Παρουσίαση του Δρ . Σταύρου Αλευρογιάννη για τα Βλαστοκύτταρα στην Ορθοπαιδική

1. CLINICAL USE OF STEM CELLS IN
ORTHOPAEDICS
current practice – clinical controversies
Dr. S. Alevrogiannis, M.D., MS (Ortho.), Ph.D.
Senior Consultant Orthopaedic Surgeon,
METROPOLITAN GENERAL HOSPITAL Robotic Knee & Hip Surgery Dept.
Chief Surgeon & Medical Director

2. Regenerative Medicine
► Process of creating living, functional tissues to repair
or replace tissue or organ function lost due to age,
disease, damage, or congenital defects
Gene therapy Cell therapy Tissue Bioengineering

3. STEM CELLS
Undeveloped biological cells capable of proliferation, self renewal,
conversion to differentiated cells and regenerating tissues
► TYPES
• embryonic
• adult
• cord-blood stem cells
• allogeneic adult stem cells
• placental or amniotic stem cells
• induced pluripotent stem cells (iPS or
iPSCs)
• very small embryonic-like or embryonic-like
stem cells (VSELs or ELSCs)
► SOURCES
• Bone marrow
• Adipose tissue
• Periosteum
• Amniotic fluid
• Placenta
• Dental pulp
• Blood
• Synovial tissue
• Skin
• Umbilical cord
► ISOLATION
► Unselected ( bone marrow
concentrate)
► Selected & cultivated (MSC’s)
► ROUTE OF
ADMINISTRATION
• Surgically
• Local injection
• intravenously

4. MESENCHYMAL STEM CELLS (MSC’s)
► “Natural body’s drugstores”
or
► Medicinal Signaling Cells
or
► Caplan’s cells….
….Msc’s are going to change the
way for future medicine
practice…..
Dr Arnold Caplan, Prof. in Biology,
Oncology & General Medicine/
Univ. Cleveland
(“father of MSC’s”)

5. MESENCHYMAL STEM CELLS
(MSC’s)
► the cells must be plastic-adherent
when maintained under standard
culture conditions;
► they must express CD73, CD90,
and CD105 markers and should
not express CD34, CD45, CD14,
HLA-DR, CD11b, or CD19; and
► they should be able to
differentiate into osteoblasts,
chondroblasts, and adipocytes in
vitro
► Homing ability
► immunomodulatory
► express less major histocompatibility
complex (MHC) class I molecules, which
avoids MSCs from removal by killer cells
► do not express MHC class II molecules -gives
the potential to avoid identification by
alloreactive CD4+ T cells
► interact with immune cells and can suppress
and modulate alloreactivity.
► immunosuppressive
► can hamper T cell proliferation and activation
by secreting soluble factors like hepatocyte GF,
TGF-β1, IL-10, prostaglandin E2
 Paracrine effect
• Secrete growth factors & cytokines (BMPs, TGF-
b, VEGF)

6. Clinical Use of Adult Stem Cells in Orthopaedics
•Treated and induced osteogenesis
Bone fracture
Non-union
•Promotes healing in the same way as a core decompression but makes more
intuitive sense to use BMAC compared to dead graft
AVN of Femoral Head
•Has been shown to promote healing equal to iliac crest bone graft with much
less morbidity
Spine Fusions (best
documented uses of BMAC)
•Offers nonsurgical solutions to chronic problems that are recalcitrant to
treatment (lateral epicondylitis study)
Chronic Tendonitis & Partial
muscle or tendon Tears
•Shown to reduce time to MRI homogeneity of the ACL graft by more than 48%
(179 days to 369 days)
ACL tears
•Significant case reports of angiogenesis and increasing collateral circulation
Compartment Syndrome
•Promotes tenogenesis and healing
Rotator Cuff Injuries
(partial or complete tears)
Meniscal tear •Regeneration partially or through scaffold

7. Bone Marrow Concentrate
A Novel Strategy for Bone Defect Treatment
The local application of BMC / bone aspirate in the treatment of bone
deficiencies may be a promising alternative to autogenous bone grafting and
help reduce donor site morbidity.
Current Stem Cell Research & Therapy, 2009,4, 34-43 © 2009 Bentham Science Publishers Ltd.Bone Marrow
Concentrate: A Novel Strategy for Bone Defect Treatment Marcus Jager*, Eva M. Jelinekl, Kai M. Wessl, Axel
Scharfstadtl, May Jacobson, Sherwin V. Kevy and Rodiger Krauspel
Number of cells
A graft needed to contain at least > 1000 MSCs per cm3 to
achieve union.
Hernigou P, Poignard A, Beaujean F, Rouard H. Percutaneous autologous bone marrow grafting for
nonunions: influence of the number and concentration of progenitor cells. J Bone Joint Surg [Am]
2005;87-A:1430-7.

