Gelatin

Gelatin represents a derivative of collagen, extracted by collagen hydrolysis from the skin, bones, and/or connective tissues of animals. It is a cost effective, biocompatible, and biodegradable polymer, which supports cross-linking of functional groups. Gelatin is a versatile polymer that is known for his wealth merits [174]. Pharmaceutical or medical grade gelatin has fragility and transparency for tablet coatings, suspensions, capsule formulations, and nano-formulations (Figure 9).

**Figure 9.** Biomedical and pharmaceutical uses of gelatin.

Because of their great biocompatibility, the injected gelatin-loaded nanoparticles have been reported in the skeletal system [24,175,176]. It is a polyampholyte at pH 9 (gelatin A) and pH 5 (gelatin B). Gelatin nanoparticles are used as a biomaterial for the delivery of biomolecules and therapeutic agents [177]. However, digestive process of gelatin showed low antigenicity, with the formation of harmless metabolic products. In order to prevent infectious disease transmission, genetic engineering approaches were used for the production of human recombinant gelatin [178,179].

At the nanoscale, gelatin shows high biocompatibility, biodegradability, and low immunogenicity [180]. The presence of a higher number of functional groups on polymer backbone helps with crosslinking and chemical modification [181]. The cross-linking is necessary to stabilize the macromolecular structure of gelatin is not stable at normal body temperature due to the low melting temperature [182,183].

Gelatin methacryloyl (GelMA) hybrid hydrogel demonstrated a wide range of tissue engineering applications. When exposed to light irradiation, GelMA scaffolds convert into hydrogels with tunable mechanical properties [184]. Gelatin enables therapeutic cell adhesion without comprising cell phenotypes [185]. Porous HA-gelatin microparticles (1 to 100 μm) support human osteoblast-like Saos-2 cells growth and cell delivery [186]. A mechanically strong gelatin–silk hydrogel composite was prepared by direct blending of gelatin with amorphous Bombyxmori silk fibroin (SF) [187]. Gelatin coated polyamide (PA) scaffold showed good biomechanical, cell attachment, and wound healing characteristics while being transplanted to nude rats [188]. Poly(lactide-co-glycolide) (PLGA)–gelatin fibrous scaffolds possess the highest Young's modulus (770 ± 131 kPa) and tensile strength (130 ± 7 kPa) [189]. Methacrylamide-modified gelatin (GelMOD) 3D CAD scaffolds showed excellent stability in culture medium and support porcine mesenchymal stem cell adhesion and subsequent proliferation [190].

Gelatin-based microcarriers used embryonic stem cell delivery for the applications in tissue engineering [191]. The magnetic nanoparticles were assembled with magnetic gelatin membranes to produce 3D multilayered scaffolds (Figure 10), which are used for controlled distribution of magnetically labeled stem cells [192].

**Figure 10.** (**A**) Fabrication of a multilayered magnetic gelatin scaffold. (**B**) Magnetic gelatin membranes with increasing MNPs concentration from left to right as well as a representation of the properties of the magnetic gradient. (Adapted with permission from © 2015 American Chemical Society [192]).
