Skin rejuvenation with equine collagen type 1
Andrea Corbo, Cecilia Luci, and Giovanni Merone discuss the findings from their study evaluating dosage, patient compliance, degree of satisfaction, and treatment protocol for equine collagen injections to treat the signs of ageing
In recent years there has been a growing interest in rejuvenating therapies for cosmetic medicine. These are based on both physical methods, such as radiofrequency, laser and pulsed light, and biochemical methods through injectables. Several injectables are available for this purpose, comprised of non-crosslinked hyaluronic acid, polynucleotides, vitamins, organic silicon, and others.
Bio-rejuvenation therapies are essentially based on the repetition of several treatment sessions, according to various protocols, which aim to provide sub-continuous anabolic stimulation to dermal fibroblasts. The result is an increase in the biosynthesis of dermal matrix components and hydration, a skin tightening effect, and a general improvement of the fibrillar network. Bio‑rejuvenation therapy outcomes are generally satisfactory for mild to moderate photo and chrono-aging but require maintenance sessions. In the following study, the authors tested a new Class III medical device for bio‑rejuvenation, based on equine collagen type I, useful for all grades of skin ageing. For this purpose, the authors evaluated the best dosage for use, patient compliance, degree of satisfaction, and the best protocol for result maintenance.
PRODUCT CHARACTERIZATION AND RATIONAL
In the present study, the equine collagen was micronized, and the resulting powder placed in vials and sterilized. Immediately before use, the micronized powder was mixed with 0.9% saline or water for injection and a little anaesthetic, obtaining a fluid suspension, which m
ust be injected intradermally.
The supposed mechanism of action is based primarily on the presence of tripeptides, in particular, Pro-Hyp-Gly derived from collagen hydrolysis. In fact, an hydrolysis of peptidic bonds could occur both in vivo, after product injection in the receiving tissue, and in vitro, in the same vial after product reconstitution. Once in thesolution, equine collagen undergoes spontaneous hydrolysis, producing tripeptides and collagenous amino acids. This guarantees the total absence of any risk of immunogenicity because the molecules capable of eliciting an immune response must be larger than 10 kDa, while the molecules in the solution are 3–6 kDa at a maximum (tripeptides)8.
Tripeptides are known as biological messengers and act similar to growth factors; interacting with transmembrane receptors, they activate anabolic pathways and stimulate the fibroblast cell cycle. The Pro-Hyp-Gly tripeptide works as a competitive inhibitor of matrix metalloproteinases (MMP), which is responsible for the enzymatic degradation of dermal collagen (collagenase)9–12.
MATERIALS AND METHOD
RESULTS
All enrolled patients completed the study, with no drop-off occurring.
In the first group treated with three different amounts of collagen, one patient reported side-effects lasting a few hours to one day in the 50 mg sub-group, one patient reported side-effects lasting a few hours to one day in the 100 mg sub-group, while 8 patients reported side-effects lasting a few hours to one day in the 200 mg group. Side‑effects consisted of mild redness associated with mild skin pain/discomfort.
Efficacy was evaluated via patient-reported improvement to the skin after four treatment sessions: 20 patients in the 50 mg sub-group reported improvement of the skin appearance after four treatment sessions, while 38 patients in the 100 mg sub-group reported skin appearance improvement, and 39 patients in the 200 mg sub-group (Figure 1).
In the second group of 321 patients treated with 100 mg of equine collagen over four sessions, data collected from the self-assessment questionnaire is outlined below.
The main side-effects lasting a few hours to one day in less than 1% of patients were: erythema, itching, mild pain or discomfort of treated areas (Figure 2). Side effects lasting a few minutes, as transient discomfort at the end of the treatment session wasn’t taken into consideration for data collection as they would be common to all injections, no matter the material used. All data from the patient questionnaire was reported in the study.
Patient evaluations revealed a significant improvement of texture, consistency, brightness, and skin hydration in more than 95% of cases (Figure 3).
Photographic documentation showed improvement in chrono- and photo-aging (Figures 4 and 5).
In the split face test (the third group studied) the authors found a significant reduction in effectiveness when non-fresh product was used. Product that had been made days in advance instigated less of a treatment response. Areas in which the authors used solution prepared 4 days earlier showed a very poor response, while the preparation stored for two days before treatment responded a little better. Only the areas treated with freshly formulated suspension showed the expected results, as revealed by patient evaluation (Figure 6). The reported data confirmed clinical judgment.
DISCUSSION
In the field of cosmetic medicine, we are observing an increasing request for skin appearance improvement, and a more rejuvenating-like effect from treatments rather than only corrective or volume shaping outcomes. For this reason, a lot of injectable products are currently available on the market for rejuvenating purposes. In particular, non-crosslinked hyaluronic acid is widely used. Hyaluronic acid for skin rejuvenation predominantly effects dermal hydration, associated with the ROS scavenger effect, but it is not free from doubt14,15.
On the other side, in fact, it seems to activate metalloproteinase gene expression, leading to an increase in dermal matrix degradation14,15. For this reason, it is recommended to associate the use of other products for bio-stimulation that can increase dermal collagen production and shut down metalloproteinase.
The main limit of classical bio-rejuvenation/bio-stimulation injective procedures (polynucleotides, vitamins) is the residual anabolic capacity of old fibroblasts. Therefore, the novel use of equine collagen, which is proven to stimulate fibroblast mitosis and tissue regeneration, should be explored. Younger fibroblasts resulting from mitosis should have greater anabolic capacity and should be committed to producing a greater amount of collagen type III than the older fibroblasts. Finally, the equine collagen has no allergic reaction reported in more than 3 decades of use, showing a high degree of safety, which is essential for a cosmetic injection procedure.