The Miracle of Autologous Growth Factors Enriched Bone Graft Matrix (Sticky Bone) In Regenerative Endodontic Micro-Surgery.

The use of platelet concentrates in dentistry evolves frequently, from the initial platelet-rich plasma (PRP) to sophisticated centrifugation procedures and injectable PRF preparations. Alveolar ridge augmentation, periodontal surgery, implant surgery, and endodontic regeneration are just a few of the disciplines that have used platelet concentrates for hard and soft tissue healing.

With breakthroughs in surgical approaches, some authors have proposed the combination of platelet concentrates with bone graft materials such as synthetic bone, xenografts and allografts, a novel idea that involves creating “sticky bone,” a growth factor-enriched bone graft matrix. This composite biomaterial, is a promising autologous material, results in a significant release of cytokines and autologous growth factors that responsible for healing and tissue recovery, in addition, these growth factors promote proliferation of mesenchymal stem cells, fibroblasts, and osteoblasts, impacting the development of tissue neoformation.

Sticky bone application in regenerative endodontic surgery in cases of through and through lesions, apico-marginal defects, and non-healed large apical lesions after root canal treatment will modulate the microenvironment in periapical defects that demand guided tissue regeneration (GTR), which combines the use of bone graft material plus a resorbable or non-resorbable membrane, and this may elicit some immunological response. So, using sticky bone after apicoectomy provides us with an autologous growth factor-enriched bone graft matrix that simplifies handling during the surgical operations due to its optimal moldability without disintegration into the surrounding soft tissues. It also allows stabilization of the bone graft in the defect to accelerate tissue healing with the elimination of graft loss and inhibits the ingrowth of soft tissue in the graft, which results in complementing the surgery and increasing the success rate.

Keywords: platelet concentrates, injectable PRF, sticky bone, Regenerative Endodontics, micro-surgery.

The necrosis of pulp tissue not adequately treated can lead to periapical periodontitis, which is the result of inflammatory pathologies of the periapical tissues of the tooth (alveolar bone and periodontal ligament) [1,2]. Endodontic surgery consists of the reduction or elimination of persistent periapical pathology when primary orthograde endodontics or retreatment have failed or are not feasible [3]. The surgical endodontics field has advanced significantly since its inception. Its origins may be traced back to Aetius’s groundbreaking work on incision and drainage about 1500 years ago [4]. Historically, conventional endodontic surgery, which involved larger surgical access and less sophisticated instrumentation, often presented challenges in achieving predictable outcomes. Nevertheless, with the introduction of microsurgical techniques and the integration of cutting-edge technologies, the field of endodontics has evolved significantly [5]. However, the potential to accelerate bone regeneration in periapical surgical defects could be of great interest to the clinician to proceed earlier with permanent rehabilitation, given that endodontic surgery is linked to a less predictable prognosis compared to orthograde endodontic treatment [6] and even a single tooth can be strategically important in the whole oral prosthetic rehabilitation.

The current surgical strategy, recommends a narrower entry through the cortical bone in order to see, enucleate, and manage the resected root end, as compared to the traditional apical surgical process where the osteotomy is naturally broad. The development of the microscope and other microsurgical instruments is primarily responsible for this minimally intrusive approach to endodontic surgery [7]. The outcome of endodontic surgery may be improved by these advancements in surgical procedures and technical instruments [8]. Actually, success rates following retrograde filling and root-end resection were increased to approximately 80–90% with the use of microsurgical methods and contemporary obturation materials [9, 10]. Hormones, growth factors, and plasma derivatives have been recommended for local application to promote bone regeneration and soft tissue repair following oral surgery [11]. To encourage the surgical site’s ability to recover, local applications of platelet-rich plasma (PRP), bone morphogenic proteins (BMPs), platelet-derived growth factor (PDGF), parathyroid hormone (PTH), and enamel matrix proteins (EMD) have been applied [8]. However, their applicability in endodontic surgery is still debatable, and the benefits they offer to the patient and surgeon have been found to be modest and contentious [12, 13, 14, 15, 16, 17].

Lesion size is one of the parameters that can affect the outcome of endodontic microsurgery [18, 19]. Scar development comes from the highest rate of wound repopulation by epithelial cells during the healing phase [20]. Once complete osseous regeneration of a defect cannot be possible, the defect will be filled by fibrous connective tissue [21]. It has been demonstrated that 26% of defects radiographically larger than 10 mm result in scar formation after endodontic microsurgery [22]. Thus, application of grafting materials and membrane in cases with large lesion size (>10 mm diameter) is highly recommended [18, 19, 23].

Four types of bone grafts are present: autogenous grafts, allogeneic grafts, xenogeneic grafts and alloplastic materials. Autogenous grafts and allogeneic grafts are osteoinductive materials, however xenogeneic grafts and alloplastic materials are osteoconductive materials due to their lack of growth factors [24]. It has been stated that a combination of osteoconductive materials (e.g., an organic bovine bone mineral (ABBM)) and growth factors results in faster and better healing of bone in endodontic microsurgery than osteoconductive materials only [25, 26].

