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Platelet Rich Plasma PDF
Platelet Rich Plasma PDF
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DiponEd/PRP
PRP has been investigated and used as clinical tool for several types of medical treatments,
including
Nerve injury
Tendinitis
Osteoarthritis
Cardiac muscle injury
Bone repair and regeneration
Facial plastic surgery
Oral surgery
Chronic wounds
Non-healing diabetic ulcers
Chronic diabetic foot ulcers
Refractory skin lesion
Traumatic scars
Hair growth
Soft tissue augmentation & reconstruction
Survival of fat grafts
Lower extremity ulcers
Breast contouring
Chronic pressure ulcer
Osteochondral defects
Knee injuries
Arthroscopic rotator cuff repairs
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REFERENCES
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PLATELET ALPHA-GRANULES.
Platelets contain a vast number of biologically active molecules within cytoplasmic granules
which are classified according to their respective distinct ultrastructures, densities and content.
The alpha-granule is a unique secretory organelle in that it exhibits further compartmentalization
and acquires its protein content via two distinct mechanisms: (1) biosynthesis predominantly at
the megakaryocyte (MK) level (with some vestigial platelet synthesis) (e.g. platelet factor 4) and
(2) endocytosis and pinocytosis at both the MK and circulating platelet levels (e.g. fibrinogen
(Fg) and IgG). The currently known list of alpha-granular proteins continues to enlarge and
includes many adhesive proteins (e.g. Fg, von Willebrand factor (vWf) and thrombospodin
(TSP)), plasma proteins (e.g. IgG and albumin), cellular mitogens (e.g. platelet derived growth
factor and TGF beta), coagulation factors (e.g. factor V) and protease inhibitors (e.g. alpha 2-
macroglobulin and alpha 2-antiplasmin). More recently the inner lining of the alpha-granule unit
membrane has been demonstrated to contain a number of physiologically important receptors
including glycoprotein IIb/IIIa (alpha IIb beta 3) and P-selectin. The alpha-granules originate
from small precursor granules which can be observed budding from the trans-Golgi network
within the platelet precursor cell the MK. During MK maturation the alpha-granules become
very prominent and are ultimately packaged into platelets during thrombopoiesis. The alpha-
granular contents are destined for release during platelet activation at sites of vessel wall injury
and thus play an important role in haemostasis, inflammation, ultimate wound repair and in the
pathogenesis of atherosclerosis.( Harrison P, Cramer EM. 1993)
REFERENCES
Harrison P, Cramer EM. Platelet alpha-granules. Blood Rev. 1993 Mar;7(1):52-62.
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Zhongguo Xiu et al., compared the platelet enrichment ratio of platelet-rich plasma (PRP)
prepared by different centrifuge methods and to compare the concentration of growth factors
released from autologous platelet-rich gel (APG) with the whole blood.Thirteen diabetic patients
with refractory skin lesions were enrolled in APG treatment. (1) Three kinds of centrifuge
methods were selected for PRP by 11 diabetic patients: A (n = 6): 529 x g for 4 minutes in the
first centrifuge and 854 x g for 6 minutes in the second centrifuge; B (n = 5): 313 x g for 4
minutes in the first centrifuge and 1,252 x g for 6 minutes in the second centrifuge; C (n = 5):
176 x g for 5 minutes in the first centrifuge and 1,252 x g for 5 minutes in the second
centrifuge. Platelet counted on the whole blood and PRP was determined. The APG, produced by
combining the PRP with thrombin and calcium gluconate (10:1) was used by patients. (2) PDGF-
BB, TGF-beta1, VEGF, EGF, and IGF-1 were measured in the APG and the whole blood using
the enzyme-linked immunosorbent assay method.(1) The average platelet concentration was
higher in group B [(1,363.80 +/- 919.74) x 10(9)/L] than in groups A [(779.67 +/- 352.39) x
10(9)/L)] and C [(765.00 +/- 278.78) x 10(9)/L] and the platelet recovery rate was 75.2% +/-
21.0% in group B. (2) The concentration of growth factors all increased with the
increasing platelet number. On average, for the wholeblood as compared with APG, the PDGF-
BB concentration increased from (145.94 +/- 133.24) pg/mL to (503.81 +/- 197.86) pg/mL (P <
0.05); TGF-beta1 concentration increased from (3.31 +/- 2.27) ng/mL to (5.67 +/- 4.80) ng/mL
(P < 0.05); IGF-1 concentration increased from (14.54 +/- 35.34) ng/mL to (110.56 +/- 84.36)
ng/mL (P < 0.05); and EGF concentration increased from (160.73 +/- 71.10) pg/mL to (265.95
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+/- 138.43) pg/mL (P < 0.05). No increase was found for VEGF (P > 0.05). (3) There was
positive correlation between the platelet concentration and PDGF-BB and TGF-beta1 (r = 0.627,
r = 0.437, P < 0.05). (4) Thirteen diabetic repractory dermal ulcers received APG treatment for
18 times, 9 ulcers (69.2%) and 10 sinuses (88.3%) were cured at the end of 12-week treatment.
