Effects of platelet-rich plasma on bone healing in combination with autogenous bone and bone substitutes in critical-size defects. An animal experiment

OBJECTIVES: An animal study was carried out to investigate the influence of platelet-rich plasma (PRP) on the regeneration of bony defects. MATERIAL AND METHODS: Critical-size defects in the forehead region of a mini-pig were filled with randomly distributed combinations of autogenous bone, tricalcium-phosphate granules (CeraSorb), bovine spongious blocks (BioOss) and a bovine bone inducing collagenous sponge (Colloss) with and without PRP in two preparations (Cusasan, 3i). The animals were killed after 2, 4 and 12 weeks. The specimens were evaluated microradiographically and immunohistologically. RESULTS: Autologous bone (38 +/- 9.9%) and Colloss (52.6 +/- 4.0%) showed the highest remineralization rates at 2 weeks. The initial high expression of BMP-2 in the Colloss-group gives evidence of an early initiation of bony regeneration. At 2 weeks PRP ad modum 3i was able to enhance bone healing significantly (P=0.028) only when applied in combination with autogenous bone (62.8 +/- 1.6%). Four weeks after surgery, both PRP preparations did no longer increase bony regeneration in the autogenous groups. The osteoconductive effect of Bio-Oss (38.7 +/- 5.5%) and CeraSorb (41+/-4.9%) was remarkable as well 4 weeks after surgery. Nevertheless, the addition of PRP hardly influenced bony regeneration, ceramic degradation or cytokine expression when bone substitutes were applied. At 12 weeks, the level of reossification had adjusted similarly in all groups. CONCLUSION: PRP did not add additional benefit when xenogenic bone substitutes were used. However, a significant effect on bone regeneration was found in the autogenous group initially when PRP is added.     

Platelet-rich plasma and fibrin as delivery systems for recombinant human bone morphogenetic protein-2

The aim of the present study was (1) to test whether or not platelet-rich plasma (PRP) or commercially available fibrin can increase bone regeneration compared with non-treated defects and (2) to test whether or not PRP or fibrin increases bone regeneration when used as a delivery system for recombinant human bone morphogenetic protein-2 (rhBMP-2). In 16 New Zealand White rabbits, four evenly distributed 6 mm diameter defects were drilled into the calvarial bone. The following five treatment modalities were randomly allocated to all 64 defects: (0) untreated control, (1) fibrin alone, (2) PRP alone, (3) fibrin with 15 microg rhBMP-2 and (4) PRP with 15 microg rhBMP-2. For the fibrin gels and the PRP containing rhBMP-2, the 15 microg rhBMP-2 was incorporated by precipitation within the matrices before their gelation. After 4 weeks, the animals were sacrificed and the calvarial bones were removed for histological preparation. The area fraction of newly formed bone was determined in vertical sections from the middle of the defect by applying histomorphometrical analysis. A mean area fraction of newly formed bone was found within the former defect of 23.4% (+/-13.5%) in the control sites, of 28.4% (+/-17.4%) in the fibrin sites and of 34.5% (+/-17.4%) in the PRP sites. The statistical analysis revealed no significant difference in bone formation between the three groups (ANOVA). Addition of 15 microg rhBMP-2 in the fibrin gel (59.9+/-20.3%) and the PRP gels (63.1+/-25.3%) increased bone formation significantly. No significant difference was observed between sites, where PRP or fibrin has been used as a delivery system for rhBMP-2 (ANOVA). In conclusion, the application of fibrin gels or PRP gels to bone defects is not superior to leaving the defect untreated. Regarding the amount of bone formation, the application of 15 microg rhBMP-2 in bone defects enhances the healing significantly at 4 weeks. In this animal model, commercially available fibrin and autologous PRP gels are equally effective as delivery systems for rhBMP-2.     

