Applications of Leukocyte - and Platelet-Rich Plasma (L-PRP) in Trauma

Current Pharmaceutical Biotechnology, 2012, 13, 1173-1184 1173
Applications of Leukocyte- and Platelet-Rich Plasma (L-PRP) in Trauma

Surgery
Ting Yuan1, Shang-Chun Guo2, Pei Han1, Chang-Qing Zhang1* and Bing-Fang Zeng1
1
Department of Orthopedics, Shanghai Sixth Peoples Hospital, Shanghai Jiaotong University, Shanghai, China;
2
Institute for Microsurgery Extremities, Shanghai Sixth Peoples Hospital, Shanghai Jiaotong University, Shanghai,
China
Abstract. Leukocyte- and platelet-rich plasma (L-PRP) contains high concentrations of platelet, leukocytes and other bio-
activities, which play an prominent role in both bone and soft tissue healing processes. Large numbers of studies provide
evidence for application of L-PRP in experiments and clinical practice. It has been identified to improve cellular chemo-
taxis, proliferation and differentiation, angiogenesis, and production of extracellular matrix, but also responsible for stimu-
lating defense mechanisms against infections. L-PRP is now playing an increasing role in the management of patients with
traumatic injuries. However, most studies are only anecdotal or case reports, and then larger controlled studies are needed.
This article introduces the reader to L-PRP properties and L-PRP applications in trauma surgery, including applications of
L-PRP in bone healing, acute soft tissue wound healing, and repairing of acute muscle, tendon, ligament, nerve and carti-
lage injury caused by trauma.
Keywords: Blood platelet, growth factor, trauma, fracture, wound healing, platelet-rich plasma.
1. INTRODUCTION rich material may also have increased concentrations of leu-

kocytes, fibrin and some bioactive proteins [17]. In view of
Leukocyte- and platelet-rich plasma (L-PRP) is a volume
the general state of confusion, it is necessary to use a pre-
of plasma fraction of autologous blood having platelet and
cisely defined terminology for platelet-rich preparations. In
leukocyte concentrations above baseline. It has been utilized
terminology chapter the authors presented that it might be
in surgery for much of the past 2 decades for its healing
properties attributed to the increased concentrations of more appropriate to apply the term L-PRP, for this osteoin-
growth factors and bioactive proteins. When platelets are ductive biomaterial is rich in platelets, leukocytes and related
activated by thrombin, alpha granules contained in platelet active substances.
release a number of growth factors, such as platelet-derived In recent years, L-PRP has been showing its advantages
growth factor (PDGF), transforming growth factor-beta in the fields of trauma surgery for facilitating bone and soft
(TGF-), insulin-like growth factor (IGF), epidermal growth tissue healing experimentally and clinically. In experimental
factor (EGF), and vascular endothelial growth factor studies, L-PRP has been identified to improve cellular che-
(VEGF), which play an prominent role in both bone and soft motaxis, proliferation and differentiation, angiogenesis, and
tissue healing processes [1, 2]. In addition, L-PRP contains production of extracellular matrix, but also responsible for
high concentration of leukocytes, which contribute to local stimulating defense mechanisms against infections [18-20].
debridement and exhibit bactericidal activities in acute and Clinically, thanks to the development of commercially L-
chronic wounds [3]. Up to now, L-PRP has been safely used PRP preparation devices, L-PRP can be produced easily and
and documented in various fields including: maxillofacial safely in clinical practice, requiring only approximately 15-
surgery, dentistry, neurosurgery, ophthalmology, otorhino- 30 minutes. The recent technologic advances have enabled
laryngology, wound healing, cosmetic, cardiothoracic, sports the administration of L-PRP to move from the hospital set-
medicine, and orthopedics. ting into outpatient and ambulatory surgical centers, even
L-PRP has been described in the literature under different into physicians offices. Clinical studies also show the bene-
names and abbreviations, such as platelet-rich plasma (PRP) ficial effects of L-PRP, which include more rapid reepithe-
[4], autologous platelet concentrate (APC) [5, 6], platelet lialization and bone formation, reduced need for blood trans-
concentrate (PC) [7, 8], platelet-rich concentrate (PRC) [9, fusion, reduction in postoperative swelling, bruising, and
10], platelet gel (PG) [11], platelet-rich fibrin (PRF) [12, 13], pain; shorten hospital stay and early return to mobility [21-
autologous growth factors (AGF) [14, 15], and platelet- 24].
leukocyte gel (PLG) [16]. Some authors define platelet-rich Although the majority of studies about L-PRP have
materials as only platelets whereas others note that platelet- yielded excellent outcomes, most are only anecdotal or case
reports, and then larger controlled studies are needed. This
*Address correspondence to this author at the Department of Orthopedics, article introduces the reader to L-PRP properties and L-PRP
Shanghai Sixth Peoples Hospital affiliated to Shanghai Jiaotong University, applications in trauma surgery.
No. 600 Yishan Road, 200233, Shanghai, PR China; Tel.: 00 86 21 6436
9181; Fax: 00 86 21 64 701361; E-mail: yuanting3000@yahoo.com.cn
1873-4316/12 $58.00+.00 2012 Bentham Science Publishers

