Introduction <p>Atrophic scars, caused by insufficient collagen deposition and ECM production during wound healing, significantly affect patients’ quality of life. Conventional treatments often fail to achieve complete skin regeneration, prompting interest in regenerative medicine. This review evaluates the efficacy and safety of emerging regenerative therapies, including extracellular vesicles, conditioned media, stromal vascular fraction, and mesenchymal stem cells, in improving atrophic scars.</p> Method <p>A systematic search was conducted on PubMed, Scopus, and Web of Science up to November 23, 2024. Relevant keywords, including "conditioned media," "Secretome," "extracellular vesicles," "atrophic scar," "rejuvenation," and "lightening," were used to identify studies. Articles meeting inclusion criteria underwent data extraction focusing on study design, population characteristics (mean and range), intervention details (including duration), comparison groups, clinical outcomes with statistical results, and reported adverse effects, ensuring comprehensive analysis and adherence to PRISMA guidelines.</p> Result <p>Out of 186 initially identified articles, 11 studies involving 177 participants (89 females, 59 males, and 29 undefined, mean age 31.52 years) were reviewed, focusing on treatments for acne scars (82%) and striae distensae (18%). These studies evaluated stromal vascular fraction (SVF), cell-conditioned medium (CM), mesenchymal stem cells (MSC), and extracellular vesicles (EV). Significant improvements were observed with various treatments, including a 32.5% decrease in ECCA scores with adipose tissue stem cell exosome (ASCE) treatment, and greater acne scar improvements with Fractional CO₂ Laser combined with platelet-rich plasma compared to stem cell-conditioned medium (SC-CM). Other promising results included enhanced skin elasticity and collagen density with ADSC-CM and a 28.5% reduction in scar volume with HSCM combined with FCL. SVF treatments, including gel and Subcision, demonstrated notable improvements in striae distensae and acne scars, with significant reductions in scar volume, area, and depth. Intradermal bone marrow stem cell injections also led to significant acne scar improvements, highlighting the potential of stem cell-based and exosome treatments for skin regeneration.</p> Conclusion <p>The evaluated studies indicate promising efficacy for regenerative treatments such as SVF, CM, EV, and MSC in improving acne scars and striae distensae. Significant enhancements in scar appearance, skin hydration, and patient satisfaction were observed across various combination therapies compared to controls. While these advancements offer new hope for patients with moderate to severe skin conditions, further research is needed to establish standardized protocols and long-term efficacy. The minimal reported adverse effects highlight the safety of these regenerative interventions, suggesting that their integration into dermatological practice could improve treatment outcomes for skin texture and appearance.</p> Level of Evidence I <p>This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors <a href="https://www.springer.com/00266">www.springer.com/00266</a>.</p>