Tissue Engineering
What is Tissue Engineering?
“Tissue Engineering is an interdisciplinary field that applies
principles of engineering and life sciences towards the
development of biological substitutes that aim to maintain,
restore, or improve tissue function.”
Types of Tissue engineering
In Vivo
Manipulating cells while inside the body
In Vitro
Manipulating cells prior to implantation
Components of Tissue Engineering
Cells
Matrix or Scaffold
Bioreactor
Cytokines and Growth Factors
Cells
Cells are taken from the healthy tissue of what tissue is being
created.
Skin cells for skin, bladder cells for bladder, etc.
Cells taken from donor or patient themselves
Autologous-donor and patient are the same
Allogenic-cells from another person
Xenogenic-cells from another species
Separated and screened for pathogens and disease
Placed onto scaffolds
Scaffolding
Act as Extra Cellular Matrix for cells
Function: Delivery of cells to desired sites, define space for
formation, guide development with appropriate function
Needs to be able to control the structure and function of tissue
in a predesigned manner.
Ideally they are biocompatible and biodegradable, without
provoking inflammation or toxicity in the body.
Key Functions of Scaffolds in Tissue Engineering
1. Cell Attachment & Growth – Provides a surface for cells
to adhere, spread, and proliferate.
2. Structural Support – Maintains the shape and mechanical
integrity of developing tissues.
3. Nutrient and Waste Exchange – Facilitates diffusion of
oxygen, nutrients, and waste.
4. Biodegradability – Gradually degrades at a rate matching
tissue formation.
5. Bioactivity – Can be functionalized with growth factors or
bioactive molecules to promote cell signaling and
differentiation.
Types of Scaffolding
Naturally derived
Collagen and alginate
Collagen is the most abundant and ubiquitous structural protein in
the body.
Biologically recognized
Minimal inflammatory and antigenic responses
Alginate is from sea weed
Fibronectin
Encourages cell adhesion and growth
Types of Scaffolding
Accelular Tissue Matrices
Collagen rich
Formed from a segment of bladder or small intestine
Proven to support cell growth and regeneration for several
tissues.
Polyesters
Naturally eliminated from body in form of C02 and H20
Degradation rates in body can be manipulated
Lack biological recognition
Materials for Scaffold Fabrication
Natural Polymers (Biocompatible, bioactive, but may have
mechanical limitations)
• Collagen – Mimics native ECM, supports cell adhesion.
• Alginate – Hydrophilic, useful in cartilage and wound healing.
• Chitosan – Antibacterial, enhances wound healing.
• Fibrin – Used in blood vessel and skin regeneration.
Synthetic Polymers (Tunable properties, but may lack
bioactivity)
• Polylactic acid (PLA)
• Polyglycolic acid (PGA)
• Polycaprolactone (PCL)
• Polyethylene glycol (PEG)
Ceramic-Based Materials (Used for bone tissue
engineering)
• Hydroxyapatite (HA)
• Beta-tricalcium phosphate (β-TCP)
Scaffolding
Bioreactors
System where conditions are closely controlled to permit and induce
a certain behavior in living cells or tissues
Provide controlled and steady flow of cell media
Bioreactor technologies intended for tissue engineering can be used
to grow functional cells and tissues for transplantation, and for
controlled in vitro studies on the regulation effect of biochemical and
biomechanical factors on cell and tissue development.
Factors necessary for cell growth:
pH, temp. pressure, nutrient supply, waste removal
Types of Bioreactors
Spinner Flasks, Rotating Vessels, Hollow Fiber, Perfusion reactors
Types of Bioreactors in Tissue Engineering
1.Spinner Flask Bioreactors
1. Simple system with rotating scaffolds in a nutrient-rich medium.
2. Used for cartilage, bone, and cardiovascular tissue
engineering.
3. Improves oxygenation but can lead to non-uniform cell distribution.
2. Rotating Wall Vessel (RWV) Bioreactors
1. Creates a low-shear, microgravity-like environment.
2. Enhances 3D tissue growth and cell-cell interactions.
3. Useful for cardiac, liver, and bone tissue engineering.
3. Perfusion Bioreactors
1. Pumps culture medium through the scaffold for uniform nutrient
and oxygen delivery.
