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Correspondence to Author: Nathalia de Castro Fraga¹, Felipe Santos Teixeira Martiniano², Eliane Franklin³, Samantha Regina Galo Sanches³, Adriana Farto Viana³, Délio Tiago Martins Malaquias³, Elis Muraro Consolin³, Rubens Rodrigues Tudela⁹, Mateus Assunção Costa ⁹*, Ana Luiza Trindade Bellucci⁴, Juliana Fontes³, Bruna Martinez Puglia⁵, José Antônio do Nascimento Neto⁶, Douglas Hipólito Carvalho⁷, Herbert Marchioro Drai⁷, Joel Eloi Belo Junior⁸, Roselene de Oliveira Carvalho³, Camila Faria dos Santos Dainez ¹⁰ , Thiago Augusto Rochetti Bezerra^3_11. 

1. Medical degree from Universidade Nove de Julho (UNINOVE), São Bernardo do Campo, São Paulo, Brazil; Postgraduate student in Dermatology, IPM.
2. Medical degree. Resident in Internal Medicine, Beneficência Portuguesa Hospital, Santos, São Paulo, Brazil.
3. Medical student, Ribeirão Preto University (UNAERP), Guarujá, São Paulo, Brazil.
4. Medical student, Ceres School of Medicine, São José do Rio Preto, São Paulo, Brazil.
5. Medical student, City University of São Paulo (UNICID), São Paulo, Brazil.
6. Medical Student, Central University of Paraguay. Ciudad del Este, Paraguay.
7. Medical Student, Nove de Julho University (UNINOVE), São Bernardo do Campo, São Paulo, Brazil.
8. Brazilian Air Force; Master’s Degree in Human Operational Performance; Master’s Degree in Intellectual Property and Technology Transfer for Innovation – Brazil.
9. Medical Student, São Judas Tadeu University, Cubatão, São Paulo, Brazil.
9*. Medical degree from São Judas Tadeu University, Cubatão, São Paulo, Brazil.
10. Medical student at Unoeste Medical University, Guarujá Campus, São Paulo.
11. Doctor of Medical Sciences, Ribeirão Preto School of Medicine (FMRP-USP), São Paulo, Brazil.

DOI: 10.52338/aods.2026.5297

Abstract:

Collagen biostimulators have established themselves as essential tools in minimally invasive tissue rejuvenation due to their proven ability to induce neocollagenesis, improve skin firmness, and restore dermal architecture. This systematic review analyzed studies published between 2015 and 2024, evaluating the clinical efficacy, histological mechanisms, and safety of the main biostimulators available—poly-L-lactic acid (PLLA), calcium hydroxyapatite (CaHA), and polycaprolactone (PCL). A search of the PubMed/MEDLINE, Scopus, Web of Science, Embase, and SciELO databases identified 32 eligible studies, including clinical trials, histological analyses, and systematic reviews. The results demonstrated that all biostimulators evaluated promoted a significant increase in type I and III collagen production, improving elasticity, texture, and dermal thickness. CaHA had an immediate effect followed by a delayed stimulus, while PLLA showed progressive and highly lasting results. PCL, in turn, stood out for the longer-lasting effects, with improvements maintained for up to 30 months. The safety profile was largely favorable, with a predominance of mild and transient adverse events, such as edema and local sensitivity. Serious complications, such as granulomas and persistent nodules, were rare and usually associated with inappropriate application techniques. The discussion of the studies analyzed highlights the central role of biostimulators in modern aesthetics, especially when integrated with energy technologies or combined protocols, expanding the therapeutic potential and promoting three-dimensional rejuvenation. However, the methodological heterogeneity among the studies highlights the need for standardization of techniques, dilutions, and intervals between sessions. It is concluded that biostimulators represent effective, safe, and versatile therapies, being fundamental pillars of contemporary aesthetics and promising in personalized rejuvenation protocols.

Keywords: Collagen biostimulators; Poly-L-lactic acid; Calcium hydroxyapatite; Polycaprolactone; Tissue rejuvenation; Neocollagenesis; Minimally invasive aesthetics.

Citation:

Dr. Thiago Augusto Rochetti Bezerra, Collagen Biostimulators: Clinical Evidence and Mechanisms of Tissue Rejuvenation.Annals of Dermatological Science 2026.