# Biomedical Applications of Polymeric Cryogels
## 3 Cryogels in Medical Applications
### Cryogels for Tissue Engineering  
The extracellular matrix (ECM) is a significant part of the cells and it has a great importance in maintaining support, arranging cell-cell communication, by the way, regulating cell growth, differentiation and survival [53]. ECM mainly contains of nm-sized fibers [54] and some macromolecules such as collagen, fibronectin, laminin and elastin [55]. These fibrous proteins play an essential role in cell coordination by enabling signal delivery, matrix reconstruction, etc. Cell-ECM interactions rely on signal transmission occurs in the cell membrane, by the way, organization between cytoskeleton and related molecules. When two-dimensional (2D) and three-dimensional (3D) structures of the ECM are compared, it has been proven that there is a dramatic well-defined difference in cell behavior in the form of 3D. Therefore, designated matrices should mimic the 3D structure of native tissue ECM. These matrices are conducted to support cell-ECM communication mentioned above [53]. Scaffolds can be identified as 3D biomaterials fabricated to carry out many functions. Desirable scaffolds acting as an artificial ECM should have some unique properties. They must be biocompatible by allowing cell adherence and movement towards onto the surface with stimulating remissible immune response. They also should be biodegradable for maintaining the substitution of own tissue of the cells. In addition, they must possess robust mechanical feature for efficient surgical processes and their structure should be coherent with the region into which it is planned to be implanted [56]. On the other hand, their interconnected pores provide the transportation of the nutrients within the cycle of cell-ECM-scaffold and enable the removal of wastes from the scaffolds [53; 56; 57]. Different methodologies are assembled to construct functional scaffolds serving as a cell supportive in tissue engineering. Therefore, scaffolds have potential use in the replacement/regeneration of tissues/organs and in the meantime regenerative medicine has gained great attention providing novel treatment methods for various steps of several diseases. Recently, several attempts were made to establish in vitro fundamentally target part of the body [56]. Scaffolds could be prepared in various structures such as microbeads, cryogels, hydrogels, ceramics and nanofibers. Many of them have been explored for a wide variety of applications including bladder, airway, skin, bone, ligament, tendon, liver, kidney, pancreas, intestine, esophagus, nerve, heart muscle and valve, cartilage regeneration [53]. It is noteworthy to highlight that the chosen scaffold construction method has a crucial role in the production of effective and accomplished materials, since scaffolds have similarity to their intended tissue. In recent years, cryogelation has become a rather novel approach which aims to improve tissue engineering. Among many scaffold structures, cryogels are considered as good templates and have high potential for the regeneration of indicated tissue parts. They are interconnected supermacroporous polymeric materials with 3D and hydrophilic property. Therefore, they can absorb high volume of tissue fluids and so that they got the edge over other groups of synthetic polymer networks with the advantage of swelling character and soft biocompatibility. It should be also noted that their gel formed structure with high porosity facilitates cell penetration, contact and migration preserving the chemical and mechanical stability. In addition, the preparation step of cryogels is very simple and cost-effective [53]. Considering all these features, it is not surprising that these interesting and individual polymeric materials has come up in tissue engineering in recent decades. Natural and/or synthetic polymers, widely used for scaffold production, have been promising tools in biomedical applications. Natural polymers such as agarose, alginate, hyaluronic acid, chitosan, gelatin, collagen and silk show biocompatibility with eliciting minimal immune response.