Does PRP enhance bone integration with grafts, graft substitutes, or implants? A systematic review

Autologous bone represents the gold standard for bone replacement, because it offers minimal immunological rejection, complete histocompatibility, provides the best osteoconductive and osteoinductive properties, and is inexpensive and easy to obtain [55]. Nevertheless, it also has some drawbacks, such as donor site morbidity, need for general anesthesia or sedation, occasional need for more than one surgical site and limited availability [55]. Several studies have reported its use in combination with PRP to improve bone implant integration.

In 2005 Raghoebar et al. [30] analysed 30 patients that underwent floor augmentation of the maxillary sinus and were randomly assigned to autologous bone graft and PRP or autologous bone alone. No differences between treatments were observed, thus showing no additional value of PRP on implant integration. Conversely, in 2006 Consolo et al. [28] reported the regenerative potential of PRP when used with autologous bone, but this effect appeared to be restricted to shorter treatment times: 16 patients underwent bilateral sinus floor augmentation, using autologous bone on one side and PRP plus autologous bone contralaterally. At 4 months, the PRP group showed higher bone activities documented by histological analysis, but a progressive extinguishment of the PRP effect was recorded after a time of longer than 6–7 months. In 2008 Schaaf et al. [26] showed no significant differences in bone volume and implant failure using autologous bone graft alone or in combination with PRP in 34 sinus floor augmentations. In 2010, Badr et al. [20] used PRP in combination with bone iliac crest graft in maxilla defects: 22 patients were randomly divided into two groups: PRP augmented and controls. No significant differences were detected for implant stability or mean graft resorption and soft tissue healing indices. Only the posterior implant subgroup showed higher stability values, although not clinically significant. Finally in 2012, Khairy et al. [12] evaluated the potential benefit of PRP in conjunction with autologous bone for maxillary sinus augmentation in 15 patients; autogenous bone alone was used as the control group. PRP improved the handling properties of the graft material but did not improve bone density at 3 months. However, PRP-enriched bone grafts were associated with superior bone density at 6 months.

FDBA is derived from the removal of water by the frozen tissue with subsequent vacuum-packing and storing at room temperature for up to 5 years [3].

Kassolis et al. [36] in 2005 investigated the use of PRP in combination with FDBA in 10 patients who underwent bilateral maxillary subantral sinus augmentation. The subjects were randomly assigned to FDBA plus PRP or FDBA plus resorbable membrane of polytetrafluoroethylene (e-PTFE). Biopsies were obtained 4.5 to 6 months after treatment and revealed a significantly higher percentage of sinus vital tissue in the PRP group. A lower percentage of residual graft particles and a higher rate of bone formation, although not significant, were detected in the PRP treatment group. In 2008, Piemontese et al. [34] performed a double-blinded RCT on 60 patients with infrabony osseous defects derived from chronic periodontitis and treated with FDBA and PRP or FDBA alone. One year after treatment, both groups showed similar significant changes in the gingival index, bleeding on probing, probing depth, clinical attachment level and radiographic parameters, but a greater probing depth reduction and clinical attachment gain were seen in the PRP group. However, with regards to bone regeneration, PRP did not seem to give any additional value. Similarly, in 2009 Markou et al. [32] compared FDBA plus PRP with FDBA alone in 24 patients with severe chronic periodontitis. At six months the two treatment groups were comparable and the percentage of defect filling did not differ significantly.

BPBM is a xenograft prepared by protein extraction of bovine bone, which results in a structure similar to human cancellous bone and has the ability to enhance bone formation [56]. The advantages of xenografts include their relative abundant supply, ease of use, and potentially favourable clinical performance. Although rare, one drawback in its use concerns the possible risk of disease transmission, such as bacterial, viral, and prion transmission [57].

The combination of PRP and BPBM has been applied by many research groups, mainly focusing on periodontal regenerative therapy.

