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New progress in tissue regeneration of dental implants by autologous platelet...

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发表于 2018-9-16 15:28:07 | 显示全部楼层 |阅读模式
New progress in tissue regeneration of dental implants by autologous platelet rich plasma
A brief introduction to 1.PRP

In 1970s, PRP began to enter the field of medical research. In 1998, Marx et al. found that PRP combined with bone graft could promote the increase of bone mineral density of human mandible. Since then, PRP has been widely used as a biomaterial with high regeneration potential in the repair of oral and maxillofacial bone defects and implant osseointegration. Platelet-rich plasma (PRP), as the earliest growth factor carrier, has been extensively and adequately studied, especially in the field of implantation. PRP can be used in bone defect repair, maxillary sinus elevation, simultaneous implant osseointegration, prevention or reduction of peri-implant inflammation, and promotion of peri-implant hard tissue. And soft tissue repair to bear the load and bite, exercise normal bite function, and achieve good aesthetic repair effect.

Leukocyte-rich plasma (PRGF), pure platelet-rich plasma (pure platelet-rich plasma) and leucocyte-platelet plasma (leucocyte-platelet plasma) can be divided into two types according to whether or not the leucocyte layer is retained during the preparation process.
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 楼主| 发表于 2018-9-16 15:30:15 | 显示全部楼层
Research progress of 2.PRP on regeneration of soft tissue and hard tissue around implant

Seed cells, growth factors and biological scaffolds are indispensable in tissue engineering of oral implant. PRP contains high concentrations of platelets, various growth factors, fibrin and white blood cells, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta), vascular endothelial growth factor (VEG). F, insulin-like growth factor (IGF-1) and epidermal growth factor (EGF). These proteins belong to the family of growth factors, chemokines and cytokines. Fibrin constitutes a natural three-dimensional scaffold, which provides a good microenvironment for the proliferation and differentiation of seed cells and promotes the regeneration of alveolar bone and gingival soft tissue.

2.1 bone tissue regeneration

Implant osseointegration is the gold standard of implant success. It can bear and transmit loads under functional state. It plays an important role in the early stability and long-term effect of implant. PRP contains the necessary growth factors for bone regeneration. As an autologous fibrin glue system, PRP maintains the concentration of bone healing growth factor in the operation area by binding and slowly releasing a variety of growth factors, thereby promoting bone regeneration. Hosgor et al. found that bone-implant contact (BIC) increased significantly after PRP and osteoblast culture in sheep mandible. In vivo, Cruz et al. transplanted ADSC with PRP into canine cortical bone defect model, and observed good bone formation and bone maturation, indicating that PRP as a biological scaffold of ADSC, and played a good bone induction effect.

The application of PRP on the surface of TIO2 nano-modified hollow implants by Jiang et al found that the bone mass around the implants increased and the biomechanical properties improved. Yun et al. established a standard three-wall bone defect model (4x4x4mm) at the implantation site in dogs. After 12 weeks, PRP, hydroxyapatite (HA) and BMMSCs had the highest BMD and BIC rates, and the histological bone maturation rate was also higher than other groups, but there was no significant difference. At the same time, PRP can reverse bone loss in pathological condition. Ocana et al implants were implanted after irradiation of tibial epiphysis (1727 cGy) to irritation state. The implant success rate and BIC rate were significantly reduced in irradiation group, but the bone mass of experimental group with PRP was significantly increased, which promoted the bone binding activity between implants and irritation state bone. The two most important growth factors in PRP are PDGF, TGF- beta, BMP-2 and IGF-1.

The mitogen properties of PDGF can promote the osteogenic differentiation of bone marrow stromal cells (BMSCs), promote the migration of bone-related cells such as bone marrow stromal cells, osteoblasts and fibroblasts, and promote the regeneration of bone tissue by increasing the expression of Osterix gene and sialoprotein mRNAs. Casati et al. found that PDGF in PRP can secrete chemokines, promote the construction of actin cytoskeleton, and then promote the migration of osteoblasts.
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 楼主| 发表于 2018-9-16 15:30:40 | 显示全部楼层
PRP activates PI3K/AKT, Ras, Wnt/beta-Catenin, Smad, TABI and RANK/RANKL/NF-kappa B signaling pathways by releasing PDGF, TGF-beta and BMP-2, respectively, to synthesize and secrete cytokines, including osteogenic factors, chemokines and actin microfilaments, to promote osteogenesis of mesenchymal cells. Vasculogenic and neurogenic differentiation is beneficial to the differentiation and maturation of osteoblasts, vascular endothelial cells, Schwann cells and so on, thus promoting the macro-coordination of bone remodeling, bone metabolism, chemotactic migration and other physiological activities. ACVR2, activin type II receptor; RANK/RANKL, Receptor activator of nuclear factor-band its ligand. The proliferation of cells and osteoblasts can also inhibit the proliferation and biological activity of osteoclasts.

