Measuring vascular graft cellularity non-destructively: merging magnetic resonance imaging and tissue engineering

Despite significant growth in the field of tissue engineering over the past decades, non-invasive, non-destructive methods to characterize the cellularisation of grafts are lacking. Here, in a proof-of-concept study, a non-invasive magnetic resonance imaging method, diffusion tensor imaging (DTI), within acellular and cellularised vascular grafts is investigated. Using decellularised porcine carotid grafts, smooth muscle cells are cultured dynamically for two weeks with terminal time points at day 3, 7, and 14. Grafts are fixed at each time point and investigated by DTI in an ex vivo set up. Semi-quantitative histology is used as a ground truth for collagen, elastin, and cell density changes over time. DTI-derived metrics, namely the fractional anisotropy, mean diffusivity, and tractography, are significantly different between day 3 and day 7 grafts and distinguish between acellular and cellularised grafts. Specifically, increasing fractional anisotropy is correlated to increasing cell density. The results from this study show the potential of MR-DTI in the field of tissue engineering, offering non-invasive, non-destructive insight into graft cellularisation. </p

Measuring vascular graft cellularity non-destructively: merging magnetic resonance imaging and tissue engineering

Despite significant growth in the field of tissue engineering over the past decades, non-invasive, non-destructive methods to characterize the cellularisation of grafts are lacking. Here, in a proof-of-concept study, a non-invasive magnetic resonance imaging method, diffusion tensor imaging (DTI), within acellular and cellularised vascular grafts is investigated. Using decellularised porcine carotid grafts, smooth muscle cells are cultured dynamically for two weeks with terminal time points at day 3, 7, and 14. Grafts are fixed at each time point and investigated by DTI in an ex vivo set up. Semi-quantitative histology is used as a ground truth for collagen, elastin, and cell density changes over time. DTI-derived metrics, namely the fractional anisotropy, mean diffusivity, and tractography, are significantly different between day 3 and day 7 grafts and distinguish between acellular and cellularised grafts. Specifically, increasing fractional anisotropy is correlated to increasing cell density. The results from this study show the potential of MR-DTI in the field of tissue engineering, offering non-invasive, non-destructive insight into graft cellularisation. </p

Integrating melt electrowriting and fused deposition modeling to fabricate hybrid scaffolds supportive of accelerated bone regeneration

Emerging additive manufacturing (AM) strategies can enable the engineering of hierarchal scaffold structures for guiding tissue regeneration. Here, the advantages of two AM approaches, melt electrowriting (MEW) and fused deposition modelling (FDM), are leveraged and integrated to fabricate hybrid scaffolds for large bone defect healing. MEW is used to fabricate a microfibrous core to guide bone healing, while FDM is used to fabricate a stiff outer shell for mechanical support, with constructs being coated with pro-osteogenic calcium phosphate (CaP) nano-needles. Compared to MEW scaffolds alone, hybrid scaffolds prevent soft tissue collapse into the defect region and support increased vascularization and higher levels of new bone formation 12 weeks post-implantation. In an additional group, hybrid scaffolds are also functionalized with BMP2 via binding to the CaP coating, which further accelerates healing and facilitates the complete bridging of defects after 12 weeks. Histological analyses demonstrate that such scaffolds support the formation of well-defined annular bone, with an open medullary cavity, smooth periosteal surface, and no evidence of abnormal ectopic bone formation. These results demonstrate the potential of integrating different AM approaches for the development of regenerative biomaterials, and in particular, demonstrate the enhanced bone healing outcomes possible with hybrid MEW-FDM constructs. </p

Integrating melt electrowriting and fused deposition modeling to fabricate hybrid scaffolds supportive of accelerated bone regeneration

Emerging additive manufacturing (AM) strategies can enable the engineering of hierarchal scaffold structures for guiding tissue regeneration. Here, the advantages of two AM approaches, melt electrowriting (MEW) and fused deposition modelling (FDM), are leveraged and integrated to fabricate hybrid scaffolds for large bone defect healing. MEW is used to fabricate a microfibrous core to guide bone healing, while FDM is used to fabricate a stiff outer shell for mechanical support, with constructs being coated with pro-osteogenic calcium phosphate (CaP) nano-needles. Compared to MEW scaffolds alone, hybrid scaffolds prevent soft tissue collapse into the defect region and support increased vascularization and higher levels of new bone formation 12 weeks post-implantation. In an additional group, hybrid scaffolds are also functionalized with BMP2 via binding to the CaP coating, which further accelerates healing and facilitates the complete bridging of defects after 12 weeks. Histological analyses demonstrate that such scaffolds support the formation of well-defined annular bone, with an open medullary cavity, smooth periosteal surface, and no evidence of abnormal ectopic bone formation. These results demonstrate the potential of integrating different AM approaches for the development of regenerative biomaterials, and in particular, demonstrate the enhanced bone healing outcomes possible with hybrid MEW-FDM constructs. </p