Orthotopic bone formation in titanium fiber mesh loaded with platelet-rich plasma and placed in segmental defects

The effect of platelet-rich plasma (PRP) on bone formation was investigated in a rabbit segmental radial defect model. The purpose of the study was to evaluate the bone inductive properties of PRP with titanium fiber mesh and autologous bone chips in a 15-mm rabbit radial defect model. Eighteen New Zealand white rabbits were divided into three groups: I, PRP with autologous bone (PRP-Ti-Bone); II, autologous bone (Ti-Bone); III, control group (Ti). The implants were placed in the radial defect for 12 weeks. After sacrifice, all specimens were harvested for histological, histomorphometrical and radiographic analysis. Histomorphometrical analysis showed that bone formation was higher in the implants with PRP (PRP-Ti-Bone: 37+/-8%) than in those without PRP (Ti-bone: 25+/-6% and Ti: 25+/-5%) after 12 weeks of implantation. It was concluded that PRP has a stimulatory effect on bone formation in titanium fiber mesh filled with autologous bone graft in segmental bone defects. Titanium fiber mesh was also shown to be an excellent scaffold material for the application of autologous bone grafts with or without PRP.     

Correlation of Platelet Growth Factor Release in Jawbone Defect Repair – A Study in the Dog Mandible

Background: Platelet concentrate/platelet‐rich plasma (PRP) has been studied extensively in various experimental models and there is some agreement among workers to its early effect in bone regeneration and healing. We have earlier showed in vitro that titanium in whole blood activates the thrombogenic response to a higher degree than PRP and that a fluoridated test surface augmented the effect compared with control. Purpose: We designed this study to evaluate the effect of PRP and whole blood on bone regeneration in a dog implant defect model and, in addition, the effect of a test surface modified in hydrofluoric acid. A correlation attempt between platelet count, release of growth factors, and bone regeneration was made. Materials and Methods: Six dogs were used and simultaneously with the experimental surgery and implant installation, autologous PRP was prepared. Defects were prepared (6 mm in diameter and 5 mm deep), and implants were installed (TiO₂ gritblasted and hydrofluoric acid treated [test] or TiO₂ gritblasted [control], 5 mm in diameter and 9 mm long) in defects filled with either PRP or whole blood. Randomization of sides between PRP and whole blood, and sites for test and control implants were made. Blood samples were collected from PRP and whole blood. The dogs were killed after 5 weeks of healing, and samples with implants and surrounding bone were collected and processed for analysis. Enzyme linked immunosorbent assays were used for detection of growth factors in PRP. Results: The mean increase of platelet count was 424% in PRP. A correlation for platelet counts and transforming growth factor β was found in each dog (r² = 0.857). Approximately 50% of the region of interest (ROI) in the defects was filled with new bone after 5 weeks. No difference could be observed in ROI by using PRP or whole blood in the defects regarding new bone formation, bone in contact with implant, or distance to first bone contact. However, the fluoridated implants exhibited more new bone formation (p = .03) compared with control, regardless of comparing PRP or whole blood, and also displayed a shorter distance from first bone contact to the margin of the bone envelope (p = .05). Conclusions: Platelet concentrate/PRP failed to show more new bone regeneration in a peri‐implant defect model compared with whole blood. Implants treated with hydrofluoric acid displayed higher percentages of bone fill in the defect.     

Early effect of platelet-rich plasma on bone healing in combination with an osteoconductive material in rat cranial defects

