|Year : 2019 | Volume
| Issue : 4 | Page : 85-90
Applications of Fibrin-based products in Endodontics: A Literature Review
Behnam Bolhari, Naghmeh Meraji, Abdollah Ghorbanzadeh, Pegah Sarraf, Razieh Moayeri
Department of Endodontics, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
|Date of Submission||30-Mar-2019|
|Date of Decision||18-Apr-2019|
|Date of Acceptance||22-May-2019|
|Date of Web Publication||28-Jan-2020|
DDS, MSc, DoIBoE Naghmeh Meraji
Department of Endodontics, School of Dentistry, Tehran University of Medical Sciences, North Kargar st., Tehran
Source of Support: None, Conflict of Interest: None
Introduction: Endodontic treatment of necrotic immature teeth is quite challenging. Current concepts for revitalization of these teeth known as regenerative endodontic treatment (RET) is based on key elements necessary for tissue engineering including stem cells, three-dimensional (3D) scaffolds, and growth factors. Utilizing an applicable scaffold for narrow root canal space with adequate properties is essential for successful outcome. Fibrin-based products are materials with various advantages as a scaffold. This review article aims to discuss the properties of different types of fibrin-based products and debates whether they are appropriate scaffolds for RET or not? Methods: An electronic search was performed using databases such as Google Scholar, PubMed, PubMed Central, Science Direct, and Scopus. Keywords such as (“scaffold”)AND (“fibrin gel” OR “fibrin sealant” OR “fibrin glue” OR “fibrin tissue adhesive” OR “fibrin hydrogel” OR “platelet concentrate”) AND (“tooth” OR “teeth”) AND/OR (“regenerative endodontics” OR “dentistry”) were used. Exclusion criteria included studies published in a language other than English and abstracts from congress. Results: Fibrin gel is a protein-based natural polymer hydrogel scaffold which can be easily used in the root canal. Platelet concentrates are autologous fibrin-based products used as scaffolds for RET with various favorable properties especially due to containing various growth factors. Conclusion: It seems that fibrin gel and platelet concentrates have adequate properties for use in RET; however, more evidence is required regarding the clinical outcome of applying these products as scaffolds for RET.
Keywords: Fibrin, fibrin tissue adhesive, hydrogel, platelet concentrates, regenerative endodontics, tissue engineering, tissue scaffolds
|How to cite this article:|
Bolhari B, Meraji N, Ghorbanzadeh A, Sarraf P, Moayeri R. Applications of Fibrin-based products in Endodontics: A Literature Review. Dent Hypotheses 2019;10:85-90
| Introduction|| |
Endodontic treatment on necrotic immature teeth is a clinically challenging procedure. As pulp necrosis has occurred during root development due to damages caused by traumatic injuries, dental anomalies, or caries, these teeth have short roots, thin dentinal walls, and lack the apical root canal constriction; thus, usually they cannot be treated by routine endodontic procedures. Regenerative endodontic treatment (RET) is a biologically based approach aimed to regenerate the dentin–pulp complex and consequently cause continuation of root development., RET is a subset of tissue engineering; thus, it pursues the same goals and principles of tissue engineering, in conjunction with principles of routine endodontic treatments, such as root canal disinfection. Tissue engineering is based on the following necessary key elements: stem cells, 3D scaffold, and growth factors or morphogens.
The presence of an appropriate scaffold is necessary for regeneration. Scaffolds should promote a 3D support for stem/progenitor cell adhesion, migration, and proliferation, all of which paramount for tissue regeneration. In the case of RETs, the suggested protocol for scaffold creation entails the intentional induction of bleeding from the periapex and the formation of an intracanal blood clot. Several reports have been published demonstrating good success with blood clot scaffolds,; however, because it is not always possible to invoke bleeding in the root canal, researchers have begun examining other 3D scaffolds. Some examples include organic collagen-based scaffolds,, synthetic polymers,, calcium phosphate, platelet-rich plasma,, platelet-rich fibrin,, and hydrogel.
Fibrin-based products are materials having various advantages as a scaffold. This review article aims to discuss the properties of different types of fibrin-based products and evaluate if they can be acceptable scaffolds for RET.
| Methods|| |
An electronic search was performed using databases such as Google Scholar, PubMed, PubMed Central, Science Direct, and Scopus by using keywords such as (“scaffold”) AND (“fibrin gel” OR “fibrin sealant” OR “fibrin glue” OR “fibrin tissue adhesive” OR “fibrin hydrogel” OR “platelet concentrate”) AND (“tooth” OR “teeth”) AND/OR (“regenerative endodontics” OR “dentistry”). The last search was performed in March 2019.
