Introduction
Materials and methods
Results
Pre-clinical studies
Animal models
Publication | Treatment groups | PRP characteristics | Animal model | Protocol | Effects | |
---|---|---|---|---|---|---|
Scaffold | 1. Hokugo et al. 2005 [22] | 1) Gelatin 2) Gelatin + PRP 3) Fibrin-glue + PRP 4) PRP 5) Control (untreated) | Platelet concentration: NA Activation: NA Leukocytes: NA Allogenic Fresh/frozen: NA GFs: TGF-β1 and PDGF-BB | Rabbit ulna segmental defect (10 mm) | Hist: + X-Ray: + DEXA: + Positive results for PRP in combination with gelatin | + |
2. Sugimori et al. 2006 [23] | 1) AF 2) PRP 3) AF + PRP 4) Control (untreated) | Platelet concentration: 2.5 x Activation: NA Leukocytes: NA Allogenic Fresh/frozen: NA GFs: NA | Rat tibial cylindrical defect (3.5 mm x 4.5 mm) | Hist: + Positive results for PRP in combination with AF | + | |
3. Sarkar et al. 2006 [4] | 1) Collagen + PRP 2) Collagen | Platelet concentration: 3.5 x Activation: NA Leukocytes: yes Autologous Fresh GFs: NA | Sheep tibial segmental defect (25 mm) | Hist: = X-Ray: = μCT: = Mech: = | = | |
4. Rai et al. 2007 [24] | 1) PCL/TCP 2) PCL/TCP + PRP | Platelet concentration: NA Activation: calcium chloride\thrombin Leukocytes: NA Allogenic Fresh GFs: NA | Rat femoral segmental defect (8 mm) | Hist: = X-Ray: + μCT: + Mech: + | + | |
5. Kasten et al. 2008 [25] | 1) CDHA + BMSCs 2) CDHA + PRP 3) CDHA + PRP + BMSCs 4) CDHA 5) ABG 6) Control (untreated) | Platelet concentration: 5.3 x Activation: calcium chloride\thrombin Leukocytes: NA Allogenic Frozen GFs: NA | Rabbit radius segmental defect (15 mm) | Hist: + X-Ray: + μCT: + Mech: + | + | |
6. Lysiak-Drwal et al. 2008 [26] | 1) BOC + BG 2) BOC + BG + PRP 3) Control (untreated) | Platelet concentration: NA Activation: NA Leukocytes: yes Allogenic/autologous: NA Fresh/frozen: NA GFs: NA | Rabbit femoral cylindrical defect (5 mm) | Hist: + | + | |
7. Nair et al. 2009 [1] | 1) HASi 2) HASi + BMSCs 3) HASi + BMSCs + PRP | Platelet concentration: 1.5 x Activation: NA Leukocytes: NA Autologous Fresh GFs: NA | Goat femoral segmental defect (20 mm) | Hist: + X-Ray: + | + | |
8. Niemeyer et al. 2010 [27] | 1) HA/collagen + BMSCs 2) HA/collagen + ASCs 3) HA/collagen + ASCs + PRP 4) Control (untreated) | Platelet concentration: 4.5 x Activation: calcium chloride/thrombin Leukocytes: No Xenogenic Frozen GFs: PDGF-AB and TGF-β1 | Sheep tibial segmental defect (30 mm) | Hist: + X-Ray: + | + | |
9. Bi et al. 2010 [28] | 1) TCP/chitosan 2) TCP/chitosan + PRP 3) Control (untreated) | Platelet concentration: 5.3 x Activation: calcium chloride\thrombin Leukocytes: NA Allogenic/autologous: NA Fresh/frozen: NA GFs: TGF-β1, PDGF-BB, bFGF and VEGF | Goat tibia cylindrical defect (12 mm) | Hist: + X-Ray: + | + | |
10. Kon et al. 2010 [29] | 1) COL/HA 2) COL/HA + PRP 3) Control (untreated) | Platelet concentration: 3.2 x Activation: calcium chloride Leukocytes: yes Autologous Fresh GFs: TGF-β1, PDGF-AB and IL1 | Sheep femoral condyle cylindrical defect (7 mm x 9 mm) | Hist: − X-Ray: − | - | |
11. Kanthan et al. 2011 [30] | 1) PRP 2) Coral 3) Coral + PRP 4) Control (untreated) | Platelet concentration: 2.6 - 4.6 x Activation: calcium chloride/thrombin Leukocytes: NA Autologous Fresh GFs: NA | Rabbit tibial segmental defect (20 mm) | Hist: + X-Ray: + | + | |