1174 Current Pharmaceutical Biotechnology, 2012, Vol. 13, No. 7 Yuan et al.
2. APPLICATIONS OF L-PRP IN TRAUMA SURGERY platelet concentration required for a positive L-PRP effect on
bone regeneration seems to span a very limited range. It
Application of L-PRP appears and develops as a modifi-
showed that the variability of platelet concentration in the L-
cation of fibrin glue (fibrin sealant or fibrin gel). In the early
PRP may indeed be responsible for the published variable
1990s, fibrin glue was developed as a biomaterial with he-
results [41].
mostatic and adhesive properties. After fibrin glue was intro-
duced, the strategic modification of the fibrin to include
platelets was reported [25]. With an increasing understand-
ing of the physiological roles of platelets in wound healing,
using platelets as therapeutic tools and use of L-PRP are be-
coming more widespread, which open new avenues in
trauma surgery and other fields.
L-PRP works mainly via the degranulation of the gran-
ules in platelets, which contain the synthesized and prepack-
aged growth factors. For the platelets to become activated
and degranulate, and thus release these growth factors, an
exogenous application of thrombin and 10% calcium chlo-
ride would be often added [26, 27]. After activated by throm-
bin, L-PRP begins secreting these proteins within ten
minutes of clotting, with more than 95% of the growth fac-
tors secreted within one hour [4]. Therefore, L-PRP must be
developed in an anticoagulated state and should be used on
the wound within 10 minutes of clot initiation. Many cur- Fig. (1). L-PRP and thrombin and 10% calcium chloride are in-
rently available L-PRP preparation kits provide the suitabil- jected simultaneously through a dual syringe mixing system into the
ity, with using a dual syringe mixing system, which consists nonunion fracture site in operation.
of a 10-mL syringe housing the L-PRP and a 1-mL syringe
containing thrombin solution (usually bovine thrombin) and 2.1. L-PRP and Bone Healing
10% calcium chloride Fig. (1) [28, 29]. Both syringe plung-
Musculoskeletal injuries are the most common cause of
ers are connected to move in concert with both output ports
severe long-term pain and physical disability, and affect
connected to a dual spray applicator tip that allows both so-
hundreds of millions of people around the world. The years
lutions to be mixed as they are applied to the surgical bed.
2000-2010 have been termed the decade of bone and joint
Then L-PRP can be transformed into a platelet geland
as a global initiative to promote further research on preven-
easily used to cover or fill wound site.
tion, diagnosis, and treatment [42]. In the past years, scien-
The lifespan of platelets in a wound and their influence tists have been making great efforts to develop ways of im-
on growth factors is less than five days. As the platelets proving bone healing. In treating bone trauma, mechanical
come to the end of their life cycle, attracted macrophages stabilization has been a hallmark of orthopaedic fracture
replace the platelets as the primary source of growth factors care, and now osteobiologics are playing an increasing role
to continuously stimulate tissue regeneration [30]. It can be in the management of patients with traumatic injuries.
considered that PRP jump starts the cascade of regenera-
Bone healing process is divided into four distinct but
tive events leading to the formation of a mature tissue.
overlapping stages: hematoma creation, inflammation, callus
Although available data suggest that L-PRP may be valu- formation and remodeling. Following a fracture, vascular
able in enhancing soft tissue and osseous healing [31]. How- exposure and tissue damage at the fracture site result in
ever, some studies suggest no benefits from L-PRP [32-34], platelet aggregation and activation to form platelet plug and
even report that L-PRP inhibits bone formation [35, 36]. hematoma, and a large amount of growth factors will release
Marx pointed that studies that failed to find much benefit from platelet granules to fracture site. In the inflammatory
from L-PRP have often been compromised by improper stage, inflammatory cells (macrophages, monocytes, lym-
preparation of the L-PRP [4, 37, 38]. Truly, not all currently phocytes, and polymorphonuclear cells), mesenchymal cells,
available commercial L-PRP preparation systems may be the and fibroblasts infiltrate the bone. Because of the mitogenic
same in their ability to produce the therapeutic L-PRP. The activity of the growth factors such as TGF-, IGF and
other important reason for the confusing effects of L-PRP PDGF, mesenchymal cells and fibroblasts proliferate at the
application may be based on different platelet concentra- fracture site, resulting in the formation of granulation tissue
tions. Different concentrations result in different even oppo- and ingrowth of vascular tissue. During the callus formation
site effects. Graziani et al. [39] compared the in vitro effect stage, soft callus form around the repair site. Then the callus
of different L-PRP concentrations on osteoblasts and fibro- ossifies, forming a bridge of woven bone between the frac-
blasts and showed that the maximum effect was achieved ture fragments. Bone remodeling occurs slowly by mechani-
with a concentration of 2.5 fold, with higher concentrations cal stress placed on the bone. As the fracture site is exposed
resulting in a reduction of cell proliferation and a suboptimal to an axial loading force, bone is generally laid down where
effect on osteoblast function. Similar observations were it is needed and resorbed from where it is not needed.
found by Weibrich [40], who indicated that advantageous
During the bone healing process, repairing cells, growth
biological effects occur when L-PRP with a platelet concen-
factors and scaffolds are the important elements. Among
tration of approximately 1,000,000/microl was used, and the
Applications of Leukocyte- and Platelet-Rich Plasma (L-PRP) in Trauma Surgery Current Pharmaceutical Biotechnology, 2012, Vol. 13, No. 7 1175
these three elements, growth factors are the key component. cells, including the recruitment of osteoblast precursors and
They attract repairing cells to injury site and bind to target the expression of adhesion molecules for monocytes and
cells receptors to induce signal transduction to reach the nu- marcrophages, while inhibiting their pro-osteolytic proper-
cleus and stimulate proliferation and differentiation of mes- ties.
enchymal stem cells. L-PRP, as a concentrated source of Ogino [69] studied the capability of promoting bone
growth factors, promotes bone healing through a multitude
healing of L-PRP from the aspect of bone resorption, and
of cytokinetic processes such as recruitment of MSC, in-
demonstrated that L-PRP increased the secretion of osteopro-
crease of extracellular matrix synthesis and neovasculariza-
tegerin and suppressed osteoclastogeneisis, therefore inhibit-
tion [43-46]. In addition, L-PRP contain leukocytes and fi-
ing bone resorption. Sipe et al. [70] has even gone so far as
brin. Leukocytes are responsible for removal of tissue debris
to indentify BMP-2, -4 and -6 within platelet lysates (dam-
and also play an important role in fracture healing processes aged platelets with microparticles of cytoplasmic and mem-
[47]. Fibrin helps to form clot, a 3-dimensional organization
brane and soluble growth factors), suggesting the possibility
of a fibrin network, which supports cytokine enmeshment
that this might contribute to the role of platelets in bone for-
and cellular migration [48]. Furthermore, the fibrin matrix
mation repair [37].
serves as a scaffold for cell proliferation, cell differentiation
and ultimately for bone formation. However, the effect of L-PRP of on differentiation of
MSCs is still controversial. Several authors [71] investigated
2.1.1. In Vitro Studies the effect of L-PRP on rat BMCs and found that L-PRP
stimulates the proliferation but suppresses the differentiation.
L-PRP has been investigated in a number of in vitro stud-
Choi [72] reported that the viability and proliferation of al-
ies to affect osteoblasts, osteoclasts, and mesenchymal os-
veolar bone cells were suppressed by high L-PRP concentra-
teoprogenitor stem cells [10, 49-59].
tions, but were stimulated by low L-PRP concentrations (1-
Lucarelli [60] found that L-PRP can enhance human 5%). In Ranlys study [35], the author found L-PRP de-
stromal and mesenchymal stem cell proliferation. The effect creased the osteoinductivity of demineralized bone matrix
was dose dependent and 10% L-PRP is sufficient to induce a implanted in immunocompromised mice, and the activities
marked cell proliferation. Opera et al. [61] studied the effects of both demineralized bone matrix and L-PRP were donor-
of platelet releasate collected from activated L-PRP on rat dependent. Based on these confused study results, Hsu et al.
bone marrow derived cells. Cultures of primary rat bone [73] investigated whether negative regulators exist in the L-
marrow cells were overlaid with a fibrin matrix, and the PRP and negatively affect cells proliferation. The author
number of cells migrating within the three-dimensional ma- observed that L-PRP contains an angiogenesis inhibitor,
trix and the leading front of migration were quantified. The thrombospondin-1 (TSP-1). TSP-1 has been found to inhibit
addition of platelet releasate to the top of the fibrin gels at adhesion, proliferation, and tube formation of endothelial
different time points caused a 25% increase in the leading cells in culture and block neovascularization of the chick
front of migration and a 3.5-fold increase in the number of chorioallantoic membrane [74, 75]. So the reason of high
migrating cells. The results showed that L-PRP stimulated concentration of L-PRP decreasing proliferation of cells may
the initial recruitment of BMCs to migration and had a mito- attribute to the high concentration of TSP-1 secreted from L-
genic effect on bone cells in proliferation. Similar results PRP, which leads to the antiproliferative effect [73].
were obtained in Grubers study [62], who examined the
effects of supernatants released from thrombin-activated 2.1.2. Animal Studies
platelets on osteoclast-like cell formation in murine bone
There is a large variety of animal studies on L-PRP re-
marrow cultures and suggested that, aside from a mitogenic
search in the literature [76-80]. But the results still tend to be
effect, L-PRP application at the time of surgery enhanced
confusing. Various different animal species and L-PRP
bone healing capacity.
preparations may be the reasons. Especially in small animals,
L-PRP is a suitable carrier for MSCs transplantation in therapeutic L-PRP is not always achieved because the diffi-
tissue engineering because it coagulated immediately by a culty of collecting blood may damage platelets. Therefore,
minute introduction of thrombin and calcium. The combina- negative outcome following the use of L-PRP in animal
tion of bone marrow cell (BMC) and L-PRP has a favoring studies should be interpreted with caution.