Inclusion criteria were all in vitro, ex vivo, clinical studies, case reports or series, and review articles about fibrin gels and/or sealants and/or adhesives and/or glue and/or platelet concentrates in dentistry. Exclusion criteria included studies published in a language other than English and abstracts from congress. The articles were selected to address the following research question: Can fibrin-based products be acceptable scaffolds for RET?
| Results|| |
A total of 570 articles were identified after elimination of duplicates and articles in languages other than English by our search strategy. After evaluation of the titles, abstracts, and full texts, 103 references were included for review and evaluation. Among these articles, 14 were review articles, nine were clinical trials, and four were case reports/series.
| Discussion|| |
Scaffolds in regenerative dentistry
An ideal scaffold for regeneration should facilitate the attachment, migration, proliferation, and 3D spatial organization of cell populations in the target tissue., Biocompatibility of a scaffold is also critical to prevent adverse tissue reactions. Biodegradability is also a crucial property and must be tunable to facilitate constructive remodeling. This phenomenon is described as scaffold degradation in an appropriate rate corresponding to the rate of cell/tissue infiltration, cellular migration, proliferation and differentiation, vascularization, and replacement of the scaffold by the appropriate tissues. Another important property required for scaffolds is adequate porosity and pore size. Porosity facilitates cell seeding and diffusion of both cells and nutrients throughout whole structure of the scaffold.
Based on their origin, scaffolds can be classified into two groups: biological/natural or synthetic/artificial. They can also be classified into four groups based on their form: solid blocks, sheets, porous sponges, and hydrogels (injectable scaffolds).
Fibrin-based products are protein-based natural polymers having several advantages such as exceptional biocompatibility, controllable degradation rate, production of nontoxic degradation products, having similar viscoelastic properties to connective tissue, efficient diffusion of nutrients and waste, having tunable morphology, adequate mechanical properties,,, uniform cell distribution,, and promotion of angiogenesis., Fibrin allows the growth and differentiation of dental stem cells and thus accelerates tissue regeneration in the oral cavity. These scaffolds can be very practical for regenerative endodontics as they can be easily used and can deliver chemotactic and angiogenic factors to resident stem cells.
Structure and properties of fibrin-based products
Fibrin-based products have been initially used as bioadhesives for hemostasis in surgical procedures, wound closure, and a sealant, and their application has been growing in the past decades. Recently, the application of fibrin gels in tissue engineering has become more common.
Fibrin is a biopolymer of the fibrinogen monomer. Fibrinogen and thrombin are the main components involved in the blood-clotting process. Thrombin is a protease existing in the plasma. Thrombin-mediated cleavage of fibrinopeptide A and fibrinopeptide B from fibrinogen initiates the formation of fibrin thus creating a 3D gel.
Fibrin glue (fibrin sealant) is one of the first available fibrin-based products. It was prepared from pooled plasma. Human plasma was used as a source for fibrinogen (homologous or autologous) to reduce the potential risks of immunological reaction. Thrombin was purified from bovine plasma. Each of these two precursor solutions are stored in a separate syringe. Fibrin glue has two components: first, a freeze-dried concentrate of clotting proteins (the sealant), mainly fibrinogen, factor XIII, and fibronectin, and second, the catalyst containing freeze-dried thrombin and CaCl2 and antifibrinolytic drugs., After mixing the two components, it is directly injected to the wound site. Fibrin glue is used to create a fibrin clot for hemostasis, wound healing, and tissue adhesion. Fibrin glue can protect against infection in the wound site., Fibrin-stabilizing factor XIII found in fibrin glue can favor the migration of undifferentiated mesenchymal cells and enhances the proliferation of these cells. Fibrin glue can also be prepared from allogeneic pooled plasma, which is commercially available (i.e., Tissucol/Tisseel, Beriplast, and Quixil).
