The document summarizes recent applications of tissue engineering principles in orthopaedics. It discusses how scaffolds, signals, and cells have been combined in various tissue engineering strategies to treat fracture nonunions, osteonecrosis, and chondral/osteochondral defects. For fracture nonunions, delivering mesenchymal stem cells on an atelocollagen scaffold improved healing rates. Treating osteonecrosis with autologous mesenchymal stem cells seeded on bone grafts showed prevention of disease progression in some cases. Cell doses and scaffold properties were found to influence outcomes. Tissue engineering approaches for cartilage defects, including cell injections and composite scaffolds, demonstrated symptom improvement over baseline.
Bone and Cartilage regeneration with cells and tissue engineering products - ...Enric Caceres
Bone and Cartilage regeneration with cells and tissue engineering products - Dr. Enric Cáceres - B-Debate 17/02/2015 http://www.bdebate.org/en/forum/advanced-therapies-and-regenerative-medicine-promise-21st-century
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
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 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.
Adult Stem cells in Orthopaedics present and future perspectives.
Παρουσίαση του Δρ. Σταύρου Αλευρογιάννη που έγινε στο ξενοδοχείο Χίλτον, στις 12/06/15 στα πλαίσια Ημερίδας της Ελληνικής Εταιρείας Αναγεννητικής Ιατρικής, Αντιγήρανσης και Βιοτεχνολογίας, στο 41ο Πανελλήνιο Ιατρικό Συνέδριο.
"H θέση της αναγεννητική Ιατρικής στις παθήσεις Οστών και Αρθρώσεων"
Cartilage Repair using Stem cell & OrthobiologicsVaibhav Bagaria
Regenerating Cartilage is a challenge. What's new in this field of cartilage regeneration and the current status of the stem cell use in this field is described.
Introduction
Anatomy and Physiology of bone
Bone Tissue Engineering
Recent studies related to bone tissue engineering
Commercialized products and ongoing clinical trials
Biomedical start-ups
Concluding remarks
Introduction
Anatomy and Physiology of bone
Bone Tissue Engineering
Recent studies related to bone tissue engineering
Commercialized products and ongoing clinical trials
Biomedical start-ups
Concluding remarks
Introduction
Anatomy and Physiology of bone
Bone Tissue Engineering
Recent studies related to bone tissue engineering
Commercialized products and ongoing clinical trials
Biomedical start-ups
Concluding remarks
There are a lot of orthopedic conditions and injuries that presently have limited treatment options available.
Here regenerative technologies comes up as a ray of hope among surgeons for the treatment by functionally repairing the tissues and organs using growth factors, stem cells and products developed by genetic engineering with the advancement in the stem cells research field .
The purpose of this presentation is to first provide idea about the orthopedic conditions along with the therapeutic potential of stem cells to treat these diseases.
Bone and Cartilage regeneration with cells and tissue engineering products - ...Enric Caceres
Bone and Cartilage regeneration with cells and tissue engineering products - Dr. Enric Cáceres - B-Debate 17/02/2015 http://www.bdebate.org/en/forum/advanced-therapies-and-regenerative-medicine-promise-21st-century
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
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 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.
Adult Stem cells in Orthopaedics present and future perspectives.
Παρουσίαση του Δρ. Σταύρου Αλευρογιάννη που έγινε στο ξενοδοχείο Χίλτον, στις 12/06/15 στα πλαίσια Ημερίδας της Ελληνικής Εταιρείας Αναγεννητικής Ιατρικής, Αντιγήρανσης και Βιοτεχνολογίας, στο 41ο Πανελλήνιο Ιατρικό Συνέδριο.
"H θέση της αναγεννητική Ιατρικής στις παθήσεις Οστών και Αρθρώσεων"
Cartilage Repair using Stem cell & OrthobiologicsVaibhav Bagaria
Regenerating Cartilage is a challenge. What's new in this field of cartilage regeneration and the current status of the stem cell use in this field is described.
Introduction
Anatomy and Physiology of bone
Bone Tissue Engineering
Recent studies related to bone tissue engineering
Commercialized products and ongoing clinical trials
Biomedical start-ups
Concluding remarks
Introduction
Anatomy and Physiology of bone
Bone Tissue Engineering
Recent studies related to bone tissue engineering
Commercialized products and ongoing clinical trials
Biomedical start-ups
Concluding remarks
Introduction
Anatomy and Physiology of bone
Bone Tissue Engineering
Recent studies related to bone tissue engineering
Commercialized products and ongoing clinical trials
Biomedical start-ups
Concluding remarks
There are a lot of orthopedic conditions and injuries that presently have limited treatment options available.
