This document provides an overview of the principles of tissue engineering. It defines tissue engineering and regenerative medicine, and traces the history from early experiments in the 1970s to the development of organizational structures like TERMIS in the 2000s. The key components of tissue engineering are described as cells, scaffolds, and the cellular environment. The document discusses sources of cells including adult stem cells and challenges in obtaining and expanding cells for tissue engineering applications.
TISSUE DEVELOPMENT WITH TISSUE ENGINEERING APPROACHFelix Obi
Tissue Engineering is the development and practice of combining scaffolds, cells, and suitable biochemical factors (regulatory factors or Signals) into functional tissues. The goal of tissue engineering is to assemble functional constructs that restore, maintain, or improve damaged tissues or whole organs.
Cells are the building blocks of tissue, and tissues are the basic unit of function in the body. Generally, groups of cells make and secrete their own support structures, called extracellular matrix. This matrix, or scaffold, does more than just support the cells; it also acts as a relay station for various signaling molecules. Thus, cells receive messages from many sources that become available from the local environment. Each signal can start a chain of responses that determine what happens to the cell. By understanding how individual cells respond to signals, interact with their environment, and organize into tissues and organisms, Tissue Engineers are now able to manipulate these processes to amend damaged tissues or even create new ones.
Bioreactors are devices in which biological or biochemical processes develop under a closely monitored and tightly controlled environment. Bioreactors have been used in animal cell culture since the 1980s in order to produce vaccines and other drugs and to culture large cell populations. Bioreactors for use in tissue engineering have progressed from such devices.
A tissue engineering bioreactor can be defined as a device that uses mechanical means to influence biological processes. In tissue engineering, this generally means that bioreactors are used to stimulate cells and encourage them to produce extracellular matrix (ECM). There are numerous types of bioreactor which can be classified by the means they use to stimulate cells.
Tissue engineering and regenerative medicine Suman Nandy
Tissue engineering is the use of a combination of cells, engineering and materials methods, and suitable biochemical and physicochemical factors to improve or replace biological tissues. Tissue engineering involves the use of a scaffold for the formation of new viable tissue for a medical purpose.
Introduction
Artificial skin
Invention
Structure of human skin
Importance of skin
Key development
Biomaterials
Methods to produce artificial skin
Application
Problems
Future development
Conclusions
references
Biomaterials for tissue engineering slideshareBukar Abdullahi
An overview of Tissue Engineering with some basics in Biomaterials and Synthetic Polymers. Further references should be considered as I presented this a specific target audience.
Introduction
Definition
History
Principle
Cell sources
What cells can be used?
Scaffolds
Biomaterials
Bioreactor
How tissue engineering is done?
How does tissue engineering differ from cloning?
Tissue engineering of specific structures
Application of tissue engineering
Limitations
Conclusion
References
A presentation on Tissue Engineering made by Deepak Rajput. It was presented as a seminar requirement at the University of Tennessee Space Institute in Spring 2009.
Biomaterials were defined as “any substance, other than a drug, or a combination of substances, synthetic or natural in origin, which can be used for any period of time, as a whole or as a part of a system, which treats, augments or replaces any tissue, organ or function of the body”
TISSUE DEVELOPMENT WITH TISSUE ENGINEERING APPROACHFelix Obi
Tissue Engineering is the development and practice of combining scaffolds, cells, and suitable biochemical factors (regulatory factors or Signals) into functional tissues. The goal of tissue engineering is to assemble functional constructs that restore, maintain, or improve damaged tissues or whole organs.
Cells are the building blocks of tissue, and tissues are the basic unit of function in the body. Generally, groups of cells make and secrete their own support structures, called extracellular matrix. This matrix, or scaffold, does more than just support the cells; it also acts as a relay station for various signaling molecules. Thus, cells receive messages from many sources that become available from the local environment. Each signal can start a chain of responses that determine what happens to the cell. By understanding how individual cells respond to signals, interact with their environment, and organize into tissues and organisms, Tissue Engineers are now able to manipulate these processes to amend damaged tissues or even create new ones.
Bioreactors are devices in which biological or biochemical processes develop under a closely monitored and tightly controlled environment. Bioreactors have been used in animal cell culture since the 1980s in order to produce vaccines and other drugs and to culture large cell populations. Bioreactors for use in tissue engineering have progressed from such devices.
A tissue engineering bioreactor can be defined as a device that uses mechanical means to influence biological processes. In tissue engineering, this generally means that bioreactors are used to stimulate cells and encourage them to produce extracellular matrix (ECM). There are numerous types of bioreactor which can be classified by the means they use to stimulate cells.
