The effect of hyaluronan on bone and soft tissue and immune response in wound healing

J Periodontol. 2001 Sep;72(9):1192-200. doi: 10.1902/jop.2000.72.9.1192.


Background: The aims of this study were to investigate the anti-inflammatory effect and the effect on bone regeneration of hyaluronan in surgical and non-surgical groups.

Methods: In each of 15 individuals, 2 teeth with defects of similar character and magnitude in the upper or lower jaw were chosen. There were at least 2 teeth between the test and the control sites. In the surgical group, a bioabsorbable membrane was used for both test and control sites, and hyaluronan was placed in the intrabony pocket of the test site. In the non-surgical group, the periodontal pockets were scaled and hyaluronan was administered 3 times with an interval of 1 week in the test pockets. Alveolar bone height and bone healing patterns were analyzed using digital intraoral radiographs. Measurements of bone height were performed in the original digital black-and-white radiographs to obtain quantitative data on bone gain or loss. Bone healing patterns were studied with color-coded radiographs, using specially designed software in a personal computer with subsequent combinations of radiographs. Gingival crevicular fluid immunoglobulin (Ig)G, C3, and prostaglandin E2 (PGE2) responses; periodontal probing depth; bleeding on probing; and the presence of plaque were studied to evaluate the anti-inflammatory effect. Data were obtained at baseline before treatment, and at 2 weeks, and 1, 3, 6, and 12 months after treatment.

Results: For the surgical treatments, bone height was increased in the test group treated with hyaluronan (mean value 2.2%, corresponding to an average increase of approximately 0.5 mm) and reduced in the control group (mean value -1.8%, corresponding to an average decrease of approximately - 0.4 mm) (P<0.05) after 12 months. For the non-surgical treatments, bone height was reduced by a mean value of -1.1% (corresponding to an average decrease of approximately -0.25 mm) in the test group treated with hyaluronan and -3.3% (corresponding to an average decrease of approximately -0.75 mm) in the control group after 12 months (N.S.). According to the digital color-coded radiographs, the test sites in the surgical and non-surgical groups showed apposition of bone minerals. Immune responses showed no differences during the 12 months studied for the surgical and non-surgical sites. Mean periodontal probing depths were reduced between 2.5 mm and 4.1 mm in the surgical and non-surgical groups.

Conclusions: The observed difference in bone height between test and control sites in the surgical group after 12 months was less than 1 mm, which was only detectable on radiographs. No statistical difference was found on radiographs in the non-surgical group, where a decrease in bone height was found for both groups after scaling. Probing depth reduction after the surgical treatment, as well as after scaling and root planing, was as expected. Hyaluronan in contact with bone and soft tissues had no influence on the immune system in this study. Further studies are needed to determine the extent to which hyaluronan can lead to clinically significant healing of periodontal lesions.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorbable Implants
  • Adjuvants, Immunologic / pharmacology
  • Adjuvants, Immunologic / therapeutic use*
  • Adult
  • Aged
  • Aggregatibacter actinomycetemcomitans / isolation & purification
  • Alveolar Bone Loss / diagnostic imaging
  • Alveolar Bone Loss / drug therapy*
  • Alveolar Bone Loss / surgery
  • Alveolar Bone Loss / therapy
  • Bone Regeneration / drug effects*
  • Complement C3 / analysis
  • Dental Plaque Index
  • Dental Scaling
  • Dinoprostone / analysis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gingival Crevicular Fluid / chemistry
  • Gingival Crevicular Fluid / immunology
  • Gingival Crevicular Fluid / microbiology
  • Guided Tissue Regeneration, Periodontal / methods
  • Humans
  • Hyaluronic Acid / pharmacology
  • Hyaluronic Acid / therapeutic use*
  • Immunoglobulin G / analysis
  • Male
  • Membranes, Artificial
  • Middle Aged
  • Periodontal Index
  • Periodontal Pocket / drug therapy*
  • Radiography, Dental, Digital
  • Statistics, Nonparametric
  • Wound Healing / drug effects*


  • Adjuvants, Immunologic
  • Complement C3
  • Immunoglobulin G
  • Membranes, Artificial
  • Hyaluronic Acid
  • Dinoprostone