J Periodontal Implant Sci.  2023 Aug;53(4):259-268. 10.5051/jpis.2203000150.

The optimal dosage of hyaluronic acid for bone regeneration in rat calvarial defects

• Li L
• Lee J
• Cho YD
• Kim S
• Seol YJ
• Lee YM
• Koo KT

• KMID: 2557371
• DOI: http://doi.org/10.5051/jpis.2203000150

Abstract

Purpose
Hyaluronic acid (HA) affects angiogenesis and promotes the migration and differentiation of mesenchymal cells, thereby activating the osteogenic ability of osteoblasts. Although studies on the action of HA during bone regeneration are being actively conducted, the optimal dose of HA required for bone regeneration remains unclear. Therefore, the purpose of this study was to elucidate the most effective HA dose for bone formation using a rat critical-size defect model.
Methods
Thirty rats were randomly divided into 5 groups, with 6 rats in each group. An absorbable collagen sponge soaked with HA or saline was used to fill an 8-mm defect, which was then covered with a collagen membrane. Different treatments were performed for each group as follows: (1) saline control, (2) 1 mg/mL HA, (3) 25 mg/mL HA, (4) 50 mg/mL HA, or (5) 75 mg/mL HA. After a healing period of 4 weeks, micro-computed tomography and histological analysis were performed. The obtained values were analyzed using analysis of variance and the Tukey test (P<0.05).
Results
At week 4, the 75 mg/mL HA group had the highest bone volume/total volume ratio, new bone, and bone fill among the 5 groups, and these values were significantly different from those observed in the control group (P<0.01) and 1 mg/mL HA group (P<0.001). More active bone formation was observed in the higher-dose HA groups (25 mg/mL, 50 mg/mL, and 75 mg/mL HA), which included a large amount of woven bone.
Conclusions
The 75 mg/mL HA group showed better bone formation than the other groups (1, 25, and 50 mg/mL HA and control).

Keyword

Animal models; Bone; Bone regeneration; Hyaluronic acid; Rats