Here regenerative technologies comes up as a ray of hope among surgeons for the treatment by functionally repairing the tissues and organs using growth factors, stem cells and products developed by genetic engineering with the advancement in the stem cells research field .
The purpose of this presentation is to first provide idea about the orthopedic conditions along with the therapeutic potential of stem cells to treat these diseases.
Stem cells and nanotechnology in regenerative medicine and tissue engineeringDr. Sitansu Sekhar Nanda
Alexis Carrel, winner of the Nobel Prize in Physiology or Medicine in 1912 and the father of whole-organ transplant, was the first to develop a successful technique for end to end arteriovenous anastomosis in transplantation.
Stem Cells and Tissue Engineering: past, present and futureAna Rita Ramos
Tissue engineering brings together the principles of the life sciences and medicine with engineering. New biomaterials; advances in genomics and proteomics and increased understanding of healing processes contributed to the increase of this area over the past decade.
Stem cell biology is paving the way for the generation of unlimited cells of specific phenotypes for incorporation
into engineered tissue constructs.
Bone tissue engineering challenges in oral and maxillofacial surgerySeyed Mohammad Zargar
In this presentation, I talked about maxillofacial deformities, Different Reconstruction methods and at tissue engineering approach.
S.Mohammad Zargar
Biomedical Engineering Student at University of Isfahan, Iran
Myanmar Society of Oral Implantology collaborates with Myanmar Dental Association ( Yangon Division) and celebrates Yangon Dental Festival. At this event, as the President of MSOI, I present this topic. References list was collected in separate folder.
Bone marrow basics
Bone marrow targeting strategies along with case studies
Bone marrow based formulations
Bone marrow targeting based marketed formulations
Autologous Mesenchymal Stem Cells in OrthopaedicsVladimir Bobic
Nuffield Health, The Grosvenor Hospital Chester, UK
27 June 2013. GP and Physiotherapy Seminar: Autologous Stem Cell Therapies in Orthopaedics. Moderator and Presenter: Vladimir Bobic, Chester Knee Clinic
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.
The definition of tissue engineering, according to International Union of Pure and Applied Chemistry (IUPAC), is “to use of a combination of cells, engineering and materials, and suitable biochemical and physiochemical factors to improve or replace biological functions
Giant cell lesions are a group of lesions that typically display multinucleate giant cells as one of the characteristic histopathological features which are significant and aids in diagnosis.
Similar to Tissue engineering in orthopaedics (20)
Pemberton's Osteotomy for Acetabular DysplasiaLibin Thomas
This is a slideshow based on the journal- JBJS- ESSENTIAL SURGICAL TECHNIQUES, INDIAN EDITION, OCTOBER 2015, VOL.4, NO. 3, SPECIAL EDITION by Shier- Chieg, Huang, MD, PhD, Ting- Ming Wang, MD, PhD, Kuan- Wen Wu, MD, Ken N. Kuo, MD
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
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Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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.
Pharynx and Clinical Correlations BY Dr.Rabia Inam Gandapore.pptx
Tissue engineering in orthopaedics
1. Tissue Engineering in
Orthopaedics
Alexander M. Tatara, BS; Antonios G. Mikos, PhD
J Bone Joint Surg Am, 2016 Jul 06; 98 (13): 1132 -1139 .
http://dx.doi.org/10.2106/JBJS.16.00299
Investigation performed at the Department of Bioengineering, Rice University, Houston, Texas
A Journal Club presentation at Amala Institute of Medical Sciences by
Dr. Libin Thomas Manathara
3. Tissue Enigineering
• 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
• The term regenerative medicine is often used synonymously with
tissue engineering
3
5. Principles of Orthopaedic Tissue Engineering
• The tissue engineering paradigm consists of scaffolds, signals, and
cells
• These 3 elements can be combined or used independently to attempt
to generate tissues in a limitless number of arrangements
5
8. Scaffolds
• Tissue engineering scaffolds are cytocompatible biomaterials that
cells can adhere to and/or replace with extracellular matrix to
produce native tissues
• Scaffolds can be as simple as morselized autologous bone or as
complex as injectable, thermally responsive, synthetic hydrogels
capable of mineralizing in situ
• morselize- To break up or divide into small portions
• hydrogel- a gel in which the liquid component is water
8
9. Scaffolds
• On the basis of material composition, scaffolds can be divided into 3
basic classes: metals, ceramics, and polymers
• Scaffolds can be further divided by their source (naturally derived
versus synthetically fabricated) and ability to degrade (nonresorbable
versus resorbable)
9
11. Scaffolds
• Although they are stable, nonresorbable scaffolds and delivery
systems cannot be replaced by native tissues and may elicit a chronic
foreign-body reaction detrimental to tissue healing
11
12. Scaffolds
• Naturally derived scaffolds (such as those made from collagen,
chitosan, and hyaluronan) are generally all resorbable in situ and
often already possess adhesion ligands for cellular attachment
• However, naturally derived scaffolds typically have a narrow range of
available physical properties, such as mechanical strength and
degradation rate
12
13. Scaffolds
• Synthetic scaffolds can be tuned to have a wide variety of properties
by altering synthesis components and parameters
• Not all synthetic scaffolds are biodegradable, and cell adhesion motifs
may need to be added in order to promote biocompatibility
13
14. Scaffolds
• Different scaffold materials can also be combined to create composite
scaffolds that have novel properties not observed in either material
used alone
• For orthopaedics, mechanical properties and durability are
paramount to a successful device.
