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Review Article Open Access November 11, 2022

Biological Effects and Molecular Mechanisms of Platelet-Rich Plasma on Periodontal Bone Regeneration

Tie-lou Chen 1, 2,*, An-xin Yue 1, Wen-jing Chen 1,*, Pei Wang 1,*, Shi-feng Wang 2, 3, Zhi-zen Quan 1 and Yan-en Wang 1
1
Department of Periodontology, Military Oral Health Center of Changhai Hospital, Affiliated to Naval Medical University, Shanghai 200081, China
2
Key Medical laboratory of Chinese PLA
3
Naval Special Medical Center, Affiliated to Naval Medical University, Shanghai 200433, China
Publihed in: World Journal of Dental Sciences and Research (Volume 1, Issue 1, 2022)
Page(s): 16-26
DOI: 10.31586/wjdsr.2022.490
Received
October 02, 2022
Revised
November 01, 2022
Accepted
November 09, 2022
Published
November 11, 2022
Keywords
Platelet-Rich Plasma; Biological Effects; Molecular Mechanism; Periodontal Bone Regeneration; Signal Transduction; Anti-Inflammatory; Growth Factors
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright: Copyright © The Author(s), 2022. Published by Scientific Publications

Abstract

Objective: The study investigated the biological effects and molecular mechanisms of platelet-rich plasma (PRP) on periodontal bone regeneration. Methods: Electronic and manual searches were searched up to 1 October 2022 in the following databases: Pubmed, Scopus, Cochrane Library and Embase. [Platelet rich plasma or platelet or growth factors] and [periodontal] or [bone regeneration or bone defect or bone reconstruction] were used for searching. This study reviewed and analyzed published papers associated with PRP and periodontal bone defect restoration or bone regeneration or bone reconstruction. Results: Different growth factors exhibited varied biological characteristics and function. In-vitro studies, animal experiments and clinical studies confirmed that PRP displayed assorted role in periodontal bone defects repair. The growth factors secreted from PRP can promote new bone formation, soft tissue regeneration and wound healing. The fiber three-dimensional structure in PRP is conducive to the growth and migration of cells and provides strong support for the regeneration of periodontal soft and hard tissues. The anti-inflammatory characteristics of PRP are also closely related to the repair of periodontal bone defects. Conclusion: PRP played an important biological effect on periodontal bone regeneration. The mechanism is closely related to PRP promoting the growth, proliferation, differentiation and migration of periodontal ligament cells and osteoblasts, and the fiber stereo configuration of PRP and the anti-inflammatory effect of leukocytes.

1. Introduction

Periodontal bone defect is the most common clinical symptom and the most difficult problem to solve. Although there are many methods to treat bone defects, none of them proved to be completely satisfactory [1]. Therefore, it is of great significance to study a new, better and more widely used periodontal bone defect repair technology and method.

Platelet rich plasma (PRP) derived from centrifugation of autologous whole blood, with thrombin and calcium chloride. PRP includes a high concentration of platelets and a native concentration of fibrinogen [2]. PRP released various growth factors and cytokines when activated. These growth factors included platelet derived growth factor (PDGF), basic fibroblast growth factor (FGF2), insulin growth factor-1 (IGF-1), and transforming growth factor β (TGF-β), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF). They can promote wound healing and bone regeneration when tissues are damaged [3].

Marx proved that PRP can promote bone regeneration and wound healing [4]. In clinical and experimental studies, Grageda et al. proved the role of PRP in the repair of periodontal and maxillofacial bone defects [5, 6]. However, Khairy demonstrated that PRP enrichment did not significantly improve bone density or morphometric value at 3 months post graft [7, 8]. Faratzis showed that autogenous PRP had not significant effects on HA/ β- TCP promoting rabbits bone defects repair at 6 weeks post graft [9, 10]. Currently, there is no consensus on the biological characteristics of PRP and the mechanism of promoting new bone formation [11].

Although studies on PRP promoting periodontal bone defect repair and bone regeneration have been reported [12, 13]. However, the mechanism of PRP configuration and its secretion of multiple growth factors to promote bone regeneration are complex and controversial. Therefore, this paper reviews the literature to study the biological characteristics of PRP and growth factors and their biological role and molecular mechanism in periodontal bone regeneration, so as to provide a basis for the clinical application of PRP in periodontal bone defect repair [14].

2. Biological characteristics of growth factors secreted by PRP

The characteristics of growth factor in periodontal bone defect repair include osteoconductive, osteoinduction, osteogenic potential and vascularization. Growth factors can stimulate periosteal bone formation and endosteal bone resorption to achieve durable healing by regulating the growth, differentiation, and metabolism of cell [15], and regulate osteoblast proliferation and synthesis of bone matrix. PDGF can promote the synthesis of phospholipids, cholesterol esters, glycogen and prostaglandins to regulate extracellular matrix proteins [16]. The effector cells of PDGF include fibroblasts, osteoblasts, vascular smooth muscle cells and chondrocytes. FGF2 can promote bone regeneration and increase the repair of periodontal bone defects [17]. The proliferation and differentiation of bone marrow stromal cells were induced by high affinity transmembrane protein tyrosine kinase. IGF-I enhances periodontal bone regeneration by locally controlling the delivery of IGF-I in dextran co-gelatin microspheres. IGF-I can stimulate the mRNA expression of alkaline phosphate, osteopontin and osteocalcin in bone marrow stromal cells, and regulate cell proliferation and differentiation [18].

The synergistic induction of bone formation by the osteogenic proteins of the TGF-β supergene family and played a key role in the formation and development of new bone [19]. VEGF regulates angiogenesis during development. Hypoxia induces VEGF secretion, promotes angiogenesis and osteogenesis. VEGF scaffold provides a new method for tissue engineering in low vascular environment and angiogenesis and bone regeneration in bone defects [20]. EGF increased in wound fluid with burn injury. EGFR deficiency may lead to delayed primary ossification. Inhibition of EGFR tyrosine kinase activity can reduce the generation of osteoclasts in bone marrow cells [21].

3. Biological effects of PRP on periodontal bone regeneration (Table 1 [22-37], Figure 1)

Animal experiments [38, 39] and clinical studies [40, 41] showed that PRP could promote bone regeneration, mandibular reconstruction and wound healing of periodontal root bifurcation and bone defects. In vitro studies have shown that PRP can stimulate the proliferation and differentiation of fibroblasts, osteoblasts, mesenchymal stem cells (MSCs) and periodontal ligament cells, and induce bone defect repair and periodontal tissue regeneration [42, 43]. It also stimulates the proliferation of fibroblasts and induces collagen synthesis, showing beneficial effects on wound healing [44].

Table 1
Clinical Study of PRP on Periodontal Bone Regeneration
Figure 1
Preparation of PRP and its application in periodontal bone defect to promote periodontal bone reconstruction.

PRP enhanced bone formation in the first two weeks of healing, while others reported that PRP improved bone formation in 4 weeks or more [45]. Although the detailed efficacy and mechanism of PRP are still unclear, it is possible to find evidence to support the role of PRP in periodontal bone defect repair and wound healing [46].

As a controlled delivery system, PRP can release different growth factors, and then directly stimulate the growth, proliferation and differentiation of fibroblasts and osteoblasts by binding with high affinity of growth factor receptors on the cell surface. However, the half-life of growth factors is short, and it is limited to achieve long-term efficacy [47]. The study found that PRP combined with decalcified bone or BPBM/GTR or β-TCP/ePTEM treatment of bone defects showed significant bone regeneration and wound healing, indicating that the combination of PRP and biomaterials has a good effect on bone regeneration of periodontal bone defects [48, 49]. The combination of PRP and HA in the treatment of periodontal bone defects can significantly improve the periodontal clinical parameters or repair of bone defects. Chen TL [50, 51] showed that the filling and guidance of xenograft materials Bio-oss and Bio-gide membrane could be used for the repair and regeneration of periodontal bone defects or bone defects with bifurcation lesions. At present, common graft materials used in combination with PRP include BPBM, GTR, hydroxyapatite (HA), β- TCP and ePTEM.

