become a sine qua non in everyday life e.g. hair gel, nappies, contact lenses, wound healing products and medicines. They can be defined as three-dimensional, cross-linked networks of water-soluble molecules. These aggregates can assume different morphologies (micelles, vesicles, fibres, ribbons or sheets), depending on their molecular structure. Due to their composition, but also due to the conditions under which the hydrogels are formed, they present lots of interesting properties. One of these is the ability to absorb water, which is caused by the presence of hydrophilic groups within the molecules that constitute the gel. The presence of water inside the hydrogels, together with their swelling and elasticity properties, permits some solute molecules entrapped in the structure to diffuse, which is very important for the applications of these materials in drug delivery. Another important characteristic related to this application is their porosity that can be modified by controlling the density of cross-links in the gel matrix. The porosity of these materials is responsible for the release of drugs loaded into the matrix. Hydrogels can also show massive changes of their volume in response to the variation of external conditions, such as pH, temperature, solvent quality, etc. Furthermore, these materials show physicochemical similarity with the native extracellular matrix. This characteristic, accompanied by the high water content, makes them considerably biocompatible and permits their utilization in tissue engineering and in biomedical and pharmaceutical fields. Hydrogels derived by natural molecules, such as polypeptides and carbohydrates, also show natural biodegradability, high biocompatibility and low toxicity that make these materials especially suitable for this kind of application.

HYDROGELS IN TISSUE ENGINEERING

Tissue engineering has been of great interest to scientists for many years, as it holds great promise for tissue and organ regeneration. The high amount of water that hydrogels can incorporate, the presence of pores large enough to host living cells, and the similarity of these materials to the extracellular matrix, make them suitable candidates as matrices for tissue engineering. Many publications over the decades showed how they can be used for cartilage regeneration, bone and skin repair, and recently also for cardiac tissue repair (especially as injectable materials).

cuoreHydrogels used for such purposes are predominately based on natural polymers or derivatives, such as collagen, hyaluronic acid, chitosan and alginate, which allow high viability and proliferation rates for cells, due to the abundance of chemical signals. This also helps the formation of neo-tissues, which is fundamental for organ regeneration and repair.

Although hydrogels based on natural polymers show interesting properties and a wide range of biomedical applications, synthetic chemistry can also be used to produce similar materials from synthetic polymers such as poly(ethylene glycol) and pluronics. Hydrogels obtained from these polymers, however, behave as inert scaffolds for cells, due to the absence of active binding sites. To overcome this problem, peptides, growth factors and other bioactive compounds can be added to the network.

The use of hydrogels in tissue engineering has been facilitated by bio-fabrication techniques, which enable the industrial production of biomaterials. Different methods can be used for this purpose:

  1. Laser-induced forward transfer technology, which allows the precise deposition of materials and cells in small 3D structures.
  2. Inkjet printing, which permits the deposition of bioink (i.e. a hydrogel) on a substrate from a very small orifice.
  3. Robotic systems, which are dispensing systems that use disposable plastic syringes to release hydrogels with suspended cells onto a building platform.

Although hydrogels have now been studied for a number of years and their characteristics and applicability have been massively improved and tuned to many different purposes, the development of effective, low-price, non-toxic materials with high rates of water absorption, biocompatibility and biodegradability for tissue engineering still remains a challenge. However, research on hydrogels is one of the most rapidly developing fields of material science, showing their enormous potential in tissue engineering and organ regeneration.

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