12. Zhang et al. 2011 [31] | 1) Bioactive glass 2) Bioactive glass + PRP 3) Control (untreated) | Platelet concentration: NA Activation: calcium chloride/thrombin Leukocytes: NA Allogenic/autologous: NA Fresh/frozen: NA GFs: NA | Rabbit radius segmental defect (15 mm) | Hist: + X-Ray: + μCT: + | + | |
13. Parizi et al. 2012 [32] | 1) Coral 2) Coral + PRP +1 injection 4 days post op 3) Control (untreated) | Platelet concentration: 10.1 x Activation: NA Leukocytes: no Xenogenic Frozen GFs: NA | Rabbit radius segmental defect (10 mm) | Hist: + X-Ray: + Mech: + | + | |
14. Oryan et al. 2012 [33] | 1) HA 2) HA + hPRP 3) Control (untreated) | Platelet concentration: 10.1 x Activation: NA Leukocytes: No Xenogenic Frozen GFs: NA | Rabbit radius segmental defect (10 mm) | Hist: + X-Ray: + Mech: = | + | |
15. Kasten et al. 2012 [34] | 1) CDHA 2) CDHA + PRP 3) CDHA + PRP + BMSCs 4) CDHA + BMSCs 5) CDHA + BMSCs + VEGF (transfected) | Platelet concentration: 5.3 x Activation: calcium chloride/ thrombin Leukocytes: NA Allogenic Frozen GFs: NA | Rabbit radius segmental defect (15 mm) | Hist: + μCT: + | + | |
16. Kim et al. 2014 [35] | 1) Gelatin + PRP 2) Gelatin + SEW2871 micelles 3) Gelatin + SEW2871 micelles + PRP 4) Control (untreated) | Platelet concentration: 8–10 x Activation: calcium chloride Leukocytes: NA Allogenic Fresh/frozen: NA GFs: TGF-β1 and SDF-1 | Rat ulnar segmental defect (6 mm) | Hist: + X-Ray: + μCT: + | + | |
17. Filardo et al. 2014 [36] | 1) BioSiC(HaCol) 2) BioSiC (HaCol) + PRP 3) BioSiC (HaCol) + BMSCs | Platelet concentration: 2.8 x Activation: calcium chloride Leukocytes: yes Autologous Fresh GFs: NA | Sheep metatarsus segmental defect (20 mm) | Hist: + X-Ray: = | + | |
18. Zhong et al. 2014 [37] | 1) β-TCP + BMSCs 2) β-TCP + BMSCs + PRP 3) Autogenic ilium (control) | Platelet concentration: NA Activation: calcium chloride/thrombin Leukocytes: NA Autologous Frozen GFs: NA | Dog tibia cylindrical defect (10 mm) | Hist: + X-Ray: + Mech: + | + | |
19. He et al. 2015 [2] | 1) PLGA/CPC 2) PLGA/CPC + PRP | Platelet concentration: 3.3 x Activation: calcium chloride/ thrombin Leukocytes: yes Allogenic Fresh/frozen: NA GFs: NA | Rabbit femoral cylindrical defect (6 mm x 10 mm) Rabbit radius segmental defect (15 mm) |
In femoral defect:
Hist: + X-Ray: + μCT: +
In radial defect:
Hist: + X-Ray: + μCT: + | + | |
20. Chen et al. 2016 [38] | 1) CS + PRP 2) CS 3) PRP 4) BMP-2 (positive control) | Platelet concentration: 8–10 x Activation: calcium chloride/thrombin Leukocytes: NA Autologous Fresh GFs: NA | Rabbit radius segmental defect (12 mm) | Hist: + X-Ray: + : + Superior results for CS + PRP with respect to CS and PRP alone, but similar results with BMP-2 | + | |
Autograft/allograft/xenograft | 21. Dallari et al. 2006 [39] | 1) BMSCs + PRP 2) FDBA + BMSCs 3) FDBA + PRP 4) FDBA + PRP + BMSCs | Platelet concentration: 2.8 x Activation: calcium chloride/thrombin Leukocytes: yes Autologous Fresh GFs: NA | Rabbit femoral cylindrical defect (diameter: 6 mm; depth: 10 mm) | Hist: − Superior results for FDBA + PRP + BMSCs | + |
22. Kroese-Deutman et al. 2008 [40] | 1) Ti 2) Ti-Bone chips 3) Ti-Bone chips + PRP | Platelet concentration: 1000–1500 x 109 / L Activation: bovine thrombin Leukocytes: NA Autologous Fresh GFs: NA | Rabbit radial segmental defect (15 mm) | Hist: + X-Ray: = | + | |
23. Molina-Minano et al. 2009 [41] | 1) Autograft 2) PRP 3) Autograft + PRP 4) Control (untreated) | Platelet concentration: NA Activation: calcium chloride Leukocytes: NA Allogenic Fresh GFs: NA | Rabbit tibial cylindrical defect (4 mm) | Hist: = X-Ray: + at 1 m = at 2 m | + | |