PRP can induce osteoblasts or MSCs to proliferate and differentiate, reconstruct bone defects and repair wound healing. Osteoblasts were cultured with PDGF treated matrix, and cell proliferation was significantly enhanced [52]. The combination of PRP with MSCs and autologous bone showed a significant increase in new bone formation and bone reconstruction at the early stage [53]. The advantages of PRP delivery system for periodontal bone defects include minimally invasive, better biocompatibility, excellent plasticity, easy access, better bone formation, non-immune response, non-degradation in the first few weeks after transplantation, and secretion of growth factor in three-dimensional scaffolds [54]. Lucarelli E found that 10% PRP can induce the proliferation of human stromal stem cells and mineralization of extracellular matrix, showing a better effect [55.

Various growth factors secreted by PRP can be used to repair periodontal bone defects through bone tissue engineering (Figure 2). Yamada Y found that the combination of PRP and MSCs has good osteogenesis and angiogenesis [56]. PRP rich in growth factors can promote MSCs expansion and differentiation into osteoblast like cells. The combination of PRP and osteoblasts can shorten the treatment cycle [57]. MSCs cells co cultured with platelet lysates can maintain osteogenic, chondrogenic and adipogenic differentiation characteristics [58]. The combination of PRP and stem cells can promote the formation of new bone in periodontal bone defects and shorten the treatment cycle [59].

Figure 2
Simulation diagram of PRP used in bone tissue engineering to promote periodontal tissue regeneration.

Research shows that the growth factors released after PRP activation can promote the proliferation and differentiation of adipose derived stem cells into adipocytes, promote the vascularization of fat transplantation, prevent the apoptosis of transplanted adipocytes, and improve the success rate of fat grafts [60].

Meta-analysis showed that pure platelet rich plasma (P-PRP) had a significant impact on new bone formation, improved bone density, and increased alveolar bone regeneration potential [61]. Mijiritsky showed that autologous platelet concentrates (APCs) contained high levels of growth factors beneficial for periodontal regeneration and facial rejuvenation. The APCs mainly includes PRP, platelet rich fibrin (PRF) and concentrated growth factor (CGF). PRP can deliver a large number of growth factors to the target position faster to promote the formation of mature bone by mixing with autologous bone, which can be used for soft and hard tissue repair. PRF has the potential to stimulate dermal enhancement and used for soft tissue repair, such as gingival recession coverage and bifurcation defects. CGF is used for oral surgery, mainly for hard tissue regeneration [62].

4. Possible molecular mechanisms of PRP on periodontal bone regeneration (Table 2 [63-74], Figure 3)

Growth factors play a vital role in cell proliferation, migration, differentiation and angiogenesis [62]. When PRP activated and released growth factors induced bone formation, mineralized bone matrix was formed under the regulation of chemotaxis, cell migration, proliferation and differentiation [75]. This process is regulated by a complex signal network of multiple growth factors, cytokines and chemokines, involving the synergistic effect of fibroblasts, endothelial cells, MSCs, osteoblasts, macrophages and platelets, promoting cell migration, proliferation and differentiation, and further inducing new bone formation and wound healing [76].

Growth factors activate intracellular signal transduction pathways, induce cell chemotaxis, proliferation and angiogenesis, control the synthesis of collagen and extracellular matrix proteins, and promote bone regeneration and wound healing through their receptor regulated signals and signals that bind to the extracellular domain of growth factor receptors. Each stage of bone defect repair is controlled by a variety of growth factors, which use autocrine, paracrine and endocrine mechanisms to regulate the function of cells. Cell proliferation plays a role by activating protein kinase C (PKC), mitogen activated protein kinase (MAPK) and MAPK kinase (MEK) [77].

Table 2
Molecular mechanism of growth factor released by PRP on periodontal bone regeneration
Figure 3
Possible mechanism diagram of PRP used in periodontal bone defect to promote periodontal bone regeneration.

The interaction between the cell membrane receptor and its ligand causes the conformational change of the receptor, leading to the phosphorylation of the receptor domain and messenger molecules in the cell, thereby triggering cascade events. The signal is transmitted from the cytoplasm to the nucleus, where DNA binding proteins bind to regulate DNA sequences, leading to DNA replication or transcription. Thereafter, the DNA mediated reaction returns to the cytoplasm through messenger RNA, which is converted into functional proteins, and then regulates cell function. Initially, tyrosine kinase is activated, leading to phosphorylation of receptor at tyrosine residues, leading to receptor binding with other proteins, including phosphatidylinositol 3-kinase (PI3K) and phospholipase C-γ （PLCγ）、 GTPase activating protein, and various media are activated downstream, such as PI3K and PLCγ、 MAPK [78]. Under certain conditions, the serine/threonine kinase is activated, thereby phosphorylating the serine/threonine residues of the target protein. Receptor phosphorylation activates the kinase domain, which in turn activates a transcription factor named as small mother against decapentaplegic (Smad). The Smad interacts with several DNA binding proteins, leading to biological reaction of diverse gene transcripts [79].

Studies have shown that autologous platelet-poor plasma (PPP) can promote bone formation. When PPP is used for bone defects, PPP is activated, and fibrin in serum is first induced to form a network structure, which helps cell growth and promotes angiogenesis and osteogenesis at the early stage of injury [80]. In the early stage of wound healing, PPP forms fibrin scaffold to promote cell migration to the tissue defect area. This three-dimensional fiber scaffold configuration of PRP is conducive to the growth of cells, blood vessels and the formation of new bone. In the later stage, platelets support the recruitment, differentiation and crosstalk of cells by releasing a variety of bioactive factors. The fibrin network structure in serum is essential to promote angiogenesis and osteogenesis, especially in the early stage of wound repair. In conclusion, platelets and fibrin in PRP play a synergistic role in periodontal bone defect repair and tissue healing [81].

Chen LH studied the antibacterial effect of autologous platelet rich gel from diabetic skin ulcer patients in vitro, and proved the antibacterial effect of PRP on ulcer [82]. The antibacterial mechanism of PRP is mainly related to the antibacterial peptides secreted by platelets, which are the products of the host's multifunctional antibacterial defense. PRP can regulate the molecular mediators of inflammation and myogenic pathways to control the regulatory pathway of heat shock proteins and promote tissue regeneration. PRP can enhance the proliferation of PDLC and stem cells through signal transduction to form mineralized bone matrix and new bone [83]. Sundman EA [84] showed that PRP could resist infection through vitamin D binding protein, a1 macroglobulin and a2 microglobulin. Activated macrophages induce the expression of tumor necrosis factor-α, vascular endothelial growth factor, interleukin-1b, interleukin-6, etc. through toll like receptor-4, showing antibacterial effect. PRP can also increase the mRNA level of cytokines IL-1b and TGF-β1, induce the expression of myogenic regulatory factors mRNA and protein of MyoD1, Myf5, Pax7 and IGF-1, and improve the cell survival regulated by caspase-3 and NF-kB-65 apoptosis factors. In addition, it can promote tissue regeneration by regulating inflammation and myogenesis [85].

5. Conclusion

PRP activation can release a large number of growth factors, promote the migration, proliferation and differentiation of osteoblasts and fibroblasts, and thus promote periodontal bone regeneration. The three-dimensional structure and anti-inflammatory effect of fibrin in PRP are conducive to cell growth and migration, and promote periodontal tissue regeneration. According to the author's limited reading and practice, the growth factors, cytokines and chemokines secreted by PRP participate in complex signal integration, regulate the metabolic process of osteoblasts and fibroblasts through autocrine, paracrine and endocrine mechanisms, and promote wound healing and periodontal tissue regeneration. A more accurate conclusion and meta-analysis of the current theme needs further study.

