Hydrogels have been used successfully in many tissue engineering applications. However, because they are inherently soft materials, it is not always easy to get the large, interconnected pore network that enhances cell behavior and allows neovascularization of implants. Many techniques have been developed to try and create pore networks after the gelling process completes, like using salt or sugar porogens. But porogens must be removed to create the pore network, and the removal process has always been the Achilles heel of this method. Either the solvent is not biocompatible, or leftover porogens are not biocompatible, or the washing disrupts and breaks the structure of the gel.
Cryogels are created by allowing the aqueous solvent itself to be the porogen. The polymer components are dissolved in an aqueous solvent and then the entire solution is placed in the freezer. During the freezing process, the solution is partitioned between freezing water and concentrated polymer. The ice crystals behave as porogens while the concentrated polymer fraction forms crosslinks and gels. To create your macroporous hydrogel, you only need to take the cryogel out of the freezer and let the water melt.
Most of the research using cryogels for biomedical applications have used natural polymers. Synthetic polymers are often chosen because their mechanical and structural properties can be controlled more precisely than with natural polymers. But cryogellation produces many properties with natural polymers that are generally expected only from synthetic constructs, such as shape retention, pores on the order of 100-400 microns, and rapid rehydration.
Sandeep Koshy is a 4th year Research Associate in David Mooney’s lab at the Harvard School of Engineering and Applied Sciences and Harvard-MIT Division of Health Sciences and Technology. In this episode of the Natural Scaffolds Review, Mr. Koshy gives us an introduction to cryogels and discusses the developments he has made in creating injectable cryogels from natural materials. Mr. Koshy’s 2014 publication in Biomaterials is the best example of a cryogel application so far this year, but I also discuss 4 other papers that were published in the last half of 2013 that I think are worth your attention if you find cryogels a interesting topic of discussion.
Sandeep T. Koshy, et al. “Injectable, porous, and cell-responsive gelatin cryogels.” Biomaterials 35(8):2477-2487, 2014.
Additional Publications mentioned in the podcast:
Sidi A. Bencherif, et al. “Injectable preformed scaffolds with shape-memory properties.” Proceedings of the National Academy of Sciencies 109(48):19590-19595, 2012.
Timothy M.A. Henderson, et al. “Cryogels for biomedical applications.” Journal of Materials Chemistry B 1:2682-2695, 2013.
Kun-Hung Chang, et al. “Preparation and characterization of gelatin/hyaluronic acid cryogels for adipose tissue engineering: In vitro and in vivo studies.” Acta Biomaterialia 9(11):9012-9026, 2013.
Banani Kundu, et al. “Bio-inspired fabrication of fibroin cryogels from the muga silkworm Antheraea assamensis for liver tissue engineering.” Biomedical Materials 8(5):055003, 2013.
Ilyas Inci, et al. “Gelatin cryogels crosslinked with oxidized dextran and containing freshly formed hydroxyapatite as potential bone tissue-engineering scaffolds.” Journal of Tissue Engineering and Regenerative Medicine 7(7):584-588, 2013.