Nonetheless, there are significant drawbacks to using first-generation platelet concentrates, including the danger of coagulopathies, the need for anticoagulants, handling features, cost, and the fact that it also entails a tedious two-step centrifugation and purification process [27]. To address the aforementioned limitations, platelet rich fibrin (PRF) was first developed by Dohan et al. for use in oral and maxillofacial surgery, which requires neither anticoagulant nor bovine thrombin.

Platelets, leucocytes, and over 100 different growth factors, such as platelet-derived growth factor, transforming growth factor-beta 1, vascular endothelial growth factor, and bone morphogenetic protein 2 (BMP-2) are present in PRF (platelet-rich fibrin), which promotes the growth and differentiation of osteoblasts [28]. Moreover, the presence of leucocytes is helpful for their anti-infection and immunomodulatory effects [29–30]. Previously, PRF has been extensively used in dentistry, including the healing of extraction sockets [31] ridge preservation [32] maxillary sinus augmentation and the regeneration of periodontal lesions [33-37]. The combination of PRF and deproteinised bovine bone mineral has been shown to increase bone formation in maxillary sinus augmentation compared with deproteinised bovine bone mineral alone [33]. In periodontal intrabony deficiencies, using PRF with bone grafting materials has been shown in multiple trials to improve periodontal regeneration [34–37]. To put it briefly, PRF tends to promote osseous regeneration and soft tissue healing, particularly in conjunction with different bone grafting materials [38]. Additionally, studies have shown that PRF lowers postoperative pain and infections because of enhanced soft-tissue repair and the presence of immune cells that fight microbes [39]. Because bone graft material only has an osteoconductive impact and PRF’s growth factors stimulate osteoinduction, the combination of PRF and bone graft material boosts the regenerative effect of osseous tissue [40, 41]. In a histological study, bone regenerative effects of PRF mixed with Tri-Calcium Phosphate (TCP), and TCP alone were compared, and the results showed that PRF-TCP resulted in more rapid bone healing compared with the other group [25]. Although PRF has many advantages, traditional PRF is not liquid, and it is challenging to mix PRF and bone graft materials. In 2014, by adjusting spin centrifugation forces, injectable platelet-rich fibrin (i-PRF) was developed. The blood centrifuged in non-glass centrifugation tubes at lower centrifugation speeds and less time resulted in a flowable PRF version called injectable-PRF [27].

Injectable-PRF (i-PRF) is a platelet concentrate in liquid form that can be polymerized with bone graft. Being autogenous makes it less likely to cause unfavorable reactions to the implanted materials than other types of grafts, particularly immune-mediated ones. This makes it a feasible option for bone regeneration. It also allows the incorporation of graft without the use of anticoagulants or any additives, resulting in a well-agglutinated “sticky bone.” [42].

Healing is known to be a demand in surgical procedures, and it is achieved by a series of events: cellular organization, chemical signals, and extracellular matrix for tissue repair [43]. Platelet-rich fibrin used either alone or along with bone graft promotes bone growth and vascularization. This matrix promotes migration, cell attachment, and proliferation of osteoblast that leads to bone formation [44]. Cytokines released by PRF play a significant role in blood vessel formation and immune system stimulation to fight foreign pathogens [45]. Studies claim that PRF that is prepared using low centrifugal forces leads to the effective concentration of leukocytes and growth factors related to those prepared at high centrifugal forces [46].

In 2020, the effect of mixing bone graft materials with i-PRF producing sticky bone was assessed on cell characteristics of human osteoblasts. As reported by the authors [47], the human osteoblast proliferation, attachment, viability, and expression of differentiation and proliferation markers significantly increased in the i-PRF mixed with bone substitute material (BSM) compared to BSM without I-PRF. when PRF is combined with the biomaterials, the respective substitute’s revitalization power increases and is more suitable and acceptable for the defected tissue space [48]. Sticky bone application in regenerative endodontic surgery in cases of through and through lesions, apico-marginal defects, and non-healed large apical lesions after root canal treatment will modulate the microenvironment in periapical defects that demand guided tissue regeneration (GTR), which combines the use of bone graft material plus a resorbable or non-resorbable membrane, and this may elicit some immunological response. So, using sticky bone after apicoectomy provides us with an autologous growth factor-enriched bone graft matrix that simplifies handling during the surgical operations due to its optimal moldability without disintegration into the surrounding soft tissues. It also allows stabilization of the bone graft in the defect to accelerate tissue healing with the elimination of graft loss and inhibits the ingrowth of soft tissue in the graft, which results in complementing the surgery and increasing the success rate.

The combination of injectable PRP with sticky bone can be an effective treatment for endodontic microsurgical cases to enhance the bone regeneration and allowing rapid healing. A well-designed randomized clinical trial is recommended to comprehend the long-term risks and benefits of using sticky bone in regenerative endodontics.

Ethics None declared.

Conflicts of interest None declared.

Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.