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Introduction To Tissue Engineering

The document discusses tissue engineering and biomaterials, including an overview of different tissue types, cell sources for engineering tissues, important considerations for scaffold design including mimicking the extracellular matrix, and the overall goal of tissue engineering to develop functional substitutes for damaged tissues. The hierarchy of life from cells to tissues is also presented, as well as some potential labs to collaborate with on biomaterial and tissue engineering projects.

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164 views41 pages

Introduction To Tissue Engineering

The document discusses tissue engineering and biomaterials, including an overview of different tissue types, cell sources for engineering tissues, important considerations for scaffold design including mimicking the extracellular matrix, and the overall goal of tissue engineering to develop functional substitutes for damaged tissues. The hierarchy of life from cells to tissues is also presented, as well as some potential labs to collaborate with on biomaterial and tissue engineering projects.

Uploaded by

K C
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Lecture 13

Introduction to Tissue Engineering


Lab Report Format
 Introduction/Background
 Goal
 Materials and Methods
 Experimental Procedures
 Results
 Discussion
 Conclusion
 References
Shear-thinning nanocomposite hydrogels for the
treatment of hemorrhage
Bradley Olsen Group
Gelatin + silicate nanoplatelets
xNCy (x: total solid wt%; y: total nanoplatelets solid wt% )
wt%: 3, 6 and 9
Hemostasis
 A process that causes bleeding to stop, meaning to keep blood within a damaged blood
vessel. (Hemorrhage is the opposite of hemostasis.)

 The process involves blood changing from a liquid to a gel, normally within 5-6mins.

 Endothelial cells of intact vessels prevent blood clotting with a heparin-like molecule and
thrombomodulin and prevent platelet aggregation.

 Upon injury, endothelial cells stop secreting coagulation and aggregation inhibitors and
instead secrete factors to initiate clotting.

 Three steps: vascular spasm, platelet plug formation, blood clotting


Conclusion
 Nanocomposite hydrogels containing synthetic silicate disks and gelatin form injectable biomaterials that can promote
in vitro and in vivo coagulation.

Critiques
 Rheological characterizations data are not consistent through out the paper

 9NC100 exhibits the best results, why do you need gelatin to begin with?

 How applicable? Authors didn’t comment on the impact of wound size, shape, how much blood and

how quickly bleeds?

 Material novelty? Previous reported Nanoplatelets.


Biomaterials for Tissue Engineering
 Tissue Engineering: applying the principle of biology and engineering to the development of functional
substitutes for damaged tissue. (Langer and Vacanti)
STRUCTURE FUNCTION

CELL MATERIAL

BIOENGINEERING
TOOLS

Langer. R and Vacanti, J. P. Science, 1993, 260, 920.


Cell Biology:  The fundamental function and structure begin at the cell level.  Understanding of
cellular responses will be the key.

Molecular Biology:  Human Genome Project has been completed. Identify the key
genes/signaling pathways involved in tissue repair/regeneration.

Material Sciences:  Characterize the material properties of tissues and design tissue substitutes
that match the material property specs.

Engineering:  Based on the electrical/physical/mechanical properties of natural tissues, design


models to predict the function and integrity of tissue substitutes over time. 

Tissue Engineering:  All of above have to be incorporated and integrated for rationally designed
tissue substitutes.
Tissue Engineering
Tissue

Time

Scaffold
+
Cells
Cover, Chemical & Engineering News, March 13, 1995.
The Hierarchy of Life
 Cells are the building blocks for tissues.
 At each level of organization, novel properties emerge that were not present at the previous level.
The Extracellular Microenvironment
Factors Regulating Cell Phenotype
 Up or down-regulation of specific
pathways
- Integrins
- Growth factor receptors
- Modification of lipids

 Production and secretion of matrix


components, GFs and hormones.
 Never operate individually, always
tightly tied to internal and external
microenvironment of the cell
Final Project/Presentation
Potential Biomaterial Labs:
Kristi Anseth, Jennifer West, Molly Stevens: Biomaterials (PEG hydrogels)
Robert Langer: Biomaterials and Biotechnology
David Tirrell: Polypeptide-based Biomaterials
Hans Clevers, Matthias Lutolf: Organoids
Tony Weiss, Sarah Heilshorn, Ashutosh Chilkoti: Elastin-like polypeptides
David Kaplan: Silk-based Biomaterials
David Mooney, Kara Spiller: Immune-engineering
Jennifer Lewis, Jordan Miller: 3D printing, organ printing
Jason Burdick, Tatiana Segura: HA, microparticle hydrogels
Donald Ingber: Microfluidic device
Andres Garcia: Skeletal Muscle tissue engineering
Steven George, Christopher Chen, Shulamit Levenberg: Vascular tissue engineering
Ivan Martin: Cartilage and bone tissue engineering
Mark Grinstaff, Jeremy Johnson: Polymer materials
Organ Procedures/Yr
(MM)
Skin 4.75
Bone 1.34
Cartilage 1.15
Blood vessel 1.36
Tendon/Ligament 0.123
Pancreas 0.738
Tissue Across Length Scales
Why a Bioengineering Tissue?
If one can improve upon:
 A device
 A drug
 A minimally-manipulated cell (FDA)
 Surgical reconstruction
 A transplant (whole donor)
Engineered tissues = biomaterials + cells
- Biomaterials that recruit cells (acellular)
- Biomaterials that house cells (hybrid)
- Biomaterials-free structures
(hybrid w/cell-derived ECM)
Designing bioengineered tissues