OBJECTIVE: The early effect of platelet-rich plasma (PRP) on bone regeneration in combination with dense biphasic hydroxyl apatite (HA)/beta-tricalcium phosphate (TCP) particles (ratio 60%/40%) was evaluated in rat cranial defects with a diameter of 6.2 mm. We hypothesize that PRP exerts its beneficial effect on bone regeneration within the first and second week after application in a bone defect combined with an osteoconductive material. MATERIALS AND METHODS: Forty-five rats were used in the study, in which always one cranial defect was created. The defects were filled with HA/beta-TCP particles and HA/beta-TCP particles combined with PRP gel. Some defects were also left unfilled as control. One and two weeks after surgery specimens were retrieved for light microscopy [hematoxylin-eosin, trichrome staining (Masson modification Goldner) and basic fuchsin-methylene blue] and micro-CT analysis to evaluate bone formation and neovascularization. One-way analysis of variance was performed on the raw data obtained from micro-CT analyses. RESULTS: The histological evaluation showed no effect of PRP on bone formation and neovascularization for both implantation times. In the first week, the defect closure was evaluated subjectively to be between 10% and 50% in all samples, whereas no difference among the groups appeared to occur. After 2 weeks, complete bridging of the original bone defect was observed for most of the empty defects, as well as for the defects that contained HA/beta-TCP particles. The trichrome staining revealed no difference in the number of blood vessels between the PRP and non-PRP groups for both implantation times. The osteoconductive nature of dense HA/beta-TCP particles was confirmed, as the bone formation was guided by their outer surfaces and resulted in a larger amount of newly formed bone in comparison with the empty defects. The quantitative micro-CT analysis demonstrated a statistically significant difference in new bone formation between the empty defects and defects filled with particles after 1 week of implantation, but there was no difference between the non-PRP and PRP groups. In at the second week, no difference in bone formation among all groups was observed, whereas even the non-filled control defects were almost completely closed. CONCLUSIONS: A 6.2 mm cranial defect is not a critical-sized defect in rats. Rat PRP had no effect on the early stages of bone healing in addition to an osteoconductive material. Dense HA/beta-TCP particles showed a beneficial effect on bone formation already after 1 and 2 weeks of implantation in non-critical-sized cranial defects in rats.     

Bone regeneration of dental implant dehiscence defects using a cultured periosteum membrane

OBJECTIVES: This study aimed to demonstrate the feasibility of a cultured periosteum (CP) membrane for use in guided bone regeneration at sites of implant dehiscence. MATERIAL AND METHODS: Four healthy beagle dogs were used in this study. Implant dehiscence defects (4 x 4 x 3 mm) were surgically created at mandibular premolar sites where premolars had been extracted 3 months back. Dental implants (3.75 mm in diameter and 7 mm in length) with machined surfaces were placed into the defect sites (14 implants in total). Each dehiscence defective implant was randomly assigned to one of the following two groups: (1) PRP gel without cells (control) or (2) a periosteum membrane cultured on PRP gel (experimental). Dogs were killed 12 weeks after operation and nondecalcified histological sections were made for histomorphometric analyses including percent linear bone fill (LF) and bone-to-implant contact (BIC). RESULTS: Bone regeneration in the treatment group with a CP membrane was significantly greater than that in the control group and was confirmed by LF analysis. LF values in the experimental and the control groups were 72.36+/-3.14% and 37.03+/-4.63%, respectively (P<0.05). The BIC values in both groups were not significantly different from each other. The BIC values in the experimental and the control groups were 40.76+/-10.30% and 30.58+/-9.69%, respectively (P=0.25) and were similar to native bone. CONCLUSION: This study demonstrated the feasibility of a CP membrane to regenerate bone at implant dehiscence defect.     

A reentry study on the use of bovine porous bone mineral, GTR, and platelet-rich plasma in the regenerative treatment of intrabony defects in humans

This study compared the clinical effectiveness of a combination therapy consisting of bovine porous bone mineral (BPBM), guided tissue regeneration (GTR), and platelet-rich plasma (PRP) in the regeneration of periodontal intrabony defects in humans. Twenty-eight paired intrabony defects were surgically treated using a split-mouth design. Defects were treated with BPBM, GTR, and PRP (experimental), or with open-flap debridement (control). Clinical parameters evaluated included changes in attachment level, pocket depth, and defect fill as revealed by reentry at 6 months. Preoperative pocket depths, attachment levels, and transoperative bone measurements were similar for the two groups. Postsurgical measurements taken at 6 months revealed that both treatment modalities significantly decreased pocket depth and increased clinical attachment and defect fill compared to baseline. The differences between the experimental and control groups were 2.22+/-0.39 mm on buccal and 2.12+/-0.34 mm on lingual sites for pocket depth, 3.05+/-0.51 mm on buccal and 2.88+/-0.46 mm on lingual sites for gain in clinical attachment, and 3.46+/-0.96 mm on buccal and 3.42+/-0.02 mm on lingual sites for defect fill. These differences between groups were statistically significant in favor of the experimental defects. The combined therapy was also clinically more effective than open-flap debridement. The superiority of the experimental group could not be attributed solely to the surgical intervention and was likely a result of the BPBM/GTR/ PRP application. Combining BPBM, GTR, and PRP was an effective modality of regenerative treatment for intrabony defects in patients with advanced periodontitis.     