Tissue engineering and regenerative medicine Suman Nandy
Tissue engineering is the use of a combination of cells, engineering and materials methods, and suitable biochemical and physicochemical factors to improve or replace biological tissues. Tissue engineering involves the use of a scaffold for the formation of new viable tissue for a medical purpose.
Introduction
Artificial skin
Invention
Structure of human skin
Importance of skin
Key development
Biomaterials
Methods to produce artificial skin
Application
Problems
Future development
Conclusions
references
Biomaterials for tissue engineering slideshareBukar Abdullahi
An overview of Tissue Engineering with some basics in Biomaterials and Synthetic Polymers. Further references should be considered as I presented this a specific target audience.
Introduction
Definition
History
Principle
Cell sources
What cells can be used?
Scaffolds
Biomaterials
Bioreactor
How tissue engineering is done?
How does tissue engineering differ from cloning?
Tissue engineering of specific structures
Application of tissue engineering
Limitations
Conclusion
References
A presentation on Tissue Engineering made by Deepak Rajput. It was presented as a seminar requirement at the University of Tennessee Space Institute in Spring 2009.
Biomaterials were defined as “any substance, other than a drug, or a combination of substances, synthetic or natural in origin, which can be used for any period of time, as a whole or as a part of a system, which treats, augments or replaces any tissue, organ or function of the body”
A Brief History of Regenerative MedicineJohn Makohen
In the presentation ISREGEN outlines the history of regenerative medicine fro it's earliest days when Robert Briggs and Thomas King began cloning frogs to the present medicinal advancements in stem cell research and repair.
ARTIFICIAL ORGANS.
We discussed a Brief History and Introduction of Artificial Organs.
We also discussed the Various Manufacturing Process and Application of Artificial Organs and finally we discussed the Pros and Cons of Artificial Organs.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
2. OBJECTIVES
Definition
History
Goals of TE
Components of TE – Cells/Environment/Scaffolds
Application and use of TE
Strategies to engineer tissue
Tissues of significance in plastic surgery
Future of TE
Conclusion
References
3. Definition
The term “tissue engineering” as it is nowadays used was
introduced in1987.
“Tissue Engineering is the application of the principles and
methods of engineering and life sciences toward the fundamental
understanding of structure-function relationships in normal and
pathologic mammalian tissue and the development of biological
substitutes to restore, maintain, or improve function.”
4. Definition
Regenerative Medicine - "process of replacing, engineering or
regenerating human or animal cells, tissues or organs to restore or
establish normal function".
This field holds the promise of engineering damaged tissues and
organs by stimulating the body's own repair mechanisms to
functionally heal previously irreparable tissues or organs
6. History
Oldest written description - Genesis I:1:
“The Lord, breathed a deep sleep on the man and while he was asleep he
took out one of his ribs and closed up its place with flesh. The Lord God
then built up into a woman the rib that he had taken from the man.”
Tale of Eve created from Adam’s rib
8. History – The Early Years
Early 1970s - Dr. W.T. Green, a surgeon at Children’s Hospital Boston.
Experiments to generate new cartilage using chondrocytes seeded
onto spicules of bone and implanted in nude mice
Unsuccessful
Conclusion - possible to generate new tissue by seeding viable cells
onto scaffolds
1981 - Drs. John Burke and Iannas Yannos,
Tissue-engineered skin substitute using a collagen matrix to
support the growth of dermal fibroblasts.
Patents (U.S. Pat. 4,418,691 (December 6, 1983)) granted to MIT
IntegraTM by Integra LifeSciences Corp
9.
10. History – The Early Years
1983 - 1984 - Dr. Howard Green & Dr. Olaniyi Kehinde –Test tube skin;
Sheets of cultured keratinocytes transferred onto burn patients.
Formed a company - BioSurface Technology, later taken over by
the Genzyme Corporation – Epicel® (cultured epidermal autografts)
Dr. Eugene Bell seeded collagen gels with fibroblasts, referring to
them as contracted collagen gels.
11. History – The Early Years
Natural occurring scaffolds have physical and chemical properties that
cant be manipulated thus unpredictable outcomes.
Around 1985 - Dr. Joseph Vacanti, Dr. Robert Langer
Tasked to design appropriate scaffoldings for cell delivery
Extensive studies to generate functional tissue equivalents using a
branching network of synthetic biocompatible/biodegradable
polymers configured as scaffolds seeded with viable cells.
