Review Article

PRP Augmentation for ACL Reconstruction

Table 1

Synopsis of the preclinical studies dealing with the use of PRP in ACL reconstruction.
(a) Animal trials

PublicationAnimal modelStudy protocolPRP characteristicsApplication methodResults

Xie et al., JSR
2013 [26]
36 dogsPRP versus controlPlatelet count:  
 pts/L  
Activation method:  
10% calcium chloride  
Leukocyte count: —
Injected into ACL graftPRP allows an increase in expression of vascular endothelial growth factor, thrombospondin-1, neurotrophin-3, growth-associated protein-43, and nerve growth factor mRNA.

Xie et al., JSR
2013 (2) [27]
36 dogsPRP versus controlPlatelet count:  
 pts/L  
Activation method:  
10% calcium chloride  
Leukocyte count: —
Injected into ACL graftPRP alters the expression of target genes (growth factor-b1, collagen type1A1, collagen type3A1, decorin, biglycan, matrix metalloproteinase-1, matrix metalloproteinase-13, and tissue inhibitor of metalloproteinase-1 during the remodelling process (evaluations performed at 2, 6, and 12 weeks after surgery).

Mastrangelo et al., JOR
2011 [28]
8 minipigsCollagen scaffold augmented with PRP 5x versus PRP 3xPlatelet count:  
 pts/L (5x PRP)  
 pts/L (3x PRP)  
Activation method: —  
Leukocyte count: —
Collagen scaffold augmentationNo statistical difference in biomechanical properties (anteroposterior laxity and structural properties).
Histological aspects: compared to 3x PRP, 5x PRP group had significantly greater cellular density and number of vessels and better organization of cells and collagen fibres.

Joshi et al., AJSM
2009 [29]
27 pigsCollagen-PRP versus controlPlatelet count:  
 pts/mm3
Activation method: —  
Leukocyte count: —
Collagen-PRP compositeThe addition of a collagen-PRP composite for ACL repair determined a higher yield load and linear stiffness and higher cell density at 3 months.

Murray et al., JOR
2009 [30]
6 pigsPRP versus controlPlatelet count:  
times  
Activation method: —  
Leukocyte count:  
times
Injected around the suture materialNo significant difference in mechanical properties (ACL laxity, maximum tensile load, and linear stiffness) of repaired ACL.

Murray et al., JOR
2007 [31]
5 pigsCollagen-PRP versus controlPlatelet count:  
/mm3
Activation method: —  
Leukocyte count: —
Collagen scaffold augmentationSignificant improvements in mechanical properties (load at yield, maximum load, and linear stiffness) of repaired ACL compared to sutured only at 4 weeks after surgery.

Murray et al., JOR
2007 (2) [32]
10 dogsCollagen-PRP versus controlPlatelet count: —  
Activation method: —  
Leukocyte count: —
Collagen scaffold augmentationThe application of collagen-PRP scaffold allows significant effects of increasing the wound filling and enhancing the presence of fibronectin, fibrinogen, PDGF-A, TBG-b1, FGF-2, procollagen I, and vWF.

Murray et al., JOR 2006 [33]24 dogsCollagen-PRP versus controlPlatelet count: —  
Activation method: —  
Leukocyte count: —
Collagen scaffold augmentationThe application of collagen-PRP scaffold allows significant improvements of histological scores and biomechanical properties, compared to control.

Weiler et al., AJSM
2004 [34]
48 sheepPRP versus controlPlatelet count: —  
Activation method: —  
Leukocyte count: —
Injected into ACL graftSignificantly improvements between PRP group and control group concerning cross-sectional area, failure load, stiffness, and tensile stress after 3, 6, or 12 weeks; however, after 24 weeks this difference is not confirmed and mechanical scores are worse than the intact ACL.

(b) In vitro trials

PublicationsPurpose PRP characteristicsApplication method Results

Yoshida et al., JOR  
2014 [35]
Does increasing platelet concentration enhance ACL fibroblast proliferation and collagen production?Platelet count:  
PPP: ;  
PRP: (1x PRP);  
(3x PRP);  
 pts/mL (5x PRP)   
Leukocyte count:  cells/mL
Scaffold’s augmentation (collagen scaffold)Highest cell metabolism, lowest apoptosis rates, and highest collagen gene expression with PPP and 1x PRP.

Yoshida and Murray, JOR  
2013 [36]
How peripheral blood mononuclear cells (PBMCs) in PRP affect fibroblast behaviour?Platelet count:  
PRP:  pts/mL  
Leukocyte count:  
PRP: —  
PBMC:  cells/mL
Scaffold’s augmentation (collagen scaffold)PRP with PBMCs determined an increasing of type I and type III procollagen gene expression, collagen protein expression, and cell proliferation. An increase of IL-6 expression was detected in PBMCs exposed to PRP.
No effect of PBMCs without PRP.

Cheng et al., JOR  
2012 [37]
Does cell’s age influence the ACL cell response to PRP?Platelet count:  
 pts/mL  
Leukocyte count: —
Scaffold’s augmentation (collagen scaffold)PRP increases cellular metabolic activity and reduced apoptotic rate and stimulation of collagen production on immature and adolescent cells, compared to collagen only scaffold. Lower effects of PRP on adult cells.

Fallouh et al., JBJSAm  
2010 [38]
Effects of autologous PRP on cell viability and collagen synthesis of human ACL cells.Platelet count: —  
Activation method:  
10% thrombin solution  
Leukocyte count: —
PRP clot added to culture environmentPRP group had higher concentration of growth factors, cell number, and total collagen production, compared to PPP group.

Magarian et al., Knee  
2011 [39]
Age dependence of ACL fibroblast response to PRPPlatelet count:  
 pts/L  
Leukocyte count:  
 cells/L
Scaffold’s augmentation (collagen scaffold)The comparison between immature and adolescent cells showed a significantly higher cell migration and proliferation in immature group, whereas no differences were seen in scaffold contraction.

Cheng et al., TissEngA  
2010 [40]
Does PRP components (pts or PPP) independently influence ACL cells behaviour?Platelet count:  
 pts/mL  
Leukocyte count: —
Scaffold’s augmentation (collagen scaffold) with PRP, pts, or PPPThe addition of PPP, platelets, or PRP all reduced cell apoptosis and enhanced metabolic activity of fibroblasts.
Significantly higher expression of collagen only with PRP.

Mastrangelo et al., JOR  
2010 [41]
Age dependence in ACL healing Platelet count:  
 pts/L (porcine PRP);  
 pts/L (ovine PRP)
Leukocyte count:  
 cells/L (porcine PRP);  cells/L (ovine PRP)
Scaffold’s augmentation (collagen scaffold)Comparison between adult, adolescent, and immature cells concerning cell proliferation and cellular migration: better results for immature cells.

Scherping et al., CTR  
1997 [42]
Analysis of effects of single growth factors (GF) on fibroblasts harvested from medial collateral ligament and ACL of skeletally mature rabbitsGrowth factor analysed are as follows:  
epidermal GF, basic fibroblast GF, platelet derived GF-BB, acid fibroblast GF, TGF-b1, insulin-like GF-1, platelet derived GF-AA, and interleukin-1a
Epidermal GF, basic fibroblast GF, and platelet derived GF-BB determined a significantly higher fibroblast’s proliferation than the untreated cells. No significant difference reported for the others GFs analysed.