Fibrin hydrogels are another type of fibrin-based products constructed from commercially purified allogeneic fibrinogen and purified thrombin unlike fibrin glue., Fibrin hydrogels have been widely applied in tissue engineering in medicine. They have many advantages such as high seeding efficiency and uniform cell distribution, cell adhesion capabilities, and promotion of angiogenesis, and if produced from the patient’s own blood, it can be used as an autologous scaffold without the potential risk of foreign body reaction or infection. By changing the kinetic parameters, the structure of the fibrin gel can be modified. For instance, to accelerate the gelation time, the concentration of thrombin can be increased. This also can result in a more densely cross-linked network with thinner fibers, contrarily, reducing the thrombin concentration results in gel with a higher porosity.
Fibrin hydrogels are able to function as both two-dimensional (2D) and 3D cell culture scaffold. In the 2D application, the scaffold is prepared and undergoes gelation prior to cell seeding; thus, after the gelation of fibrin hydrogel, cells are seeded into the scaffold., In the 3D application, isolated cells are initially suspended in the scaffold precursor solution. Then the cell–fibrin gel precursor solution mixture can be directly injected into the target lesion in which, afterward, the fibrin gel cures., Thus, fibrin hydrogels can also act as a vehicle for cell transplantation.
Fibrin hydrogels have three major disadvantages: shrinkage, low mechanical stiffness, and rapid degradation prior to proper tissue formation. Depending on the application site and whether the disadvantages adversely affect the outcome of regenerative treatments, these disadvantages can be compensated by applying modifications to this scaffold. For instance, to increase the mechanical properties of this scaffold, if necessary, fibrin hydrogels can be combined with other scaffold materials such as polyurethane, polycaprolactone, b-tricalciumphosphate, and polyethylene glycol. For creating a more stable hydrogel with slower degradation, concomitantly optimizing the pH and concentrations of fibrinogen and calcium ion, modifying and stabilizing fibrin with a molecules such as polyethylene glycol,, adding protease inhibitors specific for plasmin and matrix metalloproteinases, or adding fibrin microbeads, small spherical dense beads with a diameter ranging from 50 to 250 μm consisting of highly condensed and cross-linked fibrin, is suggested. Its shrinkage can be reduced by adding fixing agents such as poly L-lysine. This modifiability can be an advantage for clinical regenerative treatments.
Autologous platelet concentrates (APCs) are another type of fibrin-based products that are derived from the patient him/herself. They contain high concentrations of platelets. Platelets contain various growth factors in their alpha granules such as VEGF, IGF, TGF-β, which upon activation are release due to degranulation. Therefore, can attract stem cells and induce proliferation and differentiation in them. APCs are divided into two generations: the first generation are those types which require addition of activating agents (i.e. Calcium Chloride, Bovine Thrombin) for initiation of platelet degranulation and fibrin matrix formation; whereas, in the second generation platelet activation and fibrin polymerization are triggered immediately without requiring the addition of activating agents as they are produced without any anticoagulants or gelifying agents. Platelet Rich Plasma (PRP), Plasma rich in growth factors (PRGF) and Pure Platelet Rich Fibrin (P-PRF) are categorized as the first generation whereas, Leucocyte and Platelet Rich Fibrin (L-PRF), Advanced Platelet Rich Fibrin (A-PRF) and Concentrated Growth Factor (CGF) are categorized as the second generation.
As PRP encountered major disadvantages including having a technique-sensitive and time-consuming preparation method, possibility of transmission of unknown infections from bovine thrombin to PRP recipients, susceptibility of its fibrin matrix to washout due to rapid polymerization, occurrence of maximum growth factors release before cell ingrowth, PRF was developed., PRF has several advantages over PRP including having a strong and flexible 3D fibrin network supporting cytokine enmeshment and cellular migration due to slow physiologic polymerization and also steady release of growth factors lasting up to 14-21 days.,
Application of fibrin gel in dentistry
Fibrin sealants are widely used in oral and maxillofacial surgery to treat bone defects, in preimplantation sinus lifting, mandibular nerve displacement procedures, or for simple tooth extractions to prevent bleeding in patients with hemostatic disorders. They are also used in periodontal surgery to anchor gingival grafts and enhance reconstructive procedures.
One study used fibrin sealants in patients with bleeding disorders for stopping local bleeding in tooth extraction sites and showed that the rate of postoperative bleeding was similar to that obtained with other local treatments such as gelatin sponges, sutures, or tranexamic acid mouthwash.
Autologous formulations of fibrin sealants are also used in maxillofacial surgery to affectively reduce the risk of virus infection. Furthermore, fibrin sealants have been used to approximate soft or hard tissues in surgical procedures.