Conflict of interest

None.

Acknowledgments

This study was supported by General Logistics Department Research Grants of CPLA (No.CHJ13J035) and 234 Discipline Peak Climbing Project (2020YXK028) and Education Reform Project (CHJG2020040) of the First Affiliated Hospital of Naval Medical University.

Ethical approval

Not required.

References

  1. Schroeder JE, Mosheiff R. Tissue engineering approaches for bone repair: Concepts and evidence. Injury, Int J Care Injured 2011; 42: 609-13.[CrossRef] [PubMed]
  2. Cervelli V, Gentile P, Scioli MG, et al. Application of platelet-rich plasma in plastic surgery: clinical and in vitro evaluation. Tissue Eng C Methods 2009;15(4): 625-34.[CrossRef] [PubMed]
  3. Chen TL, Liu GQ, Zhou YJ. Study of platelet-rich plasma on the healing and bone regeneration of bone defects in dental clinical. Chin J Conserv Dent 2010;20(1):46-50.
  4. Marx RE. Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg 2004;62(4):489-96.[CrossRef] [PubMed]
  5. Grageda E. Platelet-rich plasma and bone graft materials: a review and a standardized research protocol. Implant Dent 2004;13:301-9.[CrossRef] [PubMed]
  6. Chen TL,Lu HJ,Liu GQ, et al. Effect of autologous platelet-rich plasma in combination with bovine porous bone mineral and Bio-guide membrane on bone regeneration in mandible bicortical bony defects. J Craniofac Surg 2014; 25(1):215-23.[CrossRef]
  7. Khairy NM, Shendy EE, Askar NA, et al. Effect of platelet rich plasma on bone regeneration in maxillary sinus augmentation (randomized clinical trial). Int J Oral Max-illofac Surg 2013;42:249-55.[CrossRef] [PubMed]
  8. Chen TL,Lu HJ,Zhang XH,et al. The activation and osteoinduction effects of thrombin in the maxillary sinus augmentation process: does thrombin only display activation effects on platelet-rich plasma. Int J Oral Maxillofac Surg 2015; 44: 806-7.[CrossRef] [PubMed]
  9. Faratzis G, Leventis M, Chrysomali E, et al. Effect of autologous platelet-rich plasma in combination with a biphasic synthetic graft material on bone healing in critical-size cranial defects. J Craniofac Surg. 2012;23(5):1318-23.[CrossRef] [PubMed]
  10. Chen TL, Lu HJ. Why platelet-rich plasma failed to promote bone healing in combination with a biphasic synthetic graft material in bone defects: a critical comment. J Craniofac Surg, 2014; 25(4):1568-9.[CrossRef] [PubMed]
  11. Chen TL, Lu HJ,Wang SF, et a. Can platelet-rich plasma enhance bone healing during distraction osteogenesis: A novel molecular mechanism. J Craniofac Surg 2015;26:313-4.[CrossRef] [PubMed]
  12. Plachokova AS, Nikolidakis D, Mulder J, et al. Effect of platelet-rich plasma on bone regeneration in dentistry: a systematic review. Clin Oral Implants Res 2008;19:539-45.[CrossRef] [PubMed]
  13. Kotsovilis S, Markou N, Pepelassi E, et al. The adjunctive use of platelet rich plasma in the therapy of periodontal intraosseous defects: a systematic review. J Periodont Res 2010; 45: 428-43.[CrossRef] [PubMed]
  14. Mazzucco L, Borzini P, Gope R. Platelet-derived factors involved in tissue repair-from signal to function. Transfusion Medicine Reviews 2010; 24 (3): 218-34.[CrossRef] [PubMed]
  15. Steed DL. Modifying the wound healing response with exogenous growth factors. Clin Plast Surg 1998;25(3):397-405.[CrossRef]
  16. Alvarez RH, Kantarjian HM, Cortes JE. Biology of platelet-derived growth factor and its involvement in disease. Mayo Clin Proc 2006;81(9):1241-57.[CrossRef] [PubMed]
  17. Yoshinori S, Katsuyoshi T, Takehiko Y. Regenerative effect of basic fibroblast growth factor on periodontal healing in two-wall intrabony defects in dogs. J Clin Periodont 2010; 37(4): 374-81.[CrossRef] [PubMed]
  18. Werner H, Katz J. The emerging role of the insulin-like growth factors in oral biology. J Dent Res 2004;83(11):832–6.[CrossRef] [PubMed]
  19. Ripamonti U, Parak R, Klar RM, et al. The synergistic induction of bone formation by the osteogenic proteins of the TGF-β supergene family. Biomaterials 2016;104: 279-96.[CrossRef] [PubMed]
  20. Kaigler D, Wang Z, Horger K, et al. VEGF scaffolds enhance angiogenesis and bone regeneration in irradiated osseous defects. J Bone Miner Res 2006;21(5):735-44.[CrossRef] [PubMed]
  21. Wang K, Yamamoto H, Chin JR, et al. Epidermal growth factor receptor deficient mice have delayed primary endochondral ossification because of defective osteoclast recruitment. J Biol Chem 2004;279(51):53848-56.[CrossRef] [PubMed]
  22. Jalaluddin M, Mahesh J, Mahesh R, et al. Effectiveness of platelet rich plasma and bone graft in the treatment of intrabony defects: a clinico-radiographic study. Open Dent J 2018;12: 133-54.[CrossRef] [PubMed]
  23. Hanna R, Trejo PM, Weltman RL. Treatment of intrabony defects with bovine-derived xenograft alone and in combination with platelet-rich plasma: a randomized clinical trial. J Periodontol 2004;75:1668-77.[CrossRef] [PubMed]
  24. Sammartino G, Tia M, Marenzi G, et al. Use of autologous plateletrich plasma (PRP) in periodontal defect treatment after extraction of impacted mandibular third molars. J Oral Maxillofac Surg 2005;63:766-70.[CrossRef] [PubMed]
  25. Okuda K, Tai H, Tanabe K, et al. Platelet-rich plasma combined with a porous hydroxyapatite graft for the treatment of intrabony periodontal defects in humans: a comparative controlled clinical study. J Periodontol 2005; 76(6): 890-8.[CrossRef] [PubMed]
  26. Camargo PM, Lekovic V, Weinlaender M, et al. A re-entry study on the use of bovine porous bone mineral, GTR and platelet-rich plasma in the regenerative treatment of intrabony defects in humans[J]. Int J Periodontics Restorative Dent 2005; 25(1): 49-59.
  27. Dori F, Husza´r T, Nikolidakis D, et al. Effect of plateletrich plasma on the healing of intra-bony defects treated with a natural bone mineral and a collagen membrane. J Clin Periodontal 2007; 34(3): 254-61.[CrossRef] [PubMed]
  28. Christgau M, Moder D, Wagner J, et al. Influence of autologous platelet concentrate on healing in intrabony defects following guided tissue regeneration therapy: a randomized prospective clinical split-mouth study. J Clin Periodontol 2006; 33: 908-21.[CrossRef] [PubMed]
  29. Dori F, Huszar T, Nikolidakis D, et al. Effect of platelet-rich plasma on the healing of intrabony defects treated with an anorganic bovine bone mineral and expanded polytetrafluoroethylene membranes. J Periodontol 2007;78:983–90.[CrossRef] [PubMed]
  30. Ilgenli T, Dündar N, Kal BI. Demineralized freeze-dried bone allograft and platelet-rich plasma vs platelet-rich plasma alone in infrabony defects: a clinical and radiographic evaluation. Clin Oral Invest 2007; 11:51-9.[CrossRef] [PubMed]
  31. Demir B, Rengun D, Berberoglu A. Clinical evaluation of platelet-rich plasma and bioactive glass in the treatment of intra-bony defects. J Clin Periodontol 2007; 34: 709-15.[CrossRef] [PubMed]
  32. Dori F, Huszar T, Nikolidakis D, et al. Effect of platelet-rich plasma on the healing of intrabony defects treated with beta tricalcium phosphate and expanded polytetrafluoroethylene membranes. J Periodontol 2008;79(4):660-9.[CrossRef] [PubMed]