effect to accelerate bone healing and bone remodeling proc-
Most studies showed a positive effect of L-PRP in the
ess [9, 46, 63-66].
bone healing in animal models. Kasten et al. [81] investi-
Angiogenesis plays a pivotal role in skeletal development gated the efficacy of L-PRP in bone healing of a critical-size
and bone healing. Blood vessels provide nutrients and oxy- diaphyseal radius defect in a rabbit model. The bone defect
gen to bone, as well as the appropriate niche for self- was filled with calcium-deficient hydroxyapatite (CDHA),
renewing osteoprogenitors [67]. Cenni [68] studied the ef- with the addition of allogenic L-PRP, MSC or both. L-PRP
fects of L-PRP on the human umbilical vein endothelial cell yielded better bone formation than the empty CDHA scaf-
(HUVEC) to express mRNA for osteogenic growth factors fold as determined by both histology and microcomputer
and stimulate the migration of BMCs. The results showed tomography (p<0.05) after 16 weeks. The effect was similar
that L-PRP induced a remarkable increase in endothelial cell to that of MSC on the CDHA scaffold. In Nairs study [77],
proliferation, and mRNA expression of PDGF-B, intercellu- he observed the same results. The study was designed to use
lar adhesion molecule 1 (ICAM-1), and osteoprotegerin. autogenous L-PRP and BMCs in combination with a tripha-
These findings supported that L-PRP contributes to bone sic ceramic (calcium silicate, hydroxyapatite and tricalcium
repair by favoring the pro-osteogenic function of endothelial phosphate)-coated hydroxyapatite (HASi) to repair segmen-
tal bone defects created in a goat femur model. The combina- ment of Perioperative Blood Management of the Catharina
tion of the HASi with BMCs and L-PRP promoted the ex- Hospital performs close to 1600 management procedures
pression of many osteoinductive proteins, leading to faster annually, of which 60% are related to obtain whole blood
bone regeneration. Interestingly, compared to the bare HASi platelets to produce L-PRP [76]. Application of L-PRP can
group, the addition of BMCs and L-PRP leaded to faster decrease postoperative drainage, reduce narcotic require-
degradation of HASi. The author indicated the reason was ment, and facilitate an early return to mobility. Postopera-
that BMCs promote the adhesion of osteoclasts on the mate- tively, patients may experience fewer complications, recover
rial by secreting osteoinductive proteins-like osteopontin. In more rapidly, and have a reduced hospital stay [87].
both of the above studies, however, there were no significant
In human studies, L-PRP is often applied in formation of
differences in the performance in bone regeneration between
gelatineous mass resulted by bovine thrombin and used in
bone substitute + BMCs and bone substitute + BMCs + L- combination with different bone matrices. Due to the sticky
PRP.
structure of L-PRP gel, caused by the fibrin strands present
Kroese-Deutman [82] et al. evaluated the bone inductive in the gel, bone matrices are kept together, avoiding un-
properties of L-PRP with titanium fiber mesh and autologous wanted migration of bone particles. And the gelatineous
bone chips in a 15-mm rabbit radial defect model. After 12 form is easier to handle and place into the graft site [88].
weeks, Histomorphometrical analysis showed that bone for- Moreover, thrombin itself stimulates fibroblast proliferation
mation was higher in the implants with L-PRP (PRP-Ti- and synthesis of type IV collagen and some active mediators.
Bone: 378%) than in those without L-PRP (Ti-bone:
There are many articles describing the clinical use of L-
256% and Ti: 255%). In a domestic pig model, Thorwarth
PRP with both mineral and organic bone matrices [89-91].
[83] et al. used immunohistochemistry to show increased
Marx et al. [30] firstly used L-PRP clinically to enhance
osteocalcin, osteopontin, and BMP-2 production in defined
bone healing. He evaluated bone density and healing time
defects filled with collagen lyophilisat and L-PRP in com- when L-PRP was added to autogenous bone to reconstruct
parison to autogenous bone. Osteocalcin is a sensitive
mandibular continuity defects and reported a 1.62- to 2.16-
marker of the mineralization process in the later phase of
fold increase in radiographic bone density, and an increase in
bone formation, and osteopontin was early marker of bone
histologic and histomorphometric bone density. Subse-
formation. The results showed that addition of the L-PRP
quently, clinical use of L-PRP prevailed gradually for regen-
increased BMP-2 expression after 2 week and promoted ear-
eration of bone. In the following years, the easily obtainable
lier calcification of autogenous bone graft, indicating that L- L-PRP and its possible beneficial outcomes hold promise for
PRP has an osseopromotive effect.
wide applications in trauma surgery. L-PRP has been pro-
Kawasumis study [84] was to investigate the effect of L- posed as a primary or adjunctive treatment for fractures [92],
PRP on the proliferation and differentiation of rat BMCs bone defect and bone nonunion [93], osteomyelitis [3], and
using a rat limb-lengthening model. Rat BMCs embedded in spine interbody fusion [23, 94, 95].
L-PRP gel were cultured for six days and transplanted into Dallari et al. [96] reported a randomized, controlled trial
the distraction gap. The results showed that L-PRP stimu-
of L-PRP among patients undergoing a medial, opening-
lated the proliferation of rat BMCs, but did not promote os-
wedge osteotomy of the proximal tibia. The authors com-
teoblastic differentiations. The combination of L-PRP and
pared the osteogenic potential of lyophilized bone chips
BMCs had favorable effect on osteogenesis in the rat limb-
(BC) combined with L-PRP gel, or with L-PRP gel and
lengthening model.
BMCs, with that of lyophilized bone chips alone in the heal-
Some contradictory results were reported in animal stud- ing of a high tibial osteotomy. After six weeks, in compari-
ies by Rabillard et al. [79], who examined the bone healing son with Group bone chip alone, histomorphometry showed
properties of adding L-PRP to osteoconductive calcium significantly increased osteoblasts and osteoid areas in both
phosphate ceramic granules in a 2 cm bone defect of ulnar in Group L-PRP+ BC (p=0.006 and p=0.03, respectively) and
dogs. Radiographic and histological evaluations were per- Group L-PRP+ BC + BMCs (p=0.009 and p=0.001), as well
formed and showed that addition of L-PRP did not enhance as increased bone apposition on the chips (p=0.007 and
bone regeneration in critical-size bone defects. Sarkar et al. p=0.001, respectively), which was greater in Group L-PRP +
[85] reported on the effect of L-PRP on new bone regenera- BC + BMCs than in Group L-PRP + BC (p<0.05). Radio-
tion in a critical size defect in the tibial diaphysis of sheep, graphic osteointegration was significantly better in groups
supplied either with L-PRP in a collagen carrier or with col- with L-PRP than group without L-PRP at all stages of fol-
lagen alone (controls). Bone volume, mineral density, me- low-up. The study demonstrated that adding L-PRP or L-
chanical rigidity and histology of the newly formed bone in PRP combined with BMCs to lyophilized bone chips in-
the defect did not differ significantly between the L-PRP creases the osteogenetic potential of the lyophilized bone
treated and the control group, and no effect of L-PRP upon chips and may be a useful tool in the treatment of patients
bone formation was observed. And whats more, Choi [86] et with massive bone loss.
al. found that adding L-PRP to autogenous bone graft de-
As a carrier for cell transplantation, L-PRP, combined
layed bone formation compared with the contralateral control
with marrow cells, was often used to treat large bone defect.
side. In Kitohs study [97], L-PRP combined with BMCs was ap-
2.1.3. Human Studies plied during distraction osteogenesis of 32 long bones (14
femora, 18 tibiae) in 17 patients while the BMCs alone group
Clinical use of L-PRP in trauma and orthopaedics has consisted of 60 bones (25 femora,35 tibiae) in 29 patients.
increased and prevailed currently. For example, the Depart- The study concluded that transplantation of BMCs in asso-
ciation to L-PRP could shorten the treatment period L-PRP group was 62% (18 of 32 patients). The use of L-PRP
(28.67.07 days/cm in Group L-PRP + BMCs vs 36.610.1 resulted in inferior rates of arthrodesis compared with auto-
days/cm in Group BMCs, p=0.0019) and reduced the associ- genous bone graft alone.
ated complications by accelerating new bone formation
(p=0.041). 2.2. L- PRP and Healing of Traumatic Soft Tissue Injuries
In a retrospective study of lumbar spinal fusions, L-PRP Trauma frequently causes acute soft tissue injury, such as
was used with autograft and coralline hydroxyapatite in all open cutaneous wound, acute stretching or tearing of muscle,
posterior fusions, and autograft, coral and intradiscal spacer tendon and ligament. In the healing process of acute trau-
in intradiscal fusions [98]. The result showed that L-PRP matic soft tissue wound, platelets are the main regulator of
promoted early maturation of osseous fusion. the blood clot phase and the inflammatory phase, play an
Nonunion has been a challenging clinical problem in essential role in the regeneration phase, and then influence
trauma and orthopaedic field. In comparison to fresh frac- indirectly the remodeling phase [106]. So, application of L-
ture, growth factor levels at the site of the nonunion are sig- PRP could positively influence the rate and quality of wound
nificantly reduced. So, addition of L-PRP to the nonunion repair.
site brings critical growth factors to the region, resulting in First of all, the high concentration of platelets and the
the positive influence of nonunion resolution [92]. Bielecki adhesive effect of L-PRP help prevent or decrease surgical
[93] firstly reported the treatment of nonunion with L-PRP in bleeding. A study compared the hemostatic ability of PRP
2006. He injected L-PRP gel percutaneously into the and/or PPP with untreated control wounds. The results
humeral diaphyseal nonunion gap. As a minimally invasive showed that L-PRP reduced bleeding by 70% at 5 minutes
treatment method, L-PRP injection offered the advantage of when compared to controls [107]. Secondly, high concentra-
decreased morbidity associated with the classic open grafting tions of leukocytes and growth factors in L-PRP also play a
techniques. During the follow-up period, the healing process prominent role in traumatic wound healing.
on roentgenograms and increase in bone mineral density
were observed. At the 8th week over 75% of the circumfer- 2.2.1. Healing of Acute Cutaneous Wounds
ence of the bone at the defect site had resolved and during
Experimental studies have reported that with the applica-
later visits remodeling of the union was observed on X-ray
tion of L-PRP, wound healing is substantially improved by
films. In the next year, Bielecki [99] reported a case of in- increasing collagen content, promoting angiogenisis and
fected tibial nonunion with fistula treated by percutaneous L-
