Three-dimensional bioprinting is an advanced tissue fabrication technique that allows printing complex structures with precise positioning of multiple cell types layer-by-layer.Compared to other bioprinting methods,ex...Three-dimensional bioprinting is an advanced tissue fabrication technique that allows printing complex structures with precise positioning of multiple cell types layer-by-layer.Compared to other bioprinting methods,extrusion bioprinting has several advantages to print large-sized tissue constructs and complex organ models due to large build volume.Extrusion bioprinting using sacrificial,support and embedded strategies have been successfully employed to facilitate printing of complex and hollow structures.Embedded bioprinting is a gel-in-gel approach developed to overcome the gravitational and overhanging limits of bioprinting to print large-sized constructs with a micron-scale resolution.In embedded bioprinting,deposition of bioinks into the microgel or granular support bath will be facilitated by the sol-gel transition of the support bath through needle movement inside the granular medium.This review outlines various embedded bioprinting strategies and the polymers used in the embedded systems with advantages,limitations,and efficacy in the fabrication of complex vascularized tissues or organ models with micron-scale resolution.Further,the essential requirements of support bath systems like viscoelasticity,stability,transparency and easy extraction to print human scale organs are discussed.Additionally,the organs or complex geometries like vascular constructs,heart,bone,octopus and jellyfish models printed using support bath assisted printing methods with their anatomical features are elaborated.Finally,the challenges in clinical translation and the future scope of these embedded bioprinting models to replace the native organs are envisaged.展开更多
Large-gap nerve defects require nerve guide conduits(NGCs)for complete regeneration and muscle innervation.Many NGCs have been developed using various scaffold designs and tissue engineering strategies to promote axon...Large-gap nerve defects require nerve guide conduits(NGCs)for complete regeneration and muscle innervation.Many NGCs have been developed using various scaffold designs and tissue engineering strategies to promote axon regeneration.Still,most are tubular with inadequate pore sizes and lack surface cues for nutrient transport,cell attachment,and tissue infiltration.This study developed a porous spiral NGC to address these issues using a 3D-printed thermoplastic polyurethane(TPU)fiber lattice.The lattice was functionalized with poly(3-hydroxybutyrate-co-3-hydroxyvalerate)(PHBV)electrospun aligned(aPHBV)and randomly(rPHBV)oriented nanofibers to enhance cellular activity.TPU lattices were made with 25%,35%,and 50%infill densities to create scaffolds with varied mechanical compliance.The fabricated TPU/PHBV spiral conduits had significantly higher surface areas(25%TPU/PHBV:698.97 mm^(2),35%TPU/PHBV:500.06 mm^(2),50%TPU/PHBV:327.61 mm^(2))compared to commercially available nerve conduits like Neurolac™(205.26 mm^(2)).Aligned PHBV nanofibers showed excellent Schwann cell(RSC96)adhesion,proliferation,and neurogenic gene expression for all infill densities.Spiral TPU/PHBV conduits with 25%and 35%infill densities exhibited Young’s modulus values comparable to Neurotube®and ultimate tensile strength like acellular cadaveric human nerves.A 10 mm sciatic nerve defect in Wistar rats treated with TPU/aPHBV NGCs demonstrated muscle innervation and axon healing comparable to autografts over 4 months,as evaluated by gait analysis,functional recovery,and histology.The TPU/PHBV NGC developed in this study shows promise as a treatment for large-gap nerve defects.展开更多
基金Nano Mission,Department of Science&Technology(DST)(SR/NM/TP-83/2016(G))Prof.T.R.Rajagopalan R&D Cell of SASTRA Deemed University for financial and infrastructural support.We also wish to acknowledge ATGC grant,Department of Biotechnology(DBT)(BT/ATGC/127/SP41147/2021)+2 种基金Adhoc funding,Indian Council of Medical Research(ICMR)(17x3/Adhoc/23/2022-ITR)DST SERB CRG(Exponential Technologies)grant(CRG/2021/007847)for financial supportIndian Council of Medical Research(ICMR)for the senior research fellowship(3/1/1(4)/CVD/2020-NCD-1).