24. Hakimi et al. 2010 [42] | 1) Autograft 2) Autograft + PRP | Platelet concentration: 4.9 x Activation: calcium chloride/thrombin Leukocytes: yes Autologous Fresh GFs: TGF-β1 and PDGF-BB | Pig tibial cylindrical defect (11 x 25 mm) | Hist: + X-Ray: = | + | |
25. Nather et al. 2012 [43] | 1) Autograft 2) Allograft 3) Allograft + PRP | Platelet concentration: NA Activation: thrombin Leukocytes: NA Autologous Fresh GFs: NA | Rabbit tibial segmental defect (15 mm) | Hist: + at 12 w = at 24 w X-Ray: = for all the aspects related to mineralization and bone volume + for resorption index | + | |
26. Kurikchy et al. 2013 [44] | 1) Xenograft 2) Xenograft + PRP 3) Control (untreated) | Platelet concentration: 2–3 x Activation: calcium chloride Leukocytes: NA Autologous Fresh GFs: NA | Rabbit femoral cylindrical defect (3 mm) | Hist: + | + | |
27. Zhang et al. 2013 [45] | 1) DPB + PRP + BMSCs 2) DPB + BMSCs 3) DPB + PRP 4) DPB | Platelet concentration: 4 x Activation: calcium chloride\thrombin Leukocytes: NA Allogenic Fresh/frozen: NA GFs: TGF-β1, PDGF, EGF and VEGF | Rabbit radial segmental defect (15 mm) | Hist: + X-Ray: + DEXA: + for new bone tissue quality | + | |
28. Schneppendahl et al. 2015 [46] | 1) Autograft + PRP 2) Autograft | Platelet concentration: 5.4 x Activation: calcium chloride/thrombin Leukocytes: NA Autologous Fresh GFs: TGF-β1; PDGF-BB; VEGF | Rabbit radial segmental defect (15x4x3 mm) | Hist: + X-Ray: + | + | |
29. Park et al. 2016 [47] | 1) Synthetic bone 2) CGF 3) PRF 4) Control (untreated) | Platelet concentration: NA Activation: NA Leukocytes: NA Autologous Fresh GFs: TGF-β and VEGF | Dog femur cylindrical defect (8 mm) | Hist: + | + | |
Powder/granules | 30. Rabillard et al. 2009 [48] | 1) CaP 2) CaP + PRP | Platelet concentration: 3-6x Activation: calcium Borogluconate + batroxobin Leukocytes: NA Autologous Fresh GFs: NA | Dog ulnar segmental defect (20 mm) | Hist: = X-Ray: = SEM: = | = |
31. Jungbluth et al. 2010 [49] | 1) CaP 2) CaP + PRP | Platelet concentration: 4.4 x Activation: calcium chloride/ thrombin Leukocytes: NA Autogenous Fresh GFs: TGF-β1 and PDGF-BB | Pig tibial defect cylindrical defect (11x25 mm) | Hist: + X-Ray: + | + | |
32. Batista et al. 2011 [50] | 1) β - TCP + PRP 2) β - TCP + BMCs | Platelet concentration: 6.2 x Activation: calcium gluonate Leukocytes: NA Allogenic Fresh GFs: NA | Rabbit tibial cylindrical defect (3.3 mm) | Hist: + X-Ray: = μCT: + | + | |
33. Bolukbasi et al. 2013 [51] | 1) BCP 2) BCP + PRF 3) PRF 4) Control (untreated) | Platelet concentration: NA Activation: no Leukocytes: NA Autologous Fresh GFs: NA | Sheep tibial cylindrical defect (5 mm) | Hist: + | + | |
34. Hakimi et al. 2014 [52] | 1) CPG 2) CPG + BMCs 3) CPG + BMCs + PRP 4) Autografts | Platelet concentration: 4.7 x Activation: calcium chloride/thrombin Leukocytes: yes Autologous Fresh GFs: TGF-β1 and PDGF-BB | Pig tibial cylindrical defect (25 x 11 mm) | Hist: + X-Ray: + μCT: + X-Ray superior for CPG + BMSCs + PRP compared to CPG alone and CPG + BMSCs, but similar results compared to autograft | + | |
35. Yilmaz et al. 2014 [53] | 1) PRF 2) β-TCP 3) β-TCP + PRF 4) Control (untreated) | Platelet concentration: NA Activation: no Leukocytes: NA Autologous Fresh GFs: NA | Pig tibia cylindrical defect (5 mm) | Hist: + Superior results for β-TCP + PRF | + | |