increasing early wound strength [108]. The early wound
PRP injection. Microbiological examination was positive for
strength results from the ability of L-PRP to decrease the
MSSA in the fistula. Five months after L-PRP application,
inflammatory phase of wound healing and to increase early
union occurred and the wound was healed. This report indi-
deposition of glycosaminoglycan and fibronectin [109]. In an
cated that L-PRP has antibacterial activity and repairing abil-
in vitro study of cell culture with the addition of L-PRP, Kil-
ity, which may resolve infection and nonunion simultane- ian et al. [110] found that the different growth factors con-
ously. In a study of 12 patients with delayed union and 20
tained in L-PRP could work together to stimulate the migra-
with nonunion treated by percutaneous injection of L-PRP,
tion and proliferations of human endothelial and MSCs. Ka-
union achieved in all cases of delayed union on average 9.3
kudo et al. [111] examined the efficacy of L-PRP on human
weeks (rang 5-12 weeks). In the nonunion group, union was
adipose derived stem cells and human dermal fibroblast. The
observed in 13 of 20 cases and the average time to union was
addition of activated L-PRP significantly promoted the pro-
10.3 weeks (range 8-18 weeks) [100]. Sanchez et al. [101] liferation of both cell types. In addition, low PRP concentra-
applied L-PRP to clinical nonunions and reported on their
tions (1% and 5%) were suitable for human adipose derived
retrospective case series of 16 aseptic supracondylar and
stem cells proliferation, and 5% had a maximal effect on
diaphyseal atrophic nonunions after failed surgical fixation
human dermal fibroblasts.
21 months previously. The author pointed L-PRP technology
was clinically safe and could enhance the healing of non- In a animal study, L-PRP embedded with endothelial
hypertrophic nonunions. For patients with nonunion of bone progenitor cells (EPCs) and/or basal cell keratinocytes (KCs)
fracture, L-PRP may act as an alternative to surgical treat- was used to treat 20 full-thickness wounds in a pig model
ment to improve healing. [112]. All L-PRP-treated wounds showed more vascular
structure (p<0.001), and the addition of EPCs further im-
In recent years, L-PRP was used to aid in treating osteo-
proved neovascularization. L-PRP+KCs resulted in the high-
myelitis by some authors. Yuan [102] reported one case of
est reepithelialization rates (p<0.001).The author indicated
chronic osteomyelitis in bilateral femurs failed to four-year that L-PRP enhanced deposition of matrix molecules in the
conventional treatments. The application of L-PRP seemed
inflammatory and proliferative phase of wound healing, and
to prohibit the development of necrosis and reduce inflam-
the combination of L-PRP and autologous embedded EPCs
matory extravasate, and prevent recurrence for a long time.
or KCs could improve extracellular matrix organization,
Because of the properties of antimicrobial and promoting
promote angiogenesis, and accelerate reepithelialization.
tissue regeneration, L-PRP may act as a novel therapeutic
agent for osteomyelitis [103, 104]. Clinically, Kazakos [113] performed a study to assess the
efficacy of L-PRP in the treatment of acute limb soft tissue
Similarly, contradictory results of human studies exist.
wounds in 59 patients, including open fractures, closed frac-
Weiner et al. [105] evaluated two groups undergoing lumbar
tures with skin necrosis and friction burns. One group was
fusion with or without L-PRP. The fusion rate for the control
treated with conventional dressing, changed every 2 days,
group (without L-PRP) was 91% (24 of 27 patients), and the
and the other group was managed with local application of injection of L-PRP within Archilles tendon fascicles in a
L-PRP gel, which was repeated weekly. The clinical end- sheep model triggered a healing response assessed by in-
points were the healing rate and/or the time required to bring creased cell number and angiogenesis [126, 127]. The basic
about adequate tissue regeneration in order to undergo re- information gave insight into clinical application of L-PRP
constructive plastic surgery. The rate of wound healing rate in treating tendon injuries. Currently, L-PRP has been ap-
was significantly faster in the L-PRP group at weeks 1, 2, plied during the ruptured tendon surgical procedure and a
and 3 as measured by the reduction of the wound size at each significant acceleration in functional recovery may be ob-
time point (p=0.003, p<0.001 and p<0.001, respectively). served compared with a matched group who had conven-
The mean time to plastic reconstruction in the L-PRP group tional surgery [128]. In these conditions, L-PRP may offer an
was 21.3 days (40.6 days for the control group). The author alternative treatment over palliative or operative treatments
concluded that L-PRP gel treatment could aid in the man- for tendon injury.
agement of acute trauma wounds as it induces faster wound
healing rates and lowers the time to plastic reconstructive 2.2.3. Healing of Acute Nerve Injury
surgery. In Marxs article [4], he also showed the enhanced Severe trauma often results in acute nerve injury, but few
and faster healing of acute wounds when it was treated with studies have investigated the effect of L-PRP on nerve heal-
L-PRP and bovine thrombin as compared to bovine thrombin ing. In a prospective, randomized, and controlled animal
alone. And the comparison provided evidence that PRP study aimed to investigate the effects of L-PRP on facial
might reduce scar and promoted a greater melanocyte sur- nerve regeneration, L-PRP was compared with PPP and fi-
vival. brin sealant, all with or without suture after nerve transac-
In a prospective, single-blind, pilot study [114] to com- tion. The authors [129] found the best results for the return
pare the healing of acute human skin wounds treated with of function occurred when the nerve ends were sutured to-
topical L-PRP vs conventional therapy (antibiotic ointment gether. At the same time, the data demonstrated a measurable
and/or occlusive dressings), 80 full-thickness skin punch neurotrophic effect when L-PRP was present, with the most
wounds were made on the thigh of eight healthy volunteers. favorable results seen with L-PRP added to suture in com-
On day 17, the percentage of closure was 81.12.5% for the parison with fibrin sealant or PPP. Sariguney [130] observed
L-PRP-treated sites and 57.25.9% for the control sites. And similar results in a study of repairing rat sciatic nerve with L-
the L-PRP wound closure velocities were significantly faster PRP. In this study, L-PRP helped to improve remyelinization
than those of the controls (p=0.001). Histologically, L-PRP of the interrupted sciatic nerve when the epineural repair was
wounds formed earlier epithelialization and granulation. done with sutures.
Based on the above results, the application of L-PRP
2.2.2. Healing of Acute Muscle, Tendon and Ligament
might extend to the treatment of central nervous system in-
Trauma
jury, especially for traumatic brain or spinal cord injury.
Healing of muscle injuries is dependent on proliferation Theoretically, the properties of L-PRP also support this hy-
of myofibroblasts, local vascularity and regeneration of in- pothesis: the receptors of platelet derived cytokines have
tramuscular nerve branches, which may be enhanced by L- been found localized widely on the surface of neurons and
PRP [115-117]. Several growth factors within L-PRP have glia not only in the peripheral nerve but also in the central
been evaluated to enhance muscle regeneration and im- nervous system, especially after pathologic events, the high
proved muscle force after injury [118]. In a case report, a levels of these receptors are expressed in the lesion areas of
professional bodybuilder with acute adductor longus tear central nervous system [131]. So, local application of L-PRP
underwent 1 injection of L-PRP weekly for 3 weeks and got can provide large numbers of cytokines to activate these re-
healed completely [119]. Sanchez et al. [120] reported in a ceptors to regulate the gene transcription, and induce neural
study, after ultrasound guided injections of L-PRP in 22 progenitor cells proliferation, migration and differentiation to
muscle injuries of 20 high-level professional athletes, full replace the injured nerve. Up to date, there have been no
recovery of functional capabilities was restored in as early as further experimental and clinical studies to provide data
half of the expected recovery time without any evidence of about L-PRP treating central nerve injury, but L-PRP is
excess fibrosis. There are, however, no randomized con- likely to act as an important method for treating nerve in the
trolled human studies supporting the use of L-PRP for mus- coming years.
cle injuries.
3. EFFICACY OF L-PRP IN REPAIRING CARTI-
Tendon and ligament have a low metabolic rate that en-
tail slow healing after injury. However, it has been shown LAGE CAUSED BY TRAUMA
that several platelet derived growth factors can stimulate Due to the limited regenerative capacity of cartilage tis-
tendon repair after exogenous local application [121]. Some sues, articular cartilage defect caused by various lesions re-
equine and human cell studies also reported L-PRP enhanced mains a problem to be resolved. Several growth factors, es-
type I collagen gene expression in L-PPR-cultured tendon pecially PDGF and TGF-, have been proven to be effective
cells, stimulated human tenocyte proliferation and total col- for cartilage and meniscal regeneration [132-134]. Some in
lagen production, and slightly increased matrix metalloprote- vitro studies suggest the effects of L-PRP for stimulating
inase 3 (MMP-3) expression [122, 123]. Aspenberg et al. chondrocytes [134, 135]. In the arthroscopic treatment of a
[124, 125] reported greater maturation when L-PRP was large avulsion of articular cartilage in the knee of an adoles-
used to treat Achilles tendon ruptures in a rat Achilles tendon cent soccer player using L-PRP, exciting results were ob-
transaction model. Other researchers showed that repetitive served, complete articular cartilage healing was considerably
accelerated, and the functional outcome was excellent, al- Up till now, there has been no standardized method for
lowing a rapid resumption of symptom-free athletic activity L-PRP preparation. The volume of whole blood drawn, the
[136]. Kon [137] compared the efficacy of L-PRP and visco- volume of L-PRP yield, and the concentration of platelets,
supplementation (hyaluronic acid injection) for treatment of can be adjusted through different centrifugal force and time,
severe chondropathies of the knee, and observed that L-PRP to meet clinical or experimental requirements.
injections provide more and longer efficacy than hyaluronic
acid injections in reducing pain, symptoms and recovering
articular function. Even though the results need to be con-
firmed in a large cohort of patients, this technique opens new
perspectives in the area of joint cartilage repair.
4. POTENTIAL PROBLEMS AND RISKS

