Marine Gelatin-Methacryloyl-Based Hydrogels as Cell Templates for Cartilage Tissue Engineering

Abstract

Marine-origin gelatin has been increasingly used as a safe alternative to bovine and porcine ones due to their structural similarity, avoiding the health-related problems and sociocultural concerns associated with using mammalian-origin materials. Another benefit of marine-origin gelatin is that it can be produced from fish processing-products enabling high production at low cost. Recent studies have demonstrated the excellent capacity of gelatin-methacryloyl (GelMA)-based hydrogels in a wide range of biomedical applications due to their suitable biological properties and tunable physical characteristics, such as tissue engineering applications, including the engineering of cartilage. In this study, fish gelatin was obtained from Greenland halibut skins by an acidic extraction method and further functionalized by methacrylation using methacrylic anhydride, developing a photosensitive gelatin-methacryloyl (GelMA) with a degree of functionalization of 58%. The produced marine GelMA allowed the fabrication of photo-crosslinked hydrogels by incorporating a photoinitiator and UV light exposure. To improve the biological performance, GelMA was combined with two glycosaminoglycans (GAGs): hyaluronic acid (HA) and chondroitin sulfate (CS). GAGs methacrylation reaction was necessary, rendering methacrylated HA (HAMA) and methacrylated CS (CSMA). Three different concentrations of GelMA were combined with CSMA and HAMA at different ratios to produce biomechanically stable hydrogels with tunable physicochemical features. The 20% (w/v) GelMA-based hydrogels produced in this work were tested as a matrix for chondrocyte culture for cartilage tissue engineering with formulations containing both HAMA and CSMA showing improved cell viability. The obtained results suggest these hybrid hydrogels be used as promising biomaterials for cartilage tissue engineering applications.

Enhanced chondrogenic potential in GelMA-based 3D cartilage model via Wnt3a surface immobilization

“…Amongst the potential hydrogels screened, GelMA demonstrated the most appropriate properties, including tunable chemistry and support for cell viability and migration, making it the optimal choice for the 3D cartilage model. This finding is consistent with previous reports where GelMA hydrogels were shown to provide a suitable microenvironment for chondrogenic differentiation and support cartilage-specific ECM production 9 , 10 .…”

Unveiling the versatility of gelatin methacryloyl hydrogels: a comprehensive journey into biomedical applications

“…Itaconate-encapsulated ZIF-8 NPs immobilized in GelMA [159], Curcumin-incorporated GelMA [160], Methacrylated chondroitin sulfate/ methacrylated HA/GelMA [161]. Adipose-derived stromal/stem cells-incorporated GelMA/MAAmodified poly(amidoamine) [162], GelMA/ engineered cartilage gel [163], Diclofenac sodium-incorporated GelMA/acrylamide/2methacryloyloxyethyl phosphorylcholine [97], bMSCs affinity peptide sequence PFSSTKT-modified chondrocyte ECM particles/GelMA [164], Nanoclay/alginate/GelMA [165], Denatured collagen/Gel-MA/Laponite [166], Iron oxide NPs/GelMA [167], Alanyl-Glutamine-modified GelMA [168] are some of the recent studies that demonstrated favorable results in cartilage tissue repair.…”

Recent Advances in Marine Biomaterials Tailored and Primed for the Treatment of Damaged Soft Tissues

“…Various studies are exploring the use of fish byproducts to produce gelatins, offering a cost-effective and bioactive alternative with tunable physicochemical properties, thus addressing the challenge of waste valorization in the industry [80,81]. Machado et al introduced marine gelatin from the skin of Greenland halibut as cell templates for cartilage tissue engineering, combined with methacrylated HA (HAMA) and methacrylated chondroitin sulfate (CSMA) (namely, GelMA-HAMA/CSMA hydrogel) to render a photocrosslinkable property [82] (Figure 5). Live/dead assays revealed that ATDC-5 cells remained viable for up to 14 days and were distributed well within all GelMA hydrogel compositions.…”