Regarding the effect of fibrin sealants on bone healing, animal studies have shown that they produced an early enhancement of bone repair and the physical properties of the bony callus; however, these effect appeared to be short term and their strength after 5 to 7 weeks was similar to that those healed without these sealants., Lucht et al. reported that fibrin sealant had no affect on the new bone formation in tibia defects filled with autologous cancellous bone in dogs. The use of the mixture of homologous fibrin sealant and bone substitutes in bone defects has also been used in several studies, only resulting in easier handling properties and securing of the bone substitutes in the surgical site. Fibrin sealants have been used in dental implant procedures and shown to give promising outcomes.
Fibrin gel has also been used as a surgical tissue adhesive and hemostatic agent to enhance healing in bone defects and has shown promising effects. The osteoinductive properties of fibrin gels have been enhanced by combining it with bone morphogenetic proteins. It has also been used as a delivery system for other growth factors. This scaffold has been used both as a 2D and a 3D cell culture scaffold. This fibrin-based scaffold has been used as a delivery system for human mesenchymal stem cell for osteoconduction.,
Another application for fibrin gels is in salivary gland regeneration., In this application, fibrin gels have been used as a delivery system for laminin-111 protein, important for salivary gland cell cluster formation and organization, showing favorable outcome.,Additionally, fibrin gels have been used for dental pulp regeneration.,
Application of fibrin gel in endodontics
Other than common applications in endodontic surgical procedures, fibrin gels have been investigated for use in RET. Fibrin gels have the advantage of having excellent handling characteristics for dental applications, especially RET. As defects in the oral cavity are small, injectable mode of application is preferred especially in the case of RET in which the scaffold should be inserted into the root canal system, which is small and irregular. Galler et al. demonstrated that natural scaffolds were superior to synthetic scaffolds with regard to dental stem cell viability and differentiation into dental pulp-like tissue. In addition, they reported fibrin hydrogels to be the most suitable to enable generation of a pulp-like tissue and differentiation of cells into odontoblasts compared to other natural scaffolds. In another study, Galler et al. reported that fibrin hydrogels modified with polyethylene glycol allowed for the proliferation of dental stem cells and osteogenic and odontogenic differentiation depending on the source of stem cells.
Another advantage of fibrin hydrogels for RETs is that growth factors such as VEGF and FGF-2 or TGF-β can indirectly be bound to fibrin hydrogels via heparin. Additionally, bioactive short peptides can be synthesized and covalently bound to fibrin, if necessary.
Ruangsawasdi et al. studied effect of the fibrin gel in human immature premolars implanted in rats and demonstrated that the use of fibrin gel affected not only the extent of tissue ingrowth but also tissue morphology and differentiation of cells contacting the dentinal wall. The newly formed tissue was similar to normal pulp, having an inner pulp, cell-rich zone, cell-free zone, and an apparent odontoblast layer. Additionally, newly formed blood vessels were also more abundant in canals in which fibrin gel was used.
Widbiller et al. used custom-made fibrin and fibrin sealants as a scaffold for RET in an ectopic animal model. They observed tissue ingrowth when fibrin-based scaffolds were used and the amount of tissue ingrowth increased with the addition of dentin matrix proteins.
Up to now, no clinical study has evaluated the use of fibrin gels in RET cases and its outcomes. In vitro studies are fundamental and prerequisites but studies with higher levels of evidence is required.
Applications of autologous platelet concentrates in dentistry
APCs have a variety of applications in dentistry including the use in socket preservation after extraction or avulsion of tooth, bone healing, periodontal lesions, in gingival recession coverage procedure, in sinus lift procedures, in the repair of articular cartilage defects, in various cosmetic, reconstructive and facial surgery and in regenerative endodontic procedures. Studies have shown that the application of APCs caused faster radiographic bone healing,,.
Some studies have applied APCs for RET. Many have reported high incidence of apical closure,,,,,, root lengthening,,,, and/or dentinal wall thickening,,, all being among favorable outcomes for RETs. Histological evaluations revealed the formation of an odontoblastic cell layer or dentin-like structure and neoformed intracanal tissues were mainly cementum-like, bone-like, and connective tissues.,More studies with high levels of evidence are required.
| Conclusion|| |
Fibrin gels are commercially available scaffolds having favorable properties including adhesion, proliferation and differentiation of stem cells, induction of angiogenesis, and excellent handling characteristics, especially for RETs. Its properties can be desirably tailored according to its application. Platelet concentrates are autologous fibrin-based materials containing growth factors with various favorable properties for RET. In vitro and animal studies have shown good results for the use of these materials as scaffolds in RETs. They seem to have the potentials to be used in this treatment modality. Further clinical studies with higher levels of evidence is required.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Diogenes A, Henry MA, Teixeira FB, Hargreaves KM. An update on clinical regenerative endodontics. Endod Topics 2013;28:2-23.