4.1. Understand the mechanisms of manually producing
L-PRP
Although many L-PRP preparation devices have been
commercially available on the market in European and
American countries in recent years, L-PRP has to be pro-
duced manually in a large number of developing countries
today. They have no such automated devices for L-PRP
preparation. So, surgeons in these countries must completely
understand the mechanisms of producing L-PRP before they
apply L-PRP to patients. In fact, the mechanism of manual
L-PRP preparation is the same with that of automated de-
vices, separating platelets from whole blood through centri-
fugations based on different densities of blood components.
The best effective methods of preparing L-PRP should yield
platelets with high concentration and without lysing the
platelets or damaging them. After comparing centrifugations
based on varying the force and time, Landesberg et al. [138]
indicated that optimal L-PRP preparation should be with
both spins at 200g for 10 minutes, because centrifugations of
less than 5 minutes failed to achieve any significant platelet
enrichment, and forces of greater than 250g resulted in plate-
lets damage and forces of greater than 800g might reduce the
amount of TGF-.
Yuan et al. [139] studied the mechanisms of manually Fig. (2). After the first spin, PPP was divided into three equal parts
preparing L-PRP through comparing four different centrifu- and red cell was divided into two equal parts to measure platelet
gations in terms of centrifugation time and force. These four concentration.
centrifugations are quoted from published literatures [138,
4.2. Possibility of Carcinogenic Effect of L-PRP
140-143], and have been approved to be effective to yield
therapeutic L-PRP. One was single-spin centrifugation and There has been some concern about a possible carcinogenic
three are double-spin. The results showed that single-spin effect related to the stimulation of cellular proliferation and
centrifugation would not separate and concentrate platelets to the local presence of L-PRP in high concentrations. Actually,
a therapeutic level. It yielded a disappointingly low platelet no growth factor can provoke carcinogenesis. Because all
counts. After the first spin, whole blood in container is cen- growth factors contained in L-PRP are known to act on cell
trifuged into its three basic components: red blood cells, L- membranes, not the cell nucleus. They are not mutagens and
PRP, and platelet-poor plasma (PPP). Because of differential promote a normal gene expression, not an abnormal gene
densities, the red blood cell layer forms at the lowest level, expression [144].
the platelet concentrate layer in the middle, and the PPP
layer at the top. The authors divided the volume of PPP frac- 4.3. Risks of Bovine Thrombin
tion into three equal parts from top to bottom, and divided
the red cell fraction into two equal parts accordingly Fig. (2). Another consideration is that L-PRP is frequently acti-
Platelet concentrations of each layer were measured respec- vated by bovine thrombin when used. Many surgeons are
tively (Table 1). The study results showed that the most of hesitant to use a bovine thrombin in human trauma surgical
platelets stay in the lowest layer of PPP and the top layer of procedures as numerous reports have documented the devel-
red cell, especially in the latter. Excessive centrifugal force opment of anti-bovine antibodies cross reacted with human
leads to more platelets sinking into the bottom layer of red clotting factors, which led to clinical syndromes that range
cell, and this layer would be discarded after the first spin. from severe postoperative bleeding to high rates of thrombo-
Removal of the bottom layer of red cell will reduce the re- sis [145-150]. Up to now, however, no related complications
covery of platelets. have been reported. Based on the potential risks mentioned
above, and in order to overcome this problem, autologous
Table 1. After the First Spin, Platelet Concentration Yielded in Each Layer
Platelet Count (1,000/l) 1500g 6 Mins 200g 10 Mins 215g 10 Mins
Whole blood 217.5 213.5 220.0
Upper layer of PPP 3.9 68.8 65.4
Middle layer of PPP 7.4 74.3 74
Lowest layer of PPP 97.5 312.7 309.7
Upper layer of red cell 833.4 674.6 682.2
Lower layer of red cell 204.4 68.1 71.2
thrombin seems to be the logical choice, but the preparation ble diseases such as HIV, hepatitis, and West Nile fever. In
of autologous thrombin is cumbersome. In the recent years, a recent years, L-PRP is well accepted by patients.
commercial autologous thrombin kit has been developed
Although a lot of studies provide evidence for application
which produces autologous thrombin out of platelet-poor
of L-PRP, some important questions about the biologic
plasma. In addition, using recombinant human thrombin may mechanisms of L-PRP still remain unclear, such as the inter-
eliminate this risk. Some studies show that calcium sulfate is
actions between proteins, whether leukocytes have a positive
also able to induce activation of L-PRP [151], as well as acts
or negative influence, whether dense granules contained in
as a delivery system for the platelet-released growth factors
L-PRP also play a role in tissue modulation and regenera-
[152]. On the other hand, Dohan [48] suggested no use of
tion, and the molecular basis of how L-PRP can reduces
anticoagulant citrate dextrose and bovine thrombin, because
pain.
the thrombin solution leads to high speed polymerization,
which will influence the mechanical and biologic properties Conflicting data exist in clinical and experimental re-
of L-PRP gel. Instead, the author supported platelets polym- search on the efficacy of L-PRP treatment. Many studies are
erize naturally and slowly during centrifugation without bo- anecdotal or case reports, the sample sizes are frequently
vine thrombin. It would form a platelet-rich fibrin (PRF), he small, limiting the generalization of the findings. Therefore,
called the second-generation platelet concentrate, favorable further investigation of high-level studies with control group
to cytokine enmeshment and cellular migration. comparison are needed to definitively determine the role of
L-PRP, and standardized dosing and composition of L-PRP
Han [78] et al. compared the osteoinductivity of L-PRP
is necessary in order to compare the data from different stud-
on demineralized bone matrix used with bovine thrombin
ies.
activation and without thrombin activation. In vivo, L-PRP
stimulated chondrogenesis on day 14 and osteogenesis on
CONFLICT OF INTEREST
day 28 and 56, whereas thrombin-activated L-PRP inhibited
such events. Thus, the application of bovine thrombin also None declared.
must be further studied and considered in clinical applica-
tions. ACKNOWLEDGMENTS
This work was supported by a grant from the National
4.4. Clinical Contraindications of L-PRP
Natural Science Foundation of China (Grant No. 30801221)
So far, there have been no major health problems arisen
through the therapeutic use of L-PRP in published literature. REFERENCES
Obviously, contraindications to the administration of L-PRP [1] Eppley, B.L.; Woodell, J.E.; Higgins, J. Platelet quantification and
include platelet dysfunction, critical thrombocytopenia, ingrowth factor analysis from platelet-rich plasma: implications for
fection, anemia and sensitivity to bovine thrombin. And we wound healing. Plast. Reconstr. Surg., 2004, 114(6), 1502-1508.
need to know that many of these are not absolute contraindi- [2] Nikolidakis, D.; Jansen, J.A. The biology of platelet-rich plasma
cations. and its application in oral surgery: literature review. Tissue. Eng.
Part. B Rev., 2008, 14(3), 249-258.
[3] Yuan, T.; Zhang, C.Q.; Zeng, B.F. Treatment of chronic femoral
5. CONCLUSIONS osteomyelitis with platelet-rich plasma (PRP): A case report.
Transfus. Apher. Sci., 2008, 38(2), 167-173.
L-PRP is now playing an increasing role in the manage- [4] Marx, R.E. Platelet-rich plasma: evidence to support its use. J. Oral
ment of patients with traumatic injuries. The enhancement of Maxillofac. Surg., 2004, 62(4), 489-496.
bone and soft tissue healing by its placement at the site of [5] Papli, R.; Chen, S. Surgical treatment of infrabony defects with
tissue injury or surgery is supported by basic science and autologous platelet concentrate or bioabsorbable barrier membrane:
a prospective case series. J. Periodontol., 2007, 78(1), 185-193.
clinical studies. [6] Korobelnik, J.F.; Hannouche, D.; Belayachi, N.; Branger, M.;
Because it is an autogenous preparation, L-PRP is inher- Guez, J.E.; Hoang-Xuan, T. Autologous platelet concentrate as an
adjunct in macular hole healing: a pilot study. Ophthalmology,
ently safe and therefore free from concerns over transmissi- 1996, 103(4), 590-594.
[7] Liu, Y.; Kalen, A.; Risto, O; Wahlstrom, O. Fibroblast proliferation [28] Weibrich, G.; Kleis, W.K.; Buch, R.; Hitzler, W.E.; Hafner, G. The
due to exposure to a platelet concentrate in vitro is pH dependent. Harvest Smart PRePTM system versus the Friadent-Schutze plate-
Wound Repair Regen., 2002, 10(5), 336-340. let-rich plasma kit. Clin. Oral Implants Res., 2003, 14(2), 233-239.
[8] Babbush, C.A.; Kevy, S.V.; Jacobson, M.S. An in vitro and in vivo [29] Yuan, T.; Zhang, C.Q.; Tang, M.J.; Guo, S.C.; Zeng, B.F. Autolo-
evaluation of autologous platelet concentrate in oral reconstruction. gous platelet-rich plasma enhances healing of chronic wounds.
Implant Dent., 2003, 12(1), 24-34. Wounds, 2009, 21(10), 280-285.
[9] Parsons, P.; Butcher, A.; Hesselden, K.; Ellis, K.; Maughan, J.; [30] Marx, R.E.; Carlson, E.R.; Eichstaedt, R.M.; Schimmele, S.R.;
Milner, R.; Scott, M.; Alley, C.; Watson, J.T.; Horner, A. Platelet- Strauss, J.E.; Georgeff, K.R. Platelet-rich plasma: Growth factor
rich concentrate supports human mesenchymal stem cell prolifera- enhancement for bone grafts. Oral Surg. Oral Med. Oral Pathol.
tion, bone morphogenetic protein-2 messenger RNA expression, Oral Radiol. Endod., 1998, 85(6), 638-646.
alkaline phosphatase activity, and bone formation in vitro: a mode [31] Murray, M.M.; Spindler, K.P.; Ballard, P.; Welch, T.P.;
of action to enhance bone repair. J. Orthop. Trauma, 2008, 22(9), Zurakowski, D.; Nanney, L.B. Enhanced histologic repair in a cen-
595-604. tral wound in the anterior cruciate ligament with a collagen-
[10] Butcher, A.; Milner, R.; Ellis, K.; Watson, J.T.; Horner, A. Interac- platelet-rich plasma scaffold. J. Orthop. Res., 2007, 25(8), 1007-
tion of platelet-rich concentrate with bone graft materials: an in vi- 1017.