Ortolani et al. observed that PDGF / IGF-1 significantly increased bone mass and promoted bone remodeling on the 4th and 12th day in rabbit intraosseous implants, but there was little delay in PRP alone. In addition, BMP-2 promotes differentiation and maturation of osteoblasts by binding to BMP receptors of type I and type II on the cell surface and transducting TGF-beta signals from cell surface receptors to cells via Smads proteins, thus initiating specific transcription of Runx2 and Osterix genes. Zhang Bo et al. found that PRP and BMSCs in rabbits with femoral head necrosis can produce synergistic effect, through the regulation of BMP-2 / Smads signaling pathway, promote the proliferation and differentiation of femoral head osteocytes, reduce the lacuna vacancy rate. Systematic evaluation by Gomes et al also confirmed the role of BMP-2 in osteogenesis. It is suggested that BMP-2, autologous bone and PRP should be used as graft materials to repair mandibular standard bone defects.

The osteogenic effect of PRP may also be related to the inhibition of osteoclast function, in which growth factors reduce RANKL levels by releasing osteoprotegerin (OPG). The kinetics of growth factor release from PRP is one of the hotspots of current research. Many researchers have studied the changes of growth factor concentration with time in vivo and explored the release of growth factor from implant surface in vitro. Sanchez et al found that TGF-beta and PDGFs were first released in large quantities, the former could not be detected after 4 days, while the latter lasted more than 9 days. The release of VEGF was relatively mild and lasted for a long time. The total amount and rate of TGF-beta and PDGFs were related to activator and implant surface morphology.

Rai et al believed that the release of TGF-beta, PDGFs and IGF-1 was related to fibrin bioactivity and matrix degradation. In some experiments, the effect of PRP on bone regeneration was not found. Streckbein and other canine animal tests showed no PRP promoting bony reconstruction and BIC rate. Peng et al even observed the blocking effect of PRP on rabbit implant healing. The reason may be that PRP preparation methods and animal models are different, preparation methods are also different, too little or too much growth factor may have an inhibitory effect on bone formation, so no obvious osteogenesis effect was observed. In addition, some scholars believe that PRP inhibits bone formation by inhibiting the expression of BMP2 and promoting the expression of TGF-beta. The former lacks the promoter of osteoblast differentiation and maturation, while the latter hinders bone formation by promoting fibrosis.
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 楼主| 发表于 2018-9-16 15:31:02 | 显示全部楼层
2.2 soft tissue regeneration

Peri-implant soft tissue, including blood vessels, nerves, fibers, and so on, is related to the healing of peri-implant gingiva and mucosa. Insufficient restoration of gingival height, poor shape or gingival recession after implantation is one of the factors affecting the implant effect. Good peri-implant epithelial closure reduces bacterial invasion, thereby reducing the risk of implant gingivitis and periodontitis. Surgical methods to promote the healing of soft tissue will bring pain and trouble for patients with secondary surgery, while high technical sensitivity, postoperative healing effect is unstable. Many studies have shown that various growth factors released by PRP can promote the formation of gingival fibrous tissue after implantation, effectively seal the implant, provide a good environment for tissue regeneration around the implant, and make the healing of soft tissue achieve aesthetic restoration in shape. In vitro experiments showed that PRP significantly increased the proliferative activity and migration ability of human gingival fibroblasts. Dugrillon et al. Found that PRP can promote the healing of soft tissue in sutures.

Freymiller et al. found that PRP could promote wound epithelialization and reduce the occurrence of scars and pain in full thickness skin graft recipients. Lee et al. Found that PRP could promote fibrous proliferation and capillary formation in full-thickness skin defects in rabbits. Garcia et al. Found bone tissue like connective tissue formation in PRP treated canine implant models. The regeneration of peri-implant microstructure is a unified and inseparable process. Good bone bonding can promote the growth of blood vessels and nerves, and the regeneration of blood vessels and nerves can promote peri-implant bone bonding. The potential of PRP to promote blood vessel and nerve regeneration is increasing.
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 楼主| 发表于 2018-9-16 15:31:15 | 显示全部楼层
2.3 angiogenesis

The regeneration of bone and soft tissue rich in platelet aggregates is closely related to good blood supply. The formation of new blood vessels plays an important role in bone regeneration. Good blood circulation provides a good environment for bone healing, facilitates transportation of nutrients and promotes cell metabolism, and indirectly ensures the smooth progress of bone remodeling in the later period. That's ok. Thus promoting osteogenesis. On the contrary, insufficient blood supply can inhibit osteoblast activity to some extent. In promoting vascular regeneration, growth factors released by PRP bind to receptors on the surface of endothelial progenitor cells (EPCs) to guide proliferation, differentiation and migration, and enter the damaged area through the vascular endothelium to promote angiogenesis. Li Ningyi et al. found that PRP contributed to complete calcification and vascularization of bone matrix in the dog's back.

