# Biomedical Applications of Polymeric Cryogels
## 3 Cryogels in Medical Applications
### Cryogels for Tissue Engineering
#### 3.4.3 Scaffolds  
Tissue engineering have emerged for the repair, replacement and regeneration of defected bone, cartilage and skin tissues. Scaffolds have gained popularity as promising materials for these purposes. Critical-sized bone damages have been become an important problem. Their treatment using bone grafts bring along with some challenges such as high cost, integration and rejection problems, infection risk and morbidity. Cryogels have been introduced as a good choice to bone grafts [53]. A study reported that (PTAC) bioccomposite cryogels have been explored as healing tools for critical-sized cranial bone defects in Wistar rats for 4 weeks. The result of this study emphasizes the significant role of cryogels in bone regeneration and even osteoblastic differentiation [68]. In a previous study, HEMA-lactate-dextran (HEMA-LLA-D)-based biodegradable cryogel scaffolds were applied in bioreactors for the 3D ingrowth of bone cells. Osteoblast-like cell line (MG63) was used to examine the effect on cell adherence and ingrowth [69]. Bone structure mainly consists of collagen and hydroxyapatite (HA) (osteoconductive component of bone. Therefore, HA-based cryogels were used for the reproduction of bone matrix. In particular, these cryogels incorporated with collagen were constructed with the advantages of human osteoblast-like cell proliferation, human bone marrow stromal cell differentiation. In another study, HA-gelatin-based cryogels were produced and physical features were examined indicating the applicability of these materials in bone regeneration [53]. Cryogels have also been introduced as treatment agents for several bone diseases with the usage of additives. In addition, fibrous protein has been inquired into cryogelation for bone healing and they provide increasing porosity and formation of elastic scaffold structure with remaining mechanical strength [53]. Injectable cryogels have recently gained great attention due to offering appropriate matrix for the attachment and growth of the cells with the combination of physicochemical characteristics of HA and adhesion features of gelatin. To give an example research, 3T3 cell adhesion could be improved by cultivation in hyaluronic acid-co-gelatin cryogels. In addition, these matrices possess a negligible influence on bone marrow dendritic cell activation, in other words, cytocompatibility was confirmed [70]. Cartilage consists of chondrocytes, progenitor cells, and ECM, and it is essential for minimizing surface friction on the site of bone. Cartilage damages could be treated by autologous chondrocyte implantation (ACI) in which two operations even one is open are necessary with additional disadvantages of high cost, morbidity, iatrogenic pneumothorax atelectasis. Therefore, it is a requirement to use scaffolds including cryogels as a better alternative for the treatment [71]. In this field, cryogels could be modified by additives to enhance their applicability and they have also been implanted to observe their ability in treatment of cartilage damages. Skin wound repair has become a critical challenge since burns, chronic wounds and accidents lead to substantial skin loss. Cryogels as tissue engineered scaffolds provide cell migration and serve as an attractive alternative to skin grafts. Furthermore, their spongy structure eliminates fluid gathering in wound. Especially chitosan and gelatin-based cryogels were mainly preferred for the treatment of skin wound. Cryogel scaffolds used in tissue engineering for bone, cartilage and skin tissues have been demonstrated in Table 3.  
\begin{table}
\begin{tabular}{c c c} \hline \hline
**Scaffolds** & **Outcome** & **Reference** \\ \hline \hline \multirow{4}{*}{ \begin{tabular}{c} Collagen-nanoHA \\ biocomposite cryogels \\ \end{tabular}  } & Bone & \\  & In vitro: Differentiation of human bone marrow stromal cells & \\  & into osteoblastic phenotype.