The Safety Profile of a Portfolio of Hyaluronic Acid-Based Soft Tissue Fillers Manufactured Using MACRO Technology: A Systematic Review of Clinical Evidence

Hyaluronic acid (HA)-based fillers are widely used in aesthetic dermatology for their biocompatibility, reversibility, and safety; however, adverse events (AEs) may occur. This review evaluated the safety profile, focusing on short- and long-term AEs, of HA fillers manufactured with MACRO (MAtrix CROsslinking) Core Technology, encompassing both current saypha and former Princess products. A systematic PubMed search identified prospective clinical trials assessing safety outcomes following facial aesthetic use of these fillers. Eleven studies including 947 patients met the inclusion criteria. The most common short-term AEs were transient swelling, injection site pain, and bruising, which were predominantly mild to moderate and resolved within two weeks. Severe or serious treatment-related events were rare, with only one reported across all studies. Long-term AEs, such as delayed-onset nodules or inflammatory reactions, were infrequent and mild, with no granulomas, hypersensitivity responses, or vascular complications observed. Safety outcomes were consistent across formulations and between the legacy Princess and current saypha products. Overall, the saypha HA filler portfolio demonstrates a predictable and strong safety profile within the expected range reported in the broader literature, noting the limitations of cross-study comparisons. Most AEs were related to injection trauma rather than the filler itself, supporting its continued use in clinical aesthetic practice.