Effect of platelet-rich plasma on bone healing of autogenous bone grafts in critical-size defects

Aim: This study histologically analysed the effect of autogenous platelet-rich plasma (PRP), prepared according to a new semiautomatic system, on healing of autogenous bone (AB) grafts placed in surgically created critical-size defects (CSD) in rabbit calvaria.
Material and Methods: Sixty rabbits were divided into three groups: C, AB and AB/PRP. A CSD was created in the calvarium of each animal. In Group C (control), the defect was filled by blood clot only. In Group AB (autogenous bone graft), the defect was filled with particulate autogenous bone. In Group AB/PRP (autogenous bone graft with platelet-rich plasma), it was filled with particulate autogenous bone combined with PRP. All groups were divided into subgroups ( n =10) and euthanized at 4 or 12 weeks post-operatively. Histometric and histologic analyses were performed. Data were statistically analysed ( anova , t -test, p <0.05).
Results: Group C presented significantly less bone formation compared with Group AB and AB/PRP in both periods of analysis ( p <0.001). At 4 weeks, Group AB/PRP showed a statistically greater amount of bone formation than Group AB (64.44 ± 15.0% versus 46.88 ± 14.15%; p =0.0181). At 12 weeks, no statistically significant differences were observed between Groups AB and AB/PRP (75.0 ± 8.11% versus 77.90 ± 8.13%; p >0.05). It is notable that the amount of new bone formation in Group AB/PRP at 4 weeks was similar to that of Group AB at 12 weeks ( p >0.05).
Conclusion: Within its limitation, the present study has indicated that (i) AB and AB/PRP significantly improved bone formation and (ii) a beneficial effect of PRP was limited to an initial healing period of 4 weeks.     

Bone regeneration in athymic calvarial defects with Accell DBM100

Bioimplants containing bone morphogenetic proteins (BMP) such as demineralized bone matrix (DBM) are used clinically to repair bone defects because of their ability to stimulate bone regeneration. Because of handling issues, DBM granules are often combined with an inert carrier, which reduces the DBM content to 40% or less by volume. Recently, Accell DBM100 (Accell, IsoTis OrthoBiologics, Irvine, CA) has been developed, which uses processed DBM as the carrier, resulting in a DBM content of 100%. The purpose of this investigation was to evaluate the use of Accell for bone defect healing.Forty-two athymic male rats were divided into three groups. Bilateral 5 mm calvarial defects were created in each animal. In group 1, one defect was filled with Accell and the other defect was left unfilled (control). In group 2, one defect was filled with OP-1 putty (recombinant human BMP-7 and type I collagen), and the other was left unfilled. In group 3, one defect was filled with Accell and the other with OP-1. Animals were sacrificed at 4 and 8 weeks, postoperatively. Specimens were analyzed by histomorphometry to evaluate bone regeneration quantitatively.Accell and OP-1 both induced significantly more bone at 4 and 8 weeks compared with the unfilled contralateral defects. OP-1-filled defects produced significantly more total reparative tissue (bone + marrow) compared with Accell (P < 0.01); however, the increase in new bone did not reach significance at either time (P = 0.06 at 4 wk; P = 0.10 at 8 wk). In conclusion, these results suggest that Accell DBM100 will be useful in repairing craniofacial bone defects clinically.     