12. History – The Early Years
1991, a young patient with Poland’s syndrome
first human to receive a tissue-engineered implant
composed of a synthetic polymer scaffold implant
seeded with autologous chondrocytes,
Surgeons - Drs. J. Upton and J. and C. Vacanti.
Interpore's Pro-Osteon coral-derived bone graft material was
introduced in 1993
1996, Integra's Artificial Skin was approved for as an in vivo,
nonbiological tissue regeneration product
13. History – The Early Years
1998 - General and Plastic surgery approval of ‘Apligraf’, human skin
equivalent for the treatment of venous leg ulcers.
14. History – The Early Years
Tissue engineering efforts had high degree of success especially in Boston
Centers sprang up in various institutions in the United States and Europe.
Outside of Boston;
>Pittsburgh Tissue Engineering Initiative (PTEI) (early 1990s) organized by Peter
Johnson,
>The cardiovascular tissue engineering effort under the direction of Dr. Robert
Nerem at Georgia Tec
>laboratories overseen by Drs. Antonios Mikos and Larry McIntire at Rice University
in Houston,
>and an effort established at UMass Medical School by Dr. Charles A. Vacanti
15. History – The Early Years
London - Dr. Julia Polak, a pathologist and stem cell biologist in London
Spearheaded tissue engineering at the Imperial College
Organized a British-based society associated to TESI
Germany
Dr. Una Chen ,Giessen Germany (1990s); Studies in tissue engineering and
stem cell research
Dr. R. Hetzer, a cardiovascular surgeon at the University of Berlin, , and Dr.
Christof Brelsch, a liver transplant surgeon in Hamburg, established
collaborations with the Children’s Hospital in Boston
Japan
Collaboration - Boston-based labs and Kyoto University labs, headed by Dr.
Koichi Tanaka, resulting in the formation of tissue-engineering laboratories in
Kyoto
16. History – The Early Years
New Haven, Connecticut
Drs. Chris Brewer and Mark Saltzman established the Tissue
Engineering Institute at Yale University
In Asia
Dr. Minora Ueda, at the University of Nagoya, established a tissue-
engineering effort in Japan and organized the 1st meeting of the
Japanese Tissue Engineering Society (1997) in Nagoya.
China, Shanghai
The first Chinese tissue engineering effort sponsored by the
Chinese government was founded by Dr. Yi Lin Cao in Shanghai.
17. History – The Early Years
Mexico
Dr. Clemente Ibarra - National Institute for Rehabilitative Medicine in Mexico City; founded the Mexican Tissue
Engineering Society.
Toronto, University of Washington
Dr. Steven Kim/ Dr. Buddy Rattner in Seattle, at the University of Washington
Michael Sefton in Toronto
Austria, Germany, Switzerland, France
Dr. Wolfgang Pulacher opened a lab in Innsbruck.
Organization of a tri-state effort in Germany, Switzerland, and Southern France, spearheaded by Drs. R.E. Horch and
G.B. Stark at the University at Freiburg.
By mid-1990s, efforts in almost every developed country in the world
and several privately funded ventures
18. History: Development of an organizational structure
1994, the Tissue Engineering Society (TES), founded by Drs. Charles A.
and Joseph P. Vacanti in Boston.
1997, the Japanese Tissue Engineering Society, established by Dr
Minoru Ueda
The Chinese Tissue Engineering Society and Shanghai-based Tissue
Engineering Center by Dr. Yi Lin Cao.
Aligned to form the Asian branch of the international Tissue
Engineering Society, now referred to as TESi.
19. History: Development of an organizational structure
Drs. Stark and Horch of Freiberg, Germany, encouraged the formation
of a European Tissue Engineering Society (ETES).
2004
merging of the former continental branches of the former TESi.
TESi renamed TERMIS, the Tissue Engineering Regenerative Medicine
International Society
20. The Journal
The journal Tissue Engineering
Founded in 1994
By > Drs. Charles A. Vacanti, Massachusetts General Hospital and
Harvard Medical School
> Dr. Antonios Mikos of Rice University.
21.
22. Tissue Engineering and the public arena
1997 - Vacanti Mouse/ Auriculosus - “mouse with the human
ear,”
Potential of tissue-engineered cartilage
COURTESY OF THE LABORATORY FOR TISSUE ENGINEERING AND ORGAN FABRICATION, MASSACHUSETTS
GENERAL HOSPITAL, BOSTON, MA, USA, DR. JOSEPH P. VACANTI, DIRECTOR.