36. Malhotra et al. 2014 [54] | 1) BCP + 33 % PRP 2) BCP + 66 % PRP 3) BCP + 100 % PRP 4) Autografts 5) BCP 6) Control (untreated) | Platelet concentration: 2.9 x Activation: calcium chloride/thrombin Leukocytes: 0.6 x Fibrinogen: 0.6 x Autologous Fresh GFs: TGF-β1 | Sheep femoral cylindrical defect (11x20 mm) | Hist: + X-Ray: + μCT: + Highest dose of PRP: greater micro-CT bone volume compared with BCP alone All PRP doses: better histomorphometric parameters vs BCP alone | + | |
37. Qi et al. 2015 [55] | 1) BMSCs + PRP gel 2) CaP 3) CaP + PRP gel 4) CaP + BMSCs 5) CaP + BMSCs + PRP gel 6) Control (untreated) | Platelet concentration: 6 x Activation: calcium chloride/ thrombin Leukocytes:NA Allogenic Fresh/frozen: NA GFs: NA | Rat femur cylindrical defect (2.5 x 5 mm) | Hist: + X-Ray: + SEM:+ Superior results for CaP + BMSCs + PRP gel | + | |
38. Velev et al. 2015 [56] | 1) TCP cement 2) TCP cement + PRP 3) TCP cement + GH | Platelet concentration: NA Activation: No Leukocytes: No Autologous Fresh GFs: NA | Rabbit tibia cylindrical defect (6 mm) | Hist: + for qualitative analysis = for quantitative analysis | + | |
PRP alone | 39. Simman et al. 2008 [57] | 1) PRP 2) Control (untreated) | Platelet concentration: 2.7 x Activation: calcium chloride/thrombin Leukocytes: NA Allogenic Fresh/frozen: NA GFs: TGF-β1, P-selectin and BMP-2 | Rat femoral fracture | Hist: + X-Ray: + Mech: = | + |
40. Gumieiro et al. 2010 [58] | 1) PRP 2) Control (untreated) | Platelet concentration: 4x Activation: calcium chloride Leukocytes: NA Allogenic Fresh GFs: NA | Rat tibial cylindrical defect (3 mm) | Hist: + The effect of PRP is present more in the first 14 days | + | |
41. Souza et al. 2012 [59] | 1) PRP 2) Control (untreated) | Platelet concentration: 338 % Activation: calcium chloride Leukocytes: NA Autologous Fresh GFs: NA | Dog radial fracture with 2 mm gap | Hist: + X-Ray: + DEXA: + Mech: + | + | |
42. Chen et al. 2013 [60] | 1) High conc PRP 2) Medium conc PRP 3) Low conc PRP 4) PPP 5) Control (untreated) | Platelet concentration (high/medium/low) Activation: calcium chloride/thrombin Leukocytes: NA Allogenic Fresh/frozen: NA GFs: TGF-β1 and PDGF-BB | Rat femoral fracture | Hist: + X-Ray: + Mech: + Superior results for medium conc. of PRP | + | |
43. Neves et al. 2013 [61] | 1) PRP 2) HBO 3) PRP+ HBO 4) Control (untreated) | Platelet concentration: 2x Activation: No Leukocytes: No Autologous Fresh GFs: NA | Rabbit fibula segmental fracture | Hist: + | + | |
44. Hernandez – Fernandez et al. 2013 [62] | 1) PRP 2) Control (untreated) | Platelet concentration: 4.6 x Activation: calcium chloride Leukocytes: No Autologous Fresh/frozen: NA GFs: NA | Sheep femur osteotomy model | Hist: = μCT: = | = | |
45. Guzel et al. 2015 [63] | 1) PRP 2) Control (untreated) | Platelet concentration: NA Activation: calcium chloride Leukocytes: No Allogenic Fresh/frozen: NA GFs: NA | Rat femoral fracture | Hist: + Mech: + | + |
PRP preparation
Pre-clinical findings
Clinical studies
Fractures | ||||||||
---|---|---|---|---|---|---|---|---|
Publication | Study design | N of patients | Pathology | Therapeutic protocol | Platelet count and leukocytes | Activation | F-up | Main findings |
Namazi H et al., Orthop Tramatol Surg Res.2016 [72] | Randomized controlled trial | 30 patients:
n = 15 percutaneous fixation + PRP
