Proportion of Adverse Events of Injectable Collagen Biostimulators After Facial Aesthetic Treatment: A Systematic Review Protocol

Background: With the increasing demand for non-surgical facial rejuvenation, injectable collagen biostimulators such as poly-L-lactic acid (PLLA), calcium hydroxyapatite (CaHA), polycaprolactone (PCL), poly-D,L-lactic acid (PDLLA) and powdered polydioxanone (PPDO) have become widely used by facial aesthetic practitioners. These agents stimulate neocollagenesis, providing gradual improvement in skin firmness, elasticity and facial contour with long-lasting results. While manufacturers emphasize the efficacy and favorable safety profile of these products, adverse events such as nodules, edema, inflammatory reactions and, in rare cases, granulomas have been reported. To date, no comprehensive systematic review has evaluated the proportion and nature of adverse effects associated with all major collagen biostimulators in facial aesthetic procedures. This study aims to synthesize current evidence on the proportion of adverse events linked to injectable collagen biostimulators. Methods: The systematic review will include clinical studies involving adults undergoing facial aesthetic procedures with PLLA, PDLLA, CaHA, PCL and PPDO that report adverse events during or after treatment. The search will be conducted in six main databases: CENTRAL, EMBASE, LILACS, PubMed, SCOPUS and Web of Science. No restrictions will be applied regarding language or publication date. The screening process will occur in two phases: first, two independent reviewers will assess titles and abstracts against the eligibility criteria; second, the same reviewers will conduct full-text evaluations. Data will be synthesized narratively, with a meta-analysis of proportions performed if appropriate. Additionally, sample characteristics, treatment protocols, study design and main findings will be reported. The risk of bias will be assessed independently by two reviewers using appropriate tools, based on the study design, with the support of artificial intelligence. PROSPERO registration number: CRD420251062785.