ABSTRACT Introduction Poly‐ l ‐lactic acid (PLLA) and micro‐focused ultrasound (MFU) are widely used for skin rejuvenation, each promoting collagen remodeling through distinct mechanisms. While combined use is common in practice, the optimal treatment sequence and safety profile remain unclear. This study aimed to evaluate the synergistic effects and ideal sequencing of PLLA and MFU in a preclinical model to guide clinical protocols. Methods Three Bama miniature pigs were subjected to six treatment conditions on demarcated abdominal skin zones: (a) PLLA alone, (b) MFU alone, (c) MFU immediately before PLLA, (d) MFU 1 month before PLLA, (e) MFU 1 month after PLLA, and (f) untreated control. Löviselle PLLA was injected subcutaneously, while MFU was administered using the MFUS Pro system. Skin biopsies were collected at day 180. Histological (Masson's trichrome, Sirius Red, Verhoeff–Van Gieson, H&E), SEM, and quantitative image analyses were performed to assess dermal thickness, collagen subtype distribution, elastin regeneration, fat septa organization, and PLLA microsphere stability. Results PLLA alone increased dermal thickness by 23.7% and raised the type III/I collagen ratio to 0.79 ± 0.06 ( p 0.05). Conclusion Sequential application of MFU immediately before PLLA enhances dermal remodeling more effectively than either treatment alone, without compromising PLLA microsphere stability. These findings support the clinical potential and safety of this combinatory approach, offering evidence‐based guidance for optimizing skin rejuvenation protocols.
Jin et al. (Thu,) studied this question.