Amparo Baiget Orts, researcher of the Aimplas synthesis department, discusses the various properties of hydrogels and explains why the response of hydrogels to different stimuli such as pH make them interesting candidates for application in biomedical research.
Hydrogels are of special importance due to their high water content and their application in biomedical research.
A hydrogel is a three-dimensional network based on a polymeric cross-linked structure that can be obtained both from synthetic and natural polymers. The main property of hydrogels is their high capacity to retain water, and they can swell up to thousands of times their dry weight. This property has been used in the design of hydrogels to treat arthrosis. The hydrogel developed by Park et al.1 allows swelling with the synovial fluid, accumulated when the cartilage of joints is damaged, thus decreasing inflammation and pain1.
The formation of a hydrogel is the result of combining processes known as ‘sol-gel’. The term ‘sol’ refers to the link of macromolecular chains which leads to larger branched yet soluble polymer. The progressive crosslinking of branches form what is known as ‘gel’ and the structure is then insoluble. The transition to both physical states is called ‘sol-gel transition’ and the critical point in which gel first appears is called ‘gel point’.
Depending on the gelation process, hydrogels can be classified as physical hydrogels or chemical hydrogels.
Physical hydrogels are divided into strong (if their chains are linked in a permanent way) and weak if they are not permanent but reversible, formed by temporary associations between chains. We can find examples of physical hydrogels in lamellar microcrystals or glassy nodules. Hydrogen bonds or ionic associations are examples of the formation of weak physical hydrogels.
However, chemical hydrogels are always strong gels. The formation of chemical hydrogels involves the formation of covalent bonds. They can be formed by condensation, vulcanisation and addition polymerisation, among others.
Regarding their permanent structure, hydrogels can be classified into permanent or reversible gel.
The different properties of hydrogels are of interest for different applications. Stimuli-responsive hydrogels are sensitive to their environment. Typical stimuli are temperature, pH, electric field, light, magnetic field or concentration of solutes. Under these conditions, they can change their properties and therefore behave differently.
Another kind of hydrogel of great interest is that with self-healing properties. This property, naturally present in living organisms, has inspired scientist to prepare synthetic materials. For example, White et al2 developed a two-stage approach mimicking the response to damage to the circulatory systems of animals. The system consisted of a fast self-healing followed by a lower polymerisation to restore the mechanical properties. Another example is the research of Phadke et al3, who developed new permanently cross-linked hydrogels engineered to exhibit self-healing properties in an aqueous environment.
Zhang et al. ACS Macro Lett. 2012, 1, 1233−1236
PVA hydrogel showing self-healing behaviour. (a) Two pieces of original hydrogel with and without rhodamine B for colouration; (b) two halves of the original hydrogels cut in half; (c) self-healed hydrogel after the two parts have been in contact for twelve hours at room temperature without no external stimulus; (d) bending of the self-healed hydrogel; (e) stretching of the self-healed hydrogel to about 100% extension.
Hydrogels have been also used as gene carriers. Biological systems display pH changes between the cellular components. This behaviour has been found interesting to prepare a kind of so-called “smart” drug delivery systems. For example, pH-responsible polymers can be designed to respond to changes in the surrounding pH. It has been observed that there is an increase of the acidity in tumours compared to in normal tissues. In this sense, new materials can be developed for cancer treatment applications to act directly in the tumour. Different thermal and pH-responsive polymers have been developed based on hydrophobic polymeric matrices with hydrophilic PEG chains grafts linked by acidic labile molecules. The properties of the polymeric matrices or the molecules employed for linking grafts can be tunable to obtain desirable responses5.
Some examples of hydrogels developed in Aimplas for biomedical applications are hydrogels based on PLA-PEG-PLLA for peripheral nervous system regeneration, lactic acid and glycolide copolymers for maxillofacial surgery or hydrogels used as holders for oximeters in digestive surgeries, which help the surgeon to take better decisions during procedures.
References
(1) Therapeutic‐Gas‐Responsive Hydrogel. Park et alii. Adv. Mater. 2017, 1702859
(2) S. R. White,J.S.Moore,N.R.Sottos,B.P.Krull, W. A. Santa Cruz, R. C. R. Gergely, Science 2014, 344,620–623.
(3) Rapid self-healing hydrogels Ameya Phadke Ameya Phadkea , Chao Zhanga , Bedri Armanb , Cheng-Chih Hsuc , Raghunath A. Mashelkard,1, Ashish K. Leled , Michael J. Tauberc , Gaurav Aryab , and Shyni Varghesea,1 a Departments of Bioengineering, b NanoEngineering, and c Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093; and d National Chemical Laboratory, Pune 411008, India Contributed by Raghunath A. Mashelkar, January 23, 2012 (sent for review December 2, 2011)
(4) Zhang et alii. ACS Macro Lett. 2012, 1, 1233−1236
(5) Dirk Schmaljohann. Advanced Drug Delivery Reviews 58 (2006) 1655–1670