Pick a function Select ingredients

Organ Function
Skin Barrier
 Cells  Fabrication
Kidney Secretory - somatic (adult cells) - assembly
Pancreas Insulin Production
- stem cells (morphogenesis)
Cartilage Compression
Tendon/Ligament Tensile mechanical - organoids - bioprocessing
Bladder Compliance  Biomaterials - preservation

 Nutrients
Cells
 Cells are the major players, but they need guidance.

 Isolated cells from tissue can perform regular function (memory effect) if similar tissue
environment is provided in vitro.

 Cell functions can be easily altered by its environment.

 Need sufficient quantity, maintains desired phenotype free of pathogen and


contamination.

 Understand normal development in morphogenesis and wound healing

 For commercial applications, cell bank is desired.


Culturing Cells
 Confluent, passaging
Hayflick Limit 1965

 Telomeres, molecular clock!


 Senescence: loss of a cell’s
power of division and growth
 Stem cells, immortal!
Cell Source
 Autologous (differentiated cells): patient’s own cells, immune acceptable, not readily available.
 Allogeneic (differentiated cells): from other human sources; need to overcome immune problem; could be
made off-the-shelf
 Xenogeneic: from different species, require immune acceptance, possible animal virus transmission, readily
available
 Adult stem cells/progenitor cells: if recruited from the host to an acellular substitute or delivery vehicle, can
provide for an immune acceptable, off-the-shelf product or strategy
 Embryonic stem cells: capable of developing into any cell type; requires destruction or manipulation of
embryo, ethical controversy; ESCs derived from embryos, not feasible to create patient-matched embryonic
stem cell lines.
 iPSCs (induced pluripotent stem cells, four specific transcription factors: Myc, Oct3/4, Sox2 and Klf4;
pioneered Shinya Yamanaka, Nobel Prize 2012) derived directly from adult tissues, bypass the need for
embryos, patient-specific, unlimited supplies of autologous cells and can transplants without the risk of immune
rejection, not mature technology yet.
 Stimulus-triggered acquisition of pluripotency (STAP) cells that could grow into tissues for use anywhere in the body.
Materials Design (matrix or scaffold)
 Scaffolds are temporary 3D ECM, provide opportunity for cells to synthesize and secret their
own matrix, end goal is to replicate the native tissue ECM.
 Traditional scaffolds: hydrolytically degradable 3D micro-porous, passive mechanical support.
 New scaffold: interacts with encapsulated cells, responsive, bioactive, capable of presenting
biological cues in a spatially and temporally controlled fashion.
 Scaffolds play an instructive role for cell behavior and tissue development
 Tissue engineering is a remodeling problem
 Cell microenvironment:
- matrix composition, microstructure/architecture, biocompatibility
- mechanical properties, dynamics
- biochemical environment
 Scaffold degradation should mirror the native ECM production
Tissues
 A group of cells and surrounding extracellular matrix that function together to
perform one or many specialized activities is called a tissue.
 About 200 different cells in the body, cell morphology versus functions.
 Four primary types of tissues based on function:
- Epithelial (only cells)

- Connective (cells and matrix)

- Nervous (neurons unique cell morphology)

- Muscle (3 types)
Epithelial Tissues
 Lining the structure of outer or inner surfaces of many
organs, e.g. raspatory tract, digestive system.

 Tightly packed cells with very little cell space; apical


and basal layer.

 Line outer or inner surfaces of body or organs

 Functions include:
- Absorption (lining of the small intestine, gas, nutrient exchange)

- Secretion (glands)

- Transport (kidney tubules)

- Protection (skin)

- Sensory receptors (taste buds)


Intestine lining, SEM
Classification of Epithelial Tissues: Shape and Layer
Simple: one cell layer Stratified: multiple cell layers

https://www.youtube.com/watch?v=0NEV-Rd7OgA
 Characteristics:
- Turnover every 7 days
- Cell-cell tight junctions and desmosomes
- Apical and basal surfaces, polarity
- Microvilli or cilia on apical surface, adsorption
- Avascular but innervated
- Regenerative
Protection from
abrasion

Diffusion
Absorption
Secretion
Simple cuboidal epithelium

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