  33. Piemontese M, Aspriello SD, Rubini C, et al. Treatment of periodontal intrabony defects with demineralized freeze-dried bone allograft in combination with platelet-rich plasma. J Periodontol 2008;79(5):802-10.[CrossRef] [PubMed]
  34. Dori F, Nikolidakis D, Huszar T, et al. Effect of platelet-rich plasma on the healing of intrabony defects treated with an enamel matrix protein derivative and a natural bone mineral. J Clin Periodontol 2008; 35:44-50.
  35. Harnack L, Boedeker RH, Kurtulus I, et al. Use of platelet-rich plasma in periodontal surgery- a prospective randomised double blind clinical trial. Clin Oral Invest 2009; 13(2):179–87.[CrossRef] [PubMed]
  36. Pradeep AR, Pai S, Garg G, et al. A randomized clinical trial of autologous platelet rich plasma in treatment of mandibular degree II furcation defects. J Clin Periodontol 2009; 36: 581-8.[CrossRef] [PubMed]
  37. Yilmaz S, Cakar G, Ipci SD, et al. Regenerative treatment with plateletrich plasma combined with a bovine-derived xenograft in smokers and non-smokers: 12-month clinical and radiographic results. J Clin Periodontol 2010; 37: 80-7.[CrossRef] [PubMed]
  38. Schwarz F, Ferrari D, Podolsky L, et al.Initial pattern of angiogenesis and bone formation following lateral ridge augmentation using rhPDGF and guided bone regeneration: an immunohistochemical study in dogs. Clin Oral Implants Res 2010;21:90-9.[CrossRef] [PubMed]
  39. Lee C,Kim S,Kim J, et al. Supplemental periodontal regeneration by vertical ridge augmentation around dental implants. A preclinical in vivo experimental study. Clin Oral Implants Res 2019;30: 1118-25.[CrossRef] [PubMed]
  40. Malik R,Gupta A,Bansal P, et al. Evaluation of alveolar ridge height gained by vertical ridge augmentation using titanium mesh and novabone putty in posterior mandible. J Maxillofac Oral Surg 2020;19: 32-9.[CrossRef] [PubMed]
  41. McAllister BS, Haghighat K, Prasad HS, et al. Histologic evaluation of recombinant human platelet derived growth factor-BB after use in extraction socket defects: a case series. Int J Periodontics Restorative Dent 2010;30:365–73.
  42. Oka H, Mouri M, Kihara H. F-Spondin inhibits migration and differentiation of osteoclastic precursors. J Periodontol 2011, 82(12):1776-83[CrossRef] [PubMed]
  43. Garzon-Alvarado DA, Cardenas Sandoval RP, Vanegas Acosta JC. A mathematical model of medial collateral ligament repair: migration, fibroblast proliferation and collagen formation. Comput Methods Biomech Biomed Engin 2012;15(6): 571-83[CrossRef] [PubMed]
  44. Han J, Meng HX, Tang JM, et al. The effect of different platelet-rich plasma concentrations on proliferation and differentiation of human periodontal ligament cells in vitro. Cell Prolif 2007;40:241-52.[CrossRef] [PubMed]
  45. Kasten P, Vogel J, Geiger F, et al. The effect of platelet-rich plasma on healing in critical-size long-bone defects. Biomaterials 2008: 29: 3983-92.[CrossRef] [PubMed]
  46. Griffin XL, Smith CM, and Costa ML. The clinical use of platelet-rich plasma in the promotion of bone healing: a systematic review. Injury 2009; 40(2): 158-62.[CrossRef] [PubMed]
  47. Nimni ME. Polypeptide growth factors: targeted delivery systems. Biomaterials 1997;18:1201-25.[CrossRef]
  48. Parimala M and Mehta DS. Comparative evaluation of bovine porous bone mineral. J Indian Soc Periodontol 2010; 14: 126-31.[CrossRef] [PubMed]
  49. Chen TL, Liu GQ, Wu ZF. Effects and progress of xenographic bone graft on periodontal bone defects. Chin J Conserv Dent 2007; 17:481-4.
  50. Chen TL，Liu GQ，Zhao HJ. Clinical evaluation of Bio-Oss collagen and Bio-gide bioabsorbable collagen barrier in the treatment of periodontal intrabony defects. J Clin Stomatol 2007; 23:515-7.
  51. Chen TL, Wang G, Chen T. Clinical research of guide bone regeneration and guide tissue regeneration on bone loss of furcation involvement of periodontitis. Stomatology 2006;26 :404-7.
  52. Bateman J, Intini G, Margarone J, et al. Plateletderived growth factor enhancement of two alloplastic bone matrices. J Periodontol 2005;76:1833-41.[CrossRef] [PubMed]
  53. Ito K.Yamada Y, Nagasaka T, et al. Osteogenic potential of injectable tissue-engineered bone: A comparison among autogenous bone, bone substitute (Bio-oss), platelet-rich plasma, and tissue-engineered bone with respect to their mechanical properties and histological findings. J Biomed Mat Res Part A 2005;73A: 63-72.[CrossRef] [PubMed]
  54. Intini G. The use of platelet-rich plasma in bone reconstruction therapy . Biomaterials 2009;30:4956-66.[CrossRef] [PubMed]
  55. Lucarelli E, Beccheroni A, Donati D, et al. Platelet-derived growth factors enhance proliferation of human stromal stem cells. Biomaterials 2003; 24: 3095-100.[CrossRef]
  56. Yamada Y, Ueda M, Naiki T, et al. Autogenous injectable bone for regeneration with mesenchymal stem cells and platelet-rich plasma: tissue-engineered bone regeneration. Tissue Eng 2004; 10(5-6): 955-64.[CrossRef] [PubMed]
  57. Kitoh H, Kitoh H, Kitakoji T, et al. Transplantation of marrow-derived mesenchymal stem cells and platelet-rich plasma during distraction osteogenesis: a preliminary result of three cases. Bone 2004; 35: 892-8.[CrossRef] [PubMed]
  58. Doucet C, Ernou I, Zhang Y, et al. Platelet lysates promote mesenchymal stem cell expansion: a safety substitute for animal serum in cell-based therapy applications. J Cell Physiol 2005; 205(2): 228-36.[CrossRef] [PubMed]
  59. Yamada Y, Ito K, Nakamura S, et al. Promising cell-based therapy for bone regeneration using stem cells from deciduous teeth, dental pulp, and bone marrow. Cell Transplantation, 2011; 20: 1003-13.[CrossRef] [PubMed]
  60. Chen TL, Zhang XH, Wang XM, et al. Does platelet-rich plasma really need to be activated in fat grafts. Journal of Plastic, Reconstructive & Aesthetic Surgery,2021;74:1355-1401.[CrossRef] [PubMed]
  61. Anitua E, Allende M, Alkhraisat MH. Unravelling alveolar bone regeneration ability of platelet-rich plasma: a systematic review with meta-analysis. Bioengineering (Basel). 2022; 9(10):506.[CrossRef] [PubMed]
  62. Mijiritsky E, Assaf HD, Peleg O,et al. Use of PRP, PRF and CGF in periodontal regeneration and facial rejuvenation-a narrative review. Biology (Basel), 2021;10(4): 317.[CrossRef] [PubMed]
  63. Javed F, Al-Askar M, Al-Rasheed A, et al. Significance of the platelet-derived growth factor in periodontal tissue regeneration. Archives Oral Biology 2011;56:1476-84.[CrossRef] [PubMed]
  64. Schmahl J, Raymond CS, Soriano P. PDGF signaling specificity is mediated through multiple immediate early genes. Nat Genet 2007;39:52-60.[CrossRef] [PubMed]
  65. Barrientos S, Brem H, Stojadinovic O, et al. Clinical application of growth factors and cytokines in wound healing. Wound Repair Regen 2014;22: 569-78.[CrossRef] [PubMed]
  66. Sahni A, Francis CW. Vascular endothelial growth factor binds to fibrinogen and fibrin and stimulates endothelial cell proliferation. Blood 2000;96:3772-8.[CrossRef] [PubMed]
  67. Savchenko E,Teku GN,Boza-Serrano A, et al. FGF family members differentially regulate maturation and proliferation of stem cell-derived astrocytes. Sci Rep 2019;9: 9610.[CrossRef] [PubMed]