Effectiveness of a combination of platelet-rich plasma,bovine porous bone mineral and guided tissue regeneration in the treatment of mandibular grade II molar furcations in humans

OBJECTIVE: A combination of platelet-rich plasma (PRP), bovine porous bone mineral (BPBM) and guided tissue regeneration (GTR) has been shown to be effective as regenerative treatment for intrabony periodontal defects. The purpose of this study was to evaluate the effectiveness of PRP, BPBM and GTR used in combination as regenerative treatment for grade II molar furcation defects in humans. MATERIAL AND METHODS: Using a split-mouth design, a total of 52 grade II mandibular molar furcation defects were treated either with PRP/BPBM/GTR (experimental group, n=26) or with an open flap debridement (control group, n=26). The primary outcomes evaluated in this study included changes in pocket depth, attachment level and re-entry bone levels (horizontal and vertical) between baseline and 6 months postoperatively. RESULTS: The results showed that the experimental group presented with significantly greater pocket reduction (4.07+/-0.33 mm for experimental and 2.49+/-0.38 mm for control sites), gain in clinical attachment (3.29 +/- 0.42 mm for experimental and 1.68+/-0.31 mm for control sites), vertical defect fill (2.56+/- 0.36 mm for experimental and -0.19+/-0.02 for control sites) and horizontal defect fill (2.28+/-0.33 mm for experimental and 0.08+/-0.02 mm for control sites) than the control group. CONCLUSIONS: It was concluded that the PRP/BPBM/GTR combined technique is an effective modality of regenerative treatment for mandibular grade II furcation defects. Further studies are necessary to elucidate the role played by each component of the combined therapy in achieving these results.     

胶原膜与骨形成蛋白复合物的成骨作用研究

目的：评价rhBMP-2／胶原复合膜对大鼠颅内缺损修复的作用。方法：将rhBMP-2与胶原膜复合,在大鼠颅骨制备直径5mm的骨缺损,分别予双侧覆盖复合膜、外侧覆盖复合膜,外侧覆盖胶原膜作为空白对照,于术后2、4、6周,取标本进行X线检查、荧光显微镜检查及常规组织学观察。结果：在各组内、覆盖复合膜的缺损成骨面各百分比及新生骨面积均明显高于覆盖胶原的缺损组（P＜0．01）,术后6周,双侧覆盖复合膜的缺损已达骨性愈合。结：胶原膜与BMP的复合物不但具有机械性的阻挡作用,而且具有骨诱导性,可加速骨愈合。     

Effect of platelet-rich plasma on the healing of intra-bony defects treated with a natural bone mineral and a collagen membrane

BACKGROUND: Regenerative periodontal therapy with a combination of platelet-rich plasma (PRP)+a natural bone mineral (NBM)+guided tissue regeneration (GTR) has been shown to result in significantly higher probing depth reductions and clinical attachment-level gains compared with treatment with open flap debridement alone. However, at present, it is unknown to what extent the use of PRP may additionally enhance the clinical outcome of the therapy compared with treatment with NBM+GTR. AIM: To clinically compare treatment of deep intra-bony defects with NBM+PRP+GTR with NBM+GTR. MATERIAL AND METHODS: Thirty patients suffering from advanced periodontal disease, and each of whom displayed one advanced intra-bony defect were randomly treated with a combination of either NBM+PRP+collagen membrane (GTR) or NBM+GTR. The following clinical parameters were evaluated at baseline and at 1 year after treatment: plaque index, gingival index, bleeding on probing, probing depth (PD), gingival recession and clinical attachment level (CAL). CAL changes were used as the primary outcome variable. RESULTS: No differences in any of the investigated parameters were observed at baseline between the two groups. Healing was uneventful in all patients. At 1 year after therapy, the sites treated with NBM+PRP+GTR showed a reduction in mean PD from 8.9+/-2.3 mm to 3.4+/-2.0 mm (p<0.001) and a change in mean CAL from 10.9+/-2.2 mm to 6.4+/-1.8 mm (p<0.001). In the group treated with NBM+GTR, the mean PD was reduced from 8.9+/-2.5 mm to 3.4+/-2.3 mm (p<0.001), and the mean CAL changed from 11.1+/-2.5 mm to 6.5+/-2.3 mm (p<0.001). In both groups, all sites gained at least 3 mm of CAL. CAL gains of > or = 4 mm were measured in 80% (i.e. in 12 out of 15 defects) of the cases treated with NBM+PRP+GTR and in 87% (i.e. in 13 out of 15 defects) treated with NBM+GTR. No statistically significant differences in any of the investigated parameters were observed between the two groups. CONCLUSIONS: Within its limits, the present study has shown that (i) at 1 year after regenerative surgery with both NBM+PRP+GTR and NBM+GTR, significant PD reductions and CAL gains were found, and (ii) the use of PRP has failed to improve the results obtained with NBM+GTR.     

