Background. An inflammatory foreign-body reaction and the neosynthesis of collagen and the extracellular matrix through injectable collagen stimulators have coexisted since the introduction of the first sterile water-reconstituted poly-L-lactic acid (PLLA) formulation around the turn of the century. The PLLA-LASYNPRO™ microspheres for subdermal implants are a groundbreaking technological advancement that challenges the foreign-body reaction paradigm. The concept of non-inflammatory collagen and extracellular matrix regeneration, along with the initial insights into the rationale and role of the new-technology subdermal implants in aesthetic and regenerative medicine, was central to the discussions among thirteen distinguished experts in micro-invasive aesthetic medicine, aesthetic plastic surgery, and dermatology. This document summarizes their conclusions regarding the PLLA-LASYNPRO™ concept—subdermal microsphere implants designed to facilitate collagen and extracellular matrix regeneration while negligibly triggering persistent inflammation. Additionally, it offers preliminary yet authoritative suggestions from the board for the safe and effective use of the novel JULÄINE™ medical device based on the new-technology microspheres. Methods. An online survey of the experts, preceded by a board discussion in Milan, Italy, focused on skin regeneration and the rationale for the new PLLA technology, drawing on the board experts’ direct experience. The topics surveyed included the anticipated benefits of the new JULÄINE™ medical device and some initial suggestions for its safe and effective use. Results and Conclusions. This document outlines the board’s considerations regarding the shift, driven by the innovative PLLA-LASYNPRO™ ingredient and the CE-approved JULÄINE™ medical device, from the historically dominant FBR paradigm to a new strategy focusing on non-inflammatory collagen and extracellular matrix regeneration. Additionally, it presents practical, albeit preliminary, suggestions based on current clinical research for utilizing the new JULÄINE™ medical device and reaping its anticipated benefits.

How injectable collagen stimulators promote the neosynthesis of collagen and other components of the extracellular matrix in connective tissues has typically been linked to an inflammatory foreign-body reaction (FBR). A shift from the long-dominant inflammatory FBR paradigm to a new focus on non-inflammatory collagen and extracellular matrix regeneration may have emerged with the next-generation PLLA-LASYNPRO™ microspheres of the CE-approved JULÄINE™ medical device, which preclinical studies suggest are negligibly likely to trigger inflammation. A survey and subsequent discussions during a board meeting held in Milan, Italy, which involved thirteen distinguished experts in micro-invasive aesthetic medicine, aesthetic plastic surgery, and dermatology, led to this document and the accompanying manuscript “First Insights on the Upcoming Role of Next-Generation PLLA-LASYNPRO™ in Aesthetic and Regenerative Medicine. A Survey of Experts — Practical Suggestions”. This first paper outlines the initial insights and discussion of the experts on the basis and the value of the non-inflammatory rationale proposed for PLLA-LASYNPRO™ subdermal implants in aesthetic and regenerative medicine.