  68. Harmer NJ. Insights into the role of heparan sulphate in fibroblast growth factor signalling. Biochem Soc Trans 2006;34: 442-5.[CrossRef] [PubMed]
  69. Chen FM, Zhao YM, Wu H, et al. Enhancement of periodontal tissue regeneration by locally controlled delivery of insulin-like growth factor-I from dextran-co-gelatin microspheres. J Control Release 2006;114(2): 209-22.[CrossRef] [PubMed]
  70. Chetty A, Cao GJ, Nielsen HC. Insulin-like growth factor-I signaling mechanisms, type I collagen and alpha smooth muscle actin in human fetal lung fibroblasts. Pediatr Res 2006;60: 389-94.[CrossRef] [PubMed]
  71. Fan JB,Liu W,Zhu XH, et al. microRNA-7 inhibition protects human osteoblasts from dexamethasone via activation of epidermal growth factor receptor signaling. Mol Cell Biochem 2019;460: 113-21.[CrossRef] [PubMed]
  72. Müller-Deubert S,Seefried L,Krug M, et al. Epidermal growth factor as a mechanosensitizer in human bone marrow stromal cells.Stem Cell Res 2017;24:69-76.[CrossRef] [PubMed]
  73. Ramachandran A,Ravindran S,Huang CC, et al. TGF beta receptor II interacting protein-1, an intracellular protein has an extracellular role as a modulator of matrix mineralization. Sci Rep 2016;6: 37885.[CrossRef] [PubMed]
  74. Elsafadi M,Manikandan M,Dawud RA, et al. Transgelin is a TGFβ-inducible gene that regulates osteoblastic and adipogenic differentiation of human skeletal stem cells through actin cytoskeleston organization. Cell Death Dis 2016;7: e2321.[CrossRef] [PubMed]
  75. Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg 2004;114:1502-8.[CrossRef] [PubMed]
  76. Schilephake H. Bone growth factors in maxillofacial skeletal reconstruction. Int J Oral Maxillofac Surg 2002;31:469-84.[CrossRef] [PubMed]
  77. Kano MR, Morishita Y, Iwata C, et al. VEGF-A and FGF-2 synergistically promote neoangiogenesis through enhancement of endogenous PDGF-B-PDGFRbeta signaling. J Cell Sci 2005;118:3759-68.[CrossRef] [PubMed]
  78. Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev 2008;22: 1276-312.[CrossRef] [PubMed]
  79. Attisano L, Wrana JL. Signal transduction by the TGF-β superfamily. Science 2002;296:1646-7.[CrossRef] [PubMed]
  80. Torigoe I, Sotome S, Tsuchiya A, et al. Bone regeneration with autologous plasma, bone marrow stromal cells, and porous β-tricalcium phosphate in nonhuman primates. Tissue Engineering:Part A 2009; 15( 7):1489-99.[CrossRef] [PubMed]
  81. Chen TL, Liang XJ, Zhang XH. Do the Fibrin scaffold and growth factors in platelet-rich fibrin play the most vital roles in bone regeneration. J Craniofac Surg ,2019;30(6):1923-6.[CrossRef] [PubMed]
  82. Chen LH, Wang C, Liu HC, et al. Antibacterial effect of autologous platelet-rich gel derived from subjects with diabetic dermal ulcers in vitro. J Diabetes Res 2013:1-5 Article ID 269527.[CrossRef] [PubMed]
  83. Lu HJ, Chen TL, Zhang XH, et al. Antibacterial Effects of Platelet-Rich Plasma in Promoting Facial Scars Healing in CombinationWith Adipose-Derived Stromal Vascular Fraction Cells. J Craniofac Surg 2015; 26(7):e670-e672.[CrossRef] [PubMed]
  84. Sundman EA, Cole BJ, Karas V, et al. The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. Am J Sports Med 2014;42:35-41.[CrossRef] [PubMed]
  85. Dimauro I, Grasso L, Fittipaldi S, et al. Platelet-rich plasma and skeletal muscle healing: a molecular analysis of the early phases of the regeneration process in an experimental animal model. PLoS One 2014;9:1-13e102993.[CrossRef] [PubMed]
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APA Style
Chen, T. , Chen, T. Yue, A. , Yue, A. Chen, W. , Chen, W. Wang, P. , Wang, P. Wang, S. , Wang, S. Quan, Z. , & Quan, Z. (2022). Biological Effects and Molecular Mechanisms of Platelet-Rich Plasma on Periodontal Bone Regeneration. World Journal of Dental Sciences and Research, 1(1), 16-26. https://doi.org/10.31586/wjdsr.2022.490
ACS Style
Chen, T. ; Chen, T. Yue, A. ; Yue, A. Chen, W. ; Chen, W. Wang, P. ; Wang, P. Wang, S. ; Wang, S. Quan, Z. ; Quan, Z. Biological Effects and Molecular Mechanisms of Platelet-Rich Plasma on Periodontal Bone Regeneration. World Journal of Dental Sciences and Research 2022 1(1), 16-26. https://doi.org/10.31586/wjdsr.2022.490
Chicago/Turabian Style
Chen, Tie-lou, Tie-lou Chen. An-xin Yue, An-xin Yue. Wen-jing Chen, Wen-jing Chen. Pei Wang, Pei Wang. Shi-feng Wang, Shi-feng Wang. Zhi-zen Quan, and Zhi-zen Quan. 2022. "Biological Effects and Molecular Mechanisms of Platelet-Rich Plasma on Periodontal Bone Regeneration". World Journal of Dental Sciences and Research 1, no. 1: 16-26. https://doi.org/10.31586/wjdsr.2022.490
AMA Style
Chen T, Chen TYue A, Yue AChen W, Chen WWang P, Wang PWang S, Wang SQuan Z, Quan Z. Biological Effects and Molecular Mechanisms of Platelet-Rich Plasma on Periodontal Bone Regeneration. World Journal of Dental Sciences and Research. 2022; 1(1):16-26. https://doi.org/10.31586/wjdsr.2022.490 
@Article{wjdsr490,
AUTHOR = {Chen, Tie-lou and Yue, An-xin and Chen, Wen-jing and Wang, Pei and Wang, Shi-feng and Quan, Zhi-zen and Wang, Yan-en},
TITLE = {Biological Effects and Molecular Mechanisms of Platelet-Rich Plasma on Periodontal Bone Regeneration},
JOURNAL = {World Journal of Dental Sciences and Research},
VOLUME = {1},
YEAR = {2022},
NUMBER = {1},
PAGES = {16-26},
URL = {https://www.scipublications.com/journal/index.php/WJDSR/article/view/490},
ISSN = {3065-4645},
DOI = {10.31586/wjdsr.2022.490},
ABSTRACT = {Objective: The study investigated the biological effects and molecular mechanisms of platelet-rich plasma (PRP) on periodontal bone regeneration. Methods: Electronic and manual searches were searched up to 1 October 2022 in the following databases: Pubmed, Scopus, Cochrane Library and Embase. [Platelet rich plasma or platelet or growth factors] and [periodontal] or [bone regeneration or bone defect or bone reconstruction] were used for searching. This study reviewed and analyzed published papers associated with PRP and periodontal bone defect restoration or bone regeneration or bone reconstruction. Results: Different growth factors exhibited varied biological characteristics and function. In-vitro studies, animal experiments and clinical studies confirmed that PRP displayed assorted role in periodontal bone defects repair. The growth factors secreted from PRP can promote new bone formation, soft tissue regeneration and wound healing. The fiber three-dimensional structure in PRP is conducive to the growth and migration of cells and provides strong support for the regeneration of periodontal soft and hard tissues. The anti-inflammatory characteristics of PRP are also closely related to the repair of periodontal bone defects. Conclusion: PRP played an important biological effect on periodontal bone regeneration. The mechanism is closely related to PRP promoting the growth, proliferation, differentiation and migration of periodontal ligament cells and osteoblasts, and the fiber stereo configuration of PRP and the anti-inflammatory effect of leukocytes.},
}
%0 Journal Article
%A Chen, Tie-lou
%A Yue, An-xin
%A Chen, Wen-jing
%A Wang, Pei
%A Wang, Shi-feng
%A Quan, Zhi-zen
%A Wang, Yan-en
%D 2022
%J World Journal of Dental Sciences and Research