23. Examples from nature
The liver has been known to self-regenerate
A salamander regrows its legs
The fetus repairs wounds with minimal scarring
Humans have the capacity to gain and lose adiposity rapidly
Ruptured tendons can regenerate across gaps when their ends are
retained within their synovial sheath where their matrix and cellular
environment are maintained and axial mechanical force signals are
transduced into biochemical stimulation.
24. The goal
To assemble functional constructs that restore, maintain, or
improve damaged tissues or whole organs.
Growth of cell in three dimensional systems
Delivery systems for protein therapeutics
Cell cultivation methods for culturing recalcitrant cells
Transgenic protein expression in transplantable cells
Vehicles for delivering transplantable cells
Avoiding immunogenicity in transplantation systems
Development of markers for tracking transplanted cell
Developing in vivo and ex vivo biosensors for monitoring cell
behaviour during tissue production.
25. Tissue engineering
Tissues can be viewed as a composite of:
(1) cells (both parenchymal and stromal)
(2) matrix and
(3) blood vessels.
Cell maintenance and behavior including growth and regeneration are
influenced by biochemical and biomechanical interplay.
The development of a functional tissue must be vascularized to
ensure survival of the neotissue.
Each of these components is the purview of the tissue engineer.
27. Cell sources for tissue engineering
Cells used for TE,
Autologous - preferred due to the lack of immunogenicity
Heterologous,
Xenogeneic and each type may be
mature differentiated
precursor stem cell form.
28. Cell sources for tissue engineering
Chondrocytes for cartilage
Osteocytes for bone
Schwann cells for nerves
Fibroblasts for ligament and tendon engineering
All these have significant proliferative potential in vitro
Adult cardiomyocytes, hepatocytes, and adipocytes
Challenge - difficult to culture and expand in vitro
29.
30. Cell sources for tissue engineering
A second challenge
Collection of cells – biopsy; uncomfortable and impossible due to
diseased state of the tissue
Solution
Utilize stem cells; expanded and differentiated ex vivo.
Multiple types of stem cells exist
E.g. embryonic, adult, and induced pluripotent stem cells.
Discuss embryonic stem cells
Focus on stem cell types most relevant to the plastic surgeon; sources
of cells, advantages and disadvantages, use in TE
32. Embryonic stem (ES) cells
Totipotent
Infinitely proliferative
Differentiate into all tissue types
Are also unstable and form teratomas
Ethical and legal concerns - sourcing and utilization
Successful differentiation protocols have been found to induce ES cells along
specific lineage pathways from all germ layers towards many specific tissues and
organs.
These cells are probably immunogenic and ethical issues will persist.
Regulatory and organizational issues
33. Adult stem cells
Multipotent
Limited in their proliferation capacity and differentiation potential.
Collected and expanded from tissue biopsies through a process
referred to as the colony forming unit (CFU) assay
Adult stem cells in bone marrow:
Hematopoietic stem cells (HSCs), which differentiated into the white
blood cell population and
Mesenchymal stem cells (MSCs),
Progenitors of bone, cartilage, fat, and muscle.
Endothelial progenitor cells (EPCs) have been isolated and cultured from
adult peripheral blood.
34. Adult stem cells
MSCs and EPCs also present in fat tissue associated with the
microvasculature
Known as adipose-derived stem cells (ASCs).
Relevant stem cells in Plastics
Mesenchymal stem cell
Adipose-derived stem cell
Endothelial progenitor cell.
35. Mesenchymal stem cells
Do not express MHC class II markers
Showed to be immune-privileged and may be used as allografts.
36. Mesenchymal stem cells
Paracrine-growth factor hormonal- cytokine immune-modulatory
effects probably account for the benefits seen with these stem cells.
E.g., Ischemia increases homing of these cells to the injured site
MSCs release high levels of vascular endothelial growth factor (VEGF)
This modulates the repair of capillaries.
MSCs injected intravenously in cardiac infarct models do not implant in
the heart nor become heart tissue
Lodge in the lung
Activated to secrete the anti-inflammatory protein TSG-6
Probably the anti-inflammatory factor that induces the beneficial effects.
