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The bone is a connective, vascularized, and mineralized tissue that confers protection to organs, and participates in the support and locomotion of the human body, maintenance of homeostasis, as well as in hematopoiesis. However, throughout the lifetime, bone defects may arise due to traumas (mechanical fractures), diseases, and/or aging, which when too extensive compromise the ability of the bone to self-regenerate. To surpass such clinical situation, different therapeutic approaches have been pursued. Rapid prototyping techniques using composite materials (consisting of ceramics and polymers) have been used to produce customized 3D structures with osteoinductive and osteoconductive properties. In order to reinforce the mechanical and osteogenic properties of these 3D structures, herein, a new 3D scaffold was produced through the layer-by-layer deposition of a tricalcium phosphate (TCP), sodium alginate (SA), and lignin (LG) mixture using the Fab@Home 3D-Plotter. Three different TCP/LG/SA formulations, LG/SA ratio 1:3, 1:2, or 1:1, were produced and subsequently evaluated to determine their suitability for bone regeneration. The physicochemical assays demonstrated that the LG inclusion improved the mechanical resistance of the scaffolds, particularly in the 1:2 ratio, since a 15 % increase in the mechanical strength was observed. Moreover, all TCP/LG/SA formulations showed an enhanced wettability and maintained their capacity to promote the osteoblasts' adhesion and proliferation as well as their bioactivity (formation of hydroxyapatite crystals). Such results support the LG inclusion and application in the development of 3D scaffolds aimed for bone regeneration.

The development of strategies capable of eliminating metastasized cancer cells and preventing tumor recurrence is an exciting and extremely important area of research. In this regard, therapeutic approaches that explore the synergies between nanomaterial-mediated phototherapies and immunostimulants/immune checkpoint inhibitors have been yielding remarkable results in pre-clinical cancer models. These nanomaterials can accumulate in tumors and trigger, after irradiation of the primary tumor with near infrared light, a localized temperature increase and/or reactive oxygen species. These effects caused damage in cancer cells at the primary site and can also (i) relieve tumor hypoxia, (ii) release tumor-associated antigens and danger-associated molecular patterns, and (iii) induced a pro-inflammatory response. Such events will then synergize with the activity of immunostimulants and immune checkpoint inhibitors, paving the way for strong T cell responses against metastasized cancer cells and the creation of immune memory. Among the different nanomaterials aimed for cancer immuno-phototherapy, those incorporating near infrared-absorbing heptamethine cyanines (Indocyanine Green, IR775, IR780, IR797, IR820) have been showing promising results due to their multifunctionality, safety, and straightforward formulation. In this review, combined approaches based on phototherapies mediated by heptamethine cyanine-loaded nanomaterials and immunostimulants/immune checkpoint inhibitor actions are analyzed, focusing on their ability to modulate the action of the different immune system cells, eliminate metastasized cancer cells, and prevent tumor recurrence.

Gold core silica shell (AuMSS) nanorods present excellent physicochemical proper-ties that allow their application as photothermal and drug delivery agents. Herein,AuMSS nanorods were dual‐functionalized with Polyethylene glycol methyl ether(PEG‐CH3) and Gelatin (GEL) to enhance both the colloidal stability and uptake byHeLa cancer cells. Additionally, the AuMSS nanorods were combined for the firsttime with IR780 (a heptamethine cyanine molecule) and its photothermal and pho-todynamic capacities were determined. The obtained results reveal that the en-capsulation of IR780 (65 μg per AuMSS mg) increases the photothermal conversionefficiency of AuMSS nanorods by 10%, and this enhanced heat generation wasmaintained even after three irradiation cycles with a NIR (808 nm) laser. Moreover,the IR780‐loaded AuMSS/T‐PEG‐CH3/T‐GEL presented≈2‐times higher uptake inHeLa cells, when compared to the non‐coated counterparts, and successfullymediated the light‐triggered generation of reactive oxygen species. Overall, thecombination of photodynamic and photothermal therapy mediated by IR780‐loadedAuMSS/T‐PEG‐CH3/T‐GEL nanorods effectively promoted the ablation of HeLacancer cells.