2A Morphogenesis & Bioprinting I

Tissue Engineering

  • Focus on Morphogenesis & 3D Bioprinting of Cells

  • Presented at Gilman Hall, Johns Hopkins, Whiting School of Engineering

3D Printing Developments

Breakthrough in Organ Printing

  • Scientists successfully 3D printed an organ and performed a transplant into an animal, demonstrating functionality.

  • Reference: HuffPost article (Feb 27, 2016), based on Kang et al., Nat. Biotech. 2016.

Personalized Cardiac Constructs

  • Noor et al. (2019) reported on 3D printing personalized thick and perfusable cardiac patches and hearts in Advanced Science.

3D Structure of the Heart

  • Development involves complex morphogenic processes essential for proper structural organization of myocardial tissues.

  • The 3D printed structure's spatial arrangement of cell types affects organ functionality.

Lecture Outline

Tissue Patterning

  • Learning from embryonic development

    • Concept of ‘positional values’

    • Concept of ‘inductive cues’

3D Cell Printing

  • Types of 3D printing techniques

  • Bioink development and examples

Learning from Embryology

  • Viktor Hamburger's quote on the embryo as a teacher.

Questions from Embryology

Spatial Location and Tissues

  • Key inquiries:

    • How do cells recognize their location in an embryo?

    • Are cell fates genetically predetermined or influenced by microenvironments?

    • What occurs if cells are relocated within the embryo?

    • Do cells convey instructive cues?

Concept of Positional Values

  • Explains how cells understand their location and destiny during development, highlighted with the salamander example of blastema formation at injury sites.

Pattern Formation & Inductive Interactions

  • Cell phenotypes are influenced by their spatial positions during embryonic development.

  • Inductive cues from early developing cells influence neighboring cells and guide pattern formation.

Inductive Mechanisms

  • Interactions occur through:

    • Diffusible signals

    • ECM-mediated cues

    • Direct cell-cell contact

Heterotypic Cell-Cell Interactions

Types of Induction

  • Negative Induction: Restricts differentiation potential of cells.

  • Instructive Induction: Leads to differentiation of responder cells.

  • Permissive Induction: Responders need a permissive environment despite having necessary information.

  • Reciprocal Induction: Tissues mutually signal each other to differentiate.

Epithelial and Mesenchymal Cell Comparison

Epithelial Cells

  • Arrange in contiguous sheets with cuboidal shapes and tight connections.

  • Serve protective and absorptive functions, forming glands and linings.

Mesenchymal Cells

  • Characterized by loose or solitary connections, often bipolar or stellate.

  • Interactions between epithelia and mesenchyme lead to tissue complexity.

Cell Fate Influences

  • Examining inductive cues from mesenchyme on cell differentiation and fate, showing varied outcomes based on interactions with different types of mesenchymal cells like stomach and liver.

Directed Tissue Self-Assembly

  • Concepts of using clumps of cells, modified printing technologies, and thermoreversible gels to create complex tissue structures.

3D Printing of Organs

Hype vs. Substance

  • Discussion on the potential of bioprinting technologies to fabricate human tissues on demand, easing transplant wait times.

Cellular Communication

  • Functional sub-units consisting of multiple cell types necessary for maintaining tissue-specific functions.

Reading Material

  • Key articles for further understanding:

    • Mironov et al. on organ printing.

3D-Printing Spheroids in Bio-Ink

  • Overview of fabricating spheroids as building blocks in bioprinted constructs.

Self-Assembly in Tissues

  • Describes spontaneous reaggregation of cells to form functional units, emphasizing the significance of cellular environments in development.

Philosophy of 3D Tissue Printing

  • Advocates for an organic self-assembly of tissues, mimicking embryogenesis to achieve rapid and scalable production of tissue constructs.

Printing Vascular Structures

  • Building vascular trees using functional units to enhance tissue engineering capabilities.

Bio-inks Necessities

  • Importance of bioink characteristics: biocompatibility, functionality, mechanical integrity.

Printing Technologies Overview

Categories of Bioprinters

  • Different bioprinting methods and their principles including extrusion, inkjet, and laser-assisted techniques.

Manufacturing Considerations

  • Key factors to consider for maintaining cell viability and achieving functional tissue constructs during the printing process.

Additional Reading Assignments

  • List of recommended studies for continued exploration of tissue engineering and 3D printing techniques.