37. Adipose-derived stem cells
Abundant
Ease of harvest by liposuction
Preferred autologous stem cell source
Similar properties to bone marrow-derived stem cells
More easily cultured
Grows more rapidly
Cultured for longer periods than bone marrow stem cells before
senescence
Richer source of stem cells
One gram of adipose tissue can yield 5000 stem cells
ASC population may also have low immunogenicity
38. Endothelial progenitor cells
Incorporation of a functional vasculature network in the neotissue is important
Endothelial progenitor cell (EPC) most promising
First identified in 1997 by Asahara et al.,
Present in adult circulation
Isolated and expanded from peripheral blood collected through simple
venipuncture.
Two distinct EPC populations that participate in vascular repair and angiogenesis
via different mechanisms.
Circulating angiogenic cells (or colony forming unit–Hill cells) – support via paracrine
signalling
Endothelial colony forming cells (ECFCs) – regenerate an endothelial population
39. Challenges associated with adult stem cells
Advantages
An autologous and/or non-immunogenic source of cells.
Limitations
Patient-to-patient variations in their prevalence, proliferative
capacity, and differentiation potential
Additionally, their utility is also a factor of age and disease
state of the donor
Exit the cell proliferation cycle (prematurely senesce) or
prematurely lose differentiation potential during ex vivo
expansion
Schipper B, Marra K, Zhang W, et al. Regional anatomic and age effects on cell function of human adipose-derived stem cells. Ann Plast
Surg. 2008;60:538–544
40. Induced pluripotent stem cells (iPS)
Unlimited proliferation capacity
Ability to differentiate into cells from all germ layers both in vitro/vivo
Major problem - Requires genetic manipulation of the cells
Two of the genes used in this process (c-Myc and KLF4) are oncogenes
Zhou et al. (2009) delivered the 4 proteins that the above-mentioned
genes code for directly into the cell
Protein-induced pluripotent stem cells (piPSCs)
Bypasses the need for viral or plasmid transfection and reduces the risks of
cancer formation.
Drawback - efficiency of the protein induction is very low
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell (2006) 126(4):663–76.
doi:10.1016/j.cell.2006.07.024
41.
42. Induced pluripotent stem cells (iPS)
Challenge
Not immune privileged requiring collection, induction, expansion, and
differentiation of autologous cells.
Costly and time-consuming
Solution
Create a bank of iPS cells that can be HLA matched to the patient
43. Cellular interactions with their environment
Many cell types are exquisitely sensitive to stimuli present in the
environment.
Stimuli include;
Soluble molecules
Molecular recognition sites present in the solid phase (ECM or
biomaterial)
Interactions with other cells
Substrate stiffness and the micro/nanostructure of the
surroundings
44. Soluble signals
Soluble biomolecules eg Metalloproteins
Growth factors
Chemokines
Play vital roles locally and systemically in repair and tissue
development.
Understand the appropriate soluble signaling molecules
to maintain cell viability both during culture and in vivo,
to maintain cellular phenotype,
to drive lineage specific differentiation of stem cells
45. Matrix signals
Cells also possess receptors such as integrins and syndecans that bind
to a variety of ligands present in the extracellular matrix (ECM)
Many cell types are adhesion dependent
Also the number and strength of bonds with the external matrix
affects a wide variety of cellular behaviors ranging from adhesion,
focal adhesion formation and migration to morphology.
Additionally, the ECM binds and sequesters growth factors that also
drive cellular function.
46. Intercellular signals
Cells also interact with neighboring cells in both native tissue and in ex vivo culture
Two main methods: >Direct contact via receptors such as cadherins
>Soluble signaling through paracrine factors
In traditional cell culture, single populations of cells are grown in isolation,
implanted and rely on recruitment of supporting cellular structures and matrix to
evolve into a stable, functional tissue
However, co-culturing cells with other types prior to implantation can facilitate
their survival and function. E.g.
Endothelial cells for vasculature
MSCs for paracrine effects or for their ability to incorporate into developing
tissues in vivo like blood vessels
Beating cardiomyocytes with ASCs in vitro to differentiate into cardiac lineage
47. Mechanics and structure of the environment
Cells respond to the mechanical properties and dimensionality of
their environment.
Response of cells to environmental stiffness and dimensionality is a
tool that can be used to direct cell function.