In 2004, Hanna et al. [15] reported their experience in the treatment of periodontal intrabony defects using BPBM and PRP: 13 patients were randomly assigned to BPBM or BPBM plus PRP groups. After 6 months significant benefits with both treatments were revealed, but in the PRP group better results were found in probing reduction and clinical attachment level. In 2007, Dori et al. [48] investigated the use of BPBM/GTR alone or in combination with PRP for the treatment of 24 intrabony defects related to chronic periodontal disease, and showed no differences in any of the studied parameters. Similar results were reported in another RCT performed by the same author, who in 2007 analysed 30 patients treated with BPBM/GTR/PRP or BPBM/GTR alone: PRP did not give any additional value [50]. Conversely, a good clinical outcome was reported by Torres et al. [46] two years later: 87 patients underwent sinus floor augmentation with BPBM alone or in combination with PRP. Histological analysis revealed that bone regeneration was significantly higher in sites treated with PRP and BPBM, whereas graft resorption was similar in both groups.

Ceramics have been widely used for their osteoconductive properties. Most calcium phosphate ceramics currently under investigation are synthetic and composed of HA (Ca₁₀[PO₄]₆[OH₂]), TCP (Ca₃[PO₄]₂), or a combination of the two [3]. Clinically good short-term results have been reported for bone grafting with ceramic bone substitute materials [58].

MGCSH is a material that has a long history of clinical use, thanks to its biocompatibility and rapid and complete resorption, although these properties can sometimes be a drawback in the healing process. MGCSH can be used as a carrier to deliver GFs. In 2012, Kutkut et al. [62] reported promising results with PRP and MGCSH: after extraction of a tooth 16 patients received a combination of MGCSH/PRP (test group) or collagen resorbable plug dressing material (control group). The rate of new vital bone after 3 months of healing was 66.5% in the test group compared to 38.3% in the control group. Moreover, PRP enhanced rapid bone healing with respect to PRP-free collagen resorbable graft, but the difference in the material used in the study group prevents a true assessment of the role of PRP.

Biomaterials can also be used in combination to incorporate all the favourable material properties in one implant.

In 2010, Torres et al. [63] investigated the role of PRP in alveolar ridge augmentation with Ti-mesh and BPBM. Higher bone augmentation and no Ti-mesh exposure were seen in the PRP group. One year later, Kaushick et al. [41] investigated the use of PRP together with HA/b-TCP: defects of 10 patients were randomly assigned to test (PRP/HA/b-TCP) or saline-HA/b-TCP. PRP permitted a greater reduction in probing pocket depth, gain in attachment level and amount of radio density with respect to the control group.

The present analysis suggests that PRP might not be indicated for b-TCP implants, controversial results are obtained with autologous bone, whereas a better potential seems to lie in the augmentation of HA implants. In particular, only 2 out of 6 papers showed good results for the integration of β-TCP, 5 out of 10 for autologous bone, 1 out of 3 for FDBA, 2 out of 11 for BPBM (4 with less clear evidence of PRP effect), whereas 2 out of 3 papers showed good results for the integration of HA (the third one showed some benefit but with less clear evidence).

Only a few orthopaedic papers were found in the present search. In 2007, Smrke et al. [43] described the use of allogenic PRP in combination with autologous cancellous bone for the treatment of a tibial fracture and delayed union after insufficient initial osteosynthesis in a 50-year-old type 2 diabetic man. After 6 months, the graft was incorporated, the bone defect was fully bridged and full weight-bearing capacity was achieved. No side effects and no signs of platelet or HLA I antibodies were reported. In the same year, Dallari et al. [51] also showed good results in 33 patients undergoing high tibial osteotomy to treat genu varum. Subjects treated with lyophilized bone chips and PRP, with or without bone marrow stromal cells showed better osseointegration and faster bone healing. In 2011 Sys et al. [49] assessed both the clinical and radiological effect of PRP with autogenous bone in posterior lumbar interbody fusion. Forty patients were randomly treated with autogenous bone alone or in combination with PRP; the subjects were examined at 3, 6, 12, and 24 months postoperatively. The radiographic outcome showed uneventful osseous healing in all patients with no significant differences, but clinical improvement was more pronounced (even if not significantly) in patients who received autografts with PRP. More recently, Wei et al. [45] investigated the use of the same construct to treat 276 calcaneal fractures: the subjects were randomly divided into 3 groups: autogenous bone alone; allograft bone with PRP; and allograft alone. Results showed that PRP augmented the favourable outcome of allografts in the management of displaced calcaneal fractures: at 12 months no significant differences were found between 3 groups, but at 24 and 72 months the results of autologous bone and the allograft with PRP were similar and both were significantly better than the allograft alone.