There is positive correlation between the platelet concentration and PDGF-BB and TGF-
beta(Yuan N et al. 2008)
Hong JP et al studied the healing effect of recombinant human epidermal growth factor (EGF) on
chronic diabetic foot ulcers. A total of 89 patients enrolled for the prospective, open-label trial,
crossover study. Predetermined criteria were used for diagnosis and classification of ulcer. The
average duration of ulcer was 6 months (range from 3 to 27 months) prior to study. Upon study,
the ulcers were debrided and treated with hydrocolloid or composite dressing depending on the
condition of the wound. If treatment effect was minimal using advanced dressing for 3 weeks,
patients were crossed over to twice-a-day treatment with 0.005% EGF and advanced dressing.
Among the patients, 21 patients showed improvement using hydrocolloid or composite dressing
alone and 68 patients were crossed over to treatment with EGF and advanced dressing. In the
EGF-treated patients, complete healing was noted in 52 patients within an average of 46 days
(range from 2 to 14 weeks). Recurrence was not noted during the 6-month observation. But 5
patients showed new lesions different from the prior site. Sixteen patients required further
interventions. Results suggests that topical treatment with EGF combined with advanced
dressing may have positive effects in promoting healing of chronic diabetic foot wounds. (Hong
JP et al., 2008)
Recombinant human epidermal growth factor (REGEN-D 150), which was cloned and over
expressed in E. coli, has shown enhanced healing of chronic diabetic foot ulcers (DFU) by
significantly reducing the duration of healing in addition to providing excellent quality of wound
healing and reepithelization. Post-marketing surveillance (PMS) study of REGEN-D 150 in 135
patients of DFU in India was compared with Phase III clinical trial data of REGEN-D 150 in
India. Statistical analysis of study data determined that the empirical survival probability
distribution, in terms of non-healing of ulcers, was lowest in the case of PMS study, better than
that for Phase III; more DFU patients were healed in PMS study. Percentage of patients cured in
any given week (e.g., in week 10) is above 90% in PMS study, as compared to 69% in Phase III
clinical trial; this percentage was around 18% for the control group with placebo in the Phase III
trial. The average wound healing time was significantly lower in PMS study, 4.8 weeks, while it
was 9 weeks in Phase III clinical trials while the average wound healing with REGEN-D 150
was found to be 86% in this study. REGEN-D 150 has been found to result in healthy
granulation and stimulate epithelization, thus leading to final wound closure. The PMS study has
established the efficacy of REGEN-D 150 in fasterhealing of diabetic foot ulcers. (Mohan VK
2007)
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REFERENCES
2. Hong JP, Jung HD, Kim YW Recombinant human epidermal growth factor (EGF) to
enhance healing fordiabetic foot ulcers. Ann Plast Surg. 2006 Apr;56(4):394-8;
discussion 399-400.
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Nakamura et al., evaluated the effects of platelet-rich plasma (PRP) on resorption and adipocyte
survival in autologous fat-graft of rats prepared with isogenous PRP. Fat grafts prepared without
PRP (control group) became united to the tissue adjacent to the implantation site and were
significantly resorbed from 30 days. On the other hand, fat grafts prepared with PRP (PRP
group) demonstrated little resorption from 30 to 120 days and appeared pink, had a soft, supple
feel, and were easily compressible. Histologic sections of grafts in the control and PRP groups at
10 days exhibited similar consolidation of the grafted tissue, which contained morphologically
normal adipocytes with different degrees of granulation and capillary formation. From 20 days
normal adipocytes were obviously decreased in the control group, while the PRP group
demonstrated increased granulation tissue and capillary formation and good maintenance of
normal adipocytes for at least 120 days.( Nakamura S et al., 2010 )
Autologous fat theoretically provides one of the most ideal mediums for soft-tissue
augmentation and reconstruction, although its clinical applications have been marked with
skepticism because of its documented unreliable survival. Over the years, numerous unsuccessful
efforts have set forth to elucidate modifications in the application process of autologous fat grafts
to allow the medium greater clinical predictability. Kevin et al., investigated the effects of
platelet-rich plasma (PRP) on autologous fat grafts when used in conjunction with each other in
soft tissue augmen- tation and reconstruction.study is Retrospective review, over a 30-month
period, of consecutive patients with results greater than 6 months in duration.based on clinical
experiences representing 2033 grafts in 448 consecutive patients using PRP additives and in the
previous 132 patients who had syringe harvest without use of PRP. All PRP isolates were
harvested via the Smart Prep system. Results were based on clinical observations and patient
satisfaction. Of the 580 patients in the experimental group, essentially all showed greater graft
volume retention over extended time intervals compared with control subjects (nongraft areas).