%@ 3065-4645
%V 1
%N 1
%P 16-26

%T Biological Effects and Molecular Mechanisms of Platelet-Rich Plasma on Periodontal Bone Regeneration
%M doi:10.31586/wjdsr.2022.490
%U https://www.scipublications.com/journal/index.php/WJDSR/article/view/490

TY  - JOUR
AU  - Chen, Tie-lou
AU  - Yue, An-xin
AU  - Chen, Wen-jing
AU  - Wang, Pei
AU  - Wang, Shi-feng
AU  - Quan, Zhi-zen
AU  - Wang, Yan-en
TI  - Biological Effects and Molecular Mechanisms of Platelet-Rich Plasma on Periodontal Bone Regeneration
T2  - World Journal of Dental Sciences and Research
PY  - 2022
VL  - 1
IS  - 1
SN  - 3065-4645
SP  - 16
EP  - 26
UR  - https://www.scipublications.com/journal/index.php/WJDSR/article/view/490
AB  - Objective: The study investigated the biological effects and molecular mechanisms of platelet-rich plasma (PRP) on periodontal bone regeneration. Methods: Electronic and manual searches were searched up to 1 October 2022 in the following databases: Pubmed, Scopus, Cochrane Library and Embase. [Platelet rich plasma or platelet or growth factors] and [periodontal] or [bone regeneration or bone defect or bone reconstruction] were used for searching. This study reviewed and analyzed published papers associated with PRP and periodontal bone defect restoration or bone regeneration or bone reconstruction. Results: Different growth factors exhibited varied biological characteristics and function. In-vitro studies, animal experiments and clinical studies confirmed that PRP displayed assorted role in periodontal bone defects repair. The growth factors secreted from PRP can promote new bone formation, soft tissue regeneration and wound healing. The fiber three-dimensional structure in PRP is conducive to the growth and migration of cells and provides strong support for the regeneration of periodontal soft and hard tissues. The anti-inflammatory characteristics of PRP are also closely related to the repair of periodontal bone defects. Conclusion: PRP played an important biological effect on periodontal bone regeneration. The mechanism is closely related to PRP promoting the growth, proliferation, differentiation and migration of periodontal ligament cells and osteoblasts, and the fiber stereo configuration of PRP and the anti-inflammatory effect of leukocytes.
DO  - Biological Effects and Molecular Mechanisms of Platelet-Rich Plasma on Periodontal Bone Regeneration
TI  - 10.31586/wjdsr.2022.490
ER  -
  1. Schroeder JE, Mosheiff R. Tissue engineering approaches for bone repair: Concepts and evidence. Injury, Int J Care Injured 2011; 42: 609-13.[CrossRef] [PubMed]
  2. Cervelli V, Gentile P, Scioli MG, et al. Application of platelet-rich plasma in plastic surgery: clinical and in vitro evaluation. Tissue Eng C Methods 2009;15(4): 625-34.[CrossRef] [PubMed]
  3. Chen TL, Liu GQ, Zhou YJ. Study of platelet-rich plasma on the healing and bone regeneration of bone defects in dental clinical. Chin J Conserv Dent 2010;20(1):46-50.
  4. Marx RE. Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg 2004;62(4):489-96.[CrossRef] [PubMed]
  5. Grageda E. Platelet-rich plasma and bone graft materials: a review and a standardized research protocol. Implant Dent 2004;13:301-9.[CrossRef] [PubMed]
  6. Chen TL,Lu HJ,Liu GQ, et al. Effect of autologous platelet-rich plasma in combination with bovine porous bone mineral and Bio-guide membrane on bone regeneration in mandible bicortical bony defects. J Craniofac Surg 2014; 25(1):215-23.[CrossRef]
  7. Khairy NM, Shendy EE, Askar NA, et al. Effect of platelet rich plasma on bone regeneration in maxillary sinus augmentation (randomized clinical trial). Int J Oral Max-illofac Surg 2013;42:249-55.[CrossRef] [PubMed]
  8. Chen TL,Lu HJ,Zhang XH,et al. The activation and osteoinduction effects of thrombin in the maxillary sinus augmentation process: does thrombin only display activation effects on platelet-rich plasma. Int J Oral Maxillofac Surg 2015; 44: 806-7.[CrossRef] [PubMed]
  9. Faratzis G, Leventis M, Chrysomali E, et al. Effect of autologous platelet-rich plasma in combination with a biphasic synthetic graft material on bone healing in critical-size cranial defects. J Craniofac Surg. 2012;23(5):1318-23.[CrossRef] [PubMed]
  10. Chen TL, Lu HJ. Why platelet-rich plasma failed to promote bone healing in combination with a biphasic synthetic graft material in bone defects: a critical comment. J Craniofac Surg, 2014; 25(4):1568-9.[CrossRef] [PubMed]
  11. Chen TL, Lu HJ,Wang SF, et a. Can platelet-rich plasma enhance bone healing during distraction osteogenesis: A novel molecular mechanism. J Craniofac Surg 2015;26:313-4.[CrossRef] [PubMed]
  12. Plachokova AS, Nikolidakis D, Mulder J, et al. Effect of platelet-rich plasma on bone regeneration in dentistry: a systematic review. Clin Oral Implants Res 2008;19:539-45.[CrossRef] [PubMed]
  13. Kotsovilis S, Markou N, Pepelassi E, et al. The adjunctive use of platelet rich plasma in the therapy of periodontal intraosseous defects: a systematic review. J Periodont Res 2010; 45: 428-43.[CrossRef] [PubMed]
  14. Mazzucco L, Borzini P, Gope R. Platelet-derived factors involved in tissue repair-from signal to function. Transfusion Medicine Reviews 2010; 24 (3): 218-34.[CrossRef] [PubMed]
  15. Steed DL. Modifying the wound healing response with exogenous growth factors. Clin Plast Surg 1998;25(3):397-405.[CrossRef]
  16. Alvarez RH, Kantarjian HM, Cortes JE. Biology of platelet-derived growth factor and its involvement in disease. Mayo Clin Proc 2006;81(9):1241-57.[CrossRef] [PubMed]
  17. Yoshinori S, Katsuyoshi T, Takehiko Y. Regenerative effect of basic fibroblast growth factor on periodontal healing in two-wall intrabony defects in dogs. J Clin Periodont 2010; 37(4): 374-81.[CrossRef] [PubMed]
  18. Werner H, Katz J. The emerging role of the insulin-like growth factors in oral biology. J Dent Res 2004;83(11):832–6.[CrossRef] [PubMed]
  19. Ripamonti U, Parak R, Klar RM, et al. The synergistic induction of bone formation by the osteogenic proteins of the TGF-β supergene family. Biomaterials 2016;104: 279-96.[CrossRef] [PubMed]
  20. Kaigler D, Wang Z, Horger K, et al. VEGF scaffolds enhance angiogenesis and bone regeneration in irradiated osseous defects. J Bone Miner Res 2006;21(5):735-44.[CrossRef] [PubMed]
  21. Wang K, Yamamoto H, Chin JR, et al. Epidermal growth factor receptor deficient mice have delayed primary endochondral ossification because of defective osteoclast recruitment. J Biol Chem 2004;279(51):53848-56.[CrossRef] [PubMed]