tro study. J. Orthop. Trauma, 2009, 23(3), 195-200. [32] Dori, F.; Nikolidakis, D.; Huszar, T.; Arweiler, N.B.; Gera, I.;
[11] Whitman, D.H.; Berry, R.L.; Green, D.M. Platelet gel: an autolo- Sculean, A. Effect of platelet-rich plasma on the healing of in-
gous alternative to fibrin glue with applications in oral and maxillo- trabony defects treated with an enamel matrix protein derivative
facial surgery. J. Oral Maxillofac. Surg., 1997, 55(11), 1294-1299. and a natural bone mineral. J. Clin. Periodontol., 2008, 35(1), 44-
[12] Choukroun, J.; Diss, A.; Simonpieri, A.; Girard, M.O.; Schoeffler, 50.
C.; Dohan, S.L.; Dohan, A.J.; Mouhyi, J.; Dohan, D.M. Platelet- [33] Dori, F.; Huszar, T.; Nikolidakis, D.; Arweiler, N.B.; Gera, I.;
rich fibrin (PRF): a second-generation platelet concentrate. Part V: Sculean, A. Effect of platelet-rich plasma on the healing of in-
histologic evaluations of PRF effects on bone allograft maturation trabony defects treated with an anorganic bovine bone mineral and
in sinus lift. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. En- expanded polytetrafluoroethylene membranes. J. Periodontol.,
dod., 2006, 101(3), 299-303. 2007, 78(6), 983-990.
[13] Dohan, D.M.; Choukroun, J.; Diss, A.; Dohan, S.L.; Dohan, A.J.; [34] Slapnicka, J.; Fassmann, A.; Strasak, L.; Augustin, P.; Vanek, J.
Mouhyi, J.; Gogly, B. Platelet-rich fibrin (PRF): a second- Effects of activated and nonactivated platelet-rich plasma on prolif-
generation platelet concentrate. Part II: platelet-related biologic fea- eration of human osteoblasts in vitro. J. Oral Maxillofac. Surg.,
tures. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod., 2008, 66(2), 297-301.
2006, 101(3), 45-50. [35] Ranly, D.M.; Lohmann, C.H.; Andreacchio, D.; Boyan, B.D.;
[14] Jenis, L.G.; Banco, R.J.; Kwon, B. A prospective study of Autolo- Schwartz, Z. Platelet-rich plasma inhibits demineralized bone ma-
gous Growth Factors (AGF) in lumbar interbody fusion. Spine J., trix-induced bone formation in nude mice. J. Bone Joint Surg. Am.,
2006, 6(1), 14-20. 2007, 89(1), 139-147.
[15] Hee, H.T.; Majd, M.E.; Holt, R.T.; Myers, L. Do autologous [36] Arpornmaeklong, P.; Kochel, M.; Depprich, R.; Kubler, N.R.;
growth factors enhance transforaminal lumbar interbody fusion. Wurzler, K.K. Influence of platelet-rich plasma (PRP) on os-
Eur. Spine J., 2003, 12(4), 400-407. teogenic differentiation of rat bone marrow stromal cells. An in vi-
[16] Everts, P.A.; Van, Z.A.; Schonberger, J.P.; Devilee, R.J.; Knape, tro study. Int. J. Oral Maxillofac. Surg., 2004, 33(1), 60-70.
J.T. What do we use: Platelet-rich plasma or platelet-leukocyte gel? [37] Mehta, S.; Watson, J.T. Platelet rich concentrate: basic science and
J. Biomed. Mater. Res. A, 2007, 85(4), 1135-1136. current clinical applications. J. Orthop. Trauma, 2008, 22(6), 432-
[17] Mishra, A.; Woodall, J.J.; Vieira, A. Treatment of tendon and mus- 438.
cle using platelet-rich plasma. Clin. Sports Med., 2009, 28(1), 113- [38] Anitua, E.; Sanchez, M.; Nurden, A.T.; Nurden, P.; Orive, G.;
125. Andia, I. New insights into and novel applications for platelet-rich
[18] Dohan, D.M.; Choukroun, J.; Diss, A.; Dohan, S.L.; Dohan, A.J.; fibrin therapies. Trends Biotechnol., 2006, 24(5), 227-234.
Mouhyi, J.; Gogly, B. Platelet-rich fibrin (PRF): a second- [39] Graziani, F.; Ivanovski, S.; Cei, S.; Ducci, F.; Tonetti, M.; Gab-
generation platelet concentrate. Part III: leucocyte activation: a new riele, M. The in vitro effect of different PRP concentrations on os-
feature for platelet concentrates. Oral Surg. Oral Med. Oral Pathol. teoblasts and fibroblasts. Clin. Oral Implants Res., 2006, 17(2),
Oral Radiol. Endod., 2006, 101(3), 51-55. 212-219.
[19] Cieslik-Bielecka, A.; Gazdzik, T.S.; Bielecki, T.M.; Cieslik, T. [40] Weibrich, G.; Hansen, T.; Kleis, W.; Buch, R.; Hitzler, W.E. Effect
Why the platelet-rich gel has antimicrobial activity. Oral Surg. of platelet concentration in platelet-rich plasma on peri-implant
Oral Med. Oral Pathol. Oral Radiol. Endod., 2007, 103(3), 303- bone regeneration. Bone, 2004, 34(4), 665-671.
306. [41] Pietrzak, W.S.; Eppley, B.L. Platelet rich plasma: biology and new
[20] Li, S.B.; Zhang, C.Q.; Yuan, T. Osteogenic potential of platelet- technology. J. Craniofac. Surg., 2005, 16(6), 1043-1054.
rich plasma combined with cells and artificial bone. Zhongguo Xiu [42] Sampson, S.; Gerhardt, M.; Mandelbaum, B. Platelet rich plasma
Fu Chong Jian Wai Ke Za Zhi, 2007, 21(1), 58-64. injection grafts for musculoskeletal injuries: a review. Curr. Rev.
[21] Chandra, R.K.; Handorf, C.; West, M.; Kruger, E.A.; Jackson, S. Musculoskelet. Med., 2008, 1(3), 165-174.
Histologic effects of autologous platelet gel in skin flap healing. [43] Gandhi, A.; Doumas, C.; O'Connor, J.P.; Parsons, J.R.; Lin, S.S.
Arch. Facial Plast. Surg., 2007, 9(4), 260-263. The effects of local platelet rich plasma delivery on diabetic frac-
[22] Bhanot, S; Alex, J.C. Current applications of platelet gels in facial ture healing. Bone, 2006, 38(4), 540-546.
plastic surgery. Facial Plast. Surg., 2002, 18(1), 27-33. [44] Fennis, J.P.; Stoelinga, P.J.; Jansen, J.A. Mandibular reconstruc-
[23] Gardner, M.J.; Demetrakopoulos, D.; Klepchick, P.R.; Mooar, P.A. tion: a histological and histomorphometric study on the use of
The efficacy of autologous platelet gel in pain control and blood autogenous scaffolds, particulate cortico-cancellous bone grafts and
loss in total knee arthroplasty. An analysis of the haemoglobin, platelet rich plasma in goats. Int J. Oral Maxillofac. Surg., 2004,
narcotic requirement and range of motion. Int. Orthop., 2007, 33(1), 48-55.
31(3), 309-313. [45] Fennis, J.P.; Stoelinga, P.J.; Jansen, J.A. Reconstruction of the
[24] Berghoff, W.J.; Pietrzak, W.S.; Rhodes, R.D. Platelet-rich plasma mandible with an autogenous irradiated cortical scaffold, autoge-
application during closure following total knee arthroplasty. Ortho- nous corticocancellous bone-graft and autogenous platelet-rich-
pedics, 2006, 29(7), 590-598. plasma: an animal experiment. Int. J. Oral Maxillofac. Surg., 2005,
[25] Nurden, A.T.; Nurden, P.; Sanchez, M.; Andia, I.; Anitua, E. Plate- 34(2), 158-166.
lets and wound healing. Front. Biosci., 2008, 13, 3532-3548. [46] Frechette, J.P.; Martineau, I.; Gagnon, G. Platelet-rich plasmas:
[26] Man, D.; Plosker, H.; Winland-Brown, J.E. The use of autologous growth factor content and roles in wound healing. J. Dent. Res.,
platelet-rich plasma (platelet gel) and autologous platelet-poor 2005, 84(5), 434-439.
plasma (fibrin glue) in cosmetic surgery. Plast. Reconstr. Surg., [47] Bielecki, T.; Gazdzik, T.S.; Szczepanski, T. Re: "The effects of
2001, 107(1), 229-239. local platelet rich plasma delivery on diabetic fracture healing".
[27] Smith, S.E.; Roukis, T.S. Bone and wound healing augmentation What do we use: Platelet-rich plasma or platelet-rich gel. Bone,
with platelet-rich plasma. Clin. Podiatr. Med. Surg., 2009, 26(4), 2006, 39(6), 1388-1389.
559-588.
[48] Dohan, D.M.; Choukroun, J.; Diss, A.; Dohan, S.L.; Dohan, A.J.; rich plasma and human bone marrow stromal cells for tissue engi-
Mouhyi, J.; Gogly, B. Platelet-rich fibrin (PRF): a second- neering. J. Mater. Sci. Mater. Med., 2009, 20(1), 45-50
generation platelet concentrate. Part I: technological concepts and [66] Kasten, P.; Vogel, J.; Beyen, I.; Weiss, S.; Niemeyer, P.; Leo, A.;
evolution. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod., Luginbuhl, R. Effect of platelet-rich plasma on the in vitro prolif-
2006, 101(3), 37-44. eration and osteogenic differentiation of human mesenchymal stem
[49] Bolander, M.E. Regulation of fracture repair by growth factors. cells on distinct calcium phosphate scaffolds: the specific surface
Proc. Soc. Exp. Biol. Med., 1992, 200(2), 165-170. area makes a difference. J .Biomater. Appl., 2008, 23(2), 169-188.
[50] Lo, W.C.; Chiou, J.F.; Gelovani, J.G.; Cheong, M.L.; Lee, C.M.; [67] Towler, D.A. The osteogenic-angiogenic interface: novel insights
Liu, H.Y.; Wu, C.H.; Wang, M.F.; Lin, C.T.; Deng, W.P. Trans- into the biology of bone formation and fracture repair. Curr. Os-
plantation of embryonic fibroblasts treated with platelet-rich teoporos. Rep., 2008, 6(2), 67-71.
plasma induces osteogenesis in SAMP8 mice monitored by mo- [68] Cenni, E.; Ciapetti, G.; Granchi, D.; Fotia, C.; Perut, F.; Giunti, A.;
lecular imaging. J. Nucl. Med., 2009, 50(5), 765-773. Baldini, N. Endothelial cells incubated with platelet-rich plasma
[51] Creeper, F.; Lichanska, A.M.; Marshall, R.I.; Seymour, G.J.; express PDGF-B and ICAM-1 and induce bone marrow stromal
Ivanovski, S. The effect of platelet-rich plasma on osteoblast and cell migration. J. Orthop. Res., 2009, 27(11), 1493-1498.
periodontal ligament cell migration, proliferation and differentia- [69] Ogino, Y.; Ayukawa, Y.; Kukita, T.; Atsuta, I.; Koyano, K. Plate-
tion. J. Periodontal. Res., 2009, 44(2), 258-265. let-rich plasma suppresses osteoclastogenesis by promoting the se-
[52] Cenni, E.; Perut, F.; Ciapetti, G.; Savarino, L.; Dallari, D.; Cenac- cretion of osteoprotegerin. J. Periodontal. Res., 2009, 44(2), 217-
chi, A.; Stagni, C.; Giunti, A.; Fornasari, P.M.; Baldini, N. In vitro 224
evaluation of freeze-dried bone allografts combined with platelet [70] Sipe, J.B.; Zhang, J; Waits, C.; Skikne, B.; Garimella, R.; Ander-
rich plasma and human bone marrow stromal cells for tissue engi- son, H.C. Localization of bone morphogenetic proteins (BMPs)-2, -
neering. J. Mater. Sci. Mater. Med., 2009, 20, 45-50. 4, and -6 within megakaryocytes and platelets. Bone, 2004, 35(6),
[53] Gassling, V.L.; Acil, Y.; Springer, I.N.; Hubert, N.; Wiltfang, J. 1316-1322.
Platelet-rich plasma and platelet-rich fibrin in human cell culture. [71] Ogino, Y.; Ayukawa, Y.; Tsukiyama, Y.; Koyano, K. The effect of
Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod., 2009, platelet-rich plasma on the cellular response of rat bone marrow
108(1), 48-55. cells in vitro. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. En-
[54] Celotti, F.; Colciago, A.; Negri-Cesi, P.; Pravettoni, A.; Zaninetti, dod., 2005, 100(3), 302-307.
R.; Sacchi, M.C. Effect of platelet-rich plasma on migration and [72] Choi, B.H.; Zhu, S.J.; Kim, B.Y.; Huh, J.Y.; Lee, S.H.; Jung, J.H.
proliferation of SaOS-2 osteoblasts: role of platelet-derived growth Effect of platelet-rich plasma (PRP) concentration on the viability
factor and transforming growth factor-beta. Wound Repair Regen., and proliferation of alveolar bone cells: an in vitro study. Int. J.
