Design and fabrication of GelMA/chitosan nanoparticles composite hydrogel for angiogenic growth factor delivery

Abstract

The cellular microenvironment plays a crucial role in improving cell response and function of an engineered tissue. Scaffolds mimicking the native ECM and capable of releasing growth factors are great candidates for tissue engineering applications. Gelatin methacryloyl (GelMA) hydrogel, a photocrosslinkable biomaterial possessing tunable properties, has been widely used in tissue engineering. It has been suggested that incorporating micro/nano carriers in GelMA could provide a sustained release of growth factors. Specifically, chitosan nanoparticles can be used for growth factor delivery due to its biocompatibility, easy method of synthesis, and preventing the biomolecule from degradation. In this study, GelMA/chitosan nanoparticles composite hydrogel was developed to deliver an angiogenic growth factor (bFGF). The hydrogel was prepared by photopolymerization and its chemical and physical properties were characterized. Its degradation and swelling characteristics were also evaluated. The size of nanoparticles was evaluated and the profile of bFGF release from the hydrogel and its effect on the viability of fibroblast cells was studied. The results showed that GelMA/chitosan nanoparticles can significantly promote cell proliferation due to its biocompatible structure and providing a sustained profile of bFGF release. This hydrogel scaffold can be used for efficient delivery of bFGF in various applications and especially for angiogenesis.

Recent Advances in Photo-Crosslinkable Hydrogels for Biomedical Applications

“…Moreover, some organic and inorganic materials such as chitosan nanoparticle, 4-arm PEG-tetra-acrylate (PEGTA), methacryloyl-substituted tropoelastin and nickel have been shown to reduce degradation rate of the GelMA hydrogel [72,7577]. In fact, the degradation rate of GelMA-based hydrogel construct should match with the pace of neo-tissue formation for tissue engineering applications, or the drug-release kinetics for drug-delivery applications [72,75]. …”

“…Moreover, by integrating a dielectrophoresis system with gold microparticle-laden GelMA hydrogels, the controlled release of drugs was achieved with a concentration gradient for high-throughput drug screening applications [34]. On the other hand, by incorporating chitosan nanoparticles into GelMA hydrogel, which provides a sustained release of basic fibroblast growth factor, this hybrid hydrogel can be used for angiogenesis in various diseases, particularly ischemic diseases [75]. Furthermore, a coacervate microdroplet-laden hydrogel consisting of GelMA and oxidized, methacrylated alginate was developed for the controlled release of growth factors to the encapsulated stem cells for stem-cell-based therapies [63] (Figure 3C).…”

Potential core–shell designed scaffolds with a gelatin‐based shell in achieving controllable release rates of proteins for tissue engineering approaches

“…The design of biomaterials enables to encapsulate biomolecules effectively, release them significantly, and enhance scaffolds regenerative capacity . With this regard, some strategies have focused on the appropriate design and development of biomaterial scaffolds that are incorporated with biomolecules to regulate their release profiles and modulate optimal cell behavior …”

“…2,3 With this regard, some strategies have focused on the appropriate design and development of biomaterial scaffolds that are incorporated with biomolecules to regulate their release profiles and modulate optimal cell behavior. [4][5][6] Electrospun nanofibers are regarded as a promising ECMmimicking platform and the effective delivery system of biomolecules which can provide physical support for cellular growth to modulate tissue regeneration. [7][8][9][10][11] Incorporating biomolecules into scaffold interiors can be obtained by directly mixing the biomolecules in a polymer solution during the electrospinning process (as named blend electrospinning) and provides bioactive scaffolds with an initial burst release followed by a sustained release.…”

Three‐dimensional printing biotechnology for the regeneration of the tooth and tooth‐supporting tissues

“…Prepolymerized cell‐laden GelMA hydrogels have also been used successfully for bioprinting applications (Bertassoni et al, ) and regeneration dentistry (E. E. Smith et al, ; Khayat et al, ). Gelatin contains many arginine‐glycine‐aspartic acid (RGD) sequences that are necessary for cell attachment, as well as sequences of matrix metalloproteinase (MMP) that help cells degrade the substrate and migrate (Modaresifar, Hadjizadeh, & Niknejad, ). To form gelatin‐based crosslinked hydrogels, gelatin was chemically modified.…”