  22. Jalaluddin M, Mahesh J, Mahesh R, et al. Effectiveness of platelet rich plasma and bone graft in the treatment of intrabony defects: a clinico-radiographic study. Open Dent J 2018;12: 133-54.[CrossRef] [PubMed]
  23. Hanna R, Trejo PM, Weltman RL. Treatment of intrabony defects with bovine-derived xenograft alone and in combination with platelet-rich plasma: a randomized clinical trial. J Periodontol 2004;75:1668-77.[CrossRef] [PubMed]
  24. Sammartino G, Tia M, Marenzi G, et al. Use of autologous plateletrich plasma (PRP) in periodontal defect treatment after extraction of impacted mandibular third molars. J Oral Maxillofac Surg 2005;63:766-70.[CrossRef] [PubMed]
  25. Okuda K, Tai H, Tanabe K, et al. Platelet-rich plasma combined with a porous hydroxyapatite graft for the treatment of intrabony periodontal defects in humans: a comparative controlled clinical study. J Periodontol 2005; 76(6): 890-8.[CrossRef] [PubMed]
  26. Camargo PM, Lekovic V, Weinlaender M, et al. A re-entry study on the use of bovine porous bone mineral, GTR and platelet-rich plasma in the regenerative treatment of intrabony defects in humans[J]. Int J Periodontics Restorative Dent 2005; 25(1): 49-59.
  27. Dori F, Husza´r T, Nikolidakis D, et al. Effect of plateletrich plasma on the healing of intra-bony defects treated with a natural bone mineral and a collagen membrane. J Clin Periodontal 2007; 34(3): 254-61.[CrossRef] [PubMed]
  28. Christgau M, Moder D, Wagner J, et al. Influence of autologous platelet concentrate on healing in intrabony defects following guided tissue regeneration therapy: a randomized prospective clinical split-mouth study. J Clin Periodontol 2006; 33: 908-21.[CrossRef] [PubMed]
  29. Dori F, Huszar T, Nikolidakis D, et al. Effect of platelet-rich plasma on the healing of intrabony defects treated with an anorganic bovine bone mineral and expanded polytetrafluoroethylene membranes. J Periodontol 2007;78:983–90.[CrossRef] [PubMed]
  30. Ilgenli T, Dündar N, Kal BI. Demineralized freeze-dried bone allograft and platelet-rich plasma vs platelet-rich plasma alone in infrabony defects: a clinical and radiographic evaluation. Clin Oral Invest 2007; 11:51-9.[CrossRef] [PubMed]
  31. Demir B, Rengun D, Berberoglu A. Clinical evaluation of platelet-rich plasma and bioactive glass in the treatment of intra-bony defects. J Clin Periodontol 2007; 34: 709-15.[CrossRef] [PubMed]
  32. Dori F, Huszar T, Nikolidakis D, et al. Effect of platelet-rich plasma on the healing of intrabony defects treated with beta tricalcium phosphate and expanded polytetrafluoroethylene membranes. J Periodontol 2008;79(4):660-9.[CrossRef] [PubMed]
  33. Piemontese M, Aspriello SD, Rubini C, et al. Treatment of periodontal intrabony defects with demineralized freeze-dried bone allograft in combination with platelet-rich plasma. J Periodontol 2008;79(5):802-10.[CrossRef] [PubMed]
  34. Dori F, Nikolidakis D, Huszar T, et al. Effect of platelet-rich plasma on the healing of intrabony defects treated with an enamel matrix protein derivative and a natural bone mineral. J Clin Periodontol 2008; 35:44-50.
  35. Harnack L, Boedeker RH, Kurtulus I, et al. Use of platelet-rich plasma in periodontal surgery- a prospective randomised double blind clinical trial. Clin Oral Invest 2009; 13(2):179–87.[CrossRef] [PubMed]
  36. Pradeep AR, Pai S, Garg G, et al. A randomized clinical trial of autologous platelet rich plasma in treatment of mandibular degree II furcation defects. J Clin Periodontol 2009; 36: 581-8.[CrossRef] [PubMed]
  37. Yilmaz S, Cakar G, Ipci SD, et al. Regenerative treatment with plateletrich plasma combined with a bovine-derived xenograft in smokers and non-smokers: 12-month clinical and radiographic results. J Clin Periodontol 2010; 37: 80-7.[CrossRef] [PubMed]
  38. Schwarz F, Ferrari D, Podolsky L, et al.Initial pattern of angiogenesis and bone formation following lateral ridge augmentation using rhPDGF and guided bone regeneration: an immunohistochemical study in dogs. Clin Oral Implants Res 2010;21:90-9.[CrossRef] [PubMed]
  39. Lee C,Kim S,Kim J, et al. Supplemental periodontal regeneration by vertical ridge augmentation around dental implants. A preclinical in vivo experimental study. Clin Oral Implants Res 2019;30: 1118-25.[CrossRef] [PubMed]
  40. Malik R,Gupta A,Bansal P, et al. Evaluation of alveolar ridge height gained by vertical ridge augmentation using titanium mesh and novabone putty in posterior mandible. J Maxillofac Oral Surg 2020;19: 32-9.[CrossRef] [PubMed]
  41. McAllister BS, Haghighat K, Prasad HS, et al. Histologic evaluation of recombinant human platelet derived growth factor-BB after use in extraction socket defects: a case series. Int J Periodontics Restorative Dent 2010;30:365–73.
  42. Oka H, Mouri M, Kihara H. F-Spondin inhibits migration and differentiation of osteoclastic precursors. J Periodontol 2011, 82(12):1776-83[CrossRef] [PubMed]
  43. Garzon-Alvarado DA, Cardenas Sandoval RP, Vanegas Acosta JC. A mathematical model of medial collateral ligament repair: migration, fibroblast proliferation and collagen formation. Comput Methods Biomech Biomed Engin 2012;15(6): 571-83[CrossRef] [PubMed]
  44. Han J, Meng HX, Tang JM, et al. The effect of different platelet-rich plasma concentrations on proliferation and differentiation of human periodontal ligament cells in vitro. Cell Prolif 2007;40:241-52.[CrossRef] [PubMed]
  45. Kasten P, Vogel J, Geiger F, et al. The effect of platelet-rich plasma on healing in critical-size long-bone defects. Biomaterials 2008: 29: 3983-92.[CrossRef] [PubMed]
  46. Griffin XL, Smith CM, and Costa ML. The clinical use of platelet-rich plasma in the promotion of bone healing: a systematic review. Injury 2009; 40(2): 158-62.[CrossRef] [PubMed]
  47. Nimni ME. Polypeptide growth factors: targeted delivery systems. Biomaterials 1997;18:1201-25.[CrossRef]
  48. Parimala M and Mehta DS. Comparative evaluation of bovine porous bone mineral. J Indian Soc Periodontol 2010; 14: 126-31.[CrossRef] [PubMed]
  49. Chen TL, Liu GQ, Wu ZF. Effects and progress of xenographic bone graft on periodontal bone defects. Chin J Conserv Dent 2007; 17:481-4.
  50. Chen TL，Liu GQ，Zhao HJ. Clinical evaluation of Bio-Oss collagen and Bio-gide bioabsorbable collagen barrier in the treatment of periodontal intrabony defects. J Clin Stomatol 2007; 23:515-7.
  51. Chen TL, Wang G, Chen T. Clinical research of guide bone regeneration and guide tissue regeneration on bone loss of furcation involvement of periodontitis. Stomatology 2006;26 :404-7.
  52. Bateman J, Intini G, Margarone J, et al. Plateletderived growth factor enhancement of two alloplastic bone matrices. J Periodontol 2005;76:1833-41.[CrossRef] [PubMed]
