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