8. Non-Unions, Delayed Unions, Fusions
Osteogenesis and angiogenesis are the goal
 Scaffold for osteoconductivity; signal proteins; stem cells to
become osteogenic
 Using BMAC to help change results of synthetic grafts and
allografts
to equal autograft and with significantly lower morbidity
Shah, et al; J Spinal Disorders Vol 23, No 1, Feb 2010
 BMAC used with synthetic graft resulted in similar fusion rates as
rib autograft
Shah, et al; J Spinal Disorders Vol 23, No 1, Feb 2010
 Reduced time to heal distal tibia fractures by 50%
Liebergall, et al; Mol Ther 2013 Aug; 21(8); 1631-8
 BMAC with synthetic graft resulted in healing equal to autograft
Kitchel; The Spine J 6(2006) 405-412

9. R. Wade McKenna, D.O., Brussels, 2013
► Most commonly diagnosed condition of the elbow:
1 to 3% of the population
► Can be severe enough to remove people from the work force
or affect ADLs
► Current treatments include stretches, steroid injections,
surgery
► Two year follow up study showing results using BMAC
continued to improve and were better than steroid injections
Gosens, Peerbooms, Oudsten, et al AOSM Vol 39, No 6
► Steroids are detrimental to tendons
Fubini, et al Ortho Res 2001
► Even in patients with the need for surgical intervention, we
have seen dramatic changes in post operative rehab and
symptoms
Lateral Epicondylitis

10. Achilles Tendon Injuries
► Goal of use of BMAC is to repopulate the collagen scaffold of
the torn tendon
► Reduces time to healing and promotes stronger tissue
ingrowth
Adams, et al; Foot Ankle Int. 2014 Jan 8
► Arthroscopy and Laparoscopy
 Use of PRP lowered incidence of draining portal and
synovial tracking
 Using BMAC has helped promote chondrogenesis in
published studies on sheep, rabbits, equine and humans

11. F.A.I hip syndrome

12. BANKART LESION

13. ROTATOR CUFF TEAR

14. ACL Reconstructions
► Average time to heal - over one year to achieve complete
healing without the use of biologics
► 50-patient study showed using BMAC+PRP reduced time of
healing by almost 50% (179 days compared to 369 days)
Radice, Yanez, et al; Journal of Arthros and Related Surgery Vol 26, 1, Jan 2010; 50-57
 Autograft has a much higher morbidity than allograft
 In partial tear local injection under fluoroscopy
 If we can show allograft heals just as fast and with lower
complications, we can dramatically change time lost in
sports and at work
 Also looking at proximal tibia draws versus iliac crest
draws as far as influence in healing of the graft

15. ACL grafts with BMAC average time out 12 weeks
Uses of Bone Marrow Concentrate
ACL reconstructed grafts 6 m. out without
biologics

16. Meniscal regeneration post
partial meniscectomy in
arthritic knees
► 150x106 Adult Human allogeneic
MSC’s Delivered via Intra-Articular
Injection to the Knee Following
Partial Medial Meniscectomy.
– more than 15% increase in meniscal
volume in quantitative MRI scan 6
m.p.o.
- evidence of meniscus regeneration
and improvement in knee pain in
arthritic knees
A Randomized, Double-Blind,
Controlled Study
C. Thomas Vangsness Jr., MD, Jack Farr II, MD, Joel
Boyd, MD, David T. Dellaero, MD, C. Randal Mills,
PhD,and Michelle LeRoux-Williams, PhD

17. Indications for stem
cell applications in
spine
► Disc herniation:
Goal:
1. Fill discectomy defect
2. prevent recurrent
herniation ( 5-20%),
3. Prevent disc collapse and
4. future degeneration/pain
► Discogenic Pain :
Goal:
1. Eliminate pain
2. prevent degeneration

