Tissue Engineering Notes

Definition

  • Tissue engineering is an interdisciplinary field using engineering and life science principles.
  • It develops biological substitutes to restore, maintain, or improve tissue functions.
  • Often involves in vitro cultivation of tissues for therapeutic or research purposes.

Clinical Need

  • Tissue and organ failure is a major health concern.
  • Current reliance on donated tissues and organs is insufficient.
  • Millions suffer from conditions treatable by tissue engineering.

What is Tissue Engineering?

  • Applies biology and engineering principles to develop functional substitutes for damaged tissue.
  • The TE triad: cells, scaffold, and signals.
  • Multidisciplinary fields combining biology, chemistry, engineering, medicine, and material science.

Cells

  • Key component for successful tissue engineering.
  • Used to create or replace new tissue.
  • Can be used alone or with support matrices.
  • Cell Source Considerations:
    • Adequate environment crucial.
    • Cell manipulation creates new avenues.
    • Scaffold design influences environment.

Scaffolds

  • Artificial 3D structures mimicking extracellular matrix.
  • Provide support for cell attachment, growth, and tissue formation.
  • Key Characteristics:
    • Biocompatible and biodegradable.
    • Highly porous with interconnected network.
    • Suitable surface chemistry.
    • Mechanical properties matching target tissue.
  • Fabrication Techniques:
    • Lyophilization, freeze casting, gas foaming.
    • Solvent casting, compression molding.
    • 3D printing, electrospinning.
  • Considerations:
    • Cell distribution and penetration.
    • Degradation rate matching tissue growth.
    • Incorporation of growth factors or bioactive cues.

Signals and Growth Factors

  • Definition: Bioactive molecules regulating cellular processes.

  • Types of signals:

    • Soluble factors: Growth factors, hormones, small molecules.
    • Insoluble cues: ECM stiffness, mechanical stimulation, fluid flow.
  • Key growth factors:

    • VEGF, FGF: Promote endothelial cell migration and proliferation.
    • PDGF-BB: Stimulates pericyte adhesion and blood vessel maturation.
    • BMP-2: Induces bone formation.
    • TGF-β: Regulates cell growth and differentiation.
  • Challenges:

    • Short half-life and rapid inactivation.
    • Need for controlled delivery.

Tissue Engineering – a famous example (Mouse and the Ear)

  • The scientists created an ear-like scaffold of porous, biodegradable polyester fabric and then distributed human cartilage cells throughout this form. The entire construct was then implanted onto the back of the nude mouse.
  • Develop Biocompatible Artificial Tissues and Organs.

The Mouse and the Ear

  • Key components of the study:
    • Scaffold – nonwoven poly(glycolic acid) (PGA)/poly(lactic acid) (PLA) mesh, shaped within a plaster mold of an ear.
    • Cells – Calf chondrocytes (cartilage cells) harvested from the articular surfaces of a calf, which were seeded onto scaffold.
    • Signals - In vitro and in vivo maturation: After 12 weeks in the back of athymic mice, cell seeded scaffolds supported extensive cartilage formation.

The Mouse and the Ear

  • Some limitations of this study:
    • Skin coverage is missing. (How might this be addressed clinically?).
    • Immature bovine chondrocytes were used.
    • An athymic or immunodeficient mouse model is used here – need to test in larger animal with functional immune system.
    • Necessity of growth rate of engineered tissue to match that of normal growth rate of a child.
    • Little consideration given to optimizing nutrient transport to cells within centre of scaffold (in vitro or in vivo).

Cellular and Tissue Engineering - Purposes

  • To understand cellular dynamics
  • To control cellular behavior
  • To make cellular networks
  • To develop tissue and organs
  • To enhance biocompatibility of implanted materials

Bioreactor

  • Any manufactured device or system that supports a biologically active environment.
  • Applications of bioreactors in tissue engineering
    • Cell seeding and expansion
    • Vascularization
    • 3D tissue construction
    • Mimicking physiological conditions
    • Scaling up production

Automated Cell Culture System

  • The full apparatus
    supporting the
    development of a cell
    culture

Tissue dynamics

  • Replication: increase in the number of cells
  • Differentiation: change in gene expression to reflect particular functions
  • Death: controlled cell death
  • Motion: control of the motion of the cell in a structure
  • Adhesion: binding of the cell to the environment (other cell, extracellular matrix, artificial surface

Types of tissue and organ transplants

  • Homotransplantation
    • Transplantation from individuals of the same species
  • Xenotransplantation
    • Transplantation from a different species
  • Autotransplantation
    • Transplantation from one’s own body
  • Artificial
    • Mechanoelectric
    • Biomaterial
    • Biological

Skin grafts

  • Simple example of tissue engineering.
  • Skin is made of Dermis and Epidermis -> both can be easily cultured
  • Skin grafts are used for generating new skin from skin of another part of the body

Skin Graft

  • Skin is taken from the body
  • Specific parts are cultured
  • Implants can be made with a collagen substrate
  • New skin is implanted

Example (AUTOLOGOUS CHONDROCYTE IMPLANTATION)

  • Chondrocyte transplantation

Examples

  • Cardiovascular regeneration

Stem Cells

  • Undifferentiated or partially differentiated cells that can:
    • Replicate indefinitely
    • Change into various cell types
  • Embryonic: acquired from fertilized eggs, somatic cell nuclear transfer
  • Adult: acquired from bone marrow, cord blood or specific tissue

Adult vs. Embryonic

  • Adult
    • Restricted in ability to differentiate
    • No issues of rejection
    • Can be easily acquired
  • Embryonic
    • Pluripotent cell, can differentiate into any tissue
    • Ethical concerns

Potential problems

  • Uncontrolled mass proliferation
  • Differentiation -> how to make the cell become the type of cell you need
  • Immune rejection
  • Positioning
  • Functional maintenance after transplantation
  • Development of teratoma
  • Tumor

Xenotransplantation

  • Cells / Scaffolds
  • Compatible organs or tissue is grown on animals for Transplantation in humans

Xenotransplantation - barriers

  • Immunological and Technical Barriers
  • Infectious Barriers
  • Physiological Barriers
  • Social and Ethical Barriers
  • Healthcare Resource-Based Barriers