E.g. chondrocytes change morphology and lose their chondrogenic capacity in
2D monolayer culture but can maintain these features in 3D culture
Uses;
Distraction osteogenesis
Periods of stretch promote proliferation and migration
Relaxation incites cells to cluster together and terminally differentiate
into bone
48. Mechanics and structure of the environment
3D cultures on biomaterial supports such as
Porous scaffolds
Hydrogels
Microspheres
Under conditions designed for the desired cell attachment, migration,
proliferation, and differentiation
Development of new biomaterials with tailored properties
Direct the fabrication of these materials into three-dimensional
scaffolds to maximize the healing process
49. Biomaterials used in tissue engineering
Components of solid tissues
Cells
Extracellular matrix - structure and biochemical signals to the cells
When cells are expanded outside the body, they grow in monolayers,
not the intricate patterns of a fully realized 3D tissue
Thus, cells are seeded onto a 3D scaffold
Biomaterial scaffolds can be thought of as artificial ECMs
50.
51. Biomaterials used in tissue engineering
Early tissue engineering used known materials.
Polymers used in degradable sutures
Natural materials such as coral, alginate and collagen.
Recently, numerous alternatives have been formulated
Biomaterials for TE
Naturally occurring in the body
From other natural or synthetic sources
Ceramics
Polymers
Hydrogels
Composites of these
Decellularized tissues
52. Biomaterials used in tissue engineering
The physical form of biomaterials can also vary to suit the application
Solid materials
Porous scaffolds
Microspheres
Hydrogels
Injectable materials that may cross-link in situ etc.
Simplicity - facilitate regulatory approval and translation into clinical
application
Selection depends on the specific requirements of the tissue being
targeted
53. Biodegradable materials
Most are biodegradable, to be replaced by neotissue
Rate of degradation and loss of integrity will depend on;
Type of biomaterial
Site of implantation
Properties of the biomaterial construct such as surface area to
volume ratio, size, and surface chemistry
Challenges - Prevention of sudden loss of physical integrity
- Rapid degradation - excessive concentrations of the
degradation products and can cause adverse tissue
reactions.
54. Natural biomaterials
Chemically similar or identical to molecules in the body
Readily degraded in vivo
Interact with cells on a molecular level
Difficult to obtain and purify
Vary in properties between batches
Difficult to sterilize
Alter their properties during storage,
Elicit significant immunogenic responses.
55. Natural biomaterials
Examples;
Proteins (e.g., collagen, gelatin, silk)
Polysaccharides (e.g., chitosan, hyaluronic acid)
Polynucleotides
Extracts of ECM components
Increased interest - Decellularized extracellular matrix (dECM)
In decellularization, cells are removed from allografts or xenografts to
reduce immunogenicity but much of the complex composition and
architecture of the ECM may be retained
56. Decellularization is the process used in biomedical engineering to isolate the extracellular
matrix (ECM) of a tissue from its inhabiting cells, leaving an ECM scaffold of the original tissue.
57. Polymeric biomaterials
1. Hydrophobic polymers
Biodegradable polymers that could be used in TE
The polyesters
poly(glycolic acid) (PGA)
poly(lactic acid) (PLA)
poly(ε-caprolactone) (PCL)
and their copolymers such as poly(lactide-co-glycolide) (PLGA)
Mechanical strength & degradation rate – altered by changing the
polymer properties (molecular weight, composition, molecular
architecture, crystallinity, hydrophobicity)
58. Polymeric biomaterials
2. Hydrogels
Water-swollen cross-linked polymer networks which can absorb up to
thousands of times their dry weight of water.
Advantage of being more like most natural tissues and allowing mass
transport to and from cells.
Naturally derived
Collagen
Gelatin
Hyaluronic acid
Alginate
Synthetic
Poly(ethylene glycol) (PEG)-based polymers
59. Ceramic biomaterials
Ceramic biomaterials are primarily utilized in tissue engineering of
hard tissues.
Calcium phosphates, such as hydroxyapatite, and bioactive glasses
have been developed as bioceramics for bone tissue engineering.
Characteristics
Bioceramics are brittle but have high compressive strength, can bond
strongly to bone, and can be osteoinductive.
60. Advanced biomaterials for tissue engineering
1. Tailored delivery systems
Growth factors, anti-inflammatory peptides, and drugs may be
incorporated into biomaterial delivery vehicles for release at the
desired time during tissue development.
Release systems are designed to deliver multiple molecules over
different timescales via continuous or pulsatile delivery, which may
be programmed or triggered by some change in the local
environment.
Fabricated from biodegradable polymers in the form of
micro or nanoparticles
capsules,
within walls/surfaces of scaffolds or hydrogels
61. Advanced biomaterials for tissue engineering
2. Smart Polymers
Changes in environmental conditions - changes to the molecular
conformation of many materials.
Environmentally-induced changes may be harnessed, thus smart
polymers.
