Age-related loss of collagen impairs the integrity of the skin’s extracellular matrix. Dermal fillers made from hyaluronic acid are considered the gold standard for smoothing wrinkles and restoring volume to the face. A recently published study focused on the question of which biochemical processes underlie the effects achieved by cross-linked hyaluronic acid fillers in light-aged skin.
The extracellular matrix (ECM) of the skin represents a complex network of macromolecules and is used for mechanical stabilization but also for the regulation of various other cellular mechanisms. Around 80-90% of the ECM consists of type I collagen, but it also contains elastin and collagen [1]. Dermal fibroblasts produce type I collagen and the interaction between the ECM and dermal fibroblasts is crucial for cell function. As the skin ages, increased expression and enzymatic activity of metalloproteinases (MMPs) leads to fragmentation of type I collagen. This weakens the collagen scaffold, which makes it more difficult for fibroblasts to bind [2].
Microscopic analyses show collagen accumulation
Previous studies have shown that injections of cross-linked hyaluronic acid ( CL-HA) can reverse these changes. Wang et al. aimed to further decipher the biochemical mechanism of CL-HA action [2]. In one study, they injected CL-HA and a vehicle preparation (saline solution) into the light-aged skin of people aged ≥60 years. The fibroblasts showed activation 1 week to 6-9 months after the injection. Microscopic analyses were performed to assess whether fibroblast activation led to the accumulation of skin collagen. The multiphoton microscopy 1 week after the injection shows that the fibroblasts have stretched, which indicates improved mechanical support of the skin. A microscopic analysis four weeks after the injection showed densely packed collagen bundles around the pools of injected CL-HA. The accumulation of thick collagen bundles was also detectable 12 months after the injection and a considerable amount of CL-HA was present.
| Summary Overall, the results of the study by Wang et al. indicate that the injection of cross-linked hyaluronic acid (CL-HA) can permanently and rapidly activate fibroblasts, leading to subsequent collagen deposition. More specifically, CL-HA injection stimulated the synthetic activation and elongation of fibroblasts permanently (for 6-9 months) and rapidly (within one week). The result was an accumulation of tightly packed type 1 collagen bundles. This began after just four weeks and lasted for at least a year after the injection. It could thus be shown that the accumulation of dermal collagen is an important mechanism of action for the sustained clinical effects achieved by CL-HA derma-fillers. |
| according to [2] |
Which biomechanical processes are involved?
Wang et al. analyzed the processes underlying these effects and came to the following conclusions [2]:
- Injection of CL-HA triggered the activation and elongation of fibroblasts, resulting in densely packed and thick type I collagen bundles four weeks after injection and persisting until at least week 52.
- Important components of the TGF-β (transforming growth factor β) signaling pathwaywere stimulated. This is clinically relevant because components of the TGF-β signaling pathway are reduced in light-aged skin, which reduces the synthesis of type 1 procollagen. The results indicate that activation of the TGF-β signaling pathway regulates the response of fibroblasts in terms of better mechanical support of the skin, the authors said.
- After CL-HA injection, the N-proteinase and C-proteinase enzymes involved in collagen synthase increased rapidly. These enzymes are particularly involved in the formation of intact type 1 collagen.
According to the authors, the clinical improvements in the skin achieved immediately after CL-HA injection are related to the fact that the filler takes up space in the ECM and thus has a favorable effect on mechanical support. This effect is further enhanced by the thickly packed collagen bundles that accumulate within a month. The fact that the collagen bundles accumulated until at least week 52 is a possible indication that the type 1 procollagen is converted into permanent and stable dermal type 1 collagen after the CL-HA injection. In addition, the presence of the injected CL-HA filler after 12 months indicates a long-lasting clinical benefit.
Literature:
- Fisher GJ, Varani J, Voorhees JJ: Looking older: fibroblast collapse and therapeutic implications. Arch Dermatol 2008; 144(5): 666-672.
- Wang F, et al: Implications for cumulative and prolonged clinical improvement induced by cross-linked hyaluronic acid: An in vivo biochemical/microscopic study in humans. Exp Dermatol 2024 Jan; 33(1): e14998.
- Chin T, et al: The role of cellular senescence in skin aging and age-related skin pathologies. Front Physiol 2023; 14: 1297637. www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2023.1297637/full,(last accessed 11.04.2024).
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