This systematic review evaluates injectable hyaluronic acid for interdental papilla reconstruction, suggesting potential benefits over placebo.
Aims Interdental papilla loss produces unaesthetic “black triangles” that impair function and patient satisfaction. While surgical and non-surgical techniques exist, hyaluronic acid (HA) injections have emerged as a minimally invasive option, but their comparative effectiveness and certainty of evidence remain unclear. This systematic review aimed to evaluate the clinical outcomes of injectable HA for interdental papilla reconstruction. Materials and methods MEDLINE/PubMed and EMBASE were searched from inception through May 2025 for peer-reviewed randomized and non-randomized trials, cohort studies, or split-mouth designs in adults aged 18 years or older. Eligible studies compared injectable HA to surgical (e.g., connective tissue grafts) or non-surgical approaches (e.g., platelet-rich fibrin, saline placebo). The risk of bias was assessed using Cochrane RoB 2.0 and the ROBINS-I tool. Where appropriate, meta-analyses were performed, and heterogeneity was evaluated using the I 2 statistic. Results Three trials ( n = 39; 138 papillae) were included. Compared with saline, HA reduced the surface area of black triangles (SABT) (MD: −43.0 mm 2 ), increased papilla height (MD 0.22 mm), and improved patient satisfaction (MD: 17 VAS points). However, comparisons with active regenerative comparators showed no statistically significant differences. Quantitative synthesis was limited by very high heterogeneity ( I 2 up to 97%), small sample sizes, and methodological concerns; all included trials were judged to have some concerns regarding risk of bias. Discussion Hyaluronic acid offers short-term esthetic improvements over placebo, but evidence certainty is low to moderate, and no clear superiority over other regenerative approaches was demonstrated. Substantial heterogeneity and limited methodological robustness limit the confidence in quantitative conclusions. Conclusions Injectable HA may improve interdental papilla esthetics in the short term compared with placebo; however, its clinical advantage over other regenerative materials remains uncertain. Given the high heterogeneity, small sample sizes, and risk of bias, larger, well-designed randomized trials with standardized protocols and longer follow-up are required before firm clinical recommendations can be made. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251051629 , identifier CRD420251051629.
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