Patients in the PRP-added experimental group displayed less postoperative ecchymosis and
edema, which also led to greater patient satisfaction in this group. Adding PRP to autologous fat
aids in graft volume retention and survival when used clinically for soft- tissue augmentation and
reconstruction (Kevin S et al., 2006)
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dissection from the scapular area of the own animal) in the ears and were randomised into two
groups. Group 1 (PRP group) was given the combination of 0.8 g of free fat graft and 1 ml of
PRP. Group 2 (control group) received 0.8 g of free fat graft and 1 ml of saline solution. The
rabbits were followed up for a period of 6 months after the procedure and then euthanised. The
grafted tissue was stained with haematoxylin-eosin and submitted to microscopical evaluation.
Graft histopathology was investigated for adipocyte viability, number of blood vessels and the
presence of necrosis and fibrosis. All data were statistically analysed by the differences between
the study groups.Three major effects of the addition of PRP in the free fat graft were observed.
Group 1 showed a significantly higher fat survival weight as compared with the control group
(P<0.05). Histopathological investigations revealed that the number of viable adipocytes and
blood vessels was higher in group 1, and still, a larger number of necrotic areas and fibrosis were
detected between group 2 (P<0.05). Application of autogenous PRP can enhance free fat graft
survival in rabbits.( Pires Fraga MF et al., 2010)
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showed an improvement in reepithelialisation; in fact after 9.7 weeks, they underwent a 97.8% ±
1.5% reepithelialisation compared to 89.1% ± 3.8% of the second control group (only PRP;
p<0.05). As reported e-SVF and PRP mixed with fat grafting were the two treatments evidencing
improvement in the healing of patients post-traumatic extremity ulcers.(Cervelli Vet al,.2011)
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and microcyst formation. Theoretically, if PRP reduces the time needed for the grafted cells to be
accepted in its recipient site, there will be less loss of graft cells to prolonged inflammation and
necrosis, and improved
clinical efficacy,". In the last few years, development of an affordable and convenient method of
isolating PRP has made its uses in outpatient surgeries much more enriching all processed fat
with PRP, regardless of the volume of grafts and whether the material will be used for immediate
transfer, or frozen for delayed grafting. Currently, he uses "plain" PRP (not activated with the
addition of calcium chloride and thrombin) isolated with technology able to spin down a useful
volume of platelet concentrate from a reasonably small sample of blood. A 16- to 18- cc
blood specimen yields about 3 cc of PRP, while 10 cc of PRP is obtained from 54 cc of blood.
(Cheryl Guttman 2004)
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REFERENCES
3. Cheryl Guttman Platelet-rich plasma offers vast fat graft benefits PRP-enrichment
increases cellular survival and proliferative potential Cosmetic Surgery Times, 2004.
4.
JAMES E. FULTON, M.D., PH.D. Breast contouring with "gelled" autologous fat
5. Kevin S. Sadati, DO; Anthony C. Corrado, DO; Robert W. Alexander, MD, DMD:
Platelet-Rich Plasma (PRP) Utilized To Promote Greater Graft Volume Retention
in Autologous Fat Grafting 2006
8. Pires Fraga MF, Nishio RT, Ishikawa RS, Perin LF, Helene A Jr, Malheiros
CAIncreased survival of free fat grafts with platelet-rich plasma in rabbits. J Plast
Reconstr Aesthet Surg. 2010 Dec;63(12):e818-22. Epub 2010 Aug 13.
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Recently, autologous platelet-rich plasma (PRP) has attracted attention in various medical fields,
including plastic and orthopedic surgery and dermatology, for its ability to promote wound
healing. PRP has been tested during facelift and hair transplantation to reduce swelling and pain
and to increase hair density.PRP was prepared using the double-spin method and applied to
dermal papilla (DP) cells. The proliferative effect of activated PRP on DP cells was measured.
