Progress in Gelatin as Biomaterial for Tissue Engineering

Abstract

Tissue engineering has become a medical alternative in this society with an ever-increasing lifespan. Advances in the areas of technology and biomaterials have facilitated the use of engineered constructs for medical issues. This review discusses on-going concerns and the latest developments in a widely employed biomaterial in the field of tissue engineering: gelatin. Emerging techniques including 3D bioprinting and gelatin functionalization have demonstrated better mimicking of native tissue by reinforcing gelatin-based systems, among others. This breakthrough facilitates, on the one hand, the manufacturing process when it comes to practicality and cost-effectiveness, which plays a key role in the transition towards clinical application. On the other hand, it can be concluded that gelatin could be considered as one of the promising biomaterials in future trends, in which the focus might be on the detection and diagnosis of diseases rather than treatment.

Keywords: biomaterials; gelatin; regenerative medicine; tissue engineering.

Figure 1

Illustrative image of the latest advances in the design process of gelatin-based systems. Reprinted from International Journal of Pharmaceutics, 562, Echave et al. [30,40]. Enzymatic crosslinked gelatin 3D scaffolds for bone tissue engineering, 151–161, copyright 2019, with permission from Elsevier; Acta Biomaterialia, 94, Tygtal et al. [30,40]. Additive manufacturing of photo-crosslinked gelatin scaffolds for adipose tissue engineering, 340–350, copyright 2019, with permission from Elsevier.

Figure 2

Gelatin-based 4D-printed hydrogel: (a) manufacturing process of 4D-printed hydrogel; (b) DAPI/MHC cross-sectional images of fibers after 21 days. Adapted with permission from Yang et al. [43]. Theranostics, published by Ivyspring International Publisher, copyright 2021.

Figure 3

Effect of freeze-drying technique in gelatin-based systems: (a) macroscopic and microscopic (SEM) images of freeze-drying effect in gelatin-based hydrogels and viability assay of the cells within gelatin-based hydrogels; (b) SEM images and quantitative analysis of the effect of different temperatures and polymer concentration on pore size. ** p ≤ 0.01, **** p ≤ 0.0001. Adapted with permission from (a) Yuan et al. [47]. Small, published by John Wiley and Sons, copyright 2021; (b) Singh et al. [12]. Biomacromolecules 2019, 20 (2), 662–673. Copyright 2022, American Chemical Society.

Figure 4

Schematic illustration of 3D portable printer and in vivo outcomes in skeletal muscle: (a) graphic diagram; (b) images of GelMA-based hydrogel implantation; (c) in vivo results of fibrosis in nontreated and treated groups. Adapted with permission from Quint et al. [16]. Advanced Healthcare Materials, published by John Wiley and Sons, copyright 2021.

Figure 5

Functionalized gelatin-based hydrogel: (a) graphic representation of sprayable hydrogel; (b) in vivo implantation of hydrogel into the myocardial tissue; (c) trichrome staining results after 28 days of hydrogel implantation. Adapted with permission from Tang et al. [59]. Advanced Healthcare Materials, published by John Wiley and Sons, copyright 2021.

Figure 6

Representative graphic of gelatin-based drug delivery systems. Adapted with permission from Hu Y et al. [77]. ASC Nano. Copyright 2022, American Chemical Society; reprinted from Chemical Engineering Journal, 435, Li D et al. [84]. Osteoimmunomodulatory injectable Lithium-Heparin hydrogel with Microspheres/TGF-β1 delivery promotes M2 macrophage polarization and osteogenesis for guided bone regeneration, 134991, copyright (2022), with permission from Elsevier.