2006, 14(2), 195-202. Oral Maxillofac. Surg., 2005, 34(4), 420-424.
[55] Cenni, E.; Ciapetti, G.; Pagani, S.; Perut, F.; Giunti, A.; Baldini, N. [73] Hsu, C.W.; Yuan, K.; Tseng, C.C. The negative effect of platelet-
Effects of activated platelet concentrates on human primary cul- rich plasma on the growth of human cells is associated with se-
tures of fibroblasts and osteoblasts. J. Periodontol., 2005, 76(3), creted thrombospondin-1. Oral Surg. Oral Med. Oral Pathol. Oral
323-328. Radiol. Endod., 2009, 107(2), 185-192.
[56] Ferreira, C.F.; Carriel, G.M.C.; Filho, J.S.; Granjeiro, J.M.; [74] Iruela-Arispe, M.L.; Lombardo, M.; Krutzsch, H.C.; Lawler, J.;
Oliveira, S.C.M.; Magini, R.S. Platelet-rich plasma influence on Roberts, D.D. Inhibition of angiogenesis by thrombospondin-1 is
human osteoblasts growth. Clin. Oral. Implants Res., 2005, 16(4), mediated by 2 independent regions within the type 1 repeats. Cir-
456-460. culation, 1999, 100(13), 1423-1431.
[57] Goto, H.; Matsuyama, T.; Miyamoto, M.; Yonamine, Y.; Izumi, Y. [75] Bornstein, P.; Sage, E.H. Thrombospondins. Methods Enzymol.,
Platelet-rich plasma/osteoblasts complex induces bone formation 1994, 245, 62-85.
via osteoblastic differentiation following subcutaneous transplanta- [76] Everts, P.A.; Knape, J.T.; Weibrich, G.; Schonberger, J.P.;
tion. J .Periodontal. Res., 2006, 41(5), 455-462. Hoffmann, J.; Overdevest, E.P.; Box, H.A.; Van, Z.A. Platelet-rich
[58] Kanno, T.; Takahashi, T.; Tsujisawa, T.; Ariyoshi, W.; Nishihara, plasma and platelet gel: a review. J. Extra. Corpor. Technol., 2006,
T. Platelet-rich plasma enhances human osteoblast-like cell prolif- 38(2), 174-187.
eration and differentiation. J. Oral Maxillofac. Surg., 2005, 63(3), [77] Nair, M.B.; Varma, H.K.; Menon, K.V.; Shenoy, S.J.; John, A.
362-369. Reconstruction of goat femur segmental defects using triphasic ce-
[59] Hu, Z.M.; Peel, S.A.; Ho, S.K.; Sandor, G.K.; Clokie, C.M. Com- ramic-coated hydroxyapatite in combination with autologous cells
parison of platelet-rich plasma, bovine BMP, and rhBMP-4 on and platelet-rich plasma. Acta. Biomater., 2009, 5(5), 1742-1755.
bone matrix protein expression in vitro. Growth Factors, 2009, [78] Han, B.; Woodell-May, J.; Ponticiello, M.; Yang, Z.; Nimni, M.
27(5), 280-288. The effect of thrombin activation of platelet-rich plasma on demin-
[60] Lucarelli, E.; Beccheroni, A.; Donati, D.; Sangiorgi, L.; Cenacchi, eralized bone matrix osteoinductivity. J. Bone Joint Surg. Am.,
A.; Del, V.A.M.; Meotti, C.; Bertoja, A.Z.; Giardino, R.; Fornasari, 2009, 91(6), 1459-1470.
P.M.; Mercuri, M.; Picci, P. Platelet-derived growth factors en- [79] Rabillard, M.; Grand, J.G.; Dalibert, E.; Fellah, B.; Gauthier, O.;
hance proliferation of human stromal stem cells. Biomaterials, Niebauer, G.W. Effects of autologous platelet rich plasma gel and
2003, 24(18), 3095-3100. calcium phosphate biomaterials on bone healing in an ulnar ostec-
[61] Oprea, W.E.; Karp, J.M.; Hosseini, M.M.; Davies, J.E. Effect of tomy model in dogs. Vet. Comp. Orthop. Traumatol., 2009, 22(6),
platelet releasate on bone cell migration and recruitment in vitro. J. 460-466.
Craniofac. Surg., 2003, 14 (3), 292-300. [80] Li, N.Y.; Yuan, R.T.; Chen, T.; Chen, L.Q.; Jin, X.M. Effect of
[62] Gruber, R.; Karreth, F.; Fischer, M.B.; Watzek, G. Platelet-released platelet-rich plasma and latissimus dorsi muscle flap on osteogene-
supernatants stimulate formation of osteoclast-like cells through a sis and vascularization of tissue-engineered bone in dogs. J. Oral
prostaglandin/RANKL-dependent mechanism. Bone, 2002, 30(5), Maxillofac. Surg., 2009, 67(9), 1850-1858.
726-732. [81] Kasten, P.; Vogel, J.; Geiger, F.; Niemeyer, P.; Luginbuhl, R.;
[63] Dallari, D.; Fini, M.; Stagni, C.; Torricelli, P.; Nicoli, A.N.; Giava- Szalay, K. The effect of platelet-rich plasma on healing in critical-
resi, G.; Cenni, E.; Baldini, N.; Cenacchi, A.; Bassi, A.; Giardino, size long-bone defects. Biomaterials, 2008, 29(29), 3983-3992.
R.; Fornasari, P.M.; Giunti, A. In vivo study on the healing of bone [82] Kroese-Deutman, H.C.; Vehof, J.W.; Spauwen, P.H.; Stoelinga,
defects treated with bone marrow stromal cells, platelet-rich P.J.; Jansen, J.A. Orthotopic bone formation in titanium fiber mesh
plasma, and freeze-dried bone allografts, alone and in combination. loaded with platelet-rich plasma and placed in segmental defects.
J. Orthop. Res., 2006, 24(5), 877-888. Int. J. Oral Maxillofac. Surg., 2008, 37(6), 542-549.
[64] Lucarelli, E.; Fini, M.; Beccheroni, A.; Giavaresi, G.; Di, B.C.; [83] Thorwarth, M.; Rupprecht, S.; Falk, S.; Felszeghy, E.; Wiltfang, J.;
Aldini, N.N.; Guzzardella, G.; Martini, L.; Cenacchi, A.; Di, M.N.; Schlegel, K.A. Expression of bone matrix proteins during de novo
Sangiorgi, L.; Fornasari, P.M.; Mercuri, M.; Giardino, R.; Donati, bone formation using a bovine collagen and platelet-rich plasma
D. Stromal stem cells and platelet-rich plasma improve bone al- (prp)--an immunohistochemical analysis. Biomaterials, 2005,
lograft integration. Clin. Orthop. Relat. Res., 2005, 435, 62-68. 26(15), 2575-2584.
[65] Cenni, E.; Perut, F.; Ciapetti, G.; Savarino, L.; Dallari, D.; Cenac- [84] Kawasumi, M.; Kitoh, H.; Siwicka, K.A.; Ishiguro, N. The effect of
chi, A.; Stagni, C.; Giunti, A.; Fornasari, P.M.; Baldini, N. In vitro the platelet concentration in platelet-rich plasma gel on the regen-
evaluation of freeze-dried bone allografts combined with platelet eration of bone. J. Bone Joint Surg. Br., 2008, 90(7), 966-972.
[85] Sarkar, M.R.; Augat, P.; Shefelbine, S.J.; Schorlemmer, S.; Huber- [106] Eppley, B.L.; Pietrzak, W.S.; Blanton, M. Platelet-rich plasma: a
Lang, M.; Claes, L.; Kinzl, L.; Ignatius, A. Bone formation in a review of biology and applications in plastic surgery. Plast. Re-
long bone defect model using a platelet-rich plasma-loaded colla- constr. Surg., 2006, 118(6), 147e-159e.
gen scaffold. Biomaterials, 2006, 27(9), 1817-1823. [107] Pietrzak, W.S.; An, Y.H.; Kang, Q.K.; Demos, H.A.; Ehrens, K.H.
[86] Choi, B.H.; Im, C.J.; Huh, J.Y.; Suh, J.J.; Lee, S.H. Effect of plate- Platelet-rich and platelet-poor plasma: development of an animal
let-rich plasma on bone regeneration in autogenous bone graft. Int. model to evaluate hemostatic efficacy. J. Craniofac. Surg., 2007,
J. Oral Maxillofac. Surg., 2004, 33(1), 56-59. 18(3), 559-567.
[87] Floryan, K.M.; Berghoff, W.J. Intraoperative use of autologous [108] Tischler, M. Platelet rich plasma. The use of autologous growth
platelet-rich and platelet-poor plasma for orthopedic surgery pa- factors to enhance bone and soft tissue grafts. N. Y. State Dent. J.,
tients. AORN J., 2004, 80(4), 668-674. 2002, 68(3), 22-24.
[88] Everts, P.A.; Overdevest, E.P.; Jakimowicz, J.J.; Oosterbos, C.J.; [109] Pierce, G.F.; Tarpley, J.E.; Yanagihara, D.; Mustoe, T.A.; Fox,
Schonberger, J.P.; Knape, J.T.; Van, Z.A. The use of autologous G.M.; Thomason, A. Platelet-derived growth factor (BB homodi-
platelet-leukocyte gels to enhance the healing process in surgery, a mer), transforming growth factor-beta 1, and basic fibroblast
review. Surg. Endosc., 2007, 21(11), 2063-2068. growth factor in dermal wound healing. Neovessel and matrix for-
[89] Sanchez, A.R.; Sheridan, P.J.; Kupp, L.I. Is platelet-rich plasma the mation and cessation of repair. Am. J. Pathol., 1992, 140(6), 1375-
perfect enhancement factor? A current review. Int. J. Oral Maxillo- 1388.
fac. Implants, 2003, 18(1), 93-103. [110] Kilian, O.; Flesch, I.; Wenisch, S.; Taborski, B.; Jork, A.; Schnet-
[90] Kim, S.G.; Chung, C.H.; Kim, Y.K.; Park, J.C.; Lim, S.C. Use of tler, R.; Jonuleit, T. Effects of platelet growth factors on human
particulate dentin-plaster of Paris combination with/without plate- mesenchymal stem cells and human endothelial cells in vitro. Eur.
let-rich plasma in the treatment of bone defects around implants. J. Med. Res., 2004, 9(7), 337-344.
Int. J. Oral Maxillofac. Implants, 2002, 17(1), 86-94. [111] Kakudo, N.; Minakata, T.; Mitsui, T.; Kushida, S.; Notodihardjo,
[91] Ito, K.; Yamada, Y.; Nagasaka, T.; Baba, S.; Ueda, M. Osteogenic F.Z.; Kusumoto, K. Proliferation-promoting effect of platelet-rich
potential of injectable tissue-engineered bone: a comparison among plasma on human adipose-derived stem cells and human dermal fi-
autogenous bone, bone substitute (Bio-oss), platelet-rich plasma, broblasts. Plast. Reconstr. Surg., 2008, 122(5), 1352-1360.
and tissue-engineered bone with respect to their mechanical proper- [112] Vermeulen, P.; Dickens, S.; Degezelle, K.; Van den Berge S; Hen-
ties and histological findings. J. Biomed. Mater Res. A, 2005, drickx, B.; Vranckx, J.J. A plasma-based biomatrix mixed with en-
73A(1), 63-72. dothelial progenitor cells and keratinocytes promotes matrix forma-
[92] Gandhi, A.; Bibbo, C.; Pinzur, M.; Lin, S.S. The role of platelet- tion, angiogenesis, and reepithelialization in full-thickness wounds.
rich plasma in foot and ankle surgery. Foot Ankle Clin., 2005, Tissue. Eng. Part. A, 2009, 15(7), 1533-1542.
10(4), 621-637. [113] Kazakos, K.; Lyras, D.N.; Verettas, D.; Tilkeridis, K.; Tryfonidis,
[93] Bielecki, T.M. Percutaneous injection of autogenous growth factors M. The use of autologous PRP gel as an aid in the management of
in patient with nonunion of the humerus. A case report. J. Ortho- acute trauma wounds. Injury, 2009, 40(8), 801-805.
paedics, 2006, 3(3), e15. [114] Hom, D.B.; Linzie, B.M.; Huang, T.C. The healing effects of
[94] Hartmann, E.K.; Heintel, T.; Morrison, R.H.; Weckbach, A. Influ- autologous platelet gel on acute human skin wounds. Arch. Facial
ence of platelet-rich plasma on the anterior fusion in spinal injuries: Plast. Surg., 2007, 9(3), 174-183.
a qualitative and quantitative analysis using computer tomography. [115] Yokota, K.; Ishida, O.; Sunagawa, T.; Suzuki, O.; Nakamae, A.;
Arch. Orthop. Trauma. Surg., 2009, 130(7), 909-914. Ochi, M. Platelet-rich plasma accelerated surgical angio-genesis in
[95] Li, H.; Zou, X.; Xue, Q.; Egund, N.; Lind, M.; Bunger, C. Anterior vascular-implanted necrotic bone: an experimental study in rabbits.
lumbar interbody fusion with carbon fiber cage loaded with bioce- Acta. Orthop., 2008, 79(1), 106-110.
ramics and platelet-rich plasma. An experimental study on pigs. [116] Sariguney, Y.; Yavuzer, R.; Elmas, C.; Yenicesu, I.; Bolay, H.;
Eur. Spine J., 2004, 13(4), 354-358. Atabay, K. Effect of platelet-rich plasma on peripheral nerve re-
[96] Dallari, D.; Savarino, L.; Stagni, C.; Cenni, E.; Cenacchi, A.; For- generation. J. Reconstr. Microsurg., 2008, 24(3), 159-167.
