1. PRP, visco-supplementation and
stem cells in MSC diseases
A.Sadauskas, MD
Head of Karoliniskes Day surgery center and Surgical departement
LACA conference
Arthroscopic joint pathology treatment methods
2016 04 08, Kaunas

2. PRP History
Proven role in healing of soft and hard tissues
First introduced in the 1980s for the treatment of
cutaneous ulcers. (Margolis et al, Diabetes Care 2001)
Use expanded in the 1990s in the maxillofacial and plastic
surgery fields. (Marx, J Oral Maxillofac Surg 2004)
Its use in orthopedic surgery began roughly a decade ago
– Initially used with bone grafts to augment spinal fusion and
fracture healing
Mechanism of action comprises anti-inflammatory
activity and activation of cell-signalling cascades
(Barry 2001, Sevens 2004)

3. PRP Definition
Platelet-Rich Plasma
Is defined as autologous blood fraction with platelet
concentration exceeding original blood concentration
(200.000 platelets/µL) by 2-6 times
Mazzucco L et al. Vox Sang. 2009; 97(2): 110-118
Arnoczky et al, JAAOS 2010

4. Platelet activation
Resting platelets Activated platelets
http://orthoregensr.com/regenerative-medicine-scien.html

5. Platelet activation (2)
PRIME. GROWTH FACTORS IN ANTI-AGEING, REGENERATIVE, AND AESTHETIC MEDICINE. DANIEL L. SISTER / MAY 14, 2015

6. Healing processes in case of injury
− 70% within 10 minutes, almost 100% within 1 hour
− Platelets continue the excretion of small amounts of GF within next 7-10 days
http://orthoregensr.com/regenerative-medicine-scien.html
Platelet degranulation takes place mainly during I inflammation phase

7. Growth factors (found in α granules) facilitates
cartilage and synovium regeneration
Akeda K et al. Osteoarthritis Cartilage. 2006; Wu W et al. J Oral Maxillofac Surg. 2007
Saito M et al. Clin Exp Rheumatol. 2009

8. PRP application in clinical practice
Tendinosis, tendinopathies (patelar tendinosis, Achiles tendinopathy)
Enthesopathies (epicondylitis, plantar fasciitis)
Ligamentous injury (ACL reconstrcution surgery)
Cartilage injury
Osteoarthritis
Osteochondritis dissecans
Avascular femoral head necrosis
Muscle injuries
Bone augmentation (fusion, non-unions)
Chronic non-healing wounds

9. Pain scores change after PRP (time-dependent effect)
vs. treatment for control patients
I. Andia et al. Br Med Bull 2014; 110:99-115
Forest plot of WMD showing time-dependent effect on pain scores in entesopathies treatment

10. PRP improves RTP/RTS (return to play/sport)
time for elite athletes by 6 days*
…can get you back to what you love to do
*Laver L. et al. Knee Surg Sports Traumatol Arthrosc. 2015 Nov; 23(11):3383-92*

11. Evidence of PRP benefit
in the treatment of osteoarthritis
Greater effect in younger patients (<60 years old)
Better pain reduction in grade I-II osteoarthritis
G. Filardo, E. Kon, A. Roffi, B. Di Matteo, M. L. Merli, M. Marcacci
Platelet-rich plasma: why intra-articular? A systematic review of preclinical studies and
clinical evidence on PRP for joint degeneration
Knee Surg Sports Traumatol Arthrosc 2015; 23:2459–2474

12. Effect of repeated PRP injections
for early OA (Kellgren-Lawrence I-II)
KOOS pain score and sports activities improvement
Gobbi A et al. Knee Surg Sports Traumatol Arthrosc. 2015 Aug;23(8):2170-7
Annual repetition of PRP injections extend benefit from 12 to 18 months

13. PRP benefit in the treatment of
symptomatic patients with knee OA (1)
Gobbi A et al. Sports Health: A Multidisciplinary Approach 2012; 4(2):162-72
50 active patients with
symptomatic knee OA
(Kellgren - Lawrence
grade 1-3)
A.Gobbi, et al. PRP Treatment in Symptomatic Patients with Knee OA: Preliminary Results in a Group of Active Patients.
S1a S1b

14. Tegner scale VAS scale
Significant improvement (p < 0.001)Significant improvement (p < 0.001)
PRP benefit in the treatment of
symptomatic patients with knee OA (2)
Gobbi A et al. Sports Health: A Multidisciplinary Approach 2012; 4(2):162-72

15. PRP benefit in the treatment of
symptomatic patients with knee OA (3)
There was no significant difference in improvement between patients with
previous cartilage shaving (S1a) or microfracture (S1b) in all evaluated scores
Benefit persists without significant difference in improvement
(Mann-Whitney U test)
Gobbi A et al. Sports Health: A Multidisciplinary Approach 2012; 4(2):162-72

