# Advances in Tissue Engineering for Disc Repair
## 3 Tissue Engineering for IVD Regeneration
### Biomaterials  
In the case of severe IVDD with loss of cell volume and of the physiological disc structure, the disc height must be restored to ensure IVD function [29]. This strategy involves a tissue engineering approach using biomaterials, which may serve as functional alternatives and scaffolds for the IVD tissue [13]. Researchers are using a composite approach that utilizes cell-loaded biomaterials to provide a structural environment for mechanical stability and potential cell regeneration [56]. The biomaterials used include injectable hydrogels and synthetic polymers designed from materials such as alginate, gelatin, polyglycolic acid, polylactic acid, hyaluronic acid (HA), and collagen [57]. Hydrogels can be used as an alternative to NP due to their biophysical properties and ability to absorb water, resist repeated loads, and act as a delivery vehicle [58]. An ideal injectable biomaterial will support cell retention and survival and make it possible to maintain or promote the NP phenotype in vivo. In the absence of biomaterials, cell injection leads to rapid cell death or migration from the injection site [59; 60]. Important parameters to consider in the development of biomaterials are material viscosity, gelation rate, final gel stiffness, adhesivity, and degradation time controlled by polymer composition. HA is a key component of the NP ECM that provides resistance to compression and allows for periodic loading [61; 62]. Physiologically, HA has been demonstrated to have cartilage protective and anti-inflammatory properties, which have been shown to be associated with cell-based interventions. Therefore, some clinical trials have used HA as a cell carrier to increase the viscosity of the cell solution and enhance the retention of injected cells [63; 64]. Collagen is one of the most widely used materials for tissue regeneration as it has numerous adhesion sites, limited immunogenicity, and is injectable. However, due to  
Figure 2: Combination of cells, signaling molecules (growth factors), and biomaterials for tissue engineering applications for intervertebral disc (IVD) degeneration. its poor degradation and mechanical properties, it has not been widely used for disc repair. Composite collagen hydrogels, on the other hand, have been found to improve the compressive mechanical properties of the scaffold and control the rate of scaffold degradation [27]. Fibrin is a naturally occurring biomaterial that provides intrinsic physical and soluble cues to initiate tissue repair. Biodegradable fibrin hydrogels can be produced as injectable cell carriers and can be mediated by adjusting coagulation protein levels or altering the ionic strength of the system [65; 66]. Fibrin-only hydrogels remain vulnerable to cell-mediated remodeling, while fibrin-HA composite hydrogels improve stability by increasing glycosaminoglycan (GAG) synthesis. In addition, silk to fibrin-HA gels significantly improve the mechanical properties and promote chondrogenesis [67]. Silk offers high resistance to compression, and silk-fiber stability, due to its wide range of hydrogen bonds, protein hydrophobicity, and high crystallinity, provides an advantage as a scaffold for IVD bioengineering [68]. Other biomaterials that can be used as a matrix to support AF and NP engineering are chitosan and alginate, which are inexpensive and easily accessible [12]. In addition, these two polymers have a synergistic effect combined with hybrid scaffolding [69]. Chitosan is used as a biodegradable and biocompatible polymer with low toxicity and excellent antibacterial properties. The soft, spongy chitosan-based scaffold has high porosity and pore interconnectivity to support cell adhesion and growth [70]. Alginate, one of the most abundant natural materials, mainly derived from brown algae and some bacteria, is used in a variety of biomedical applications and drug delivery systems due to its excellent biocompatibility, biodegradability, non-antigenicity, and chelation ability [69].