  53. Ito K.Yamada Y, Nagasaka T, et al. Osteogenic potential of injectable tissue-engineered bone: A comparison among autogenous bone, bone substitute (Bio-oss), platelet-rich plasma, and tissue-engineered bone with respect to their mechanical properties and histological findings. J Biomed Mat Res Part A 2005;73A: 63-72.[CrossRef] [PubMed]
  54. Intini G. The use of platelet-rich plasma in bone reconstruction therapy . Biomaterials 2009;30:4956-66.[CrossRef] [PubMed]
  55. Lucarelli E, Beccheroni A, Donati D, et al. Platelet-derived growth factors enhance proliferation of human stromal stem cells. Biomaterials 2003; 24: 3095-100.[CrossRef]
  56. Yamada Y, Ueda M, Naiki T, et al. Autogenous injectable bone for regeneration with mesenchymal stem cells and platelet-rich plasma: tissue-engineered bone regeneration. Tissue Eng 2004; 10(5-6): 955-64.[CrossRef] [PubMed]
  57. Kitoh H, Kitoh H, Kitakoji T, et al. Transplantation of marrow-derived mesenchymal stem cells and platelet-rich plasma during distraction osteogenesis: a preliminary result of three cases. Bone 2004; 35: 892-8.[CrossRef] [PubMed]
  58. Doucet C, Ernou I, Zhang Y, et al. Platelet lysates promote mesenchymal stem cell expansion: a safety substitute for animal serum in cell-based therapy applications. J Cell Physiol 2005; 205(2): 228-36.[CrossRef] [PubMed]
  59. Yamada Y, Ito K, Nakamura S, et al. Promising cell-based therapy for bone regeneration using stem cells from deciduous teeth, dental pulp, and bone marrow. Cell Transplantation, 2011; 20: 1003-13.[CrossRef] [PubMed]
  60. Chen TL, Zhang XH, Wang XM, et al. Does platelet-rich plasma really need to be activated in fat grafts. Journal of Plastic, Reconstructive & Aesthetic Surgery,2021;74:1355-1401.[CrossRef] [PubMed]
  61. Anitua E, Allende M, Alkhraisat MH. Unravelling alveolar bone regeneration ability of platelet-rich plasma: a systematic review with meta-analysis. Bioengineering (Basel). 2022; 9(10):506.[CrossRef] [PubMed]
  62. Mijiritsky E, Assaf HD, Peleg O,et al. Use of PRP, PRF and CGF in periodontal regeneration and facial rejuvenation-a narrative review. Biology (Basel), 2021;10(4): 317.[CrossRef] [PubMed]
  63. Javed F, Al-Askar M, Al-Rasheed A, et al. Significance of the platelet-derived growth factor in periodontal tissue regeneration. Archives Oral Biology 2011;56:1476-84.[CrossRef] [PubMed]
  64. Schmahl J, Raymond CS, Soriano P. PDGF signaling specificity is mediated through multiple immediate early genes. Nat Genet 2007;39:52-60.[CrossRef] [PubMed]
  65. Barrientos S, Brem H, Stojadinovic O, et al. Clinical application of growth factors and cytokines in wound healing. Wound Repair Regen 2014;22: 569-78.[CrossRef] [PubMed]
  66. Sahni A, Francis CW. Vascular endothelial growth factor binds to fibrinogen and fibrin and stimulates endothelial cell proliferation. Blood 2000;96:3772-8.[CrossRef] [PubMed]
  67. Savchenko E,Teku GN,Boza-Serrano A, et al. FGF family members differentially regulate maturation and proliferation of stem cell-derived astrocytes. Sci Rep 2019;9: 9610.[CrossRef] [PubMed]
  68. Harmer NJ. Insights into the role of heparan sulphate in fibroblast growth factor signalling. Biochem Soc Trans 2006;34: 442-5.[CrossRef] [PubMed]
  69. Chen FM, Zhao YM, Wu H, et al. Enhancement of periodontal tissue regeneration by locally controlled delivery of insulin-like growth factor-I from dextran-co-gelatin microspheres. J Control Release 2006;114(2): 209-22.[CrossRef] [PubMed]
  70. Chetty A, Cao GJ, Nielsen HC. Insulin-like growth factor-I signaling mechanisms, type I collagen and alpha smooth muscle actin in human fetal lung fibroblasts. Pediatr Res 2006;60: 389-94.[CrossRef] [PubMed]
  71. Fan JB,Liu W,Zhu XH, et al. microRNA-7 inhibition protects human osteoblasts from dexamethasone via activation of epidermal growth factor receptor signaling. Mol Cell Biochem 2019;460: 113-21.[CrossRef] [PubMed]
  72. Müller-Deubert S,Seefried L,Krug M, et al. Epidermal growth factor as a mechanosensitizer in human bone marrow stromal cells.Stem Cell Res 2017;24:69-76.[CrossRef] [PubMed]
  73. Ramachandran A,Ravindran S,Huang CC, et al. TGF beta receptor II interacting protein-1, an intracellular protein has an extracellular role as a modulator of matrix mineralization. Sci Rep 2016;6: 37885.[CrossRef] [PubMed]
  74. Elsafadi M,Manikandan M,Dawud RA, et al. Transgelin is a TGFβ-inducible gene that regulates osteoblastic and adipogenic differentiation of human skeletal stem cells through actin cytoskeleston organization. Cell Death Dis 2016;7: e2321.[CrossRef] [PubMed]
  75. Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg 2004;114:1502-8.[CrossRef] [PubMed]
  76. Schilephake H. Bone growth factors in maxillofacial skeletal reconstruction. Int J Oral Maxillofac Surg 2002;31:469-84.[CrossRef] [PubMed]
  77. Kano MR, Morishita Y, Iwata C, et al. VEGF-A and FGF-2 synergistically promote neoangiogenesis through enhancement of endogenous PDGF-B-PDGFRbeta signaling. J Cell Sci 2005;118:3759-68.[CrossRef] [PubMed]
  78. Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev 2008;22: 1276-312.[CrossRef] [PubMed]
  79. Attisano L, Wrana JL. Signal transduction by the TGF-β superfamily. Science 2002;296:1646-7.[CrossRef] [PubMed]
  80. Torigoe I, Sotome S, Tsuchiya A, et al. Bone regeneration with autologous plasma, bone marrow stromal cells, and porous β-tricalcium phosphate in nonhuman primates. Tissue Engineering:Part A 2009; 15( 7):1489-99.[CrossRef] [PubMed]
  81. Chen TL, Liang XJ, Zhang XH. Do the Fibrin scaffold and growth factors in platelet-rich fibrin play the most vital roles in bone regeneration. J Craniofac Surg ,2019;30(6):1923-6.[CrossRef] [PubMed]
  82. Chen LH, Wang C, Liu HC, et al. Antibacterial effect of autologous platelet-rich gel derived from subjects with diabetic dermal ulcers in vitro. J Diabetes Res 2013:1-5 Article ID 269527.[CrossRef] [PubMed]
  83. Lu HJ, Chen TL, Zhang XH, et al. Antibacterial Effects of Platelet-Rich Plasma in Promoting Facial Scars Healing in CombinationWith Adipose-Derived Stromal Vascular Fraction Cells. J Craniofac Surg 2015; 26(7):e670-e672.[CrossRef] [PubMed]
  84. Sundman EA, Cole BJ, Karas V, et al. The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. Am J Sports Med 2014;42:35-41.[CrossRef] [PubMed]
  85. Dimauro I, Grasso L, Fittipaldi S, et al. Platelet-rich plasma and skeletal muscle healing: a molecular analysis of the early phases of the regeneration process in an experimental animal model. PLoS One 2014;9:1-13e102993.[CrossRef] [PubMed]