Reconstructive Peri-Implantitis Therapy by Using Bovine Bone Substitute with or without Hyaluronic Acid: A Randomized Clinical Controlled Pilot Study

Rakaševic, D.; Šćepanovic, M.; Mijailovic, I.; Mišic, T.; Janjic, B.; Soldatovic, I.; Markovic, A. J. Funct. Biomater. 2023, 14, 149.

The aim of the study was to assess the efficiency of cerabone® plus in peri-implantitis reconstructive surgery with focus on the role of hyaluronic acid.



Patients with at least one implant (bone- or tissue- level) with peri-implantitis defined as radiographic bone loss greater 2 mm, with bleeding on probing (BOP) at least on one side around the implant and a peri-implant probing depth (PPD) greater 5 mm were included.

Peri-implant bone defects were randomly treated either with bovine bone graft with hyaluronic acid (cerabone® plus; test group) or bovine bone graft without hyaluronic acid (cerabone®; control group). Grafted sites were covered with a porcine acellular dermal collagen matrix (mucoderm®).

PPD, clinical attachment level (CAL), BOP, implant stability (ISQ), and radiographic changes in vertical and horizontal marginal bone levels were assessed at 6 months post-operative. Keratinized mucosa width and mucosal thickness were measured to determine soft tissue maturation. Patient discomfort was evaluated using visual analogue scale (VAS) during surgical intervention and within 4 weeks post-surgery.





Implant-related outcomes

  • 19 peri-implantitis sites (13 patients) diagnosed at 6.03 ± 1.61 years post implant loading were treated
  • All implants were successfully maintained during the whole follow-up period
  • Greater ISQ values in the test group at 3- and 6-months post-operative (p = 0.009 and 0.032, respectively)

Healing outcomes

  • Post-operative VAS score at 4 weeks was recorded as zero in both groups
  • Significant BOP reduction in both groups 6 months post-operative
  • Complete reduction in BOP (modified bleeding index: 0) in the test group

Results on soft tissue regeneration

  • Higher gain of keratinized mucosa width (KMW) and mucosal thickness (MT) in the test group
  • Mean KMW gain at 6 months post-operative: 0.9 ± 1.9 mm (test), 0.42 ± 0.96 mm (control)
  • Mean MT gain at 6 months post-operative: 0.9 ± 0.47 mm (test), 0.6 ± 0.54 mm (control)

Results on hard tissue regeneration

  • Treatment success (no BOP, PPD < 5 mm, and no further bone loss) was achieved in 75% of patients and 83% of implants in both groups (Fig. 1)
  • Significant marginal bone gain (Δ BG) in both groups 6 months post-operative (p < 0.05)
  • Greater vertical marginal Δ BG at mesial, distal, and oral sites in the test group (p < 0.05) (Fig. 2)

Fig. 1. Peri-implant probing depth (PPD) at baseline and 6 months post-operative. *statistically significant (p < 0.05)

Fig. 2. Vertical marginal bone gain around the implants at 6 months post-operative. *statistically significant (p < 0.05)



The proposed surgical approach demonstrates successful peri-implantitis reconstruction for both groups.

cerabone® plus shows improved outcomes in terms of implant stability, peri-implant bleeding, and marginal bone gain compared to the group without hyaluronic acid.

The adjunctive use of mucoderm® contributes to stable marginal soft tissues with an increase in both keratinized tissue and gingival thickness.