Growth and Amelogenin‐Like Factors in Periodontal Wound Healing. A Systematic Review

BACKGROUND: Regeneration of tooth-supporting structures destroyed by periodontitis is a major goal of periodontal therapy. Periodontal tissue engineering utilizing growth and amelogenin-like factors (GAFs) applies advances in materials science and biology to regenerate alveolar bone, periodontal ligament, and cementum. Amelogenin-like factors (e.g., enamel matrix derivative EMD) and growth factors (e.g., platelet-derived growth factor PDGF and bone morphogenetic proteins BMPs, also considered morphogens) have demonstrated pleotrophic effects on the stimulation of several key events required for tissue regeneration including DNA synthesis, chemotaxis, differentiation, and matrix synthesis. RATIONALE: GAFs have been used for the treatment of periodontal disease as shown in preclinical and clinical studies. This systematic review evaluates the evidence to support the utilization of EMD and growth factors (GFs) for periodontal repair and regeneration associated with natural teeth. FOCUSED QUESTION: In patients with periodontal osseous defects, what is the effect of GAFs compared with controls on clinical, radiographic, histologic, adverse, and patient-centered outcomes? SEARCH PROTOCOL: Two investigators searched MEDLINE, pre-MEDLINE, and the Cochrane Oral Health Group trials register for clinical and preclinical studies published in English. Hand searches were performed on the International Journal of Periodontics and Restorative Dentistry, Journal of Clinical Periodontology, Journal of Dental Research, Journal of Periodontology, and Journal of Periodontal Research. Searches were performed for articles published through April 2002. In addition, investigators contacted manufacturers of GAF products for related unpublished data and studies in progress. INCLUSION CRITERIA: Randomized controlled clinical trials (RCTs), cohort studies, case-control studies, case reports, and preclinical (animal) randomized controlled investigations that included a cohort population diagnosed with periodontal disease and presenting data on intrabony/interproximal defects and/or furcation defects were screened. EXCLUSION CRITERIA: In vitro studies or those that did not include quantifiable data with respect to clinical or bone measures were not included. DATA COLLECTION AND ANALYSIS: Meta-analyses were performed for studies that fulfilled the eligibility criteria for the following continuous variables: clinical attachment level (CAL), probing depth (PD), or bone level (radiographic, re-entry, or histologic). Heterogeneity was assessed to determine whether the differences among therapies were due to systematic confounding factors (as noted in study quality assessments). MAIN RESULTS: 1. Eight studies, representing 7 RCTs and 1 quasi-experimental study, representing a total population of 511 subjects were analyzed with respect to EMD. 2. The majority of the remaining papers had a low evidence rating. 3. Most reports were case studies or case series without controls. 4. There were insufficient data to conduct a meta-analysis on the effect of growth factors used in periodontal repair around teeth. REVIEWERS' CONCLUSIONS: 1. There is evidence supporting the use of EMD for periodontal osseous defects to improve CAL and reduce PD, although long-term benefits have not been established. 2. EMD has demonstrated notable consistency among the studies investigated in terms of superiority to controls (in general compared to open flap debridement OFD). 3. EMD appears to be safe for single and multiple administrations in terms of lack of elicitation of antibody responses or other local/systemic inflammatory events. 4. Preclinical and initial clinical data for growth factors appear promising but are insufficient to draw definitive conclusions at this time.