Leveraging 3D Bioprinting and Photon‐Counting Computed Tomography to Enable Noninvasive Quantitative Tracking of Multifunctional Tissue Engineered Constructs

• Published in: Advanced healthcare materials 2023-12, Vol.12 (31), p.e2302271-n/a
• Main Authors: Gil, Carmen J., Evans, Connor J., Li, Lan, Allphin, Alex J., Tomov, Martin L., Jin, Linqi, Vargas, Merlyn, Hwang, Boeun, Wang, Jing, Putaturo, Victor, Kabboul, Gabriella, Alam, Anjum S., Nandwani, Roshni K., Wu, Yuxiao, Sushmit, Asif, Fulton, Travis, Shen, Ming, Kaiser, Jarred M., Ning, Liqun, Veneziano, Remi, Willet, Nick, Wang, Ge, Drissi, Hicham, Weeks, Eric R., Bauser‐Heaton, Holly D., Badea, Cristian T., Roeder, Ryan K., Serpooshan, Vahid
• Format: Article
• Language: English
• Subjects: 3-D printers; 3D bioprinting; Accuracy; Animals; Biocompatibility; bioinks; Bioprinting - methods; Computed tomography; Contrast agents; Contrast media; Customization; Gadolinium; Gadolinium oxides; Gold; Implants; Iodine; longitudinal quantitative imaging; Mice; Nanoparticles; Photons; photon‐counting computed tomography; Precision medicine; Printing, Three-Dimensional; Reagents; Regenerative medicine; Reproducibility of Results; Scaffolds; Structure-function relationships; Three dimensional printing; Tissue engineering; Tissue Engineering - methods; tissue engineering scaffolds; Tissue Scaffolds - chemistry; Tomography; Tomography, X-Ray Computed
• ISSN: 2192-2640; 2192-2659; 2192-2659
• DOI: 10.1002/adhm.202302271

3D bioprinting is revolutionizing the fields of personalized and precision medicine by enabling the manufacturing of bioartificial implants that recapitulate the structural and functional characteristics of native tissues. However, the lack of quantitative and noninvasive techniques to longitudinally track the function of implants has hampered clinical applications of bioprinted scaffolds. In this study, multimaterial 3D bioprinting, engineered nanoparticles (NPs), and spectral photon‐counting computed tomography (PCCT) technologies are integrated for the aim of developing a new precision medicine approach to custom‐engineer scaffolds with traceability. Multiple CT‐visible hydrogel‐based bioinks, containing distinct molecular (iodine and gadolinium) and NP (iodine‐loaded liposome, gold, methacrylated gold (AuMA), and Gd2O3) contrast agents, are used to bioprint scaffolds with varying geometries at adequate fidelity levels. In vitro release studies, together with printing fidelity, mechanical, and biocompatibility tests identified AuMA and Gd2O3 NPs as optimal reagents to track bioprinted constructs. Spectral PCCT imaging of scaffolds in vitro and subcutaneous implants in mice enabled noninvasive material discrimination and contrast agent quantification. Together, these results establish a novel theranostic platform with high precision, tunability, throughput, and reproducibility and open new prospects for a broad range of applications in the field of precision and personalized regenerative medicine. Integration of 3D bioprinting and photon‐counting computed tomography (PCCT) enables manufacturing of CT traceable, tissue engineered scaffolds of varying geometry, while maintaining adequate physiomechanical and biological properties. PCCT visible, bioprinted constructs can be tracked in vitro and in vivo in a noninvasive, longitudinal, and quantitative manner.