1A Introduction to Tissue Engineering Part 1

Tissue Engineering

• Introduction and Cell Adhesion

  • Location: Gilman Hall, Johns Hopkins, Whiting School of Engineering

Topics Overview

1. Fundamentals

   • Cell Adhesion & Morphogenesis

2. Fundamentals

   • Tissue Structure & Immune System

3. Engineering Tissues

4. Clinical Applications

NIH Definition of Tissue Engineering

• Definition: Tissue engineering evolved from biomaterials development.

  • Combines scaffolds, cells, and biologically active molecules into functional tissues.

  • Goal: To create constructs that restore, maintain, or improve damaged tissues or organs.

  • Applications:

    • Medical: Healing and restoration.

    • Non-therapeutic: Biosensors for biological and chemical threats, toxicity testing of medications using tissue chips.

  • Reference: National Institute of Biomedical Imaging and Bioengineering.

Organ-on-a-Chip

• Concept: Utilizes tissue engineering principles at the micro-scale to model human organs and diseases.

In Vitro Models

• Significance: Some tissues are difficult to study in humans and differ significantly from animal models (e.g., brain).

  • Design Criteria: Must generate physiologically relevant in vitro models in bioreactors.

Artificial Food

• Example: $330,000 lab-grown hamburger at Johns Hopkins, Whiting School of Engineering.

Historical Context of Tissue Engineering

• First Clinical Application: Engineered skin for burn patients in 1981.

• Significant Milestone: First successful kidney transplant in Boston, 1954.

  • Reference: Langer, R., and Vacanti, J. P. (1993). Science 260: 920–926.

Components of Tissue Engineering

• Key Components:

  • Cells

  • Engineering Graft

  • Substrates (gels and scaffolds)

  • Bioactive Factors

Tissue Engineering Approach

• Process:

  • Obtain cells from a biopsy.

  • Culture them into a monolayer and expand the cell population.

Functional Tissue Engineering (FTE)

• Components:

  • Cells

  • Substrates (gels and scaffolds)

  • Bioactive Factors

  • Biophysical Cues

  • Graft must be functional.

The Biomimetic Principle

• Studies on various tissues (heart, ligaments, cartilage) focusing on biomimicry.

  • Notable Research: Radisic et al, Hung et al, Altmann et al.

Milestones in Tissue Engineering

• Notable Innovators:

  • Anthony Atala (bladder, heart valve)

  • Doris Taylor (heart)

  • Stephen Badylak (finger)

  • Charles Vacanti (ear, trachea)

  • Laura Niklason (lungs)

Tissues/Organs Engineered In Vitro Since 1993

• Engineered tissues:

  • Heart, Bladder, Blood Vessels, Urethra, Smooth Muscle, Vagina, Skeletal Muscle, Heart Valves, Penis, Breast, Trachea, Cornea, Bone, Retina, Cartilage, Salivary Glands, Ligament, Esophagus, Tendon

  • Note: Red indicates use in human patients; (*) are acellular.

Challenges in Engineering

• Question: Which organ would be the easiest to engineer?

  • Options include heart, brain, hand, or skin.

Challenges to Growing Tissues

• Notable challenge: Why it is difficult to grow a 1 cm³ piece of:

  • Bone

  • Heart

  • Cartilage

  • Neural Tissues

Design Challenges in Tissue Engineering

• Key Considerations:

  • Biological systems are complex and unpredictable compared to physical systems.

  • Design Parameters:

    • Number of cells required

    • Oxygen and nutrient delivery

    • Growth factor diffusion rates and binding kinetics

    • Scaffold mechanics and structure

    • Application of biophysical or physiological stimuli

  • Outputs:

    • Functionality assessment

    • Real-time, non-invasive evaluation

Cell Adhesion & Morphogenesis

• Focus Areas:

  • Cell-cell and cell-material interactions (cell adhesion and mechanobiology)

  • Cell development into tissues (tissue development, regeneration, vascularization)

  • Quantitative metrics for tissue engineering (growth, oxygen distribution, biomechanics)

  • Bioreactor Design to facilitate engineering processes.