Murray PE, Garcia-Godoy F, Hargreaves KM. Regenerative endodontics: a review of current status and a call for action. J Endod 2007;33:377-90.
Diogenes A, Ruparel NB, Shiloah Y, Hargreaves KM. Regenerative endodontics: a way forward. J Am Dent Assoc 2016;147:372-80.
Nakashima M, Reddi AH. The application of bone morphogenetic proteins to dental tissue engineering. Nat Biotechnol 2003;21:1025-32.
Yu J, Shi J, Jin Y. Current approaches and challenges in making a bio-tooth. Tissue Eng Part B Rev 2008;14:307-19.
Galler KM. Clinical procedures for revitalization: current knowledge and considerations. Int Endod J 2016;49:926-36.
Ding RY, Cheung GS, Chen J, Yin XZ, Wang QQ, Zhang CF. Pulp revascularization of immature teeth with apical periodontitis: a clinical study. J Endod 2009;35:745-9.
Banchs F, Trope M. Revascularization of immature permanent teeth with apical periodontitis: new treatment protocol? J Endod 2004;30:196-200.
Nosrat A, Homayounfar N, Oloomi K. Drawbacks and unfavorable outcomes of regenerative endodontic treatments of necrotic immature teeth: a literature review and report of a case. J Endod 2012;38:1428-34.
Prescott RS, Alsanea R, Fayad MI, Johnson BR, Wenckus CS, Hao J et al.
In vivo generation of dental pulp-like tissue by using dental pulp stem cells, a collagen scaffold, and dentin matrix protein 1 after subcutaneous transplantation in mice. J Endod 2008;34:421-6.
Zhang W, Walboomers XF, van Kuppevelt TH, Daamen WF, Bian Z, Jansen JA. The performance of human dental pulp stem cells on different three-dimensional scaffold materials. Biomaterials 2006;27:5658-68.
Demarco FF, Casagrande L, Zhang Z, Dong Z, Tarquinio SB, Zeitlin BD et al.
Effects of morphogen and scaffold porogen on the differentiation of dental pulp stem cells. J Endod 2010;36:1805-11.
Sung HJ, Meredith C, Johnson C, Galis ZS. The effect of scaffold degradation rate on three-dimensional cell growth and angiogenesis. Biomaterials 2004;25:5735-42.
Iohara K, Murakami M, Takeuchi N, Osako Y, Ito M, Ishizaka R et al.
A novel combinatorial therapy with pulp stem cells and granulocyte colony-stimulating factor for total pulp regeneration. Stem Cells Transl Med 2013;2:521-33.
Shivashankar VY, Johns DA, Maroli RK, Sekar M, Chandrasekaran R, Karthikeyan S et al.
Comparison of the effect of PRP,PRF and induced bleeding in the revascularization of teeth with necrotic pulp and open apex: a triple blind randomized clinical trial. J Clin Diagn Res 2017;11:ZC34-9.
Bezgin T, Yilmaz AD, Celik BN, Kolsuz ME, Sonmez H. Efficacy of platelet-rich plasma as a scaffold in regenerative endodontic treatment. J Endod 2015;41:36-44.
Faizuddin U, Solomon RV, Mattapathi J, Guniganti SS. Revitalization of traumatized immature tooth with platelet-rich fibrin. Contemp Clin Dent 2015;6:574-6.
] [Full text]
Zhou R, Wang Y, Chen Y, Chen S, Lyu H, Cai Z et al.
Radiographic, histologic, and biomechanical evaluation of combined application of platelet-rich fibrin with blood clot in regenerative endodontics. J Endod 2017;43:2034-40.
Chrepa V, Austah O, Diogenes A. Evaluation of a commercially available hyaluronic acid hydrogel (Restylane) as injectable scaffold for dental pulp regeneration: an in vitro evaluation. J Endod 2017;43:257-62.
Galler KM, D’Souza RN, Hartgerink JD, Schmalz G. Scaffolds for dental pulp tissue engineering. Adv Dent Res 2011;23:333-9.
