In situ forming microporous gelatin methacryloyl hydrogel scaffolds from thermostable microgels for tissue engineering

Abstract

Converting biopolymers to extracellular matrix (ECM)-mimetic hydrogel-based scaffolds has provided invaluable opportunities to design in vitro models of tissues/diseases and develop regenerative therapies for damaged tissues. Among biopolymers, gelatin and its crosslinkable derivatives, such as gelatin methacryloyl (GelMA), have gained significant importance for biomedical applications due to their ECM-mimetic properties. Recently, we have developed the first class of in situ forming GelMA microporous hydrogels based on the chemical annealing of physically crosslinked GelMA microscale beads (microgels), which addressed several key shortcomings of bulk (nanoporous) GelMA scaffolds, including lack of interconnected micron-sized pores to support on-demand three-dimensional-cell seeding and cell-cell interactions. Here, we address one of the limitations of in situ forming microporous GelMA hydrogels, that is, the thermal instability (melting) of their physically crosslinked building blocks at physiological temperature, resulting in compromised microporosity. To overcome this challenge, we developed a two-step fabrication strategy in which thermostable GelMA microbeads were produced via semi-photocrosslinking, followed by photo-annealing to form stable microporous scaffolds. We show that the semi

Controlled Release of Epigenetically-Enhanced Extracellular Vesicles from a GelMA/Nanoclay Composite Hydrogel to Promote Bone Repair

“…GelMA hydrogels have been utilised for numerous tissue engineering applications due to its high biocompatibility, biodegradability and photosensitivity [ 40 , 41 ]. Although employed for different bone tissue engineering applications [ 54 ], the inherent lack of mechanical strength for GelMA hinders its application for load-bearing tissues.…”

“…Gelatin methacryloyl (GelMA) is a photosensitive hydrogel widely utilised for several tissue engineering applications due to its biocompatibility, biodegradability and low cost [ 38 , 39 ]. Moreover, the photo-crosslinkable nature of GelMA allows for in situ gelation following injection or 3D printing into complex anatomical structures [ 40 , 41 ]. In recent years, GelMA has been employed as a cell carrier given its hydrated 3D microenvironment as well as its ability to support cellular adhesion and functionality.…”

Mechanical reinforcement of granular hydrogels

“…The resulting granular hydrogels possess storage moduli ranging from a few kPa 41,54,55 to 10 kPa. 56 Within 60 s of moderate UV exposure (10 mW cm À2 ), jammed microgels are converted into granular hydrogels with a compressive modulus of 100 kPa and a tensile modulus of 30 kPa; 56 these mechanical properties are similar to those of a human muscle. However, radical polymerization is prone to oxygen quenching, which can compromise the crosslinking efficiency and lead to inferior mechanical properties of granular hydrogels.…”

Zwitterionic Nanogels and Microgels: An Overview on Their Synthesis and Applications

“…Templates or scaffolds deriving out of several polymer matrices serve as a platform in the development of in vitro tissue models and in vivo regenerative medicinal treatments. [161,162] Recently, microgels have been proved to be one of the promising matrices for cell migration, transportation of nutrients, and growth of metal nanoparticles (MNPs) due to the presence of interstitial void spaces between the cross-linked building blocks with high porosity. [27,163] In particular, microgels are better scaffolds over polymer microbeads in terms of achieving a higher number of nanoparticles (NPs) in their interior and also for more homogeneous distribution of the so-formed NPs in the microgel matrix.…”