Leveraging 3D bioprinting for processing stem cell-laden biomaterials has unlocked a tremendous potential for fabricating living 3D constructs for bone tissue engineering. Even though several bioinks developed to date display suitable physicochemical properties for stem cell seeding and proliferation, they generally lack the nanosized minerals present in native bone bioarchitecture. To enable the bottom-up fabrication of biomimetic 3D constructs for bioinstructing stem cells pro-osteogenic differentiation, herein we developed multi-bioactive nanocomposite bioinks that combine the organic and inorganic building blocks of bone. For the organic component gelatin methacrylate (GelMA), a photocrosslinkable denaturated collagen derivative used for 3D bioprinting was selected due to its rheological properties display of cell adhesion moieties to which bone tissue precursors such as human bone marrow derived mesenchymal stem cells (hBM-MSCs) can attach to. The inorganic building block was formulated by incorporating mesoporous silica nanoparticles functionalized with calcium, phosphate and dexamethasone (MSNCaPDex), which previously proven to induce osteogenic differentiation. The newly formulated photocrosslinkable nanocomposite GelMA bioink incorporating MSNCaPDex nanoparticles and laden with hBM-MSCs was successfully processed into a 3D bioprintable construct with structural fidelity, and well dispersed nanoparticles throughout the hydrogel matrix. These nanocomposite constructs could induce the deposition of apatite in vitro, thus showing attractive bioactivity properties. Viability and differentiation studies showed that hBM-MSCs remained viable and exhibited osteogenic differentiation biomarkers when incorporated in GelMA/MSNCaPDex constructs and without requiring further biochemical, nor mechanical stimuli. Overall, our nanocomposite bioink has demonstrated excellent processability via extrusion bioprinting into osteogenic constructs with potential application in bone tissue repair and regeneration.
Scaffolds for bone tissue regeneration should provide the right cues for stem cell adhesion and proliferation, but also lead to their osteogenic differentiation. Hydrogels of modified platelet lysates (PLMA) show the proper mechanical stability for cell encapsulation and contain essential bioactive molecules required for cell maintenance. We prepared a novel PLMA-based nanocomposite for bone repair and regeneration capable of releasing biofactors to induce osteogenic differentiation. Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) were encapsulated in PLMA hydrogels containing bioactive mesoporous silica nanoparticles previously loaded with dexamethasone and functionalized with calcium and phosphate ions. After 21 d of culture, hBM-MSCs remained viable, presented a stretched morphology, and showed signs of osteogenic differentiation, namely the presence of significant amounts of alkaline phosphatase, bone morphogenic protein-2 and osteopontin, hydroxyapatite, and calcium nodules. Developed for the first time, PLMA/MSNCaPDex nanocomposites were able to guide the differentiation of hBM-MSCs without any other osteogenic supplementation.
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