nasari, P.M.; Albisinni, U.; Rimondi, E.; Baldini, N.; Giunti, A. [117] Caceres, M.; Hidalgo, R.; Sanz, A.; Martinez, J.; Riera, P.; Smith,
Enhanced tibial osteotomy healing with use of bone grafts supple- P.C. Effect of platelet-rich plasma on cell adhesion, cell migration,
mented with platelet gel or platelet gel and bone marrow stromal and myofibroblastic differentiation in human gingival fibroblasts.
cells. J. Bone Joint Surg. Am., 2007, 89(11), 2413-2420. J. Periodontol., 2008, 79(4), 714-720.
[97] Kitoh, H.; Kitakoji, T.; Tsuchiya, H.; Katoh, M.; Ishiguro, N. [118] Kasemkijwattana, C.; Menetrey, J.; Bosch, P.; Somogyi, G.; More-
Transplantation of culture expanded bone marrow cells and platelet land, M.S.; Fu, F.H.; Buranapanitkit, B.; Watkins, S.S.; Huard, J.
rich plasma in distraction osteogenesis of the long bones. Bone, Use of growth factors to improve muscle healing after strain injury.
2007, 40(2), 522-528. Clin. Orthop. Relat. Res., 2000, (370), 272-285.
[98] Lowery, G.L.; Kulkarni, S.; Pennisi, A.E. Use of autologous [119] Loo, W.L.; Lee, D.Y.; Soon, M.Y. Plasma rich in growth factors to
growth factors in lumbar spinal fusion. Bone, 1999, 25(2 Suppl. 1), treat adductor longus tear. Ann. Acad. Med. Singapore, 2009, 38(8),
47S-50S. 733-734.
[99] Bielecki, T.; Gazdzik, T.S. Percutaneous injection of autologous [120] Sanchez, M.; Anitua, E.; Orive, G.; Mujika, I.; Andia, I. Platelet-
platelet-rich gel in a patient with an infected nonunion of the tibia. rich therapies in the treatment of orthopaedic sport injuries. Sports
A case report and review of the literature. J. Orthop. Trauma Surg. Med., 2009, 39(5), 345-354.
Rel. Res., 2007, 2(6), 69-72. [121] Molloy, T.; Wang, Y.; Murrell, G. The roles of growth factors in
[100] Bielecki, T.; Gazdzik, T.S.; Szczepanski, T. Benefit of percutane- tendon and ligament healing. Sports Med., 2003, 33(5), 381-394.
ous injection of autologous platelet-leukocyte-rich gel in patients [122] Schnabel, L.V.; Mohammed, H.O.; Miller, B.J.; McDermott, W.G.;
with delayed union and nonunion. Eur. Surg. Res., 2008, 40(3), Jacobson, M.S.; Santangelo, K.S.; Fortier, L.A. Platelet rich plasma
289-296. (PRP) enhances anabolic gene expression patterns in flexor digito-
[101] Sanchez, M.; Anitua, E.; Cugat, R.; Azofra, J.; Guadilla, J.; Seijas, rum superficialis tendons. J. Orthop. Res., 2007, 25(2), 230-240.
R.; Andia, I. Nonunions treated with autologous preparation rich in [123] de Mos M; der Windt AE, v.; Jahr, H.; van, S.H.T.; Weinans, H.;
growth factors. J. Orthop. Trauma, 2009, 23(1), 52-59. Verhaar, J.A. ; van, O.G.J. Can platelet-rich plasma enhance tendon
[102] Yuan, T.; Zhang, C.Q.; Zeng, B.F. Treatment of chronic femoral repair? A cell culture study. Am. J. Sports Med., 2008, 36(6), 1171-
osteomyelitis with platelet-rich plasma (PRP): a case report. Trans- 1178.
fus. Apher. Sci., 2008, 38(2), 167-173. [124] Aspenberg, P.; Virchenko, O. Platelet concentrate injection im-
[103] Jia, W.T.; Zhang, C.Q. Comment on "Platelet-Rich Plasma as a proves Achilles tendon repair in rats. Acta. Orthop. Scand., 2004,
novel therapeutic agent in osteomyelitis". Med. Hypotheses, 2009, 75(1), 93-99.
73(2), 270-271. [125] Virchenko, O.; Aspenberg, P. How can one platelet injection after
[104] Namazi, H. Platelet-Rich Plasma as a novel therapeutic agent in tendon injury lead to a stronger tendon after 4 weeks? Interplay be-
osteomyelitis. Med. Hypotheses, 2007, 69(3), 706. tween early regeneration and mechanical stimulation. Acta. Or-
[105] Weiner, B.K; Walker, M. Efficacy of autologous growth factors in thop., 2006, 77(5), 806-812.
lumbar intertransverse fusions. Spine, 2003, 28(17), 1968-1970. [126] Anitua, E.; Sanchez, M.; Nurden, A.T.; Zalduendo, M.; de la
Fuente M; Orive, G.; Azofra, J.; Andia, I. Autologous fibrin matri-
ces: a potential source of biological mediators that modulate tendon preparation Discussion. J. Oral Maxillofac. Surg., 2000, 58(3),
cell activities. J. Biomed. Mater. Res. A, 2006, 77(2), 285-293. 297-301.
[127] Anitua, E.; Sanchez, M.; Nurden, A.T.; Zalduendo, M.; de la [139] Yuan T.; Guo, S.C.; Zhang, C.Q. A study on methods and principle
Fuente M; Azofra, J.; Andia, I. Reciprocal actions of platelet- of preparing platelet-rich plasma. The 4th International Congress of
secreted TGF-beta1 on the production of VEGF and HGF by hu- Chinese Orthopaedic Association; Xiamen, China, 19-22 Novem-
man tendon cells. Plast. Reconstr. Surg., 2007, 119(3), 950-959. ber 2009; pp. 436.
[128] Sanchez, M.; Anitua, E.; Azofra, J.; Andia, I.; Padilla, S.; Mujika, [140] Anitua, E. Plasma rich in growth factors: preliminary results of use
I. Comparison of surgically repaired Achilles tendon tears using in the preparation of future sites for implants. Int. J. Oral Maxillo-
platelet-rich fibrin matrices. Am. J. Sports Med., 2007, 35(2), 245- fac. Implants, 1999, 14(4), 529-535.
251. [141] Aghaloo, T.L.; Moy, P.K.; Freymiller, E.G. Investigation of plate-
[129] Farrag, T.Y.; Lehar, M.; Verhaegen, P.; Carson, K.A.; Byrne, P.J. let-rich plasma in rabbit cranial defects: A pilot study. J. Oral Max-
Effect of platelet rich plasma and fibrin sealant on facial nerve re- illofac. Surg., 2002, 60(10), 1176-1181.
generation in a rat model. Laryngoscope, 2007, 117(1), 157-165. [142] Petrungaro, P. Platelet-rich plasma for dental implants and soft-
[130] Sariguney, Y.; Yavuzer, R.; Elmas, C.; Yenicesu, I.; Bolay, H.; tissue grafting. Interview by Arun K. Garg. Dent. Implantol. Up-
Atabay, K. Effect of platelet-rich plasma on peripheral nerve re- date, 2001, 12(6), 41-46.
generation. J Reconstr. Microsurg., 2008, 24(3), 159-167. [143] Petrungaro, P.S. Using platelet-rich plasma to accelerate soft tissue
[131] Shen, Y.X.; Fan, Z.H.; Zhao, J.G.; Zhang, P. The application of maturation in esthetic periodontal surgery. Compend. Contin. Educ.
platelet-rich plasma may be a novel treatment for central nervous Dent., 2001, 22(9), 729-732.
system diseases. Med. Hypotheses, 2009, 73(6), 1038-1040. [144] Marx, R.E. Platelet-rich plasma (PRP): what is PRP and what is not
[132] Bhargava, M.M.; Attia, E.T.; Murrell, G.A.; Dolan, M.M.; Warren, PRP. Implant Dent., 2001, 10(4), 225-228.
R.F.; Hannafin, J.A. The effect of cytokines on the proliferation [145] Intini, G. The use of platelet-rich plasma in bone reconstruction
and migration of bovine meniscal cells. Am. J. Sports Med., 1999, therapy. Biomaterials, 2009, 30(28), 4956-4966.
27(5), 636-643. [146] Sands, J.J.; Nudo, S.A.; Ashford, R.G.; Moore, K.D.; Ortel, T.L.
[133] Collier, S.; Ghosh, P. Effects of transforming growth factor beta on Antibodies to topical bovine thrombin correlate with access throm-
proteoglycan synthesis by cell and explant cultures derived from bosis. Am. J. Kidney. Dis., 2000, 35(5), 796-801.
the knee joint meniscus. Osteoarthritis Cartilage, 1995, 3(2), 127- [147] Chouhan, V.D.; De, La Cadena, R.A.; Nagaswami, C.; Weisel,
138. J.W.; Kajani, M.; Rao, A.K. Simultaneous occurrence of human an-
[134] Drengk, A.; Zapf, A.; Sturmer, E.K.; Sturmer, K.M.; Frosch, K.H. tibodies directed against fibrinogen, thrombin, and factor V follow-
Influence of platelet-rich plasma on chondrogenic differentiation ing exposure to bovine thrombin: effects on blood coagulation, pro-
and proliferation of chondrocytes and mesenchymal stem cells. tein C activation and platelet function. Thromb. Haemost., 1997,
Cells Tissues Organs, 2009, 189(5), 317-326. 77(2), 343-349.
[135] Akeda, K.; An, H.S.; Okuma, M.; Attawia, M.; Miyamoto, K.; [148] Christie, R.J.; Carrington, L.; Alving, B. Postoperative bleeding
Thonar, E.J.; Lenz, M.E.; Sah, R.L.; Masuda, K. Platelet-rich induced by topical bovine thrombin: report of two cases. Surgery,
plasma stimulates porcine articular chondrocyte proliferation and 1997, 121(6), 708-710.
matrix biosynthesis. Osteoarthritis Cartilage, 2006, 14(12), 1272- [149] Israels, S.J.; Israels, E.D. Development of antibodies to bovine and
1280. human factor V in two children after exposure to topical bovine
[136] Sanchez, M.; Azofra, J.; Anitua, E.; Andia, I.; Padilla, S.; Santiste- thrombin. Am J. Pediatr. Hematol. Oncol., 1994, 16(3), 249-254.
ban, J.; Mujika, I. Plasma rich in growth factors to treat an articular [150] Zehnder, J.L.; Leung, L.L. Development of antibodies to thrombin
cartilage avulsion: a case report. Med. Sci. Sports Exerc., 2003, and factor V with recurrent bleeding in a patient exposed to topical
35(10), 1648-1652. bovine thrombin. Blood, 1990, 76(10), 2011-2016.
[137] Kon, E.; Mandelbaum, B.; Filardo, G.; timoncini, A.; Delcogliano, [151] Intini, G.; Andreana, S.; Margarone, J.E3rd .; Bush, P.J.; Dziak, R.
M.; fornasari, P.M.; Giannini, s.; Marcacci, M. PRP intra-articular Engineering a bioactive matrix by modifications of calcium sulfate.
injection versus viscosupplementation as treatments for early os- Tissue Eng., 2002, 8(6), 997-1008.
teoarthritis. 2010Annual Meeting Information Podium Presenta- [152] Bateman, J.; Intini, G.; Margarone, J.; Goodloe, S.; Bush, P.;
tions-AAOS, [Online] 2010, podium(685). Lynch, S.E.; Dziak, R. Platelet-derived growth factor enhancement
http://www3.aaos.org/education/anmeet/anmt2010/podium/podium of two alloplastic bone matrices. J. Periodontol., 2005, 76(11),
.cfm?Pevent=685 [Accessed on: 24th May 2010] 1833-1841.
[138] Landesberg, R.; Roy, M.; Glickman, R.S. Quantification of growth
factor levels using a simplified method of platelet-rich plasma gel
Received: April 04, 2010 Revised: June 10, 2010 Accepted: September 06, 2010

Applications of Leukocyte - and Platelet-Rich Plasma (L-PRP) in Trauma

Uploaded by

Copyright:

Available Formats

Applications of Leukocyte - and Platelet-Rich Plasma (L-PRP) in Trauma

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Applications of Leukocyte - and Platelet-Rich Plasma (L-PRP) in Trauma

Uploaded by

Copyright:

Available Formats

Current Pharmaceutical Biotechnology, 2012, 13, 1173-1184 1173

Applications of Leukocyte- and Platelet-Rich Plasma (L-PRP) in Trauma

1. INTRODUCTION rich material may also have increased concentrations of leu-

1873-4316/12 $58.00+.00 2012 Bentham Science Publishers

4. POTENTIAL PROBLEMS AND RISKS

Platelet Count (1,000/l) 1500g 6 Mins 200g 10 Mins 215g 10 Mins

Whole blood 217.5 213.5 220.0

Upper layer of PPP 3.9 68.8 65.4

Middle layer of PPP 7.4 74.3 74

Lowest layer of PPP 97.5 312.7 309.7

Upper layer of red cell 833.4 674.6 682.2

Lower layer of red cell 204.4 68.1 71.2

You might also like