To understand the mechanisms of activated PRP on hair growth, we evaluated signaling
pathways. In an in vivo study, mice received subcutaneous injections of activated PRP, and their
results were compared with control mice, Results suggest that Activated PRP increased the
proliferation of DP cells and stimulated extracellular signal-regulated kinase (ERK) and Akt
signaling. Fibroblast growth factor 7 (FGF-7) and beta-catenin, which are potent stimuli for hair
growth, were upregulated in DP cells. The injection of mice with activated PRP induced faster
telogen-to-anagen transition than was seen on control mice this research provides support for
possible clinical application of autologous PRP and its secretory factors for promotion of hair
growth(Li ZJ et al., 2012)
Treatments for alopecia are in high demand, but not all are safe and reliable. Dalteparin and
protamine microparticles (D/P MPs) can effectively carry growth factors (GFs) in platelet-rich
plasma (PRP). Takikawa M et al., analyzed the effects of PRP-containing D/P MPs (PRP&D/P
MPs) on hair growth.with 26 volunteers Participants with thin hair who received five local
treatments of 3 mL of PRP&D/P MPs (13 participants) or PRP and saline (control,13
participants) at 2- to 3-week intervals and were evaluated for 12 weeks. Injected areas comprised
frontal or parietal sites with lanugo-like hair. Experimental and control areas were photographed.
Consenting participants underwent biopsies for histologic examination. Results suggest that D/P
MPs bind to various GFs contained in PRP. Significant differences were seen in hair cross-
section but not in hair numbers in PRP and PRP&D/P MP injections. The addition of D/P MPs to
PRP resulted in significant stimulation in hair cross-section. Microscopic findings showed
thickened epithelium, proliferation of collagen fibers and fibroblasts, and increased vessels
around follicles. PRP&D/P MPs and PRP facilitated hair growth but D/P MPs provided
additional hair growth. The authors have indicated no significant interest with commercial
supporters.( Takikawa M et al., 2011 )
ACell (Matristem) attracts Adult Stem Cells to the site of injury (in this case Hair
Transplantation) and converts them into active progenitor cells which is what becomes missing
during hair miniatuization. It also sets up a non crosslinked temporary scaffolding for the tissue
reconstruction mimicking the surrounding healthy but damaged tissue. This scaffolding contains
and slowly releases growth factors (VEGF etc.). The Acell also contains an abundance of
necessary materials for remodeling including Collagen IV.This process has resulted in increased
hair counts in the grafts in the recipient area (increased hair density) plus remarkable healing in
the donor area. Much has been written as of late in the use of PRP (Platelet Rich Plasma)
Injections to slow down or stop balding as well as to re-grow miniaturizing scalp hairs. A lot of
the early reported variable successes have been attributed to the fact that there are significant
vital proteins (Collagen IV etc.) as well as multiple growth factors (ie: VGRF) that are vital to
terminal hairs along with hair survival and enhancement in general. It has been postulated that
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the addition of ECM (Extracellular matrix) may significantly improve the results.( Greco, J,
2009)
REFERENCES
1. Greco, J, Brandt, R. The effects of autologous platelet rich plasma and various
growth factors on non-transplanted miniaturized hair. Hair Transplant Forum
Int’l, Vol 19:2, 49-50, March /April 2009
2. Li ZJ, Choi HI, Choi DK, Sohn KC, Im M, Seo YJ, Lee YH, Lee JH, Lee Y
Autologous Platelet-Rich Plasma: A Potential Therapeutic Tool for Promoting Hair
Growth. Dermatol Surg. 2012 Mar 27. doi: 10.1111/j.1524-4725.2012.02394.x
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REFERENCES
1. Cervelli V, Gentile P, Scioli MG, Grimaldi M, Casciani CU, Spagnoli LG, Orlandi A.
Application of platelet-rich plasma in plastic surgery: clinical and in vitro
evaluation. Tissue Eng Part C Methods. 2009 Dec;15(4):625-34
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3. Farrior E, Ladner K Platelet gels and hemostasis in facial plastic surgery.. Facial Plast
Surg. 2011 Aug;27(4):308-14. Epub 2011 Jul 26.