Costello BJ, Shah G, Kumta P, Sfeir CS. Regenerative medicine for craniomaxillofacial surgery. Oral Maxillofac Surg Clin North Am 2010;22:33-42.
Patel H, Bonde M, Srinivasan G. Biodegradable polymer scaffold for tissue engineering. Trends Biomater Artif Organs 2011;25:20-9.
Gathani KM, Raghavendra SS. Scaffolds in regenerative endodontics: a review. Dent Res J (Isfahan) 2016;13:379-86.
Ahmed TA, Dare EV, Hincke M. Fibrin: a versatile scaffold for tissue engineering applications. Tissue Eng Part B Rev 2008;14:199-215.
Li Y, Meng H, Liu Y, Lee BP. Fibrin gel as an injectable biodegradable scaffold and cell carrier for tissue engineering. Sci World J 2015;2015:685690.
Swartz DD, Russell JA, Andreadis ST. Engineering of fibrin-based functional and implantable small-diameter blood vessels. Am J Physiol Heart Circ Physiol 2005;288:H1451-60.
Urech L, Bittermann AG, Hubbell JA, Hall H. Mechanical properties, proteolytic degradability and biological modifications affect angiogenic process extension into native and modified fibrin matrices in vitro. Biomaterials 2005;26:1369-79.
Galler KM, Cavender AC, Koeklue U, Suggs LJ, Schmalz G, D’Souza RN. Bioengineering of dental stem cells in a PEGylated fibrin gel. Regen Med 2011;6:191-200.
Undas A, Ariens RA. Fibrin clot structure and function: a role in the pathophysiology of arterial and venous thromboembolic diseases. Arterioscler Thromb Vasc Biol 2011;31:e88–99.
Shinohara K, Kobayashi E, Yoshida T, Toyama N, Kiyozaki H, Fujimura A et al.
Effect of fibrin glue on small and large bowel anastomoses in the rat. Eur Surg Res 1998;30:8-12.
Whitmore E. Preparation of autologous plasma and fibrin gel. Google Patents; 1999.
Carless PA, Anthony DM, Henry DA. Systematic review of the use of fibrin sealant to minimize perioperative allogeneic blood transfusion. Br J Surg 2002;89:695-703.
Kawamura M, Sawafuji M, Watanabe M, Horinouchi H, Kobayashi K. Frequency of transmission of human parvovirus B19 infection by fibrin sealant used during thoracic surgery. Ann Thorac Surg 2002;73:1098-100.
Ito K, Yamada Y, Naiki T, Ueda M. Simultaneous implant placement and bone regeneration around dental implants using tissue-engineered bone with fibrin glue, mesenchymal stem cells and platelet-rich plasma. Clin Oral Implants Res 2006;17:579-86.
Ahmed TA, Griffith M, Hincke M. Characterization and inhibition of fibrin hydrogel-degrading enzymes during development of tissue engineering scaffolds. Tissue Eng 2007;13:1469-77.
Jockenhoevel S, Zund G, Hoerstrup SP, Chalabi K, Sachweh JS, Demircan L et al.
Fibrin gel − advantages of a new scaffold in cardiovascular tissue engineering. Eur J Cardiothorac Surg 2001;19:424-30.
Blomback B, Bark N. Fibrinopeptides and fibrin gel structure. Biophys Chem 2004;112:147-51.
Chien CS, Ho HO, Liang YC, Ko PH, Sheu MT, Chen CH. Incorporation of exudates of human platelet-rich fibrin gel in biodegradable fibrin scaffolds for tissue engineering of cartilage. J Biomed Mater Res B Appl Biomater 2012;100:948-55.
Hong H, Stegemann JP. 2D and 3D collagen and fibrin biopolymers promote specific ECM and integrin gene expression by vascular smooth muscle cells. J Biomater Sci Polym Ed 2008;19:1279-93.
Lee CR, Grad S, Gorna K, Gogolewski S, Goessl A, Alini M. Fibrin-polyurethane composites for articular cartilage tissue engineering: a preliminary analysis. Tissue Eng 2005;11:1562-73.
Van Lieshout M, Peters G, Rutten M, Baaijens F. A knitted, fibrin-covered polycaprolactone scaffold for tissue engineering of the aortic valve. Tissue Eng 2006;12:481-7.