18. 0 4>
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Percutaneous drilling for the treatment of
secondary osteonecrosis of the knee
G. Μ aru land a,
Τ. M. SEVIER,
Ν. H. SHEIKH,
M. A. MONT
From the Sinai
Hospital of
Baltimore,
Baltimore, USA
Osteonecrosis of the knee comprises two separate
disorders, primary spontaneous osteonecrosis which is
often a self-limiting condition and secondary osteonecrosis
which is associated with risk factors and a poor prognosis.
In a series of 61 knees (38 patients) we analysed secondary
osteonecrosis of the knee treated by a new technique using
multiple small percutaneous 3 mm drillings.
Total knee replacement was avoided in 59 knees (97%) at
a mean follow-up of 3 years (2 to 4). Of the 61 knees, 56
(92%) had a successful clinical outcome, defined as a Knee
Society score greater than 80 points. The procedure was
successful in all 24 knees with small lesions compared with
32 of 37 knees (86%) with large lesions. All the procedures
were performed as day cases and there were no
complications. This technique appears to have a low
morbidity, relieves symptoms and delays more invasive
surgery.
JBJS B June 2006

19. Treatment of Osteonecrosis of the
Femoral Head with Implantation of
Autologous
Bone-Marrow Cells
A Pilot Study
By Valerie Gangji, MD, Jean-Philippe Hauzeur, MD, PhD, celso Matos, MD, Viviane De Maertelaer, PhD,
Michel Toungouz, MD, PhD, and Micheline Lambermont, PharmD
Investigation performed at the Department of Rheumatology and Physical Medicine, the Department of Radiology, and the
Cellular and Molecular Therapy Unit, Erasme University Hospital, Brussels, Belgium

20. Pre op . Immediate post op . 6 weeks po.

21. MSCs in cartilage repair
Autologous MSCs were expanded ex vitro, embedded in
a collagen gel and re-implanted into areas of articular
cartilage defect in osteoarthritis patients.
Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, Yoneda M. Human autologous culture expanded bone marrow
mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage
2002;10:199-206.

22. Osteochondral Lesions of the Knee
Mesenchymal stem cells represent 2% to 3% of the total
mononuclear cells in bone marrow and have the ability to
differentiate into various lineages, including osteoblasts and
chondroblasts. The rationale of the ''one-step technique'' is
based on the idea of transplanting the entire bone-marrow
cellular pool instead of isolated and expanded mesenchymal
stem Cells.
Osteochondral Lesions of the Knee: A New One-Step Repair Technique with Bone-Marrow-Derived Cells. By
Roberto Buda, MD, Francesca Vannini, MD, PhD, Marco Cavallo, MD, Brunella Grigolo, PhD, Annarita Cenacchi,
MD, and Sandro Giannini, MD
J Bone Joint Surg Am. 2010;92 Suppl 2:2-11 d doi:10.2106/JBJSJ.00813

23. Reality
for 10 million
Americans
Desire
OSTEOARTHRITIS

24. Stem Cell injections for knee arthritis:
13 papers published up to 2020
HUGELY DIFFERENT THERAPIES
 Processed Cell Mixtures
 Cultured Expanded and Isolated Cells
 Different Cell Sources
► Cultured expanded bone marrow MSCs
► Culture-expanded adipose MSCs
► Stromal Vascular Fraction (SVF)
► Culture expanded placental MSCs
► Culture expanded umbilical cord MSCs
► Bone Marrow Concentrate (BMC) with PRP

26. Critical questions
►Which stem cells are best supported by
the data?
►Which stem cells are the most effective at
repairing and healing bone and cartilage?
►Which stem cells best treat arthritis?
►Which procedure is less invasive and
safer?

27. BM-MSC’S
do not need cultivation to differentiate to
musculoskeletal tissue

28. up to 2013: 30 publications for ADSC’s !
up to 2013: 2054 publications for BMSC’s !
2013-2020 : 305 publications for ADSC’s
2013-2020 : 293 publications for BMSC’s

29. ADSC’s
► Obtained in larger
volumes with adipose
tissue
► Low risk
► Minimal invasive
► Low complication rate
► Easy to extract
► Does not cause cancer
or teratomas

31. ADMSC’s
• 2.000 times more MSC’s in fat than in bone marrow
• MSC’s represent about 1-5% of the TNC in fat versus 0.1-0.5% for bone marrow. That is 10X more
MSC’s in fat than bone marrow.
• Each ml of bone marrow had about 100 times more nucleated cells per ml of fat.
• HSCs are not found in fat in any significant quantity (more than 1%+ in bone marrow)
• For every ml bone marrow we take ,we get 150x106 TNC, that’s 1.5x106 HSCs per ml injected
• Bone marrow also contains newly discovered OCR cells specific for orthopaedic tissue repair