In ectopic osteogenesis experiment, Yamada et al. combined PRP with MSCs showed the effect of promoting angiogenesis. Kasten et al. found that neovascularization was also observed when PRP and BMSCs were used to repair the standard radial defect in rabbits. Xian et al found that the concentration of VEGF increased significantly after PRP co cultured with osteoblasts and fibroblasts. As one of the main growth factors released by PRP, VEGF shows strong angiogenic effect.
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 楼主| 发表于 2018-9-16 15:31:53 | 显示全部楼层
2.4 nerve regeneration

In recent years, the study of proprioception around dental implants has been deepening. Peri-implant nerve feedback pathway plays an important role in the coordination of the bite system. Many preclinical studies have demonstrated that PRP plays a role in peripheral nerve regeneration. It has been found that PRP and its fiber scaffolds can not only protect and promote nerve regeneration, but also transport neuroinflammatory mediators, thereby promoting the recovery of functional sensory and motor neuromuscular units. Neurophilic factors such as nerve growth factor (NGF), bone derived growth factor (BDGF), insulin-like growth factor 1 (IGF-1), platelet derived growth factor (PGF) are released. Factor, PDGF, neurotrophic factors such as fibrin (febrin), fibronectin (febrinectin), vitronectin (vitronectin) and so on.

The possible mechanism of PRP in peri-implant nerve regeneration remains unclear. Current studies have shown that there are three main mechanisms of PRP in promoting nerve regeneration: releasing a variety of cytokines to form a permissible and neuro-induced microenvironment, promoting angiogenesis, promoting the proliferation and differentiation of BMSCs into Schwann cells (SC) and promoting the axis. Terminal development. However, most scholars believe that many growth factors in PRP may activate the transcription of neuro-related genes through PI3K-Akt and Ras/ECK signaling pathways, and regulate the process of neural precursor cells and neural remodeling. PRP not only releases growth factors with neurotrophic functions, but also promotes the proliferation and differentiation of BMSCs into Schwann cells (SC). TGF-beta, as a multifunctional basic anti-inflammatory factor in vivo, not only participates in the inflammatory response in vivo and the repair of soft and hard tissues, but also provides a guarantee for some nerve growth factors to play a physiological role.

Xia Changsuo et al found that PRP could promote the differentiation of BMSCs into SC, and the BMSCs induced by PRP had some functions of SC in vivo. Huang et al. observed the existence of peripheral axons and myelinated nerve fibers in the implants histologically, and both of them were regulated by external mechanical stress to varying degrees.
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 楼主| 发表于 2018-9-16 15:32:16 | 显示全部楼层
New progress in clinical research of 3.PRP

PRP has been widely used in dental surgery such as tooth extraction, periodontal surgery, dental implantation and drug-induced jaw necrosis because of its advantages of regeneration and safety. At present, bone deficiency before implantation, alveolar ridge defect and postoperative periodontitis are common problems in implant repair. PRP can achieve good clinical results.

3.1 maxillary sinus lifting

Maxillary sinus lifting is an important surgical method to ensure the good retention and stability of the implant. The combination of PRP shows a good effect on bone mass and soft tissue healing to some extent. Taschieri et al. found that PRP combined with short implants (6.5-8.5mm) had a higher rate of new bone formation than long implants (10 mm or more) with maxillary sinus elevation, but there was no significant difference. At the same time, Taschieri et al. found that PRGF combined with short implants in maxillary sinus elevation peri-implant bone resorption rate decreased, but there was no statistical significance. Many scholars are exploring the personalized best plan for tissue engineering of maxillary sinus elevation.

Taschieri et al. found that PRP combined with biphasic calcium phosphate or demineralized bovine matrix combined with bone in maxillary sinus elevation showed a higher rate of new bone formation (18.6% and 21.9%), and more type I collagen was observed in PRP and biphasic calcium phosphate groups. Schwartz et al. proposed the effect of onlay bone grafting (OBG) in the treatment of severe mandibular defects through a retrospective trial of 137 months, that is, bone grafts were combined with Bio-oss bone powder and PRP, and the surface was covered with PPP membrane.