2. Enhances vascularization in engineered tissues.
3. Used for bone, cartilage, and cardiac tissues.
4. Compression/Mechanical Stimulation Bioreactors
1. Provides cyclic compression, tensile, or shear forces to mimic
in vivo mechanical stresses.
2. Essential for muscle, tendon, and cartilage tissue engineering.
Objectives of Bioreactor
The primary objectives of these systems are
To establish spatially uniform cell distributions
on three dimensional scaffolds
To maintain desired concentrations of gases and
nutrients in the culture medium
To expose developing tissue to appropriate
physical stimuli.
Why Bioreactor is needed?
The bioreactor needs
To provide the appropriate physical stimulation to cells.
To continuous supply of nutrients (e.g. glucose, amino
acids), biochemical factors and oxygen.
To diffusion of chemical species to the construct interior,
as well as continuous removal of by-products of cellular
metabolism (e.g. lactic acid).
To monitor of tissue growth in functional tissue
engineering.
Moreover, a bioreactor has to be able to operate over
long periods of time under aseptic conditions since
maturation of a functional tissue may take up to 3-4
months.
Growth Factors
There are numerous growth factors for each tissue that can be
engineered
Found naturally in body and help facilitate wound healing and
cellular growth
Cytokines are widely used for multiple tissue types
Strings of amino acids that when attached to ECM initiate rapid
multiplication of cells
Others include Epidermal Growth Factor (EGF), Fibroblast Growth
Factor (FGF) and Platelet-Derived Growth Factor (PDGF)
All have many forms
Key Growth Factors & Their Roles
1. Angiogenesis & Vascularization
These growth factors promote blood vessel formation, crucial for thick tissue
constructs.
•Vascular Endothelial Growth Factor (VEGF) – Stimulates endothelial cell
proliferation and capillary formation.
•Basic Fibroblast Growth Factor (bFGF) – Induces angiogenesis and
supports fibroblast and mesenchymal cell growth.
•Platelet-Derived Growth Factor (PDGF) – Encourages pericyte recruitment
and stabilizes new blood vessels.
2. Bone & Cartilage Regeneration
Critical for bone tissue engineering and skeletal repair.
•Bone Morphogenetic Proteins (BMPs, e.g., BMP-2, BMP-7) – Induce
osteoblast differentiation and bone formation.
•Transforming Growth Factor-beta (TGF-β1, TGF-β3) – Regulates
chondrocyte proliferation and cartilage repair.
•Insulin-like Growth Factor-1 (IGF-1) – Stimulates cartilage and bone matrix
production.
3. Muscle & Tendon Regeneration
Support myogenesis and musculoskeletal tissue repair.
•IGF-1 – Promotes muscle regeneration by stimulating myoblast proliferation.
•TGF-β – Involved in tendon and ligament healing but can lead to fibrosis if
overexpressed.
•Myostatin Inhibitors – Enhance muscle growth by blocking myostatin, a
negative regulator of muscle mass.
4. Skin & Wound Healing
Essential for epithelialization, collagen synthesis, and tissue remodeling.
•Epidermal Growth Factor (EGF) – Stimulates keratinocyte proliferation and
wound healing.
•Fibroblast Growth Factor (FGF-2, FGF-10) – Promotes fibroblast
proliferation and ECM deposition.
•Keratinocyte Growth Factor (KGF, FGF-7) – Enhances keratinocyte
migration and stratification.
5. Neural Tissue Regeneration
Supports nerve regeneration and neuroprotection.
•Nerve Growth Factor (NGF) – Promotes neuronal survival and axon
outgrowth.
•Brain-Derived Neurotrophic Factor (BDNF) – Supports synaptic plasticity
and neural repair.
•Glial Cell-Derived Neurotrophic Factor (GDNF) – Enhances survival of
dopaminergic neurons, useful for Parkinson’s therapy.
Delivery Strategies for Growth Factors
To ensure efficient, localized, and sustained release, different
delivery approaches are used:
1. Scaffold-Embedded Delivery – Growth factors are incorporated
into biodegradable scaffolds (e.g., hydrogels, nanoparticles).
2. Gene Therapy-Based Delivery – Uses viral or non-viral vectors
to encode and express growth factors at the injury site.
3. Microparticle/Nanoparticle Encapsulation – Provides
controlled, slow-release for long-term tissue regeneration.
4. Platelet-Rich Plasma (PRP) – A natural source of multiple growth
factors for wound healing and bone regeneration.