33. ADULT STEM CELLS IN ORTHOPAEDICS
MSCs
BODIES’ SUPERVISORS OF REPAIR
The most important job of MSC’s is that they
dramatically reduce (immuno-modulate)
the inflammation in an area affected by
an orthopaedic disorder. When
inflammation is reduced, repair can take
place
HSCs
TRUE WORKERS OF REPAIR
Contain cells that have short and long term
regeneration capacities
Unlike MSC’s the number of HSC’s does not
diminish greatly with age
► Drivers of tissue regeneration
► They cause angiogenesis
► They up-regulate the release of G.F
► They increase the release of other stem
cells from bone marrow through
exosomes
CD34+ and MSCs show additive effects when combined

35. EMBRYONIC OR ADULT STEM CELLS?
EMBRYONIC
► (+) easy to produce
► (-) many complications
► (-) ethical considerations
► (-) DNA mix- what in next generation?
► (-) foreign materials for the body-immune response?
► (-) transmission of genes and inheriting diseases
With present technology, embryonic stem cells
ARE NOT the answer to orthopaedic problems

37. FDA Regulatory Considerations
Human Cells, Tissues, and Cellular and Tissue-Based Products 1 (HCT/Ps)
from Adipose or Bone Marrow Tissue:
Under FDA’s risk-based HCT/P regulatory framework, which is set forth in 21 CFR Part 1271, certain
HCT/Ps are regulated solely under section 361 of the PHS Act and the regulations under
21 CFR Part 1271; no premarket review is required for these HCT/Ps. In 21 CFR 1271.10, the
regulations identify the criteria for regulation solely under section 361 of the PHS Act and
21 CFR Part 1271. An HCT/P is regulated solely under section 361 of the PHS Act and
21 CFR Part 1271 if it meets all of the following criteria (21 CFR 1271.10(a)):
1) The HCT/P is minimally manipulated;
2) The HCT/P is intended for homologous use only, as reflected by the labeling, advertising, or
other indications of the manufacturer's objective intent;
3) The manufacture of the HCT/P does not involve the combination of the cells or tissues
with another article, except for water, crystalloids, or a sterilizing, preserving, or storage agent,
provided that the addition of water, crystalloids, or the sterilizing, preserving, or storage agent does
not raise new clinical safety concerns with respect to the HCT/P; and
4) Either:
i) The HCT/P does not have a systemic effect and is not dependent upon the metabolic activity of
living cells for its primary function; or
ii) The HCT/P has a systemic effect or is dependent upon the metabolic activity of living cells for its
primary function, and:
a) Is for autologous use
b) Is for allogeneic use in a first-degree or second-degree blood relative; or
c) Is for reproductive use.
Apart from the above a hospital exemption is apparent

38. HOSPITAL EXEMPTION
► Specifically, the "hospital exemption", allows the issuance of ATMP’s
without a marketing authorization, provided that all the following
conditions are followed:
► Their preparation is not systematic
► High quality rules for preparation are followed .
► Manufactured and used in the same country area
► They are administered in a hospital environment.
► They are administered under the responsibility of the treating
physician
► They are prepared following a medical order and for a specific
patient
► Responsible for enforcing the rules of Hospital Exemption and
Administration relevant authorization are the national drug
authorities.

39. III. QUESTIONS AND ANSWERS
Q1: When does the exception in § 1271.15(b) apply?
A1: For the exception to apply, an establishment3 must meet three (3) criteria:
a. Remove and implant the HCT/Ps into the same individual from whom they
were removed (autologous use);
b. Implant the HCT/Ps within the same surgical procedure; and
c. The HCT/Ps remain “such HCT/Ps;” they are in their original form.4 The
communicable disease risks, as well as safety risks, generally would be no
different from those typically associated with surgery.

