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Enhanced osteogenesis of 3D printed β-TCP scaffolds with Cissus Quadrangularis extract-loaded polydopamine coatings.

ABSTRACT: Growing demand in bone tissue replacement has shifted treatment strategy from pursuing traditional autogenous and allogeneic grafts to tissue replacement with bioactive biomaterials. Constructs that exhibit the ability to support the bone structure while encouraging tissue regeneration, integration, and replacement represent the future of bone tissue engineering. The present study aimed to understand the osteogenic and mechanical effects of binder jet 3D printed, porous β-tricalcium phosphate scaffolds modified with a natural polymer/drug coating of polydopamine and Cissus Quadrangularis extract. Compression testing was used to determine the effect the polydopamine coating process had on the mechanical strength of the scaffolds. 3D printed scaffolds with and without polydopamine coatings fractured at 3.88 ± 0.51 MPa and 3.84 ± 1 MPa, respectively, suggesting no detrimental effect on strength due to the coating process. The osteogenic potential of the extract-loaded coating was tested in vitro, under static and dynamic flow conditions, and in vivo in a rat distal femur model. Static osteoblast cultures indicated polydopamine-coated samples with and without the extract exhibited greater proliferation after 3 days (p < 0.05). Similarly, polydopamine resulted in increased proliferation and alkaline phosphatase expression under dynamic flow, but alkaline phosphatase expression was significantly enhanced (p < 0.05) only in samples treated with the extract. Histological analysis of implanted scaffolds showed substantially more new bone growth throughout the implant pores at 4 weeks post-op in polydopamine and extract-loaded implants compared to pure β-tricalcium phosphate. These results indicated that implants coated with polydopamine and Cissus Quadrangularis extract facilitated osteoblast proliferation and alkaline phosphatase production and improved early bone formation and ingrowth while maintaining mechanical strength.

SUBMITTER: Robertson SF

PROVIDER: S-EPMC8009487 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The aim of this study was to predefine the pore structure of ?-tricalcium phosphate (?-TCP) scaffolds with different macro pore sizes (500, 750, and 1000 µm), to characterize ?-TCP scaffolds, and to investigate the growth behavior of cells within these scaffolds. The lead structures for directional bone growth (sacrificial structures) were produced from polylactide (PLA) using the fused deposition modeling techniques. The molds were then filled with ?-TCP slurry and sintered at 1250 °C, whereby the lead structures (voids) were burnt out. The scaffolds were mechanically characterized (native and after incubation in simulated body fluid (SBF) for 28 d). In addition, biocompatibility was investigated by live/dead, cell proliferation and lactate dehydrogenase assays. The scaffolds with a strand spacing of 500 µm showed the highest compressive strength, both untreated (3.4 ± 0.2 MPa) and treated with simulated body fluid (2.8 ± 0.2 MPa). The simulated body fluid reduced the stability of the samples to 82% (500), 62% (750) and 56% (1000). The strand spacing and the powder properties of the samples were decisive factors for stability. The fact that ?-TCP is a biocompatible material is confirmed by the experiments. No lactate dehydrogenase activity of the cells was measured, which means that no cytotoxicity of the material could be detected. In addition, the proliferation rate of all three sizes increased steadily over the test days until saturation. The cells were largely adhered to or within the scaffolds and did not migrate through the scaffolds to the bottom of the cell culture plate. The cells showed increased growth, not only on the outer surface (e.g., 500: 36 ± 33 vital cells/mm² after three days, 180 ± 33 cells/mm² after seven days, and 308 ± 69 cells/mm² after 10 days), but also on the inner surface of the samples (e.g., 750: 49 ± 17 vital cells/mm² after three days, 200 ± 84 cells/mm² after seven days, and 218 ± 99 living cells/mm² after 10 days). This means that the inverse 3D printing method is very suitable for the presetting of the pore structure and for the ingrowth of the cells. The experiments on which this work is based have shown that the fused deposition modeling process with subsequent slip casting and sintering is well suited for the production of scaffolds for bone replacement.

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Enhanced osteogenesis of 3D printed β-TCP scaffolds with Cissus Quadrangularis extract-loaded polydopamine coatings.

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