Erythropoietin Gel as an Adjunct to Xenograft in the Surgical Management of Intrabony Periodontal Defects
Condition: Periodontal Bone Loss
MeSH terms: Alveolar Bone Loss
Study type: Interventional
Phase: Early Phase 1

Summary: 
      The aim of the study is to evaluate the use of erythropoietin gel as an adjunct to xenograft
      in the surgical management of intrabony periodontal defects.
    

Detailed description: 
      In the periodontal disease there is an interaction of the biofilm with the immune response of
      the host which results in an imbalance between bacterial virulence and the host defense
      causing changes in bone and connective tissue homeostasis .

      Armitage's 1999 classified periodontitis to either chronic or aggressive . In 2017, the
      American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP)
      classified the periodontal disease using a new staging and grading system. Staging is
      determining the severity of the disease and the complexity of treatment of the disease, while
      grading gives additional data about the biological consideration of the disease, such as
      analyzing the history for the rate of progression and predicting the risk for further
      progression.

      Periodontitis is classified to four stages ranging from Stage I: Initial periodontitis the
      clinical attachment level (CAL=1-2mm), Stage II: Moderate periodontitis (CAL= 3-4 mm), Stage
      III: Severe periodontitis and increased potential for tooth loss (<4), and (CAL ≥5mm), Stage
      IV: Severe periodontitis with increased risk for tooth loss (≥5) and (CAL≥5mm). Grading is
      determined by the risk factors like smoking, diabetes, and outcomes of scaling and root
      debridement. Grade A: Low rate of progression (no CAL loss over 5 years), Grade B: Moderate
      rate of progression (CAL loss<2mm over 5years), and Grade C: High rate of progression (CAL
      loss ≥2 mm over 5 years) .

      The periodontal tissue break down happens because of both the direct effect of the microbial
      invasion and the indirect effect of the host immune response, this happens when the bacterial
      invasion results in bacterial products that cross the junctional epithelium which stimulates
      the host immune response resulting in tissue breakdown .

      Pattern of bone destruction in periodontitis can be horizontal or vertical .Horizontal bone
      loss appears as an even bone destruction leading to a uniform decrease in the bone height in
      relation to the teeth. Vertical bone loss results in formation of a triangular area of
      missing bone, known as triangulation. Vertical bone loss could result in angular defects and
      intrabony pocket formation which become very challenging in treatment.

      Treatment of periodontitis is targeting mainly the reduction of bacteria present in the
      subgingival biofilm. The non-surgical periodontal therapy is done by supragingival scaling
      and subgingival debridement of the roots using hand or power-driven scalers to eliminate all
      the deposits such as calculus, plaque and endotoxins

      Mechanical instrumentation alone has some limitations especially in areas with deep pocket,
      areas with bony defects and also ineffective against some bacteria, such as Aggregatibacter
      actinomycetemcomitans(AA) .Therefore the use of chemotherapeutic agents as adjuncts to
      mechanical periodontal therapy has been strongly recommended .

      Systemic and local antimicrobials are used as adjuncts to the non-surgical periodontal
      therapy, especially in patients with deep periodontal pockets and aggressive or refractory
      periodontitis .Also chemotherapeutic agents that target the host immune response result in
      better clinical effect when used as an adjunct to mechanical periodontal therapy .

      According to the recent guidelines of the European Federation of Periodontology (EFP) when
      the pocket depth is 6mm or more after the non-surgical periodontal therapy with or without
      adjunctive chemotherapeutic agent, access flap surgery is recommended. Also they recommended
      treating the residual pockets associated with intrabony defect by periodontal regenerative
      surgery .

      There is a positive correlation between the number of walls present and CAL gain,
      three-walled intrabony defects have 269% higher chance of >3mm CAL gain in comparison to
      one-walled defects .

      Siciliano et al stated that there is a reduced CAL gain in the non-contained defects .

      Different treatment approaches are used for periodontal regeneration such as barrier
      membranes, autografts, allografts, xenografts, biological agents (i.e. enamel matrix
      derivatives (EMD)), and growth factors .

      The recent guidelines of the (EFP) recommended treatment of intrabony defects by periodontal
      regenerative surgery .

      However, there is limited potential of bone grafts to enhance periodontal regeneration and
      basically they should be used to ensure space provision since the success of the periodontal
      regeneration surgery is limited by the available space under the mucoperiosteal flap .

      In addition, there are some drawbacks with the use of membrane such as membrane exposure,
      wound infection and bacterial colonization. So, various biomaterials are tested to be used in
      combination with bone grafts .

      Erythropoietin (EPO) is a hematopoietic hormone and has multiple biological effects. In 2014,
      Hamed et al showed the role of EPO in epithelial regeneration, healing process and its
      anti-inflammatory properties. In addition, it was concluded that the topical application of
      the EPO is a very safe route of administration with no systemic side effects. Also Wang et al
      in 2017 stated that the EPO upregulated the osteogenesis of the human periodontal mesenchymal
      stem cells by stimulating the expression of osteogenic genes

      According to Zheng et al in 2019 the expression of Runt-related transcription factor 2
      (Runx2), osteocalcin (OCN) and Osterix (which are transcription proteins that are responsible
      for osteoblastic differentiation) was verified in the periodontal ligament stem cells treated
      with EPO which confirms the relationship between EPO and osteogenic differentiation of
      periodontal ligament stem cells .

      In a recent study by Aslroosta et al in 2021, he proved that the local delivery of EPO gel in
      non-surgical periodontal therapy can improve clinical inflammation and enhance the CAL gain
      .However, no clinical trials have been conducted to study the effect of EPO gel in the
      intrabony defects. Therefore the present study will be carried out to evaluate the clinical
      effect of using the EPO gel as an adjunct to xenograft in the surgical management of
      intrabony periodontal defects.
    

Intervention name(s): particulate xenograft + erythropoietin gel.; particulate xenograft
Intervention type(s): Drug; Combination Product
Intervention description(s): Surgical sites will be anaesthetized using local anaesthesia.
Intrasulcular incision will be done in the periodontal pocket as close as possible to the tooth surface with the deepest point being the alveolar crest.
The incisions will be extended to the mesial papilla of the tooth before the defect and the distal papilla of the tooth after the defect.
Both buccal and lingual/palatal mucoperiosteal flaps will be raised using blunt dissection.
Mechanical debridement of the infected tissue from the intrabony defect and root debridement will be done using Gracey curettes.
In Group A (test group):
Particulate xenograft will be mixed with EPO gel and applied to fill the whole defect.; All surgeries will be performed by the same operator as follows:
Surgical sites will be anaesthetized using local anaesthesia.
Intrasulcular incision will be done in the periodontal pocket as close as possible to the tooth surface with the deepest point being the alveolar crest.
The incisions will be extended to the mesial papilla of the tooth before the defect and the distal papilla of the tooth after the defect.
Both buccal and lingual/palatal mucoperiosteal flaps will be raised using blunt dissection.
Mechanical debridement of the infected tissue from the intrabony defect and root debridement will be done using Gracey curettes.
In Group B (control group):
Particulate xenograft will be applied to fill the whole defect.
Other intervention name(s): The mix of xenograft and EPO gel; The xenograft alone
Intervention MeSH terms: Epoetin Alfa
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment