The goal of this clinical trial is to learn if a novel peptide-rich hydrogel works to achieve periodontal regeneration in adults. It will also learn about the safety of the hydrogel. The main questions it aims to answer are:

• Does the novel peptide hydrogel achieve periodontal regeneration to a similar degree as another currently used therapy (hyaluronic acid)?
• What medical problems, if any, do participants have when receiving the novel hydrogel treatment? Researchers will compare the novel peptide hydrogel to another commonly used hydrogel (hyaluronic acid) to see if the peptide hydrogel works to treat periodontal bone defects.

Participants will:

• Receive the novel hydorgel or hyaluronic acid when they undergo periodontal regenerative surgery
• Visit the clinic at regular intervals for 1 year after the surgery for follow ups

The primary objective of this study (PICOS) is to compare, in adult periodontitis patients (P), the efficacy of a P-HA hydrogel (PeriHeal) (I) to that of a commercial HA hydrogel (hyaDENT BG) (C) for the regenerative treatment of intrabony defects based on CAL changes (O) after 6 and 12 months in a RCT (S).

Additional objectives are to assess (a) changes in secondary clinical and radiographic outcomes, (b) patient-reported outcomes (PROs), and (c) molecular outcomes based on proteomic analysis of gingival crevicular fluid (GCF) (see details below).

The null hypothesis (H0) is that there are no statistically significant differences between P-HA and HA hydrogels in terms of CAL after 6 and 12 months.

The primary outcome is CAL change 6 and 12 months after regenerative surgery. Secondary outcomes measured 6 and 12 months after regenerative surgery include changes in: probing pocket depth (PPD), bleeding on probing (BoP), recession (REC), and MBL. Post-operative wound healing and patient-reported symptoms will be assessed 7 and 14 days after surgery. Patients' oral health-related quality of life (OHRQoL) will be assessed at baseline and 6 and 12 months after surgery. GCF collected at 7, 14 and 30 days after surgery will be analysed using mass spectrometry-based proteomics.

Inclusion criteria

• Adults >18 years with periodontitis (Stage III or IV)
• Systemically healthy (ASA I or II)
• Non-smokers or smoking <10 cigarettes/day
• Having undergone steps 1 (risk factor control, oral hygiene improvement including interdental hygiene) and 2 (subgingival instrumentation and biofilm control) of systematic periodontal therapy
• Indication for step 3 periodontal therapy, i.e., sites with residual/persistent pockets (PPD >5 mm and BoP or PPD >6 mm) around single- or multi-rooted teeth with mobility <grade II at re-evaluation 8-12 weeks after non-surgical instrumentation (Step 2). Further site-specific criteria include at least one site with a radiographic infrabony defect (2- or 3-walled) with a >3 mm intrabony component, not associated with an open furcation, indicated for regenerative surgery
• Full-mouth plaque score (FMPS) and full-mouth bleeding score (FMBS) ≤20% before surgery

Exclusion criteria

• Medical conditions contraindicating surgery
• Pregnancy or lactation
• Current use of systemic antibiotics
• Smoking >10 cigarettes/day
• FMPS or FMBS >20%
• Mobility grade II or greater
• Acute oral infections, active endo-perio lesions or active carious lesions on teeth associated with bone defects