Torus mandibularis bone chips combined with platelet rich plasma gel for treatment of intrabony osseous defects: clinical and radiographic evaluation

The use of platelet rich plasma (PRP) gel in combination with torus mandibularis offers a potentially useful treatment for periodontal osseous defects. Whether this combination enhances the outcome of periodontal regenerative therapy is not known. This study compared the effectiveness of torus mandibularis bone chips alone and when combined with autogenous PRP gel in treating periodontal osseous defects. 24 sites from 12 patients were selected using a split mouth design and determined by a double-blind, randomized, controlled clinical trial. Both sites received a full-thickness mucoperiosteal flap; one intrabony defect was filled with torus mandibularis bone chips alone and the other with torus mandibularis bone chips mixed with PRP gel. There was a 57% gain in the clinical attachment level and 60% reduction in the probing depth for torus mandibularis alone compared to 72% and 68% for sites treated with torus mandibularis and PRP gel (p ≤ 0.01). There was a statistically significant difference in the bone dentistry and the marginal bone loss at sites with PRP gel compared to those without gel (p ≤ 0.01). The use of mandibular tori as autogenous bone graft combined with PRP gel showed a significant improvement in the clinical outcome of periodontal therapy than mandibular tori alone.     

Periodontal repair in surgically created intrabony defects in dogs: influence of the number of bone walls on healing response

BACKGROUND: The objective of this study was to histologically evaluate periodontal healing following flap surgery in intrabony periodontal defects to determine the influence of the number of bone walls on periodontal regeneration. METHODS: One-, 2-, and 3-wall intrabony periodontal defects were surgically produced at the proximal aspect of mandibular premolars in either right or left jaw quadrants in six beagle dogs. Mucoperiosteal flaps were positioned and sutured to their presurgery position following defect preparation. The animals were euthanized at 8 weeks post-surgery, and block sections of the defect sites were collected for histologic and histometric analysis. RESULTS: Bone and cementum regeneration was positively correlated to the number of bone walls limiting the intrabony periodontal defects. The junctional epithelium averaged (+/- SD) 1.5 +/- 0.2, 1.2 +/- 0.3, and 0.9 +/- 0.2 mm for the 1-, 2-, and 3-wall defects, respectively, with the 3-wall defects being significantly different from the 1-wall defects (P <0.05). Cementum regeneration averaged 1.2 +/- 0.6, 2.0 +/- 0.6, and 2.8 +/- 0.5 mm for the 1-, 2-, and 3-wall defects, respectively; all groups were significantly different from each other (P <0.05). Bone regeneration averaged 1.5 +/- 0.5, 1.7 +/- 0.6, and 2.3 +/- 0.5 mm for the 1-, 2-, and 3-wall defects, respectively, with the 3-wall defects being significantly different from the 1-wall defects (P <0.05). CONCLUSIONS: The results suggest that the number of bone walls is a critical factor determining treatment outcomes in intrabony periodontal defects. One- and 3-wall intrabony defects appear to be reproducible models to evaluate candidate technologies for periodontal regeneration.     

