3D printed Si-CaP scaffold released SiO32- and Ca2+ to synergistically promote angiogenesis.

BACKGROUND AND PURPOSE: Structuring scaffold with both osteogenic and angiogenesis capabilities is a challenge for bone tissue engineering. Powder structured Si-CaP materials have shown excellent osteogenic properties and induction of stem cell differentiation. Our research group have successful produced 3D printed Si-CaP scaffolds by DLP technology. This study aims to explore the angiogenic effects of SiO32- and Ca2+ released by 3D printed Si-CaP scaffold, and whether there is a synergistic effect between the two ions. METHODS: The 3D printed Si-CaP scaffolds were immersed in endothelial cell medium solution for 24 h. The Si, Ca ion released was detected by Inductively coupled plasma-optical emission spectrometry. We used detected data as a standard to prepare the simulated solution to investigate the effect of SiO32-, Ca2+ separately. Experiment was divided into control group, Si ion group, Ca ion group and Si + Ca ion group. We evaluated different ionic effect on HUVECs viability, proliferation, migration, gene expression, and tube formation on different groups. RESULTS: The concentration of SiO32- was detected as 15.71 ± 0.04 µg/mL, Ca2+ as 67.14 ± 0.95 µg/mL. Na2SiO3 and CaCl2 were used to prepare the simulated solution. There were no statistically difference between simulated solution from ion released by scaffold. Si + Ca group promoted the gene expression significantly compared with the control group, p < .01. Expression of vascular-associated protein in Si + Ca ion group was higher than that in Si ion group, Ca ion group and control group. Si + Ca ion group significantly enhanced endothelial cell on migration and tube formation assay. CONCLUSION: The 3D printed Si-CaP scaffold can release effective physiological concentrations of Si, Ca ions. Si and Ca ions have a synergistic effect on promoting angiogenesis of HUVECs. 3D printed Si-CaP scaffold is promising in vascularized bone tissue engineering application.

3D Bioprinted Tissue-Engineered Bone with Enhanced Mechanical Strength and Bioactivities: Accelerating Bone Defect Repair through Sequential Immunomodulatory Properties.

In this study, a new-generation tissue-engineered bone capable of temporally regulating the immune response, balancing proinflammatory and anti-inflammatory activities, and facilitating bone regeneration and repair to address the challenges of delayed healing and nonunion in large-sized bone defects, is innovatively developed. Using the innovative techniques including multiphysics-assisted combined decellularization, side-chain biochemical modification, and sterile freeze-drying, a novel photocurable extracellular matrix hydrogel, methacrylated bone-derived decellularized extracellular matrix (bdECM-MA), is synthesized. After incorporating the bdECM-MA with silicon-substituted calcium phosphate and bone marrow mesenchymal stem cells, the tissue-engineered bone is fabricated through digital light processing 3D bioprinting. This study provides in vitro confirmation that the engineered bone maintains high cellular viability while achieving MPa-level mechanical strength. Moreover, this engineered bone exhibits excellent osteogenesis, angiogenesis, and immunomodulatory functions. One of the molecular mechanisms of the immunomodulatory function involves the inhibition of the p38-MAPK pathway. A pioneering in vivo discovery is that the natural biomaterial-based tissue-engineered bone demonstrates sequential immunomodulatory properties that activate proinflammatory and anti-inflammatory responses in succession, significantly accelerating the repair of bone defects. This study provides a new research basis and an effective method for developing autogenous bone substitute materials and treating large-sized bone defects.