Use of adjuncts in periodontal treatment for patients with diabetes

Background + Aims

• Diabetes worsens periodontitis and slows wound healing, partly through hyperglycaemia, advanced glycation end products (AGEs – sugar-modified proteins that stiffen tissues and impair repair) and impaired blood-vessel function.
• FGF-2 stimulates proliferation of periodontal ligament and mesenchymal cells and promotes angiogenesis and has shown regenerative benefit in non-diabetic periodontal models and clinical trials. Its effect under diabetic conditions was unknown.
• This study aimed to:
  • Evaluate whether topical FGF-2 improves healing of surgically created periodontal defects in rats with early streptozotocin-induced diabetes.

Materials + Methods

• 50 male Wistar rats randomised to diabetes (streptozotocin 40 mg/kg intramuscular; confirmed by glucose > 300 mg/dL) or non-diabetes (saline). n = 25 per group.

• 1 week after induction, standardised critical-size bone defects (2 × 2 × 1.7 mm) were created bilaterally at the maxillary first molars, with periodontal ligament, cementum and superficial dentin removed.

• Split-mouth design: one defect received 0.3% recombinant FGF-2 (30 μg/site) in 3% hydroxypropyl cellulose (HPC) carrier. The contralateral defect received HPC alone.

• Healing assessed at 2 and 4 weeks by microcomputed tomography (micro-CT — 3D X-ray imaging), histology (H&E, Azan–Mallory) and immunohistochemistry for:

  • PCNA (proliferating cell nuclear antigen – a marker of dividing cells)

  • VEGF (vascular endothelial growth factor – a signal for new blood-vessel formation)

  • α-SMA (α-smooth muscle actin – a marker of blood-vessel wall maturity/pericytes)

• Statistics: ANOVA with Tukey post-test; significance at p < 0.05.

Results

• Bone healing (micro-CT)
  • Diabetes cut new bone volume by ~70% at 2 weeks, with fewer, thinner trabeculae and wider gaps.
  • FGF-2 significantly increased bone volume and trabecular thickness in both groups at 2 and 4 weeks, but did not improve trabecular number or spacing in diabetic rats.
• Histology:
  • Diabetic defects showed marked epithelial downgrowth along the root. FGF-2 shortened this by more than 30% and encouraged periodontal ligament–like collagen fibres oriented obliquely to the root.
  • New cementum was almost absent in diabetic rats even with FGF-2; ankylosis (root–bone fusion) occurred only in diabetes and was less frequent with FGF-2 (1/21 vs 3/20 sites).
• Cellular and vascular changes
  • Dividing (PCNA-positive) cells were fewer in diabetes but significantly increased by FGF-2 in both groups.
  • VEGF was already elevated in diabetic tissue. FGF-2 raised it in non-diabetic rats only, suggesting it helps normalise rather than amplify the diabetic vascular response.
  • α-SMA-positive vessels rose significantly with FGF-2 in diabetic rats, indicating better maturation of new capillaries.

Limitations

• Animal model with surgically created defects and no bacterial plaque involvement, unlike human periodontitis.
• Only male rats were used and there was a short observation period (2 and 4 weeks).
• Streptozotocin induces a type 1–like acute diabetes. Findings may not translate directly to human type 2 diabetes.
• A single application at one FGF-2 concentration was tested. Combinations of growth factors or different carriers were not explored.
• New cementum formation was minimal, so periodontal regeneration was incomplete.
• Findings are hypothesis-generating for human treatment and require validation in type 2 diabetic models with longer follow-up.

Conclusion

• A single topical application of FGF-2 can partly overcome the impaired periodontal healing seen in diabetes by boosting cell proliferation, curbing epithelial downgrowth and helping new blood vessels mature – leading to more and thicker new bone. However, it does not restore cementum, meaning it cannot yet deliver true periodontal regeneration in a diabetic setting.
• Future work should test combinations of growth factors, alternative carriers or repeat dosing, together with better glycaemic control, before FGF-2 can be recommended as a stand-alone regenerative therapy for periodontal defects in patients with diabetes.