Platelet-Rich Plasma in Orthodontics. Healing and Stability Enhancement: A Review

Definition of PRP

PRP is a small volume of plasma enriched with a high concentration of platelets, key blood components that play a crucial role in the body’s healing process. Upon activation by an agent like thrombin, these platelets granules release their contents, which include a variety of inflammatory and growth factors such as transforming growth factors α and β (TGF-α, TGF-β), platelet-derived GF (PDGF), basic fibroblast GF (BFGF/FGF-2), insulin-like GF (IGF), epidermal GF (EGF), and vascular endothelial GF (VEGF).^[3]

Varieties of platelet-derived concentrates

Ehrenfest et al. (2009) introduced a classification system that identifies four main categories of platelet-derived preparations, distinguished by their cellular makeup and the structure of their fibrin matrix.^[4] As shown in Figure 1^[5], this includes Pure PRP (P-PRP) and Leukocyte- and PRP (L-PRP). Preparations such as platelet-rich fibrin (P-PRF) or leukocyte-poor PRF lack white blood cells and possess a tightly organized fibrin network. These forms exist exclusively as highly active gels and are unsuitable for use as injection or tissue sealants. Leukocyte- and PRF, often labeled as second-generation PRP, incorporates white blood cells within a compact fibrin framework. Due to the biological activity of platelets in tissue regeneration, such formulations offer valuable therapeutic benefits across medical and dental practices.^[6] Autologous platelet-based products include both PRF, a first-generation platelet concentrate, and PRP, which is considered a first-generation concentrate. Each has proven effective in promoting tissue healing and can be applied either as an injectable solution or in fibrin form.^[7]

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Figure 1: Different types of platelets concentrate.

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Rationale for using PRP in healing and regeneration

PRP's clinical application has been simplified by its ease of acquisition and application as an autologous transplant. The source of the blood used to prepare PRP has a significant impact on its safety. When the patient's autologous blood is utilized. The likelihood of adverse reactions is significantly minimized.

Moreover, adhering to sterile procedures prevents the transmission of blood-borne infections. PRP, derived from the body’s natural clotting process, contains concentrated platelets that do not support bacterial proliferation. GFs in PRP function by binding to cell membranes; they lack mutagenic properties and thus do not promote tumor development. Instead, they amplify the body’s inherent healing mechanisms.

Platelets act as key storage sites for growth factors, secreting high levels of bioactive proteins that attract cells from adjacent host tissues.^[4] These proteins encourage cellular growth and morphogenesis, aiding in the repair of bone and soft tissue, angiogenesis, and improved wound closure. In periodontal healing, they activate fibroblasts, osteoblasts, endothelial cells, and epithelial cells.^[8]

Trapped platelets discharge various cytokines, chemokines, growth factors, and other signaling molecules that enhance angiogenesis, tissue repair, and regeneration. Over the last 30 years, platelet concentrates have emerged as a valuable regenerative tool, used either alone or combined with graft materials. Given that many patients require both orthodontic treatment and tissue regeneration, this approach represents a cutting-edge innovation in orthodontics.^[9]

PRP preparation technique

Liou EJ described the preparation of autologous PRP under aseptic conditions. A 30 mL blood sample was drawn from the medial cubital vein, with 29 mL placed in a glass tube containing 3.2% sodium citrate, an anticoagulant that prevents clot formation. The remaining 1 mL was used for platelet count analysis. The citrated blood was centrifuged for 12 min at 1,000 rpm at 12 min at ambient temperature, separating into three distinct layers: platelet-poor plasma (PPP) at the top, a buffy coat filled with platelets in the middle, and red blood cells at the bottom [Figure 2].^[10] The buffy coat and PPP were gathered and centrifuged once more at 3,000 rpm for eight minutes after the RBCs were disposed of. After the majority of the PPP was eliminated, 4 mL remained, which was combined with the buffy coat to create PRP.^[11]

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Figure 2. Variations in platelet concentrate preparation (PCs). (a) Platelet-rich plasma (PRP) is obtained by a two-step centrifugation process. (b) Plasma rich in growth factors (PRGF) is generated from centrifuged blood. (c) Platelet-rich fibrin (PRF) forms a fibrin clot in the tube center.

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PRP and plasma rich in GF (PRGF) are two types of concentrates from the first generation. Because anticoagulants prevent clotting during blood collection, fibrin polymerization happens quickly, making the fibrin matrix less durable.^[12] Following activation with calcium chloride and bovine thrombin, these concentrates are applied either as a gel or in liquid form. Due to inconsistencies in preparation and outcomes with PRP and PRGF, Choukroun et al. (2001) developed a second-generation platelet concentrate called PRF.^[13]

Understanding how PRP works

The release of growth factors and cytokines from platelets' alpha-granules is the source of PRP's biological action. The coagulation process involves the release of these signaling molecules.^[14]

After an initial rapid release of PRP-derived GFs, platelets continue producing and secreting additional GFs throughout their 5–7-day lifespan. Subsequently, inflammatory macrophages further promote healing by secreting similar growth factors. Thus, the speed of wound healing depends on the platelet concentration in the blood clot adhering to surgical flaps, grafts, or wounds.

For optimal PRP efficacy, autologous sources must be used while avoiding pre-synthesized homologous preparations. This approach guarantees Human Leukocyte Antigen compatibility at the treatment site.^[15] PRP's bone-healing properties are partly attributed to its anti-inflammatory effects, though its mechanism is complex. Beyond platelets, PRP contains leukocytes, cytokines (including interleukins (ILs) and tumor necrosis factors (TNFs)), fibrin proteins, proteases, antiproteases, and fibroblasts, all contributing to its regenerative potential.

Clinical applications

PRP is a novel approach in dental treatment. As an adjuvant in mandibular reconstructive surgeries, it improved the radiographic maturation rate of the graft; its initial description in dental literature dates back to 1998 by Robert Marx.^[16]

The interplay of the growth factors released by PRP enhances the healing procedure of the bone, even though it does not include any Bone Morphogenic Protein. This is because adult mesenchymal stem cells are encouraged to multiply. Through improved Osteoconduction and enhanced bone production, they also speed up the healing rate of grafts.^[17] PRP comprises a concentration of platelets and seven critical growth factors that are released by platelets to initiate the wound healing process.^[16]

Three cell adhesion proteins, vitronectin, fibrin, and fibronectin, are present in the plasma fluid around the platelet concentration. Osteoconduction, bone matrix creation, connective tissue linkage, and epithelial migration are all essential steps in the healing process that rely on these proteins.^[18] Unlike in traditional medicine, PRP for dental operations is typically made as a gelled admix of PRP with CaCl₂ and thrombin, with an emphasis on wound healing and reconstruction. By acting like a bolus dose, this mixture causes the PRP to undergo a booster effect, resulting in the rapid release of growth factors. Nevertheless, for orthodontic treatment to be effective and continue as long as possible, it is best to release these growth factors gradually over an extended period of time.

El-Sharkawy et al.^[19] states that PRP has anti-inflammatory effects because it directly influences monocytic secretory activity. It also helps produce regulated upon activation, normal T-cell expressed and secreted (RANTES), which are usually generated and secreted by T cells and are regulated during activation. Furthermore, it inhibits monocytes from releasing monocyte chemoattractant protein-1 (MCP-1), or monocyte chemotactic protein, while increasing levels of Lipoxin A4 (LXA4), indicating that PRP promotes healing by modulating the local inflammatory response.^[20]

Mechanism of PRP in OTM

OTM is defined as an inflammatory process in which ILs and TNFs contribute to the acceleration of this movement. The concurrent use of PRP therapy may influence healing and regeneration processes,^[21,22] as its constituents exert multifactorial effects on bone tissue through multiple, overlapping interactions. In this context, OTM can also be understood as a biologically regulated process that depends on continuous bone remodeling, where bone resorption occurs on the pressure side, and new bone formation takes place on the tension side. PRP may enhance this process by providing a concentrated source of biologically active growth factors that influence cellular activity within the periodontal ligament and surrounding bone.

PRP contains several key growth factors; these molecules play an important role in regulating tissue repair and regeneration. For example, PDGF promotes the proliferation and migration of osteoblasts and periodontal ligament fibroblasts, which supports faster tissue turnover. TGF-β contributes to extracellular matrix production and stimulates osteoblastic differentiation, facilitating bone formation on the tension side. In addition, VEGF enhances angiogenesis, improving local blood supply and ensuring adequate delivery of nutrients and cells required for active remodeling.^[23]

PRP may also influence bone resorption by affecting osteoclast activity. This effect is thought to occur through modulation of the receptor activator of nuclear factor kappa-B (RANK)/(Receptor activator of nuclear factor kappa-B ligand (RANKL)/Osteoprotegerin (OPG) signaling pathway, which is central to osteoclast differentiation. Increased RANKL expression can stimulate osteoclast formation, thereby enhancing bone resorption on the pressure side and potentially accelerating tooth movement.^[24]

Beyond its effects on bone remodeling, PRP may help modulate the inflammatory response by interacting with cytokines such as ILs and TNFs, while also promoting the healing of periodontal tissues. This could be beneficial in minimizing unwanted side effects, such as root resorption, while maintaining tissue integrity during treatment.

Overall, PRP appears to create a biologically favorable environment that supports both bone resorption and formation. Enhancing these processes may contribute to faster OTM while also improving healing and post-treatment stability.

PRP's clinical uses in OTM

PRP's ability to quicken OTM has been shown in numerous studies, which could shorten the course of treatment. According to El-Timamy et al.,^[25] PRP injections effectively enhanced the rates of tooth movement. Research involving animals conducted by Rashid et al.^[26] and Güleç et al.^[20]

Showed similar encouraging outcomes, with platelet concentrates being more helpful when given during the early canine distalization after premolar extraction.^[27]Comparative research by Navya et al.^[28] found PRP superior to Vitamin D3 in accelerating tooth movement while causing less root resorption.

Clinical studies have quantified PRP's effects, showing it enhances tooth movement by 1.24 times compared to controls.^[29,30]PRP administration was associated with decreased OPG and increased soluble RANK ligand (sRANKL) levels in gingival crevicular fluid.^[29] Fatima et al.^[31] reported that both PRP and PRF reduced alignment time by 52%. While Yao et al.^[32]confirmed PRP's effectiveness in early treatment phases, they noted the need for further research on long-term outcomes and the benefits of repeated applications.

PRP has shown particular promise in complex cases, including impacted tooth retraction and molar protraction/retraction.^[33] Combined approaches, such as PRP with Piezocision, demonstrated space closure rates comparable to those with Piezocision alone.^[34] However, Bulandi et al.^[35] ranked PRP as less effective than other acceleration methods, though noting its advantage as a minimally invasive option.

Contradictory findings exist, with some studies reporting no significant acceleration of OTM with PRP. Arora et al.^[36]found no benefit using 4× concentrated PRP, while Khatib & Baba^[37] and Al-Bozaie et al.^[38] observed no effect on molar protraction or anterior retraction. These discrepancies may stem from variations in PRP preparation methods, platelet concentrations,^[39] and administration protocols.^[40]

PRP for enhanced healing and long-term stability

Post-treatment tooth relapses remain a significant clinical challenge in orthodontics. While mechanical retainers are currently the standard preventive measure, recent research has explored biological alternatives involving pharmacological agents that either inhibit osteoclast activity^[41] or enhance osteoblast function.^[42] Because of its high concentration of bone-healing growth factors, PRP has become a promising biological solution among these methods.^[43] The therapeutic potential of PRP stems from its diverse growth factor content. PDGF increases the expression of Osteopontin, promotes the synthesis of collagen, and starts the differentiation of osteoblasts from progenitor cells,^[44] all of which contribute to bone and periodontal tissue regeneration.^[45] By promoting neovascularization, bone turnover, osteoblast migration, and mineralization, the localized application of angiogenic agents, such as VEGF, has been shown to improve bone regeneration in a variety of animal models.^[46,47] TGF-β acts as an Osteoinductive which encourage the development of osteoblasts from mesenchymal cells.^[48]

In their summary of the effect of autologous PRP on bone remineralization, Abdel-Haffiez et al. found that, in comparison to the control group, periodontal injection of PRP reduced relapse by 20% after one week and by 55% after four weeks after the removal of orthodontic forces.^[49]However, PRP decreased the rate of maxillary molar distalization rather than increasing it, as demonstrated by Fargal et al.^[50] This implies that PRP might improve tooth stability and bone growth. There hasn't been any clinical study using PRP as a biological retainer. By encouraging osteogenesis and suppressing Osteoclastogenesis, the localized infusion of PRP into periodontal tissues after OTM may lessen orthodontic tooth relapse, which calls for further study.