Used to >encapsulate and release payloads of cells or drugs,
>form gels upon injection in vivo
>for cell sheet engineering.
Example - Thermo-responsive polymer N-isopropylacrylamide
(NIPAM)
Used to grow confluent cell sheets and then to detach the intact
sheet along with the ECM that the cells have deposited.
62. Advanced biomaterials for tissue engineering
3. Non Fouling Materials
Successful strategies - use of chemical surface modifications
Initial stage of FBR is the adsorption of a complex layer of
biomolecules from body fluids that can be denatured and lead to an
immune reaction.
Non-fouling materials (or stealth materials) resist the adsorption of
these proteins.
New generations of non-fouling materials - active area of research
Zwitterionic polymers
Mixed charged polymers
Polyoxazolines
63. Advanced biomaterials for tissue engineering
4. Biofunctionalized materials
Is based on a “blank slate” from the non fouling materials/surfaces.
Decorated with bioactive molecules, through covalent
immobilization.
These biofunctionalized materials interact with receptors on the cell
surface and drive cellular behavior with biological specificity.
Most common strategy - materials with ligands that engage specific
integrin receptors.
Thus, only cells that express the appropriate integrin are able to
adhere to the material.
64. Tissue engineering constructs
These biomaterials are fabricated into a tissue scaffold to support
regeneration.
Structures
Porous scaffolds and hydrogels
Meshes or microspheres
Techniques
Polymer phase separation
Particle or foam templating
Cryogelation,
Electrospinning
Rapid prototyping methods like 3D-printing.
72. Vascularization in tissue engineering
Cells and tissues vary in their oxygen needs
But generally, cells do not survive beyond 150 μm from a capillary
Survival, growth and function of an engineered construct are
highly dependent on an adequate and timely blood supply
Initial TE efforts - tissues of low oxygen requirements( cartilage,
tendon), very small thickness(skin) able to survive by diffusion
Currently, fabrication of thicker and more “oxygen-demanding”
surrogates - address the issue of vascularization
73. Vasculogenesis, Angiogenesis and Inosculation
Vasculogenesis refers to the development of new blood vessels from
progenitor stem cells.
In the embryo, mesoderm cells are stimulated by FGF-2 to form
hemangioblasts. Pool into blood islands. Peripheral hemangioblasts
differentiate first into angioblasts and then into endothelial cells.
Endothelial cells coalesce to a primary vascular plexus.
Vasculogenesis is not exclusive to the embryological period, it also takes
place in adult life driven by bone marrow-derived endothelial progenitor
cells.
74. Vasculogenesis, Angiogenesis and Inosculation
Angiogenesis - sprouting of blood vessels from preexisting ones.
Endothelial cells respond to an angiogenic signal
Increase vascular permeability - extravasation of plasma proteins that
form a transient matrix
A tip cell then migrates out of the vessel into the matrix
Leads the sprouting followed by stalk cells, which form a lumen.
Neighboring sprouts fuse
Neovessel becomes perfused
Stabilized by recruitment of pericytes and basement membrane
restitution
75. Vasculogenesis, Angiogenesis and Inosculation
Inosculation describes the process by which capillaries from a grafted
tissue connect to those of the wound bed where it is applied.
Exact mechanism - not clear.
Because it takes several days, is a limiting factor affecting prompt
perfusion of a tissue-engineered construct
Period of time is too long to survive the transplantation anoxia.
Faster inosculation - Fibroblasts or FGF-2
76. Elements and strategies of vascularization in TE
Extrinsic or Intrinsic approach.
Extrinsic approach
Direct implantation of a seeded scaffold that is gradually invaded by the
host’s vasculature, meanwhile relying solely on diffusion for survival.
Pre-vascularization -A capillary bed fabricated in vitro and then
implanted in vivo where it will become perfused by inosculation rather
than by capillary invasion
Intrinsic approach
Organism is used as a bioreactor so that capillary sprouting occurs either
before or concomitantly with cell differentiation and tissue growth
77. Elements and strategies of vascularization in TE
Elements - similar to tissue engineering itself - Cells, Scaffolds and
Growth factors
CELLS
2 cell lines,
Endothelial cells
Supportive cells.
78.
79. Scaffolds
Natural scaffolds
Collagen, Fibrin, Starch, Matrigel ®,Decellularized matrix & Silk fibrion
Synthetic materials
Polyethylene glycol, Poly (lactic glycolic) acid and Polyurethane
Clinically approved dermal substitutes such as Integra® and
Matriderm ® have also been used for prevascularization purposes by
seeding them with endothelial colony forming cells (ECFCs) in
association with either human dermal fibroblasts (hDFs) or bone
marrow-derived mesenchymal stem cells (BMSCs).