n = 15 percutaneous fixation | Distal radius fracture | Intra-articular injection of PRP immediately after percutaneous pinning fixation | Platelet count: NA Leukocytes: no | no | 6 months | PRP has significant effect on reduction of pain and functional recovery |
Rodriguez-Collazo ER et al., Strategies Trauma Limb Reconstr. 2015 [64] | Case series | 20 patient with relevant comorbidities
n = 10 BMC + PRP + DBM+ EF n =10 DBM+ EF (historical controls) | Bimalleolar fractures | PRP and BMC mixed with DBM and injected locally at the fracture site | Platelet count: NA Leukocytes: yes | no | 18 months | External fixation + DBM, BMA and PRP promoted fracture healing of the distal tibia and fibula in patients with significant co-morbidities |
Samy AM Int orthop. 2015 [68] | Randomized controlled trial | 60 patients: n =30 screw fixation n =30 screw fixation + PRP | Femoral neck fracture | PRP locally applied during surgery | Platelet count: NA Leukocytes: no | n.a. | 48 months | PRP was a beneficial adjuvant to the classical internal fixation technique: both radiologic and clinical outcome were better in PRP group |
Lee Dh et al., Clin Orthop Relat Res.2014 [67] | Randomized controlled trial | 20 patients:
n = 10 external fixation n =10 external fixation + BMC + PRP | Tibal distraction osteogenesis (limb lenghtening) | PRP + BMC locally injected at the osteotomy gap site | Platelet count: NA Leukocytes: yes | no | 24 months | BMC + PRP significantly improved bone healing in distraction osteogenesis of the tibia, allowing earlier return to weightbearing |
Griffin XL et al., BMJ Open. 2013 [69] | Randomized controlled trial | 200 patients
n = 99 screw fixation
n = 101 screw fixation + PRP | Femoral neck fracture | PRP locally applied during surgery | Platelet count: NA Leukocytes: yes | no | 12 months | There was no significant clinical difference following to PRP therapy. Only a shorter hospital stay was registered for PRP group. |
Liebergall M et al., Mol. Ther.2013 [71] | Randomized controlled trial | 24 patients
n =12 ORIF
n = 12 ORIF + DBM+ MSCs + PRP | Disttal tibial fractures | PRP and MSCs mixed with DBM and injected at the fracture site 3–6 weeks after primary surgery | Platelet count: 1.10 X 106 per mm3
Leukocytes: NA | n.a. | 12 months | The combination of PRP + MSCs + DBM is a safe therapeutic option and contributed to reduce the time of bone fusion |
Wei LC et al., J Orthop Res.2012 [70] | Randomized controlled trial | 254 patients n =101 ORIF + autograft n =85 ORIF + allograft + PRP n =90 ORIF + allograft | Calcaneal fractures | PRP mixed with bone allograft and applied locally during ORIF | Platelet count: 780000 platelets/ uL Leukocytes: NA | Thrombin + CaCl | 72 months | PRP-augmented allografts showed better radiological results compared to allograft alone |
Perbooms JC et al., Int Orthop. 2012 [66] | Randomized controlled trial | 41 patients n =20 bone chips + PRP n =21 bone chips | High tibial osteotomy | PRP mixed with the bone chips and put in the osteotomy gap site | Platelet count: NA Leukocytes: yes | Thrombin | 12 weeks | PRP provided detrimental effects with significant lower bone density around the osteotomy wedge at one and 12 weeks after surgery |
Dallari D et al., J bone Joint surg Am. 2007 [65] | Randomized controlled trial | 33 patients n =11 bone chips + PRP
n = 12 bone chips + PRP+ BMC n =10 bone chips | High tibial osteotomy | PRP mixed with the bone chips and put in the osteotomy gap site | Platelet count: 1 × 106 per mm3