文摘Three-dimensional bioprinting is an advanced tissue fabrication technique that allows printing complex structures with precise positioning of multiple cell types layer-by-layer.Compared to other bioprinting methods,extrusion bioprinting has several advantages to print large-sized tissue constructs and complex organ models due to large build volume.Extrusion bioprinting using sacrificial,support and embedded strategies have been successfully employed to facilitate printing of complex and hollow structures.Embedded bioprinting is a gel-in-gel approach developed to overcome the gravitational and overhanging limits of bioprinting to print large-sized constructs with a micron-scale resolution.In embedded bioprinting,deposition of bioinks into the microgel or granular support bath will be facilitated by the sol-gel transition of the support bath through needle movement inside the granular medium.This review outlines various embedded bioprinting strategies and the polymers used in the embedded systems with advantages,limitations,and efficacy in the fabrication of complex vascularized tissues or organ models with micron-scale resolution.Further,the essential requirements of support bath systems like viscoelasticity,stability,transparency and easy extraction to print human scale organs are discussed.Additionally,the organs or complex geometries like vascular constructs,heart,bone,octopus and jellyfish models printed using support bath assisted printing methods with their anatomical features are elaborated.Finally,the challenges in clinical translation and the future scope of these embedded bioprinting models to replace the native organs are envisaged.
基金The authors wish to acknowledge Nano Mission,Department of Science&Technology(DST)(SR/NM/TP-83/2016(G))Prof.T.R.Rajagopalan R&D Cell of SASTRA Deemed University for financial and infrastructural support+4 种基金We also wish to acknowledge ATGC grant,Department of Biotechnology(DBT)(BT/ATGC/127/SP41147/2021)Adhoc funding,Indian Council of Medical Research(ICMR)(17x3/Adhoc/23/2022-ITR)DST SERB CRG(Exponential Technologies)grant(CRG/2021/007847)for financial supportfunding support provided by the National Institutes of Health(#R01NS134604,#R01EB034202,#R01AR078908,and#R01EB030060)the U.S.Army Medical Research Acquisition Activity(USAMRAA)through the CDMRP Peer-Reviewed Medical Research Program(Award No.W81XWH2010321,PR230581,and HT94252410137).
文摘Large-gap nerve defects require nerve guide conduits(NGCs)for complete regeneration and muscle innervation.Many NGCs have been developed using various scaffold designs and tissue engineering strategies to promote axon regeneration.Still,most are tubular with inadequate pore sizes and lack surface cues for nutrient transport,cell attachment,and tissue infiltration.This study developed a porous spiral NGC to address these issues using a 3D-printed thermoplastic polyurethane(TPU)fiber lattice.The lattice was functionalized with poly(3-hydroxybutyrate-co-3-hydroxyvalerate)(PHBV)electrospun aligned(aPHBV)and randomly(rPHBV)oriented nanofibers to enhance cellular activity.TPU lattices were made with 25%,35%,and 50%infill densities to create scaffolds with varied mechanical compliance.The fabricated TPU/PHBV spiral conduits had significantly higher surface areas(25%TPU/PHBV:698.97 mm^(2),35%TPU/PHBV:500.06 mm^(2),50%TPU/PHBV:327.61 mm^(2))compared to commercially available nerve conduits like Neurolac™(205.26 mm^(2)).Aligned PHBV nanofibers showed excellent Schwann cell(RSC96)adhesion,proliferation,and neurogenic gene expression for all infill densities.Spiral TPU/PHBV conduits with 25%and 35%infill densities exhibited Young’s modulus values comparable to Neurotube®and ultimate tensile strength like acellular cadaveric human nerves.A 10 mm sciatic nerve defect in Wistar rats treated with TPU/aPHBV NGCs demonstrated muscle innervation and axon healing comparable to autografts over 4 months,as evaluated by gait analysis,functional recovery,and histology.The TPU/PHBV NGC developed in this study shows promise as a treatment for large-gap nerve defects.