4. Sclafani AP, Saman M. Platelet-rich fibrin matrix for facial plastic surgery. Facial
Plast Surg Clin North Am. 2012 May;20(2):177-86
5. Bhanot S, Alex JC Current applications of platelet gels in facial plastic surgery. Facial
Plast Surg. 2002 Feb;18(1):27-33
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Chronic pressure ulcers affect patient health, emotional state, and quality of life, causing
considerable morbidity and mortality in addition to contributing to significant health care costs
from lengthy hospitalizations to advanced home care and surgical care costs. The conventional
treatment of these wounds can be slow due to their chronic inflammatory state and the
senescence of local reparative cells. Platelet-rich plasma (PRP) therapy has been growing as a
viable treatment alternative for a number of clinical applications and has potential benefit for use
in chronic wounds. The sustained release of large quantities of autologous growth factors,
cytokines, and other mediators found in PRP plus the favorable mononuclear cell profile of PRP
may help us to stimulate wound healing and resolve chronic inflammation. Three veterans with
spinal cord injury (SCI), presenting with chronic stage IV pressure ulcers, were treated with a
sustained release PRP therapy to stimulate wound healing. Results suggest that PRP treatment
consistently resulted in the formation of granulation tissue and improved vascularity for
each of the three patients treated, while reducing the overall ulcer area and volume. The
controlled release of growth factors from PRP demonstrated a positive stimulatory effect on the
healing rate of chronic pressure ulcers in individuals with SCI.( Scott A. Sell et al., 2011)
REFERENCES
1. Scott A. Sell1,2, Jeffery J. Ericksen1,3, Timothy W. Reis1,3, Linda R. Droste4,
Mohammed B. A. Bhuiyan4, David R. Gater3,4: A case report on the use of sustained
release platelet-rich plasma for the treatment of chronic pressure ulcers The Journal
of Spinal Cord Medicine 2011 VOL. 34 NO. 1.
2. Ting Yuan, MD; Chang-Qing Zhang, MD; Ming-Jie Tang, MD; Shang-Chun Guo, MD;
Bing-Fang Zeng, MD Autologous Platelet-rich Plasma Enhances Healing of Chronic
WoundsWOUNDS 2009;21(10):280–285.
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REFERENCES
Daniel Man, M.D., Harvey Plosker, M.D., and Jill E. Winland-Brown, Ed.D., M.S.N., F.N.P.-C. THE USE OF
AUTOLOGOUS PLATELET-RICH PLASMA (PLATELET GEL) AND AUTOLOGOUS
PLATELET-POOR PLASMA (FIBRIN GLUE) IN COSMETIC SURGERY Plast.
Reconstr Surg. 107: 229, 2001.
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REFERENCES
1. Marissa J. Carter, PhD, MA,a Carelyn P. Fylling, MSN, RN, CWS, CLNC,b
and Laura K. S. Parnell, MSc Use of Platelet Rich Plasma Gel onWound Healing: A
Systematic Review and Meta-Analysis, CWS 2011
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Platelet-rich plasma (PRP), a platelet concentrate made of autogenous blood, has been used to
improve bone and soft tissue defect healing in recent years. The aim of this study was to assess
the effect of PRP on articular cartilage defects in a rabbit model. Forty-eight osteochondral
defects created in the femoropatellar groove were (a)left untreated, (b) treated with autogenous
PRP in a polylactic- glycolic acid (PLGA), or (c) with PLGA alone. Platelets were enriched
5.12-fold compared to normal blood in the PRP. After four and 12 weeks, the explanted
tissue specimens were assessed by macroscopic examination,micro-computed tomography, and
histological evaluation. Macroscopic examination, micro-computed tomography and histology of
the newly formed cartilage and bone in the defect differ significantly between the PRPtreated
and the untreated groups, and stimulatory effect of PRP on osteochondral formation was
observed. In conclusion, PRP in PLGA improves osteochondral healing in a rabbit model.( Y.
Sun et al., 2009)
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Injuries affecting the knee occur at a relatively high incidence, in athletes and causes instability
and reduced function, besides being extremely painful, especially the acute phase. Surgical
treatment is widely accepted as the therapy of choice and is recommended especially for young
athletes in need of immediate return to their activities.
In recent years the use of growth factors has been used to speed healing, with the idea of a faster
return to activity without restriction . The platelet-rich plasma (PRP) is defined as a volume
fraction of blood plasma with an autologous platelet concentration above baseline. Platelets
contain a large number of growth factors and cytokines that have a role in bone regeneration and
soft tissue maturation . The rationale for use of the PRP is the reverse relationship of red blood
cells that are less useful in the healing process and increase the recovery of platelets to . Since
the use of PRP is increasing to improve the treatment of various orthopedic pathologies, held
review in order to elucidate the efficacy of PRP in patients with knee injuries.( Romulo Soares
Paris et al.,)
REFERENCES
Contact info:
Dr. Kaushik Deb
Diponed Biointelligence LLP
#60/A, 2nd floor, Karnataka Bank Building
Jigani Link road, Bomasandra Industrial area
Bangalore, KA 560099 India
Ph-+91-9900520141
E-mail: deb@diponed.com
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