Scanningless and continuous 3D bioprinting of human tissues with decellularized extracellular matrix

Abstract

Decellularized extracellular matrices (dECMs) have demonstrated excellent utility as bioscaffolds in recapitulating the complex biochemical microenvironment, however, their use as bioinks in 3D bioprinting to generate functional biomimetic tissues has been limited by their printability and lack of tunable physical properties. Here, we describe a method to produce photocrosslinkable tissuespecific dECM bioinks for fabricating patient-specific tissues with high control over complex microarchitecture and mechanical properties using a digital light processing (DLP)-based scanningless and continuous 3D bioprinter. We demonstrated that tissue-matched dECM bioinks provided a conducive environment for maintaining high viability and maturation of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and hepatocytes. Microscale patterning also guided spontaneous cellular reorganization into predesigned striated heart and lobular liver structures through biophysical cues. Our methodology enables a light-based approach *

From Shape to Function: The Next Step in Bioprinting

“…Engineering the composition of bioinks with bioactive compounds to guide cell response often makes use of cues derived from the native extracellular environment, eventually creating an artificial, and mostly chemically defined, yet simplified ECM substitute. Rather than designing “bottom‐up” a bioink composition, a powerful approach is to use natural templates, as already provided by native ECM . Printable, cell compatible bioinks have been obtained by decellularizing and solubilizing ECM from adipose tissue, cartilage and cardiac muscle, and each of these bioinks was proven superior to collagen gels in view of their potential to induce differentiation of adipose derived stromal cells, bone‐marrow derived stromal cells, and cardiomyocites, respectively .…”

Ethical Considerations in Animal Research: The Principle of 3R's

“…The 3D bioprinting systems use tissue-specific decellularized components of the extracellular matrix as bioinks to generate physiologically-relevant functional human tissues. This technique allows for the controlled assembly of cells and biomaterials to provide well-defined microstructures with specific biomechanical properties that recapitulate key features of native microenvironments, allowing intercommunications with the surrounding matrix to form a tissue-specific function that has proven to serve as powerful tools to study tissue homeostasis and even pathologies 24 . Figure 2.…”

Emulating Human Tissues and Organs: A Bioprinting Perspective Toward Personalized Medicine

“… 390 , 394 Bioinks have been prepared using materials such as gelatin or fibrin 61 , 395 and processed using different techniques including material extrusion 392 or mask irradiation. 394 Mimicking the native organization of cardiac ECM, where the parallel arrangement of collagen fibers contributes to the alignment of CMs, is of great importance to promote the anisotropic muscular contraction. This feature has been replicated in vitro using mask irradiation with a DMD and a bioink composed of iPSC-derived CMs embedded in gelMA blended with decellularized cardiac ECM.…”

“…By patterning the bioink as parallel lines, it was possible to generate synchronous contraction along the printed structures. 394 The replication of these features in bioprinted cardiac models opens the possibility to study the effects of biochemical compounds in tissue-specific aspects such as changes in heart beating rate, force, and calcium gradients. 392 , 393 However, to create more realistic models, it becomes necessary to find a balance between architectural complexity and functionality, as demonstrated by the diminished functional outputs obtained when more structurally complex constructs were produced.…”