14
15. Scaffolds
• While a ceramic scaffold may have appropriate compressive strength
in a femoral nonunion defect, its high stiffness and weak tensile
properties would be inappropriate for use in a cartilage defect or
repairing a rotator cuff.
15
16. Scaffolds
• Another important factor to consider is the compatibility of the rate
of scaffold resorption with the rate of native tissue replacement.
• If a scaffold resorbs too rapidly, it may not be able to support the
growth of new tissues.
• If a scaffold resorbs too slowly, it may not fully integrate with
surrounding tissues and may pose risks associated with chronic
foreign bodies.
16
17. Scaffolds
• Scaffolds may be osteoconductive (i.e., permit the growth of bone,
such as the calcium sulfates) or osteoinductive (i.e., actively promote
bone growth in a defect that otherwise would not heal, such as
demineralized bone matrix).
17
20. Signals
• Signals are internally or externally derived environmental factors that
can influence the regeneration of tissues
• As in the case of scaffolds, these signals can be further broken down
into subcategories including biological, chemical, mechanical, and
electrical cues
20
21. Signals
• In orthopaedics, the most commonly utilized biological signal is
rhBMP-2, a potent osteogenic growth factor
• Has been approved for specific uses by US FDA
21
23. Signals
• However, it appears that rhBMP-2 is associated with greater risks
than originally reported
• There remain concerns about the use of growth factors in light of
their association with malignancies such as osteosarcoma
23
24. Signals
• Another common source of biological signals used in tissue
engineering strategies is platelet rich plasma (PRP) and its different
variants
• While use of PRP is appealing because of the ease of autologous
obtainment, its actual efficacy in the regeneration of musculoskeletal
tissues currently remains uncertain
24
25. Signals
• Antibiotics are another example of chemical cues often delivered in
conjunction with tissue engineering strategies
• In an infected orthopaedic defect, encapsulating antibiotics for local
drug delivery into the scaffold may be required to stimulate healing
25
26. Signals
• Mechanical cues have long been used to stimulate bone formation,
such as in distraction osteogenesis
• Recent studies have demonstrated that passive mechanical signals
provided by scaffolds (such as substrate stiffness, roughness, and
porosity) can influence the differentiation of stem cells toward
specific lineages
26
27. Signals
• Electrical cues have been demonstrated to be important in generating
functional skeletal muscle tissue as well as innervation of neotissues
but have not been explored as thoroughly relative to other cellular
signals for orthopaedic tissue engineering applications
27
29. Cells
• In order to create living tissues, as well as integrate living engineered
tissue with native host tissues, cells must be present
• Cells can be recruited into an implanted scaffold by methods such as
• the release of chemokines
• attachment of cell ligands to the scaffold
• osteoconduction
• osteoinduction
• scaffolds containing cells can be implanted into a defect
29
30. Cells
• Unlike in other tissue engineering fields, there is little controversy
regarding stem cell type in orthopaedic tissue engineering
30
31. Cells
• By far, the most commonly utilized cell type is the mesenchymal stem
cell (MSC)
• Depending on their environment, MSCs have the ability to
differentiate into
• osteoblasts
• chondroblasts
• myoblasts
• tenocytes
• as well as other adult cells
31
32. Cells
• MSCs are relatively easy to harvest from an autologous host
• The current gold standard is MSCs harvested from bone marrow
aspirate
• However, adipose-derived MSCs are gaining more traction in the field
because of their
• increased availability
• lower harvesting costs
• ease of expansion
32
33. Cells
• Amniotic fluid-derived MSCs are another intriguing source that has
recently been shown to be capable of osteogenesis and
chondrogenesis in small animal models
• Other sources of MSCs include skin, periosteum, and umbilical cord
blood
33
34. Cells
• However, ease of collection should not be the only consideration in
MSC harvesting
• MSCs from different sources have different potential for
differentiation and may affect the quality of tissue repair
34
35. Cells
• Initially, it was believed that the primary mechanism of action of
implanted MSCs within an orthopaedic defect was structural
• It was assumed that the implanted MSCs themselves would
proliferate, differentiate, and generate the extracellular matrix
required to repair the defect
• However, recent studies have revealed the tremendous pleiotropic
effects of MSCs
35
36. Cells
• Beyond their ability to terminally differentiate into adult
musculoskeletal cells, MSCs secrete a variety of cytokines and
modulate inflammatory and immune response pathways