Weinand C, Gupta R, Huang AY, Weinberg E, Madisch I, Qudsi RA et al.
Comparison of hydrogels in the in vivo formation of tissue-engineered bone using mesenchymal stem cells and beta-tricalcium phosphate. Tissue Eng 2007;13:757-65.
Rahman CV, Kuhn G, White LJ, Kirby GT, Varghese OP, McLaren JS et al.
PLGA/PEG-hydrogel composite scaffolds with controllable mechanical properties. J Biomed Mater Res B Appl Biomater 2013;101:648-55.
Eyrich D, Brandl F, Appel B, Wiese H, Maier G, Wenzel M et al.
Long-term stable fibrin gels for cartilage engineering. Biomaterials 2007;28:55-65.
Dikovsky D, Bianco-Peled H, Seliktar D. The effect of structural alterations of PEG-fibrinogen hydrogel scaffolds on 3-D cellular morphology and cellular migration. Biomaterials 2006;27:1496-506.
Rivkin R, Ben-Ari A, Kassis I, Zangi L, Gaberman E, Levdansky L et al.
High-yield isolation, expansion, and differentiation of murine bone marrow-derived mesenchymal stem cells using fibrin microbeads (FMB). Cloning Stem Cells 2007;9:157-75.
Lee F, Kurisawa M. Formation and stability of interpenetrating polymer network hydrogels consisting of fibrin and hyaluronic acid for tissue engineering. Acta Biomater 2013;9:5143-52.
Whitman DH, Berry RL, Green DM. Platelet gel: an autologous alternative to fibrin glue with applications in oral and maxillofacial surgery. J Oral Maxillofac Surg 1997;55:1294-9.
Dohan Ehrenfest DM, Rasmusson L, Albrektsson T. Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF). Trends Biotechnol 2009;27:158-67.
Alsousou J, Thompson M, Hulley P et al.
The biology of platelet-rich plasma and its application in trauma and orthopaedic surgery: a review of the literature. J Bone Joint Surg Br 2009;91:987-96.
Davis VL, Abukabda AB, Radio NM et al.
Platelet-rich preparations to improve healing. Part II: platelet activation and enrichment, leukocyte inclusion, and other selection criteria. J Oral Implantol 2014;40:511-21.
Jimenez-Aristizabal RF, Lopez C, Alvarez ME et al.
Long-term cytokine and growth factor release from equine platelet-rich fibrin clots obtained with two different centrifugation protocols. Cytokine 2017;97:149-55.
Soffer E, Ouhayoun JP, Anagnostou F. Fibrin sealants and platelet preparations in bone and periodontal healing. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:521-8.
Blinder D, Manor Y, Martinowitz U, Taicher S, Hashomer T. Dental extractions in patients maintained on continued oral anticoagulant: comparison of local hemostatic modalities. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:137-40.
Davis BR, Sandor GK. Use of fibrin glue in maxillofacial surgery. J Otolaryngol 1998;27:107-12.
Greco F, de Palma L, Specchia N, Lisai P. Experimental investigation into reparative osteogenesis with fibrin adhesive. Arch Orthop Trauma Surg 1988;107:99-104.
Keller J, Andreassen TT, Joyce F, Knudsen VE, Jørgensen PH, Lucht U. Fixation of osteochondral fractures.Fibrin sealant tested in dogs. Acta Orthop Scand 1985;56:323-6.
Lucht U, Bunger C, Moller JT, Joyce F, Plenk H Jr. Fibrin sealant in bone transplantation. No effects on blood flow and bone formation in dogs. Acta Orthop Scand 1986;57:19-24.
Marchac D, Renier D. Fibrin glue in craniofacial surgery. J Craniofac Surg 1990;1:32-4.
Schantz JT, Teoh SH, Lim TC, Endres M, Lam CX, Hutmacher DW. Repair of calvarial defects with customized tissue-engineered bone grafts I. Evaluation of osteogenesis in a three-dimensional culture system. Tissue Eng 2003; 9(Suppl 1): S113-26.
Sasaki J, Matsumoto T, Imazato S. Oriented bone formation using biomimetic fibrin hydrogels with three-dimensional patterned bone matrices. J Biomed Mater Res A 2015;103:622-7.
Karfeld-Sulzer LS, Siegenthaler B, Ghayor C, Weber FE. Fibrin hydrogel based bone substitute tethered with BMP-2 and BMP-2/7 heterodimers. Materials (Basel) 2015;8:977-91.
