Erythropoietin Gel as an Adjunct to Xenograft in the Surgical Management of Intrabony Periodontal Defects

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.

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.

Eligibility Criteria:
Inclusion Criteria:

1. Both genders within age range of 20-50 years.
2. Patients diagnosed with periodontitis (Stage III).
3. Test site criteria: probing pocket depth ≥6mm and CAL ≥3mm. All these criteria will be determined after phase I conventional periodontal therapy.
4. Patients with three-wall intrabony defect.
5. Systemically free patients as evidenced by Burket's oral health history questionnaire .
6. Ability to attend the treatment sessions and comply with its procedures, the recall visits and oral hygiene protocol.

   * Exclusion Criteria:

     1. Smokers.
     2. Pregnant or lactating females.
     3. Patients under any medication that affect periodontal healing.
     4. Vulnerable individuals