16. Not all PRP created equal
Pure PRP (Anitua’s PRGF, 1999)
PRP + leucocytes (Rizzoli Orthop Inst, Bologna
regenlab)
Platelet-rich fibrin
Platelet-rich fibrin + leucocytes
ACP

17. Effective cellular therapy requires a scaffold for cell migration,
progenitor cells which can be converted into bone or soft tissue, and
signal proteins to modulate the repair and regeneration process.
The three essential components that make
up the tissue-engineering triad
Daher, R.J. et al. New methods to diagnose and treat cartilage degeneration. Nat. Rev. Rheumatol. 2009; 5, 599-607

18. 2 from 3 essential tissue-engineering
components can be put together
PRP (GF)
Hyaluronic acid (matrix/scaffold)
Cytokine modulation
IL-Ira inhibition
Stem cells
Adipose derived SVF
BMSC
Allogenic stem cells
Search for Chondroprotection and chondrofacilitation. Mandelbaum BR. 2015

19. Two in one concept for OA treatment
Andia I, Abate M. Expert Opin Biol Ther. 2014 May; 14(5):635-49

20. Viscosupplementation for knee OA
Provides pain relief and improves mobility with 1-5 i.a.
injections of HA
Compensates the decrease of intra-articular HA
molecular weight and concentration
Benefits of HA last 6-12 months with up to 75%
response rate (25 years of clinical experience)
Network of HA chains constitutes ideal cell-friendly
matrix

21. www.cellularmatrix.info

22. User-friendly preparation and injection
A- blood sampling
B – centrifugation of the
blood for 5 min
C – PRP + HA fraction
after centrifugation
D – intraarticular knee
injection

23. Suggested rehabilitation protocol following
PRP injection
Gobbi A, Bathan L. J Knee Surg. 2009; 22:36-44.

24. All 3 essential components
can be put together (1)
PRP (GF)
Hyaluronic acid injection
Cytokine modulation
IL-Ira inhibition
Stem cells
Adipose derived SVF
BMSC (progenitor cells)
Allogenic stem cells
Bone from bone bank (scaffold)

25. All 3 essential components
can be put together (2)
Capanna R. Proceedings Biobridge Generation Congress, Venice. 2013
BMSC
Bone from the bone bank PRP (GF)

26. Tissue-engineering triad can complement the stable osteosynthesis
Before… …and after
Failed osteosynthesis before composite bone graft
(25 old male patient)**
Bone healing 3 months after composite bone graft
and stable osteosynthesis**
*Giannoudis PV, Einhorn TA, Marsh D. Injury. 2007;38 (Suppl. 4):S3-6
**Innocenti M. Proceedings Biobridge Generation Congress, Venice/Italy. 2014
Fracture healing: the diamond concept*

27. Efficacy of autologous stem cell-based therapy and
decompression for osteonecrosis of the femoral head
Daltra GC, et al. Stem Cell Research & Therapy 2015
Anteroposterior X-ray
radiograph showing
minimally invasive
decompression
Coronal T1-weighted MRI
scans of the right hip before
surgery show osteonecrotic
lesion in Ficat IIB stage
MRI scan shows delimited
marrow region of increased
signal intensity (arrow)
within the necrotic area,
hypointense line around them
due to reparative new bone
MRI scan after
autologous BMMC
implantation showing the
channel, decreased
bone edema and
changes of signal in the
superior part of the femur
Preoperative (e) and 60-
month postoperative
anteroposterior (f)
radiographs of the same
hip showing the femoral
head has maintained
the sphericity

28. Ficat and modified Ficat classification
of AVN scoring
http://radiologykey.com/imaging-of-the-hip-and-pelvis/
A-mild
B-moderate
C-severe

29. Lithuanian experience in composite bone
grafting in avascular femoral head necrosis
Prof. S.Tarasevičius. LHSU KK, Clinic of orthopedics and traumatology
Vencevičius R., MD. VUH SK, Department of orthopedics & traumatology
Jonaitis T., MD. Baltic-American clinic, Vilnius
Fiodorovas M., MD. Klaipeda city university hospital
Prof. Š.Tarasevičius. Nauja galimybė atkurti sunykusį šlaunikaulio galvos kaulą.
Lietuvos gydytojo žurnalas. 2015; 10: 66-68

30. Take home message
PRP regulates cartilage and synovium regeneration by anti-
inflammatory action and cell-signaling cascade (GF)
PRP combined with HA creates synergy in reducing inflammation,
relieving pain and restoring patient mobility
Tissue engineering triade (PRP/GF, MSC and scaffold) is a potential
treatment option in complicated cases of non-union in addition to
stable osteosynthesis
Autologous stem cell-based therapy with decompression is a
promissing treatment option for osteonecrosis of the femoral head

31. Thank you for your attention
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