Synthesis and Properties of Gelatin Methacryloyl (GelMA) Hydrogels and Their Recent Applications in Load-Bearing Tissue

Abstract

Photocrosslinked gelatin methacryloyl (GelMA) hydrogels have attracted great concern in the biomedical field because of their good biocompatibility and tunable physicochemical properties. Herein, different approaches to synthesize GelMA were introduced, especially, the typical method using UV light to crosslink the gelatin-methacrylic anhydride (MA) precursor was introduced in detail. In addition, the traditional and cutting-edge technologies to characterize the properties of GelMA hydrogels and GelMA prepolymer were also overviewed and compared. Furthermore, the applications of GelMA hydrogels in cell culture and tissue engineering especially in the load-bearing tissue (bone and cartilage) were summarized, followed by concluding remarks.

Keywords: GelMA; cell culture; load-bearing tissue; photocrosslink.

Figure 1

The effect of hydrogel properties on differentiation of EBs. (A,B) Phase contrast images of EBs. And cell proliferation was measured by using Alamarblue assay at same time point. (C) Expression of vasculogenic (PECAM1, Tie2) and cardiogenic (alpha-MHC and Gata4) in EBs after 6 days, and in EBs before encapsulation (left line). (D) Immunostaining PECAM1 (green) (scanning confocal microscopy) in EBs encapsulated in 3 wt % GelMA (left lane) and 10 wt % PEG (right lane) after 7 days culture with nuclear co-staining (PI, red) [40]. (Reproduced with permission from Qi H et al. Adv Mater; published by John Wiley and Sons, 2010).

Figure 2

3D constructed µCT tomograms of GelMA_5% (a,b) and GelMA_10% (c,d) scaffolds from day 28 of in vitro culture with MSCs [29]. (Reproduced with permission from Celikkin N et al. Journal of Biomedical Materials Research; published by John Wiley and Sons, 2017).

Figure 3

(a) Compressive moduli of PCL scaffolds; (b) hydrogels alone. GelMA reinforced with PCL scaffolds and crosslinked with either (c) 25 mM or (d) 12.5 mM APS/TEMED were one order of magnitude stiffer than the scaffolds or gel alone; (e) a comparable degree of reinforcement for reinforced alginate gels; (f) Stress–strain curves of GelMA, the PCL scaffold and reinforced GelMA, approaching the curve of native cartilage (yellow) [98]. (Reproduced with permission from Visser J et al. Nature Communications; published by Springer Nature, 2015).

Figure 4

(A) SEM images of GelMA/MBGNs and GelMA-G-MBGNs after soak in SBF in low magnification and high magnification. (B) XRD images of GelMA and GelMA-G-MBGNs after soak in SBF [101]. (Reproduced with permission from Xin T et al. ACS Applied Materials & Interfaces; published by American Chemical Society, 2017).

Figure 5

Co-culture of vascular cells in GelMA. Constructs containing both DsRed-ECFCs and CMFDA-labeled MSCs were cultured for 2, 4 and 6 d using GelMA hydrogels with different methacrylation degrees. (a,b) Numbers of DsRed-ECFCs (a) and CMFDA-MSCs (b) were separately counted at each time point under a fluorescence microscope. (c–h) Representative confocal microscopy images of DsRed-ECFCs (c–e) and CMFDA-MSCs (f–h) after day 6 in co-culture for each methacrylation degree. [28]. (Reproduced with permission from Chen Y-C et al. Advanced Functional Materials; published by John Wiley and Sons, 2012).