Innovative strategies for improved chemotactic and pro-angiogenic features of TE constructs are needed. In this study, we developed an injectable HA/CNC/PL hydrogel with improved structural and biologic properties, that not only provide a sustained release of chemotactic and proangiogenic GFs from PL but also enhance the cells' viability and angiogenic activity. As a result of their unique traits, the developed hydrogels are ideally suited to simultaneously act as a GFs controlled delivery system and as a supportive matrix for cell culture, recruitment, and revascularization induction, holding great potential for the regeneration of vascularized soft tissues, such as the dentin-pulp complex.

The currently used hemostatic agents are highly effective in stopping hemorrhages but have a limited role in the modulation of the wound healing environment. Herein, we propose an intrinsically bioactive hemostatic cryogel based on platelet lysate (PL) and aldehydefunctionalized cellulose nanocrystals (a-CNC). PL have attracted great attention as an inexpensive milieu of therapeutically-relevant proteins, however its application as hemostatic agent exhibits serious constraints (e.g., structural integrity and short shelf-life). The incorporation of a-CNC showed to reinforce the low strength PL matrix by covalent cross-link its amine groups that exhibits an elastic interconnected porous network after full cryogelation. Upon blood immersion, the PL-CNC cryogels absorbed higher volumes of blood at a faster rate than commercial hemostatic porcine gelatin sponges. Simultaneously, the cryogels released biomolecules that increased stem cell proliferation, metabolic activity and migration as well as downregulated expression of markers of the fibrinolytic process. In a in vivo liver defect model, PL-CNC cryogels showed similar hemostatic performance in comparison with gelatin sponges and normal materialinduced tissue response upon subcutaneous implantation. Overall, owing to its structure and bioactive composition, the proposed PL-CNC cryogels provide an alternative off-the-shelf hemostatic and antibacterial biomaterial with the potential to deliver therapeutically-relevant proteins in situ.

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