41. “GROW” STEM CELLS IN A LAB OR NOT?
► Number of studies suggest that manipulating them outside of the body:
(-) Financial cost
(-) Time for cultivation
(-) Risk of infection
(-) loose their effectiveness & proliferation capacity
(-) alter the genetic makeup of the cells
(-) changes in cell phenotypes and cell de-differentiation
(-) alter telomeres significantly
(-) FDA & EMA regulations
Absolute number & purity of MSC’s translate into greater success in cases of
severe arthritis
(+) Cryopreservation for future use-viability?
(+) Can treat more than one joint simultaneously
THE OUTCOME DATA SHOWS THE HIGHER NUMBER OF CULTIVATED STEM
CELLS WORK A LITTLE BETTER THAN SAME DAY PROCEDURE
 BMSC’s need more proliferation than ADSC’s

42. WHAT ABOUT THE SOIL (BONE)?
► Percutaneous stem cell assisted subchondroplasty
(PSCAS)
► MFx arthroscopic
► Nano-fracture
► Shock Wave Therapy

43. WHAT WE SHOULD AVOID BEFORE
BIOLOGICAL TREATMENT?
►Narcotics
►Statins
►NSAIDs, like ibuprofen, Motrin, Aleve, and
Celebrex.
►ACE* inhibitor blood pressure medications
►Steroid pills & injections
*ACE: Angiotensin Converting Enzyme

44. IS IT ENOUGH FOR A
SUCCESSFUL
REGENERATION PROCESS
?
The problem with repairing the
musculoskeletal system is its
complexity.

47. What is
“A SUCCESS”
in stem cell therapy
► PATIENT FUNCTIONALITY
► REGAIN OF R.O.M IN AFFECTED JOINT
► PAINLESS JOINT
1. WOMAC SCORE
2. SF-36
3. TEGNER SCORE
4. IKDC SCORE
► Can cartilage be regrown?
1. Lost cartilage is usually not the thing that causes pain
2. Problems in the bone more commonly cause pain
3. Only small holes in the cartilage can be regrown
What about X-RAYS?
CT-SCANS?
MRI SCANS?

48. EFFICACY OF MSC
Radiological Improvement
► TRUE OR FAULSE?
X-ray scam !
► X-rays: No improvement in joint
space/femoro-tibial angle with the weight-
bearing line
► MRI: Three randomized controlled studies
report that MSC therapy shows reduced
subchondral bone edema, extension of repair
tissue, stabilization of bone pathology &
increased cartilage thickness on MRI at 1-2
years follow-up; but these studies used MSC
as an anjunct to OWHTO; while other shows
only clinical improvement with no radiological
improvement
Lee KB, et al. Arthroscopy.2013;29: 2020-2028
Y.M.Pers, et al. Trial,Stem Cells Transl, 2016;5:847-856
Y.G Koh,et al. Arthroscopy.2016; 32:97-109

49. WHAT WE NEED FOR SUCCESS?
1. A Customized Approach to the Processing of
Your Tissue a small bedside machine that will treat
you like a number rather than an individual.
2. Dosing almost all clinics have no idea how many
cells they’re injecting into your knee. in knee
arthritis patients, we needed a minimum of 4x108
Total Nuclear Cells (TCN) in the sample to help
the patient achieve the best outcome.
3. Viability (the percentage of cells that are alive).
4. A Clinical Training and Certification Program
for Affiliates
5. Suitable scaffold
*1-3 need flow cytometer

50. ► BMSC’s too low for most « one-stop-shop » approaches and require ex vivo
enrichment and expansion of cartilage.
► 5ml of human BMSC’s produces 250±90 x106 mononuclear cells with
conventional separation technologies (2500 MSC ).
► In an outpatient procedure, up to about 180 ml of bone marrow aspirate or
90,000 MSC should be retrieved
► In an inpatient procedure, 10-15 ml/kg could be harvested, which would translate
into 10 cc/kg=350,000 MSC for a 70 kg patient
THESE NUMBERS ARE TOO LOW FOR MOST CARTILAGE REGENERATION
NEEDS.
THE OPTIMAL NUMBER OF MSCs TO BE APPLIED REMAINS UNKNOWN
HOW MANY STEM CELLS WE TAKE?

51. Is I.V a good way to deliver stem cells ?
►Consider that many of the places that
stem cells should be placed have a poor
blood supply
►about 97% of the cells get filtered out by
the lungs
►the cells need to be precisely placed
exactly where they need to go and that
can be done via imaging guidance

52. IO( intraosseous) injection for knee OA
(BMC only inside the bone)
► inject the bone under fluoroscopy guidance & IV sedation
Centeno C, et al, J. Transl Med. 2018 Dec 13;16(1):355
Hernigou P, et al, Int Orthop. 2020 Jul 2. doi: 10.1007/s00264-020-04687-7
Hernigou P,et al, . Int Orthop. 2020 Apr 23. doi: 10.1007/s00264-020-04571-4.