• Because of these immunomodulatory effects, implantation of
allogeneic MSCs carries minimal risk of rejection by the host and
commercially available MSCs are being explored in a number of
clinical trials for a multitude of autoimmune diseases
36
37. Cells
• From a product development and regulatory standpoint, acellular
strategies present advantages over cell-containing products, which
carry a potential risk of rejection or disease transmission, have
heterogeneous cell populations, etc
• For example, it is clear that rhBMP-2 combined with a collagen
scaffold has ample regenerative capacity for spinal fusion without the
addition of any exogenous MSCs
• However, for complex diseases such as osteonecrosis, the pleiotropic
and immunomodulatory capacities of MSCs may be required for
treatment
37
42. Fracture Nonunion
• While there is currently no standardized definition, fracture nonunion
has been defined by the FDA and others as incomplete healing at 9
months after injury and the absence of healing progression over the
following 3 consecutive months
• Despite advances in surgical techniques, fracture nonunions continue
to present clinical challenges
• As disrupted vascularity is one of the major contributors to nonunion,
strategies to enhance angiogenesis, including delivery of
hematopoietic stem cells, are being explored
42
43. Fracture Nonunion
• In one study, autologous bone marrow-derived hematopoietic stem
cells were delivered on an atelocollagen scaffold into tibial and
femoral nonunion defects in 7 patients
• This combination of cells and scaffold resulted in fracture-healing in 5
(71%) of 7 patients at 12 weeks
• While there was no control arm, the threshold of healing achieved
was 18% (2 of 11 patients)
43
44. Atellocollagen
• Collagen is a major connective tissue protein that plays an important
role in the extracellular matrix in animals.
• As such, collagen possesses good biocompatibility with animal body
tissues.
44
45. Atellocollagen
• Atelocollagen is a type of soluble collagen produced from
tropocollagen, the collagen molecule that makes up collagen fibrils,
via the elimination of the telopeptide moieties, which are considered
to account for most of collagen's antigenicity.
• Thus, atelocollagen is considered to have little immunogenicity, which
makes it a safe biomaterial.
• It is widely used for implantable medical and plastic surgical products
45
46. Fracture Nonunion
• In a retrospective review of 52 patients treated for forearm nonunion
defects at a single center, patients were categorized as being treated
with a single tissue engineering element (MSCs, a scaffold, or BMP,
i.e., “monotherapy”) or with all 3 elements of the tissue engineering
paradigm (“polytherapy”)
• With a minimum follow-up time of 1 year, patients receiving all 3
elements had significantly improved radiographic healing, clinical
success criteria, and rapidity of healing compared with patients
treated with monotherapy
46
47. Fracture Nonunion
• While that study lends support to the synergistic nature of combining
cells, scaffolds, and signals to treat severe orthopaedic defects, a
randomized prospective study would have provided stronger
evidence by minimizing bias
47
49. Osteonecrosis
• Given their necrotic nature, the lesions associated with osteonecrosis
have poor innate regenerative capacity with few or no viable MSCs
• In addition, it has been reported that, in corticosteroid-induced
osteonecrosis, there is a global decrease in available MSCs
• In theory, MSC therapy may be promising, given the
immunomodulatory properties of MSCs as well as their ability to
secrete angiogenic growth factors and recruit local vasculature
49
50. Osteonecrosis
• In a recent clinical study of 5 femoral heads in 4 patients, autologous
bone marrow-derived MSCs were seeded onto morselized allogeneic
bone as scaffold and were implanted in the defect after core
decompression
50
51. Osteonecrosis
• Unfortunately, in the patient who received treatment bilaterally,
disease progressed in both femoral heads, leading to bilateral total
hip replacement (after 13 and 19 months, respectively)
• Microcomputed tomography revealed that the treated zone was
greater in opacity than trabecular bone
• The tissue in the treated zone was histologically and mechanically
indistinguishable from the patient’s healthy trabecular bone
51
52. Osteonecrosis
• The other 3 patients had no more disease progression after treatment
(22 to 44 months of follow-up)
• As the authors noted, “Further clinical trials are necessary, including
comparison to concurrent therapies”
52
53. Osteonecrosis
• In a similar study in which cells and scaffolds were utilized in disease
treatment, 10 patients with osteonecrosis were treated with
vascularized bone grafts augmented with autologous bone marrow-
derived MSCs seeded on a β-tricalcium phosphate scaffold
53
54. Osteonecrosis
