Polymers have many different functions in the area of tissue engineering and can be processed into various forms. One of them is hydrogel. Hydrogels are usually recommended for medical applications in which 3D structure is required with combination of highly hydrated enviroment similar to native extracellular matrix (ECM). Moreover, this type of polymer scaffold can often be processed under relatively mild conditions, and may be delivered in a minimally invasive manner. Consequently, hydrogels have been analyzed as scaffold materials for drug and growth factor delivery or engineering tissue replacements.

Hydrogels are three-dimensional, hydrophilic, polymeric networks capable of absorbing large amounts of water or biological fluids. Due to their ability to absorb and retain large amount of water, porosity and relatively low stiffness, they mimic natural living tissue. They can be chemically stable or they may degrade and eventually disintegrate and dissolve.Hydrogels are able to fill a wound and also can act as a scaffolds promoting cells growth and differentiation. Hence, they can be put into internal or external injury areas as a wound dressing or implant inside the body in different way. The very interesting class is s.c stimuli-responsive hydrogels,  The response of such gels relies on initiation of gelation at certain pH, electric field, light or temperature conditions. Particularly interesting from our perspective are thermogels, in which gelation occurs at body temperature. Such  materials can be injected as solutions followed by formation of gels at body temperature at the place of tissue regeneration. Thus, materials in this form have a  huge potential in tissue engineering as a surgery substitute. Thinking about physical crosslinking, most of important hydrogels belong to polysaccharides. One of the examples of polymers which are able to crosslink at body temperature is  hyaluronan and methyl cellulose.

Classification of hydrogels:

The main classification is related to gelation (crosslinking) mechanism. There are two possible ways that gelation can take place:

- by physical linking,

- by chemical linking.

How to obtain hydrogel?

Hydrogels obtained by physical interactions are divided into materials with relatively strong physical bonds (Lamellar microcrystals, double or triple helices)  and with rather weak physical bonds (hydrogen bonds, block copolymer micelles and ionic interactions). This type of interactions is reversible. Hydrogels formed chemically consist of covalent bonds, generated by condensation, addition  or polymerization process. Hence, this type of cross-linking is permanent. Although, chemical bonds are much stronger than physical interactions, there is a possibility that chemical cross-linking agents may be toxic to living cells. Hence, it has been reported that physical cross-linking is safer and easier to produce  because of redundant additional cross-linkers [3].

Advantages

-significant water absorption ability,

-flexibility and softness similar to living tissues,

-easy formation,

-can be injectable (alternative for invasive surgery).

The main disadvantage of hydrogels are relatively poor mechanical properties. There are some methods which enable to overcome hydrogels’ mechanical problems. One of them is  structure modification by involving reinforcing of nanoparticles. One of the examples is inclusion of  electrospun nanofibers into hydrogel matrix. For that purpose layering, mixing with short fibers  or combination of electrospinning and electrospraying are  used.

It was demonstrated that electrospun nanofibers can improve additionally biological activity of hydrogels. The best  cells proliferation and differentiation has been reported for lower nanofiber diameter [1].

Materials

Hydrogels may be produced from various polymers which can be natural, synthetic or mixed. Materials commonly used as hydrogel composites [1],[2],[3],[4]:

Natural

Synthetic

Natural-Synthetic

alginate

Polylactic acid (PLA)

PEG-fibrinogen

chitosan

Polyacrylic acid (PAA)

PEG-heparin

hyaluronan

Polyethylene glycol (PEG)

PEG–chitosan

collagen

Polyethylene oxide (PEO)

PAA–alginate

methylcellulose

Polycaprolactone (PCL)

Chitin–PLGA

fibrinogen

Poly(lactic-co-glycolic acid) (PLGA)

 PAA–chitosan

gelatin

Polyvinylalcohol (PVA)

PMAA–alginate

heparin

Poly(N-isopropylacrylamide) (PNIPAAm)

Methacrylated gelatin

laminine

2-metoxyloxirane (Pluronic F127)

 

 

Application

Because of many benefits, hydrogel scaffolds  are great candidates for tissue engineering applications and technical products, e.g.:

wound care (PEG, methyl cellulose, alginate, hyaluronan),

drug delivery system (PAA,PVA, chitosan),

injectable biomaterial (polyesters, polysaccharides),

cosmetic products (alginate, heparin, chitosan),

CNS implants (methylcellulose, hyaluronan, laminine),

cardiac construction (methacrylated gelatin linked with carbon nano tubes),

cartilage and bone regeneration system (PCL-fibrin, PCL-alginate and PLA-Poly(lactide-coethylene oxide fumarate).

Literature:

  1. Annabel L. Butcher, Giovanni S. Offeddu, and Michelle L. Oyen, “Nanofibrous hydrogel composites as mechanically robust tissue engineering scaffolds”, Trends in Biotechnology November 2014, Vol. 32, No. 11.
  2. Malgosia M.Pakulska, Brian G. Balliosand Molly S.Shoichet,“Injectable hydrogels for central nervous system therapy”
  3. Syed K. H. Gulrez, Saphwan Al-Assaf and Glyn O Phillips, “Hydrogels: Methods of Preparation, Characterisation and Applications”Progress in Molecular and Environmental Bioengineering - From Analysis and Modeling to Technology Applications, Prof. Angelo Carpi (Ed.), ISBN: 978-953-307-268-5, InTech,
  4. Anwarul Hasan , Ahmad Khattab , Mohammad Ariful Islam , Khaled AbouHweij, JoyaZeitouny , Renae Waters , MalekSayegh , MdMonowar Hossain , and Arghya Paul,“Injectable Hydrogels for Cardiac Tissue Repair after Myocardial Infarction”Adv. Sci. 2015, 2, 1500122.

 

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