Bone healing in critical-size defects treated with platelet-rich plasma activated by two different methods. A histologic and histometric study in rat calvaria

Background and Objective: The purpose of this study was to analyze histologically the influence of platelet‐rich plasma (PRP) coagulated with two different activators on bone healing in surgically created critical‐size defects (CSD) in rat calvaria. Material and Methods: Forty‐eight rats were divided into three groups: C, PRP‐C and PRP‐T. An 8 mm diameter CSD was created in the calvarium of each animal. In group C, the defect was filled by a blood clot only. In groups PRP‐C and PRP‐T, the defect was filled with PRP activated with either calcium chloride or thromboplastin solution, respectively. Each group was divided into two subgroups (n = 8 per subgroup) and killed at either 4 or 12 weeks postoperatively. Histologic and histometric analyses were performed. The amount of new bone formed was calculated as a percentage of the total area of the original defect. Percentage data were transformed into arccosine for statistical analysis (analysis of variance, Tukey’s post hoc test, p < 0.05). Results: No defect completely regenerated with bone. Group PRP‐C had a statistically greater amount of bone formation than groups C and PRP‐T at both time points of analysis. No statistically significant differences were observed between groups C and PRP‐T. Conclusion: It can be concluded that the type of activator used to initiate PRP clot formation influences its biological effect on bone healing in CSD in rat calvaria.     

Periodontal repair in dogs: effect of transforming growth factor-beta 1 on alveolar bone and cementum regeneration

BACKGROUND: Transforming growth factor-beta (TGF-beta) represents a family of growth-modulating proteins with fundamental roles in connective tissue and bone development. The objective of this study was to evaluate the potential for regeneration of alveolar bone and cementum following surgical implantation of recombinant human TGF-beta 1 (rhTGF-beta 1). METHOD: Bilateral, critical size, supra-alveolar periodontal defects in 5 beagle dogs were surgically implanted with rhTGF-beta 1 in a calcium carbonate carrier (CaCO3) or with carrier alone. The animals were euthanized at 4 weeks postsurgery and block-biopsies of the defects were processed for histologic and histometric analysis. RESULTS: Surgical implantation of rhTGF-beta 1 resulted in minimal, if any, stimulation of alveolar bone or cementum regeneration. Linear bone and cementum regeneration in rhTGF-beta 1-treated defects was 1.2+/-0.6 and 0.01+0.01 mm, respectively. Corresponding values for the controls were 1.0+/-0.6 and 0.01+/-0.03 mm. CONCLUSIONS: The results suggest that, under the conditions (dose, carrier, defect type) evaluated here, treatment of periodontal defects in beagle dogs with rhTGF-beta 1 may be of limited clinical benefit.     

The bone regenerative effect of platelet-rich plasma in combination with an osteoconductive material in rat cranial defects

The effect of platelet-rich plasma (PRP) on bone regeneration, in combination with an osteoconductive material, was evaluated in a rat model. Cranial defects, 6.2 mm in diameter, were filled with HA/beta-TCP particles, HA/beta-TCP particles combined with PRP and HA/beta-TCP particles combined with PRP gel, where some were left empty as a control. After 4 weeks of implantation histological, histomorphometrical and micro-computed tomography analyses revealed no difference in new bone formation among the groups. Further, no additional effect of PRP gel in comparison with PRP liquid was detected, except for the increased handling capacity of the graft. These findings suggest that PRP had no positive effect on bone formation in addition to an osteoconductive material after an implantation period of 4 weeks. Also, no negative effect was seen, and neither PRP nor HA/beta-TCP hampered bone ingrowth into the defects.     