• At 2 years of follow-up, 9 patients had completed the protocol and 7
had no further disease progression
• In the 2 patients who had disease progression, the authors postulated
that “an imbalance between bone resorption and formation” may
have contributed to the cystic lesions observed in their femoral heads
1 year after surgery
54
55. Osteonecrosis
• Given the degradation rate of β-tricalcium phosphate (weeks to
months) and the low innate regenerative potential of the femoral
head in osteonecrosis, a mismatch in the rate of scaffold degradation
and native tissue regeneration may have resulted in collapse of the
lesion
• While a prospective randomized study is required for conclusive
evidence on treatment superiority, these studies in sum demonstrate
how selection of scaffold properties may impact the clinical outcome
55
57. Chondral and Osteochondral Defects
• Cell monotherapy for the treatment of cartilage defects is more
common than in other orthopaedic pathologies
• Despite the popularity of these monotherapies, the optimal amount
of MSCs required for efficacy is unclear
57
58. Chondral and Osteochondral Defects
• In a recent study, autologous adipose-derived MSCs in 3 different
doses were injected without scaffold or exogenous signals into
osteoarthritic knees in 18 patients
• While no patient experienced treatment-related adverse events, the
effects of dose are more difficult to ascertain as the low and medium
dosage groups had only 3 patients each
• However, patients in the high dosage group demonstrated
significantly improved clinical, radiographic, and arthroscopic
measurements compared with baseline, and these improvements
were not reflected in the low and medium dosage groups
58
59. Chondral and Osteochondral Defects
• Increasing in complexity, allogeneic chondrocytes that have been
genetically modified to express transforming growth factor-beta 1
(TGF-β1) by retroviral modification ex vivo were injected at 2 different
concentrations in 27 patients with osteoarthritis
• While the 2 groups did not show significant differences in healing
compared with one another, both groups demonstrated significantly
improved clinical scores (including reduced pain and stiffness and
increased physical function) compared with baseline values
59
60. Chondral and Osteochondral Defects
• This recent work demonstrates that cells can be programmed to
deliver signals themselves to mitigate disease in human patients,
rather than requiring exogenous delivery of the signals through non-
living vehicles such as collagen sponges or microparticles
60
61. Chondral and Osteochondral Defects
• A composite scaffold, constructed using collagen and hydroxyapatite
nanoparticles in a gradient-based fashion, was implemented in 27
patients
• Again, patients showed significant improvement compared with
baseline values at both 2 and 5 years following treatment, which is
historically not the case with osteochondral defects
61
62. Chondral and Osteochondral Defects
• While this improvement could be due to the gradient-based nature of
the acellular scaffold, without a nongradient-based control, it is
difficult to draw any definitive conclusions regarding the effects of
acellular gradient-based scaffolds on the treatment of osteochondral
defects in human disease
62
64. Future Directions and Challenges
• Although the future for orthopaedic tissue engineering is bright, there
is much work to be done
• While the small number of clinical studies reviewed in the present
work may not necessarily be a representative sample of the field as a
whole, they demonstrate that small patient numbers, lack of
randomization, and absence of control groups consisting of current
clinical treatment standards can make it difficult to determine the
efficacy of the various elements of the tissue engineering paradigm in
orthopaedics
64
65. Future Directions and Challenges
• New manufacturing techniques, such as the advent of high-resolution
bioprinting are allowing for the rapid creation of personalized devices
to an extent that was not previously possible
• Infections, which often plagued implantation of foreign materials like
scaffolds, are being mitigated by advances in anti-infective strategies
such as biofilm-repulsing surfaces and antibiotic-delivering materials
65
66. Future Directions and Challenges
• Synthetic biology and genetic engineering techniques are being
utilized to reprogram cells to optimize healing
• Ultimately, products such as INFUSE (Medtronic) and Carticel have
demonstrated that the field of orthopaedics is willing to adopt tissue
engineering strategies into clinical practice
66
67. Future Directions and Challenges
• In the past, the benchmark for successful treatment of conditions
such as osteoarthritis was lack of disease progression
• With the new therapies inspired by tissue engineering, the new
benchmark may be the absence of disease
67