The decrease in fibroblast collagen is a primary contributor to skin aging. Lactate can participate in collagen synthesis through lysine lactylation by regulating gene transcription. However, the precise mechanism by which lactate influences collagen synthesis requires further investigation. This study demonstrates that the depletion of macrophages mitigates the stimulating effect of lactate on collagen synthesis in fibroblasts. Through joint CUT&Tag and RNA‐sequencing analyses, a feedback loop between H4K12 lactylation (H4K12la) and histone deacetylase 3 (HDAC3) in macrophages that drives lactate‐induced collagen synthesis are identified. Macrophages can uptake extracellular lactate via monocarboxylate transporter‐1 (MCT1), leading to an up‐regulation of H4K12la levels through a KAT5‐KAT8‐dependent mechanism in response to Poly‐L‐Lactic Acid (PLLA) stimulation, a source of low concentration and persistent lactate, thereby promoting collagen synthesis in fibroblasts. Furthermore, H4K12la is enriched at the promoters of TGF‐β1 and TGF‐β3, enhancing their transcription. Hyperlactylation of H4K12la inhibits the expression of the eraser HDAC3, while the activation of HDAC3 reduces H4K12la in macrophages and suppresses collagen synthesis in fibroblasts. In conclusion, this study illustrates that macrophages play a critical role in lactate‐induced collagen synthesis in the skin, and targeting the lactate‐H4K12la‐HDAC3‐TGF‐β axis may represent a novel approach for enhancing collagen production to combat skin aging.

Introduction: Biofilm formation is a major cause of delayed-graft complications. Similarly to implants, dermal fillers carry the risk of biofilm formation, which can lead to the development of nodules, chronic inflammatory reactions, abscesses and other complications. In this study, we investigated the late or delayed complications associated with biofilm formation on dermal fillers.Methods: In this retrospective analysis, we analyzed all cases of complications caused by filler injections at a single center between January 2017 and December 2022, the majority of which comprised nodule formation and chronic persistent inflammatory reactions. The risk of biofilm formation with fillers was summarized and analyzed based on the results of bacterial culture and pathological examination.Results: Sixty-one patients were enrolled, including 42 cases of nodule formation, 15 of chronic inflammatory reactions, and 4 of active infection. Bacterial culture of the tissue samples obtained from seven patients after surgical treatment were positive, and comprised four cases of Staphylococcus aureus, one case of Staphylococcus epidermidis, one case of Staphylococcus saprophyticus and one case of Mycobacterium abscessus. The corresponding histopathological results indicated extensive mononuclear lymphocyte infiltration, with a giant cell reaction in the fibrous connective tissue.Conclusion: The results of this study suggest that biofilm formation is a significant risk factor for late and delayed complications following filler injection, and is caused by the contamination of resident bacteria and recessive infection at the injection site.

Background: Strengthening weakened ligament tissues with injectable fillers to improve their supportive effect may achieve the aesthetic goal of face lifting. Objectives: The aim of the study was to design an injectable technique for enhancing the true facial ligaments and dissect the ligaments to provide anatomical guidance for effective injection. Methods: Six true facial ligaments were chosen as target anatomical sites for injection. Specimens were dissected, and 3-dimensional (3D) images were reconstructed to confirm the exact location of each injection site and to confirm that the proposed injection routes will not cause dangerous vascular damage. A total of 5 patients received the injections; 3D images were taken before and after the injections for comparison and clinical outcome assessments. Results: The injection technique was designed to target 6 true facial ligaments, as follows. Site 1 targeted the temporal ligamentous adhesion region to lift the lateral ends of the eyebrows. Site 2 targeted the region of the lateral orbital thickening to lift the lateral canthus. Site 3 and site 4 targeted the zygomatic retaining ligaments and zygomatic cutaneous ligaments, respectively, to augment the soft tissues of the midface. Site 5 targeted the region of the maxillary ligament to lessen the nasolabial folds, and site 6 targeted the mandibular ligament to reduce the marionette line. Conclusions: This site-specific injection technique targeting the true ligaments may lead to increased efficiency and accuracy of face rejuvenation and exert a lifting effect. Level of Evidence: 4: