Aesthetic medicine has progressed from the early 2000s fascination with bio-stimulation to the current dominance of hyaluronic acid (HA) fillers, prized for immediate, predictable, and reversible volumizing effects. Recently, demand for more natural results, stronger emphasis on skin quality, and increased post-pandemic self-scrutiny have renewed interest in regenerative strategies, sometimes called the “second wave of bio-stimulation.” This trend highlights the need for clearer terminology and a cautious, evidence-based reading of proposed biological mechanisms. This narrative review proposes a framework in which bio-regeneration denotes a hypothesized, controlled induction of physiological processes, fibroblast activation, collagen and elastin synthesis, extracellular matrix remodeling, and immune modulation, potentially producing sustained improvements in dermal structure and function beyond simple filling. Among emerging technologies, polyethylene glycol diglycidyl ether (PEGDE) cross-linking is reported to create a stable, flexible HA scaffold with homogeneous tissue integration, favorable rheology, thermal stability, and a reduced inflammatory profile, supporting safer multimodal use with energy-based devices. The framework is illustrated with PEGDE-crosslinked HA combined with low-concentration calcium hydroxyapatite (CaHA), exemplified by a PEGDE-HA filler containing CaHA microspheres plus glycine and L-proline. These formulations aim to deliver immediate correction via HA and delayed stimulatory effects possibly driven by gradual CaHA exposure and macrophage-associated signaling. Available clinical, imaging, and histological observations, including prospective ultrasound and biopsy assessments, suggest progressive dermal thickening and predominant type I collagen expression, without pathological inflammation or granuloma formation. Although evidence remains preliminary and largely non-comparative, findings are compatible with controlled remodeling and resolving inflammation; however, the underlying mechanism and any ‘regenerative’ versus ‘reparative’ classification require controlled comparative studies.

Introduction: Both micro-focused ultrasound (MFU) and monopolar radiofrequency (MRF) interventions are relatively safe and well tolerated as a non-invasive approach to achieve rejuvenating effects, with patients reporting limited adverse effects. However, MRF uses an electrical current which can induce heating in metal, potentially causing burns or thermal injury in the skin or tissue around the implant, whereas MFU delivers focused high-energy ultrasound, which does not induce electrical currents in metal. Case Presentation: This report describes the case of a 28-year-old Thai male, who received titanium implants in the mandible bone, the mandible chin, the maxillary bone and the zygoma bone, seven years before. Because of his wish for a more sculpted and lifted facial appearance, the patient was treated with Ulthera Legacy in 2021 and with Ulthera Prime in 2024. With Ulthera Prime, visualization has significantly improved, which decreased the need to skip areas, leading to improved, more consistent results. Conclusion: This case study suggests that Ulthera Prime could be an option for skin firming and lifting effects for people with facial implants. Further research will be needed to corroborate this finding in a larger population.

Age-related deterioration of the dermal extracellular matrix is driven primarily by fibroblast dysfunction, leading to loss of collagen integrity, elasticity, and structural support. In aesthetic dermatology, injectable and biostimulatory interventions increasingly target qualitative dermal remodelling, with collagen reorganisation widely adopted as a histological endpoint. Picrosirius red (PSR) staining under polarised light remains the most frequently used method for visualising collagen architecture; however, its birefringence colour patterns are often misinterpreted as proxies for collagen subtype shifts, particularly between types I and III. This conceptual review examines the methodological basis of such interpretations. We summarise the biological roles of major dermal collagens and compare current histochemical, immunohistochemical, ultrastructural and molecular methods for collagen assessment. We propose an interpretative framework that separates architectural collagen remodelling from molecular collagen synthesis and addresses the temporal dissociation between early fibre reorganisation and later subtype-specific expression as a plausible explanation for between-study discrepancies. Practical guidance is provided to support responsible interpretation and reporting of PSR-based collagen analyses. PSR is best regarded as a complementary tool for assessing collagen architecture rather than a definitive method for collagen subtype identification.

Background: Micro‐focused ultrasound (MFU) can be used to achieve lifting of the brow, lifting of lax submental and neck areas, improving lines and wrinkles on the décolleté, through delivery of ultrasound on tiny points at different levels of the skin. This induces a wound repair reaction, which can achieve the tension and pulling effect of deep dermis and fascia. Aims: The objective of this study was to compare patient‐reported outcomes, including pain, erythema, and edema, following treatment with Ultherapy Prime and Ultherapy Legacy. Methods: A posttreatment questionnaire was used to collect data on pain, erythema, or edema after treatment with Ultherapy Prime and Ultherapy Legacy. Results: This study included 231 participants who underwent treatment with Ultherapy Legacy and Ultherapy Prime and 92 participants who underwent Ultherapy Prime as first‐time treatment. Participants reported significantly less pain, erythema, and edema after treatment with Ultherapy Prime, compared to treatment with Ultherapy Legacy, regardless of whether Ultherapy Prime was performed after Ultherapy Legacy or as first‐time treatment. Conclusion: Despite some limitations, e.g., a single‐center study performing unblinded treatment of participants, in the absence of a crossover design, participants consistently reported less pain, erythema, and edema after treatment with Ultherapy Prime, supporting its efficacy and safety in nonsurgical facial lifting. However, larger studies in more diverse geographical areas are needed to confirm these findings and rule out the impact of cultural differences on pain perception and expression.