Ogawa et al. found that PRP combined with autologous periosteal cells in maxillary sinus elevation had a more significant effect on promoting new bone formation than autologous bone grafting, cortical bone and cancellous bone were significantly increased, insertion torque was also increased when implants were placed. However, some studies have not found the promotion effect of PRP. Abdalla et al. believed that PRP had no significant effect on implant failure rate and complication rate. Lemos et al. found that PRP had no effect on the bone formation and retention rate of implants during maxillary sinus elevation by meta-analysis of implant stability, marginal bone loss and alveolar ridge height. Systematic evaluation by Avila et al showed that PRP combined with autologous bone graft had a good effect on maxillary sinus elevation only at the sixth month.

Kumar et al. found that PRP combined with autologous bone graft promoted maxillary sinus elevation, alveolar ridge height significantly increased after 6 months and 1 year later, but the effect of autologous bone and autologous venous blood was not different between the control group. Therefore, the effect of PRP in maxillary sinus lifting needs further clarifying.
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 楼主| 发表于 2018-9-16 15:32:35 | 显示全部楼层
3.2 locus preservation

Periodontal disease, trauma, etc. can cause alveolar bone defect in patients, seriously affecting the success rate of implant implantation. GBR can reconstruct the structure and function of the missing part by combining with PRP, and restore the height and width of the corresponding alveolar ridge. Eskan et al. found that PRP combined with allogeneic cancellous bone could increase alveolar ridge width and decrease bone loss in edentulous patients. Ntounis et al. found that mineralized freeze-dried allograft bone combined with PRP during post-extraction site preservation could promote bone turnover from D4 to D3 and D2, and reduce residual bone graft particles, thereby reducing healing time.

Hatakeyama et al. found that bone mineral density (BMD) significantly increased at 3 months after extraction with PRP and bovine hydroxyapatite, but there was no significant difference at 1 and 6 months after extraction.
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 楼主| 发表于 2018-9-16 15:32:50 | 显示全部楼层
3.3 immediate planting

Clinical randomized controlled trials showed that PRP also showed good results in immediate implantation. ArRejaie et al. found that PRP combined with bovine bone graft could improve bone density and marginal bone level of immediate implants, thereby reducing the risk of peri-implant bone fracture. Kundu et al. did not find any significant difference in bone height changes when PRP was added at the same time, but PRP was more effective in improving initial implant stability than square thread-form and reverse buttress thread-form implants. In the full denture supported by implant, PRP combined with deproteinized bovine bone graft restored the height of implant buccal bone plate, thereby reducing the cantilever and enhancing the stability of complete denture. Taschieri and other retrospective studies, which have been followed up for five years, have proved the long-term effect of PRP.
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 楼主| 发表于 2018-9-16 15:33:10 | 显示全部楼层
3.4 other

Peri implant inflammation is a common complication after implantation. It is one of the main reasons for failure of implant. PRP reduces bacterial entry by forming stable blood clots in a timely and effective manner, forming good epithelial cuffs. In addition, TGF-beta plays a good anti-inflammatory role in the growth factors released by PRP, and can effectively prevent the occurrence of peri-implant inflammation. Weibrick et al. found that the incidence of peri-implant inflammation decreased after PRP application in rabbit implant bone regeneration experiment. Xu Shulan et al. found that PRP in the treatment of peri-implant bone defects can promote the increase of peri-implant bone mass and improve the retention rate of implants. At the same time, in patients with underlying diseases (such as osteoporosis, diabetes, etc.) implant surgery, combined with PRP can reduce the risk, promote early stability and long-term success rate. Mozzati et al. found through a large cohort study that PRGF supplementation during dental implant surgery in patients receiving bisphosphonate therapy could reduce the implant failure rate, and there was no bisphosphonate-type jaw necrosis during the 120-month follow-up, suggesting that PRP could reduce the incidence of adverse reactions in women with osteoporosis. Assisted tissue engineering is used to promote healing.

Ibraheem et al. used dental implants with plateau metastasis to restore missing teeth in diabetic patients through a split-mouth test. PRP was added on one side and no PRP was added on the other. The bone height of both sides increased but there was no statistical difference. Getting good gingival height is one of the key points of doctors' attention. Menezes et al. found that PRP can reduce plaque index and gingival index in clinical randomized controlled trials of alveolar distraction osteogenesis, indicating the protective effect of PRP on soft tissue. PRP also has some effect in maintaining periodontal health.
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