Injectable hydrogels show great promise in developing novel regenerative medicine solutions and present advantages for minimally invasive applications. Hydrogels based on extracellular matrix components, such as collagen, have the benefits of cell adhesiveness, biocompatibility, and degradability by enzymes. However, to date, reported collagen hydrogels possess severe shortcomings, such as nonbiocompatible cross-linking chemistry, significant swelling, limited range of mechanical properties, or gelation kinetics unsuitable for in vivo injection. To solve these issues, we report the design and characterization of an injectable collagen hydrogel based on covalently modified acetyl thiol collagen cross-linked using thiol-maleimide click chemistry. The hydrogel is injectable for up to 72 h after preparation, shows no noticeable swelling, is transparent, can be molded in situ, and retains its shape in solution for at least one year. Notably, the hydrogel mechanical properties can be fine-tuned by simply adjusting the reactant stoichiometries, which to date was only reported for synthetic polymer hydrogels. The biocompatibility of the hydrogel is demonstrated in vitro using human corneal epithelial cells, which maintain viability and proliferation on the hydrogels for at least seven days. Furthermore, the developed hydrogel showed an adhesion strength on soft tissues similar to fibrin glue. Additionally, the developed hydrogel can be used as a sealant for repairing corneal perforations and can potentially alleviate the off-label use of cyanoacrylate tissue adhesive for repairing corneal perforations. Taken together, these characteristics show the potential of the thiol collagen hydrogel for future use as a prefabricated implant, injectable filler, or as sealant for corneal repair and regeneration.

Hydrogel-supported neural cell cultures are more in vivo-relevant compared to monolayers formed on glass or plastic substrates. However, there is a lack of synthetic microenvironment available for obtaining standardized and easily reproducible cultures characterized by tissue-mimicking cell composition, cell–cell interactions, and functional networks. Synthetic peptides representing the biological properties of the extracellular matrix (ECM) proteins have been reported to promote the adhesion-driven differentiation and functional maturation of neural cells. Thus, such peptides can serve as building blocks for engineering a standardized, all-synthetic environment. In this study, we have compared the effect of two chemically crosslinked hydrogel compositions on primary cerebellar cells: collagen-like peptide (CLP), and CLP with an integrin-binding motif arginine-glycine-aspartate (CLP-RGD), both conjugated to polyethylene glycol molecular templates (PEG-CLP and PEG-CLP-RGD, respectively) and fabricated as self-supporting membranes. Both compositions promoted a spontaneous organization of primary cerebellar cells into tissue-like clusters with fast-rising Ca²⁺ signals in soma, reflecting action potential generation. Notably, neurons on PEG-CLP-RGD had more neurites and better synaptic efficiency compared to PEG-CLP. For comparison, poly-L-lysine-coated glass and plastic surfaces did not induce formation of such spontaneously active networks. Additionally, contrary to the hydrogel membranes, glass substrates functionalized with PEG-CLP and PEG-CLP-RGD did not sufficiently support cell attachment and, subsequently, did not promote functional cluster formation. These results indicate that not only chemical composition but also the hydrogel structure and viscoelasticity are essential for bioactive signaling. The synthetic strategy based on ECM-mimicking, multifunctional blocks in registry with chemical crosslinking for obtaining tissue-like mechanical properties is promising for the development of fast and well standardized functional in vitro neural models and new regenerative therapies.

The selective and efficient catalytic C–H methylation of (hetero)arenes is demonstrated without involving solvents or ball milling.

Screw-bone construct failures are a true challenge in orthopaedic implant fixation, particularly in poor quality bone. Whilst augmentation with bone cement can improve the primary stability of screws, there are cements, e.g. PMMA, that may impede blood flow and nutrients and hamper bone remodelling. In this study, soft, non-setting biomaterials based on Hyalectin gels and hydroxyapatite (HA) particles with different morphological parameters were evaluated as potential augmentation materials, using a lapine ex vivo bone model. The pull-out force, stiffness, and work to fracture were considered in evaluating screw attachment. The pull-out force of constructs reinforced with Hyalectin containing irregularly shaped nano-HA and spherically shaped micro-HA particles were found to be significantly higher than the control group (no augmentation material). The pull-out stiffness increased for the micro-HA particles and the work to fracture increased for the irregular nano-HA particles. However, there were no significant augmentation effect found for the spherical shaped nano-HA particles. In conclusion, injectable Hyalectin gel loaded with hydroxyapatite particles was found to have a potentially positive effect on the primary stability of screws in trabecular bone, depending on the HA particle shape and size.

Extracellular vesicles (EVs) derived from corneal epithelial cells have shown great promise in promoting corneal wound healing and stromal regeneration, but they face challenges with rapid clearance from the eye. This study addresses these challenges by developing a biocompatible collagen-hydrogel sustained delivery system. We successfully isolated, purified, and characterized corneal epithelial EVs (CE-EVs), assessed their efficacy in corneal epithelial healing in vitro, and demonstrated their sustained delivery over 10 days followed by an on-demand release through enzymatic degradation of the hydrogel, which mimics the in vivo scenario. To develop a microscale understanding of the EV diffusion inside the hydrogel matrix, we probed the hydrogel network with several model compounds and nanoparticles by using advanced confocal microscopy analyses, followed by fitting our results to established diffusion models. Our findings suggest this innovative approach offers a safe and effective strategy to promote corneal wound healing. This technology has the potential to revolutionize corneal injury treatment and improve patient outcomes. Moreover, the possibility to tailor EV-release kinetics broadens the scope of EV research in clinical practices, as varying short- and long-term release profiles will be required for diverse medical applications.