53. How stem cells can survive and thrive in poor blood supply
tissues like knee cartilage, menisci and spinal discs?
► Mesenchymal stem cells from bone marrow have a unique trick, they can
withstand lots of hypoxia. Meaning that your bone marrow where they
originate has parts of it that instead of being 21% oxygen like sea-level air,
that have only 1-5% oxygen (hypoxic). these cells are uniquely adapted to
live in low oxygen environments and that ability keeps them from
differentiation
► Stem cells have another trick. They can secrete VEGF or Vascular
Endothelial Growth Factor. The purpose of this growth factor is to build new
blood vessels. So not only can stem cells withstand hypoxia, but they can
also build new blood vessels to help solve that problem
Once they get more oxygen, after a few weeks, they can then begin
to engraft into the area by differentiating into a needed cell type.
Antebi B, Stem Cell Res Ther. 2018 Oct 11;9(1):265.
Hofmann NA, PLoS One. 2012;7(9):e44468

54. What happens to stem cells as we age?
Is there an age limit to stem cell therapy?
► clinics often claim that your stem cells are
too old to use, hence you need to use young
stem cells from umbilical cords. Is this true?
While aging does have some impact on stem cells, it
doesn’t mean you don’t have many live and very
viable stem cells that can used to help you heal.
Getting stem cell therapy to work in older adults is
about concentrating their cells
Centeno CJ,BMC Musculoskelet Disord. 2015;16:258.
Berger D., Interventional Orthopedics Foundation Annual Meeting. Denver, 2015
Becktell L,Orthopedic Research Society Annual Meeting, New Orleans, 2018
Panero, A, American Journal of Sports Medicine, 2019 47(5), 1230–1235.

55. Second Knee Stem Cell Procedures
►stem cell procedure can last on average,
from 2-7 years
►adding in a bone injection with a
concomitant joint injection would be better
as a next procedure. It’s very possible, that
based on the research, the duration of the
positive effect can be prolonged.
Hernigou P, et al, Int Orthop. 2020 Jul 2. doi: 10.1007/s00264-020-04687-7.

56. Efficacy of MSC in knee
cartilage lesions & OA
► Literature: Conflicting & debadable
► Most of the studies: MSC therapy improves the VAS pain score, WOMAC
score & functionality, compared to placebo or conventional treatment and
can last up to 6-12 m. After then it starts showing a download trend
► Dosages: 5-50x106 in various clinical trials; both high & low dose of
intra-articular MSC administration show beneficial effects
► Route of administration: Intra-articular, intra-lesional ,intravenously,
intraosseous, encapsulated, integrated
Lee KB, et al. Arthroscopy.2013;29: 2020-2028
Y.M.Pers, et al. Trial,Stem Cells Transl, 2016;5:847-856
Y.G et al. Arthroscopy.2016; 32:97-109

57. Culture-Expanded BM-MSC’s
► many animal studies have reported improved results with the addition
of BMAC and/or BM-MSCs for the treatment of focal cartilage defects.
► Higher concentrations of MSCs allow a more robust pro-chondrogenic
effect
Mahmoud EE, et al. Cartilage. Epub 2017 May 1
► increased glycosaminoglycan and type II collagen content in MACI
implantation augmented with culture expanded BM-MSCs in a minipig
model.
McIlwraith CW, et al. Arthroscopy. 2011;27(11):1552-61
► addition of BM-MSCs to an autologous platelet-enriched fibrin scaffold
(APEF) enhance chondral repair when compared to isolated APEF.
Goodrich LR, et al. Bone Joint Surg Am.2016;98(1):23-34.

58. ► Biocompatibility: Ability of the scaffold material to integrate
into living tissue.
► Mechanical property: Resistance to local mechanical forces.
► Pore size: Influences cell aggregation and differentiation.
► Structure and geometry: Influences proliferation and
differentiation of the transplanted cells.
► Biodegradation property: Fast or slow elimination from the
body.
► Biochemical integration: Long term integration and
availability of growth factors or cytokines.
SCAFFOLD PRODUCTS CHARACTERISTICS

59. ► What is the optimal mixture ratio between the MSCs
and fibrin glue for achieving a suitable matrix environment
is not well known
► What is the optimal number of MSCs to be applied to
fibrin glue per cm2 remains also unknown
► What is the cell-matrix interaction?
► What is the cyto-protective effect of the glue?
FIBRIN GLUE as a scaffold

60. It is important to note that helping patients
is often not as simple as injecting magic
stem cells!