Sacchi V, Mittermayr R, Hartinger J, Martino MM, Lorentz KM, Wolbank S et al.
Long-lasting fibrin matrices ensure stable and functional angiogenesis by highly tunable, sustained delivery of recombinant VEGF164. Proc Natl Acad Sci USA 2014;111:6952-7.
Bensaid W, Triffitt JT, Blanchat C, Oudina K, Sedel L, Petite H. A biodegradable fibrin scaffold for mesenchymal stem cell transplantation. Biomaterials 2003;24:2497-502.
Zhou H, Xu HH. The fast release of stem cells from alginate-fibrin microbeads in injectable scaffolds for bone tissue engineering. Biomaterials 2011;32:7503-13.
Nam K, Wang CS, Maruyama CLM, Lei P, Andreadis ST, Baker OJ. L1 peptide-conjugated fibrin hydrogels promote salivary gland regeneration. J Dent Res 2017;96:798-806.
Nam K, Maruyama CL, Wang CS, Trump BG, Lei P, Andreadis ST et al.
Laminin-111-derived peptide conjugated fibrin hydrogel restores salivary gland function. PLoS One 2017;12:e0187069.
Ducret M, Montembault A, Josse J, Pasdeloup M, Celle A, Benchrih R et al.
Design and characterization of a chitosan-enriched fibrin hydrogel for human dental pulp regeneration. Dent Mater 2019;35:523-33.
Germain L, De Berdt P, Vanacker J, Leprince J, Diogenes A, Jacobs D et al.
Fibrin hydrogels to deliver dental stem cells of the apical papilla for regenerative medicine. Regen Med 2015;10:153-67.
Galler KM, Brandl FP, Kirchhof S, Widbiller M, Eidt A, Buchalla W et al.
Suitability of different natural and synthetic biomaterials for dental pulp tissue engineering. Tissue Eng Part A 2018;24:234-44.
Briganti E, Spiller D, Mirtelli C, Kull S, Counoupas C, Losi P et al.
A composite fibrin-based scaffold for controlled delivery of bioactive pro-angiogenetic growth factors. J Control Release 2010;142:14-21.
Jung Y, Chung YI, Kim SH, Tae G, Kim YH, Rhie JW et al.
In situ chondrogenic differentiation of human adipose tissue-derived stem cells in a TGF-beta1 loaded fibrin-poly(lactide-caprolactone) nanoparticulate complex. Biomaterials 2009;30:4657-64.
Ruangsawasdi N, Zehnder M, Weber FE. Fibrin gel improves tissue ingrowth and cell differentiation in human immature premolars implanted in rats. J Endod 2014;40:246-50.
Widbiller M, Driesen RB, Eidt A, Lambrichts I, Hiller KA, Buchalla W et al.
Cell homing for pulp tissue engineering with endogenous dentin matrix proteins. J Endod 2018;44:956-62.e2.
Xuan F, Lee CU, Son JS et al.
A comparative study of the regenerative effect of sinus bone grafting with platelet-rich fibrin-mixed Bio-Oss(R) and commercial fibrin-mixed Bio-Oss(R): an experimental study. J Craniomaxillofac Surg 2014;42:e47-50.
Lv H, Chen Y, Cai Z et al.
The efficacy of platelet-rich fibrin as a scaffold in regenerative endodontic treatment: a retrospective controlled cohort study. BMC oral health 2018;18:139.
Prasad J, de Ataide IN, Chalakkal P, Likhyani LK. Comparison between the Outcomes of Two Platelet-Rich Concentrates on Apexogenesis in Young Permanent Incisors Requiring Endodontic Retreatment. Contemp Clin Dent 2018;9:S156–s9.
Alagl A, Bedi S, Hassan K, AlHumaid J. Use of platelet-rich plasma for regeneration in non-vital immature permanent teeth: Clinical and cone-beam computed tomography evaluation. J Int Med Res 2017;45:583–93.
Narang I, Mittal N, Mishra N. A comparative evaluation of the blood clot, platelet-rich plasma, and platelet-rich fibrin in regeneration of necrotic immature permanent teeth: A clinical study. Contemp Clin Dent 2015;6:63–8.
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Del Fabbro M, Lolato A, Bucchi C et al.
Autologous Platelet Concentrates for Pulp and Dentin Regeneration: A Literature Review of Animal Studies. J Endod 2016;42:250–7.