80. Growth factors
VEGF-A - most important in angiogenesis.
Acts mainly by binding to
VEGF receptor 1 (VEGFR1) expressed in endothelial cells, hematopoietic
stem cells and inflammatory cells,
VEGF receptor 2,(VEGFR2) expressed mainly in endothelial cells.
FGF-2 (aka basic fibroblast growth factor, bFGF)
Mostly involved in angiogenesis
Produced by a number of differentiated cells e.g. keratinocytes, mast
cells, fibroblasts, endothelial cells and smooth muscle cells, as well as
by adult mesenchymal stem cells derived from bone marrow, adipose,
and dermal tissue.
81. Growth factors
FGF-2 - Stimulating migration and proliferation of endothelial cells in
vivo,
Mitogenesis of smooth muscle cells and fibroblasts, which induces
the development of large collateral vessels with adventitia.
FGF-2 - In the prevascularization of scaffolds - Faster inosculation of
the scaffold in vivo
PDGF-B released by endothelial cells - Angiogenesis process mainly by
attracting pericytes that will subsequently provide stability and
structural support to the newly formed vessel.
84. REPRESENTATIVE EXAMPLES OF ENGINEERED TISSUES
1. SKIN
Functions of TE Skin products
Protection—establishing a mechanical barrier to microorganisms and
vapor loss;
Procrastination—providing wound cover after early wound
debridement until permanent wound closure
Promotion—delivering to the wound bed dermal matrix components,
cytokines, and growth factors, which can promote and enhance
natural host wound healing responses
Provision—new structures, such as dermal collagen or cultured cells,
that are incorporated into the wound and persist during wound
healing and/or thereafter
85. REPRESENTATIVE EXAMPLES OF ENGINEERED TISSUES
1. SKIN
Scaffold
Collagen and fibrin most common
Cells
Keratinocytes, Fibroblasts, Human Embryonic Stem cells ,Human Adult
Stem Cells and Preadipocytes
Growth Factors
Transforming growth factor- b (TGF- b), Platelet-derived growth factor
(PDGF), Fibroblast growth factors (FGFs)
86.
87. Approaches to Skin TE
Placing a
biodegradable
matrix in the
wound to
promote the
regeneration of
the skin dermis
through a process
of host cell
migration and
proliferation
90. Emerging technologies
3D printing
Termed bioprinting or bioplotting when biological components are
included.
A wide variety of materials can be processed using different kinds of 3D
printers,
Polymers, Hydrogels, Metals, Ceramics and even Living cells.
Methods via solid freeform fabrication
Stereolithography
Selective laser sintering
3D printing
Wax printing
Fused deposition modeling
91. Emerging technologies
Others
In vitro bioreactors
Control the microenvironment of cells in vitro
To encourage the desired cellular processes and tissue development
whilst also optimizing the mass transport of oxygen, nutrients and
waste products to allow 3D tissue constructs to be developed
Computational modeling
Mathematical modeling in design of TE constructs and processes
Insights into factors governing tissue growth e.g. different cell seeding
patterns and timing can be investigated using a mathematical model
94. References
6. Bell, E. (1991). Tissue engineering: a perspective. Journal of Cellular
Biochemistry, 45(3), 239–241. doi:10.1002/jcb.240450302
7. Tissue-engineered Solutions in Plastic and Reconstructive Surgery: Principles
and Practice Sarah Al-Himdani
8. Tissue Engineering in Plastic Surgery: A Review Victor W. Wong, M.D. Kristine
C. Rustad, B.S. Michael T. Longaker, M.D., M.B.A. Geoffrey C. Gurtner, M.D.
Stanford, Calif
9. Locke M, Windsor J, Dunbar P. Human adipose-derived stem cells: isolation,
characterization and applications in surgery. ANZ J Surg. 2009;79:235–244.
10. Cui L, Yin S, Liu W, et al. Expanded adipose-derived stem cells suppress mixed
lymphocyte reaction by secretion of prostaglandin E2. Tissue Eng.
2007;13:1185–1195.
95. References
11. Puissant B, Barreau C, Bourin P, et al. Immunomodulatory effect of human
adipose tissue-derived adult stem cells: comparison with bone marrow
mesenchymal stem cells. Br J Haematol. 2005;129: 118–129.