Collagen

The main constituents of living human bone are collagen type-1 (protein) and calcium phosphate or hydroxyapatite (mineral) [162]. Collagen is the major structural protein of the soft and hard tissues in living organisms [163]. It can have a significant role in preserving biological and structural integrity of extracellular matrix (ECM) [164]. It is a versatile material that is widely used in the biomedical field (Figure 8) due to advantages including high biocompatibility and biodegradability [165]. Collagen is mainly used as a carrier for drug delivery as well as osteogenic and bone filling material [166]. Collagen matrix was also used to deliver gene promoting bone synthesis [167]. Collagen with recombinant human bone morphogenetic protein-2 was used to monitor bone formation [168].

**Figure 8.** Biomedical applications of collagen.

Bone morphogenic protein (BMP)-loaded collagen activates osteoinduction in the host tissue [169]. Collagen-based nanospheres/nanoparticles can be used as a systematic delivery carrier for various therapeutic agents or biomolecules [166]. As collagen type-I and hydroxyapatite are a basic part of the bone, hydroxyapatite and collagen were used to fabricate scaffolds that enhance osteoblast differentiation and accelerate osteogenesis [170].

Collagen-based biomaterials in various formats such as 3-D scaffolds have been employed for tissue engineering [171]. The combination of collagen with elastin was successfully fabricated and in vitro tests proved the adhesion and proliferation of cells without any cytotoxicity [172]. Collagen-based inks were used for 3D bioprinting employed for tissue repairing and scaffold fabrication. The collagen-based ink was extruded with a temperature stage of −40 ◦C, followed by freeze-drying and cross-linking by using 1-ethyl-(3-3-dimethylaminopropyl) hydrochloride solution [173].
