Imaging stem cell distribution, growth, migration, and differentiation in 3‐D scaffolds for bone tissue engineering using mesoscopic fluorescence tomography

Abstract

Regenerative medicine has emerged as an important discipline that aims to repair injury or replace damaged tissues or organs by introducing living cells or functioning tissues.Successful regenerative medicine strategies will likely depend upon a simultaneous optimization strategy for the design of biomaterials, cell-seeding methods, cell-biomaterial interactions, and molecular signaling within the engineered tissues. It remains a challenge to image three-dimensional (3-D) structures and functions of the cell-seeded scaffold in mesoscopic scale (>2 ∼ 3 mm). In this study, we utilized angled fluorescence laminar optical tomography (aFLOT), which allows depth-resolved molecular characterization of engineered tissues in 3-D to investigate cell viability, migration, and bone mineralization within bone tissue engineering scaffolds in situ. K E Y W O R D S3-D cell printing, bone mineralization, bone tissue scaffold, cell migration, mesoscopic fluorescence tomography

Cell Bioprinting: The 3D-Bioplotter™ Case

“…In the subject of stem cell applications, the majority of the papers use an alginate-based hydrogel with only three examples of methacrylated gelatin hydrogels combined [66,67,68,69,70], as reflected in Table 5.…”

“…There is also a clear relationship between cell lines and hydrogel compositions, in some cases. This can be observed with iPS and neural stem cells that use an alginate hydrogel supplemented with carboxymethyl-chitosan and agarose, with human mesenchymal stem cells for containing methacrylated gelatin as one component of their respective hydrogels [69,70]. The majority of applications are related to regenerative medicine such as the production of neural mini-tissues [60] but also related to model development for drug testing and the study of diseases such as breast cancer [67] and preeclampsia [69].…”

“…The majority of applications are related to regenerative medicine such as the production of neural mini-tissues [60] but also related to model development for drug testing and the study of diseases such as breast cancer [67] and preeclampsia [69]. Only two examples are related to the development of techniques such as dielectric impedance spectroscopy technique [68] and mesoscopic fluorescence tomography [70].…”

“…One interesting article is the proposed alternative hydrogel formulation based on lignin, which is suggested as a new concept for skin tissue bioprinting. The majority of the papers correspond to regenerative medicine, except for one on the use of mesoscopic fluorescence tomography, previously mentioned [70]. Except for the novel formulation [82], it seems that the common cross-linking method used is the chemical one, exempting the use of a photoinitiator and tyrosinase on bioprinting of living skin tissue constructs [83].…”

“…Apropos of material science and other advanced applications, some examples are those related to cell-compatible hydrogel synthesis [27], improvements on cell viability maintenance during bioprinting processes [68], and the development of new materials such as a combination between lignin and polyurethane [82]. Other examples related to the medical field, classified as other applications, are cellular characterization [94], chemical material characterization [95], development of new techniques [70,76], and gene characterization [77].…”