Leukocytes: yes | Thrombin | 12 months | PRP increased the osteogenic potential of the bone chips and provided better outcome in terms of radiologic healing of the osteotomy site. Further beneficial effects with the addition of BMC |
Non-union/delayed union | ||||||||
Malhotra R et al., Musculoskelet Surg. 2015 [78] | Case series | 94 patients | Long bone non union | PRP injection at the site of non-union | Platelet count: minimum 2 x 106 per mm3
Leukocytes: no | n.a. | 4 months | PRP was a safe and effective treatment for managing non-unions |
Say F et al., Acta Chir Orthop Traumatol Cech. 2014 [77] | Case series | 20 patients | Long bone non union/delayed union | 3 PRP injections at the site of non-union at one week interval | Platelet count: NA Leukocytes: no | CaCl | 12 months | PRP had no additional healing potential |
Golos J et al., Ortop Traumatol Rehabil. 2014 [79] | Case series | 132 patients | Long bone non union | PRP injection at the site of non-union | Platelet count: NA Leukocytes: n.a. | n.a. | 4 months | PRP was effective in treatment of delayed union of long bones |
Tarallo L et al., Eur J Orthop Surg Traumatol. 2012 [75] | Case series | 10 patients | Isolated non-union of the ulna | PRP + bone autograft locally applied during revision surgery | Platelet count: NA Leukocytes: yes | Thrombin + calcium gluconate | minimum 3 months – maximum 36 months | High rate of clinical and radiologic healing with the biologic augmentation |
Galasso O et al., J Orthop Traumatol. 2008 [80] | Case series | 22 patients | Long bone non union | PRP applied locally during revision surgery | Platelet count : NA Leukocytes: NA | Batroxobin and CaCl | 13 months | Intramedullary nailing and PRP produced comparable results with less complications |
Sanchez M et al., J Orthop Trauma. 2009 [81] | Case series | 15 patients | Non hypertrophic non union/delayed unions | PRP mebrane locally applied during revision surgery (sometimes with bone graft) PRP injection at the site of non-union (without surgery) | Platelet count: NA Leukocytes: no | CaCl | 8 months | PRP was clinically safe and enhanced the healing of non-hypertrophic non unions |
Mariconda M et al., J Orthop Trauma. 2008 [76] | Case series | 20 patients | Long bone non union | PRP locally applied during revision surgery (external fixation) | Platelet count: NA Leukocytes: NA | Thrombin + calcium gluconate | 9 months | The study failed to show any clinical usefulness of PRP |
Bielecki T et al., Eur Surg Res. 2008 [82] | Case series | 32 patients | Long bone non union | PRP injection at the site of non-union | Platelet count: 241 ± 64 X 106 per mm3
Leukocytes : yes | Thrombin + CaCl | 6 months | PRP injection was a valid strategy to obtain union |
Calori et al., Injury. 2008 [73] + Calori et al., Injury. 2006 [74] | Randomized controlled trial | 120 patients
n = 60 BMP-7
n = 60 PRP | Long bone non union | PRP or BMP-7 locally applied during revision surgery (sometimes with bone graft) | Platelet count: 1.582 x 106 per mm3
Leukocytes: NA | CaCl | mean 12.3 months | BMP-7 is significantly more effective than PRP in promoting bone healing, both at radiolofic and clinical evaluation |
Chiang CC et al., J Trauma. 2007 [83] | Case series | 12 patients | Long bone non union | PRP + bone graft applied locally during revision surgery | Platelet count: n.a. Leukocytes: NA | Thrombin + CaCl | mean 32.4 months | There was a beneficial potential of PRP in treating non unions |