Platelet rich plasma enhances osteoconductive properties of a hydroxyapatite-β-tricalcium phosphate scaffold (Skelite™) for late healing of critical size rabbit calvarial defects

The use of platelet rich plasma (PRP) in bone repair remains highly controversial. In this work, we evaluated the effect of lyophilized PRP on bone regeneration when associated with a silicon stabilized hydroxyapatite tricalcium phosphate scaffold in a rabbit calvarial defect (Skelite™). Critical defects were created in the calvaria of twenty-four rabbits. The periosteum was removed and the defects were either left empty or filled with allogeneic PRP gel; Skelite particles; Skelite and PRP gel. Four animals were killed after 4 weeks, 10 animals after 8 and 10 after 16 weeks. Specimens were processed for X-ray microtomography (μCT) and for resin embedded histology. μCT analysis revealed significant osteoid-like matrix and new bone deposition in PRP + Skelite group at both 8 and 16 weeks in respect to Skelite alone. Histologically, PRP + Skelite defects were highly cellular with more abundant osteoid deposition and more regular collagen fibres. Moreover, in vitro migration assays confirmed the chemotactic effect of PRP to endothelial and osteoprogenitor cells. We conclude that the addition of PRP influenced the local tissue microenvironment by providing key cryptic factors for regeneration, thereby enhancing progenitor cell recruitment, collagen and bone matrix deposition, and by creating a bridging interface between the scaffold and bone.     

Healing of Fresh Frozen Bone Allograft with or without Platelet‐Rich Plasma: A Histologic and Histometric Study in Rats

Purpose: This study histomorphometrically analyzed the effect of autogenous platelet‐rich plasma (PRP) on healing of fresh frozen bone allograft (FFBA) in bony defects in rat calvaria. Materials and Methods: A 5 mm–diameter defect was created in the calvarium of 30 rats. Animals were divided into three groups: C (defect was filled by blood clot only), FFBA (defect was filled with 0.01 mL of FFBA), and FFBA/PRP (defect was filled with 0.01 mL of FFBA combined with 100 µL of PRP). All animals were euthanized at 30 days postoperatively. Histomorphometry and histology analyses were performed. Data were statistically analyzed (analysis of variance, Tukey, p < .05). Results: FFBA had a statistically smaller new bone area than groups FFBA/PRP and C. No statistically significant differences were observed between groups FFBA and FFBA/PRP with regard to remaining bone graft particle area. Conclusion: It can be concluded that (1) PRP improved the incorporation of FFBA, increasing the amount of new bone formed; (2) PRP has not influenced the resorption of nonviable particles of the FFBA; and (3) presence of remaining FFBA particles might have accounted for the smaller amount of new bone observed in group FFBA when compared with control group.     

Tissue-engineered cultured periosteum used with platelet-rich plasma and hydroxyapatite in treating human osseous defects

BACKGROUND: The aim of the present controlled clinical study was to compare the clinical response of human cultured periosteum (HCP) sheets in combination with platelet-rich plasma (PRP) and porous hydroxyapatite (HA) granules to a mixture of PRP and HA in the treatment of human infrabony periodontal defects. METHODS: Thirty interproximal infrabony osseous defects in 30 healthy, non-smoking subjects diagnosed with chronic periodontitis were included in this study. The subjects were randomly assigned to the test group (HCP sheets combined with PRP and HA) or the control group (PRP with HA). Clinical and radiographic measurements were made at baseline and the 12-month post-surgical evaluation. RESULTS: Compared to baseline, the 12-month results indicated that both treatment modalities resulted in statistically significant changes (P <0.01) in the gingival index, bleeding on probing, probing depth, clinical attachment level, and radiographic infrabony defect depth. Compared to the control group, the test group exhibited a statistically significantly more favorable change in clinical attachment gain (3.9 +/- 1.6 mm versus 2.7 +/- 1.3 mm; P <0.05), vertical relative attachment gain (83.5% +/- 31.7% versus 55.0% +/- 21.9%; P <0.05), and radiographic infrabony defect fill (4.9 +/- 1.2 mm versus 3.2 +/- 1.1 mm; P <0.01). CONCLUSIONS: Compared to PRP with HA, treatment with a combination of HCP sheets, PRP, and HA led to a significantly more favorable clinical improvement in infrabony periodontal defects. A factor likely contributing to these favorable clinical results is the presence of osteogenic cells in the HCP sheets, which provided greater regeneration potential.