Collagen is a vital structural protein in skin that declines with age, leading to wrinkles, sagging and dullness. Research shows that cold plasma therapy can stimulate collagen production in skin cells, counteracting various signs of aging.

In this article, we look at how cold plasma specifically acts on the collagen synthesis pathway in fibroblasts to renew aged and photo-damaged skin.


Introduction to Collagen

Collagen comprises 70-80% of the dermis layer of skin. This fibrous structural protein provides crucial support and elasticity to the skin. Various collagen types (I, III, V, VII) work together to form crosslinked networks that keep skin firm, supple and wrinkle-free.

With increasing age, collagen production slows down while breakdown increases. This leads to thinner, fragmented, disorganized collagen fibre bundles. Clinically, skin becomes loose, thin, crepey and saggy, with wrinkles and loss of elasticity.

about collagen

By promoting new collagen formation, cold plasma therapy rejuvenates aged skin.

Collagen Synthesis Process

Fibroblasts present in the dermis are responsible for continually synthesizing new collagen to replace old, damaged fibres (Wu et al. 2022). This involves the following key steps:

  • Gene expression of pro-collagen precursor molecules like pro-a1 and pro-a2.
  • Formation and secretion of pro-collagen proteins by ribosomes using mRNA.
  • Cleavage of pro-collagen by enzymes to create tropocollagen molecules.
  • A copper dependent enzyme lysyl oxidase acts on lysine and hydroxylysines and bonds tropocollagen molecule to form a collagen fibril.
  • Cross-linking for stability and strength.

Matrix metalloproteinases (MMPs) also degrade old collagen during this cycle. This is where copper peptides can be useful for the skin in your skin care.


Cold Plasma Mechanisms

Cold plasma influences collagen turnover in aging skin via these mechanisms:

  • Upregulates pro-collagen gene expression (Schmidt et al. 2020).


  • Increases keratinocytes production (the cells that produce skin cells) due to reactive nitrogen and oxygen species effect on different cytokines and subsequent cell proliferation (Schmidt et al. 2015).


  • Due to increase skin blood flow, there is an influx of inflammatory cells and therefore this induces production of different growth factors and cytokines which stimulate cell proliferation of fibroblasts (amongst other cells), and therefore increase collagen and elastin production (Shakouri et al. 2021).


  • Increases openings on skin cell walls to increase product absorption and therefore increase the efficacy of your skin care (Leduc et al. 2009; Tan et al. 2022).


  • Induces secretion of multi-peptide factors within fibroblasts which play a crucial role in proliferation of cells in wound repair (Lee et al. 2022).


  • Induces repair of DNA damage of cells resulting in release of cell growth factors, stimulation of wound healing and promotion of tissue regeneration (Fitzpatrick et al. 2008).


  • Superficially it improves hydration of the skin and also reduces bacterial growth within the skin therefore helping acne (Busco et al. 2020).


  • Helps to enhance skin oxygenation, perfusion and penetration of lipophilic substances into the stratum corneum (uppermost layer of the skin) and thereby helps regulate the skin barrier which is often affected by many different skin conditions (Schmidt et al. 2020).


Anti-Aging Effects

By increasing new collagen formation in aging skin, regular cold plasma therapy produces significant anti-aging results:

  • Reduces fine lines and wrinkles by plumping up the dermis from within (Bogle et al. 2007).
  • Evens out crepey skin texture by improving dermal thickness and organization (Bogle et al. 2007).
  • Tightens sagging facial skin by strengthening connective tissue (Kongpanichakul et al. 2021).
  • Improves firmness and elasticity for a more defined, contoured facial outline.
  • Gives a youthful smoothness and glow to aged, irregular skin.
  • Reduces the appearance of pigmentation from sun exposure

In clinical studies, measurable increases in procollagen levels are detected in plasma treated aged skin. Objective testing confirms improvements in skin elasticity and wrinkle depth after plasma sessions (Bogle et al. 2007).



Cold plasma therapy stimulates collagen regeneration in intrinsically aged and photo-damaged skin through multiple cellular mechanisms. The plasma-induced collagen renewal counters various aesthetic signs of aging to restore smooth, firm and youthfully contoured skin. Unlike ablative lasers, cold plasma leaves layers of the epidermis intact which promotes faster recovery (Fitzpatrick et al. 2008; Kongpanichakul et al. 2021)



Bogle et al. (2007). Evaluation of plasma skin regeneration technology in low-energy full-facial rejuvenation. Archives Dermatology. 143:168–174

Busco et al. (2020). The emerging potential of cold atmospheric plasma in skin biology. Free Radical Biology and Medicine, 161, 290-304.

Fitzpatrick et al. (2008). A histopathologic evaluation of the plasma skin regeneration system (PSR) versus a standard carbon dioxide resurfacing laser in an animal model. Lasers Surg Med, 40:93–99

Kongpanichakul et al. (2021). Efficacy of Low-temperature Plasma for Treatment of Facial Rejuvenation in Asian Population. PRS Global Open,

Leduc et al. (2009). Cell permeabilization using a non-thermal plasma, New J. Phys. 11 (11) 115021,

Lee et al. (2022). Effects of Human Fibroblast-Derived Multi-Peptide Factors on the Proliferation and Migration of Nitrogen Plasma-Treated Human Dermal Fibroblasts. Clinical, Cosmetic and Investigational Dermatology, 15, 2465-2475.

Schmidt, A. et al. (2015). Non-thermal plasma activates human keratinocytes by stimulation of antioxidant and phase II pathways. J. Biol. Chem. 290, 6731–6750.

Schmidt et al. (2020). The molecular and physiological consequences of cold plasma treatment in murine skin and its barrier function. Free Radical Biology and Medicine, 161, 32-49.

Shakouri et al. (2021). In vivo study of the effects of a portable cold plasma device and vitamin C for skin rejuvenation. Scientific Reports, 11: 21915.

Tan et al. (2022). Plasma Dermatology: Skin Therapy using cold atmospheric plasma: Review. Frontiers in Oncology, 12: 918484.

Wu et al. (2022). Biochemistry, Collagen Synthesis. StatPearls Publishing.