A hydrogel that helps damaged skin by creating an environment that supports the healing process. TR Pro+® hydrates skin internally whilst providing a barrier to reduce transepidermal water loss (TEWL). TR Pro+® is able to cool and soothe skin and is effective in reducing the irritation and redness that often follows aesthetic and other minor surgical procedures.
Key Ingredients
What is Glucoprime®
The active ingredient of TR Pro+® is Glucoprime® which is a beta-glucan purified from the yeast Saccharomyces cerevisiae (ie: baker’s yeast) which is used to bake bread and brew beer. Beta-glucans are commonly found in fungi, plants and bacteria where they are a key component of the cell wall. Beta-glucans are almost totally made of sugar, with glucose being the sugar most commonly used.
There is enormous diversity in the way the millions of glucose units are linked together and their spatial location relative to adjacent molecules (Vetvicka et al. 2019). Up until recently, the extraction of beta-glucan has been difficult and expensive due to the challenges associated with retaining the complex branched structure of the molecule.
Preserving the native structure of the beta-glucan is essential because it determines its ability to interact with host cells, and studies have confirmed that beta-glucans which have maintained the natural branched structure are more effective in assisting damaged skin to heal (Kim et al. 2018). Historically however, this has been difficult to achieve with most beta-glucans breaking down during the purification process and therefore having less impact on skin repair. Tissue Repair has successfully developed a proprietary process that leaves the native structure more intact, thereby allowing Glucoprime® to exert a positive healing influence on damaged skin.
Glucoprime® supports skin regeneration
When TR Pro+® is applied topically, the Glucoprime® moves between the cells of the epidermis to the dermis where it comes into contact with macrophages. These macrophages are the ‘guard cells’ and are on alert for foreign pathogens like bacteria and yeast. The macrophages have specific receptors on their surface which recognise the yeast-derived Glucoprime® and these engage with the Glucoprime® in the same way as a lock and key fit together. As a key is able to open the lock, the Glucoprime® is able to activate the macrophages by engaging with the receptors.
Once activated, the macrophages begin to influence the tissue environment, initially by attracting more macrophages and neutrophils to the area. They also facilitate the production of cytokines and growth factors that create an inflammatory environment which is the first step in the healing process. While inflammation is necessary for healing, it must not be too severe nor progress for too long as the quality of the new skin will be compromised. Beta-glucans like Glucoprime® have been referred to as immunomodulators in the scientific literature because of their ability to manage the healing process, and in particular, ensure that the inflammatory phase is appropriate for optimal skin healing.
Not all beta-glucans benefit skin repair to the same extent
Research has shown that large beta-glucans like Glucoprime® in TR Pro+® are able to attach to macrophage receptors and activate those cells to upregulate cytokines, growth factors and collagen production. Over many years Tissue Repair has developed a proprietary process to purify Glucoprime® from baker’s yeast without significantly compromising the size. Although smaller beta-glucans can also engage with the receptors, they do not activate macrophages and therefore cannot produce the same regenerative benefits (Goodridge et al. 2011).
If topical products that contain beta-glucans are being used for skin repair, users should be informed about the origin of the beta-glucan and the size so they can be confident about the products effectiveness.
TR Pro+® stimulates macrophages to manage the healing process
Healing is a complex process that involves many different cellular components being switched on and off at the appropriate time and in the correct concentrations. Macrophages are the cells that coordinate the healing process which occurs in four phases – haemostasis, inflammation, proliferation and remodelling.
In simple terms we can consider macrophages to be one of two types – M1 or M2. M1 macrophages are the first responders and create an inflammatory tissue environment which is designed to eliminate any pathogens, breakdown and remove any damaged tissue, and prepare the site for repair. They do this by producing cytokines that increase free radicals, proteases, and phagocytosis. The inflammatory phase is typically associated with skin redness and heat and may last from 2 to 6 days.
As the healing process moves from inflammation to proliferation, the macrophages transition from the M1 to the M2 type and adjust the environment to one which supports skin regeneration. M2 macrophages produce a different array of cytokines and growth factors which enables the production of collagen, the restoration of the barrier function and the generation of new capilliaries. This proliferative phase may last for 4-24 days.
M2 macrophages are essential to build new tissue through the generation of types I and III collagen. The tissue regeneration bought about by TR Pro+® is effective for medical procedures (eg: excision, biopsy, skin cancer removal) as well as aesthetic procedures (eg: laser, all types of skin needling and chemical peels).
TR Pro+® has been shown in laboratory studies to increase the number of M2 macrophages and in this way accelerate healing and improve skin quality (Mills et al. 2024).
TR Pro+® may assist scar formation
While there have not been any clinical studies directly addressing the effect of beta-glucans like Glucoprime® on scarring, our knowledge of Glucoprime® and the published literature strongly suggests that the application of TR Pro+® can assist normal scar formation. Glucoprime® is able to increase the number of M2 macrophages and these cells play a multifaceted role in supporting scar formation by promoting fibroblast activation, collagen deposition, ECM production, and the scar remodeling processes. Their anti-inflammatory properties and ability to regulate the wound healing environment make them key players in the complex process of scar formation.
Hydrogels are the wound dressing of choice
The multifunctional nature of hydrogels, including their moisture retention, tissue adhesion, controlled drug delivery, antibacterial properties, and self-healing capabilities, makes them highly beneficial for skin healing applications. These properties enable hydrogels to create an optimal environment for wound repair, tissue regeneration, and controlled drug delivery, ultimately enhancing the overall healing process.
Hydrogels can benefit all stages of healing:
TR Pro+® supports skin regeneration in many ways
Beta-glucans like Glucoprime® can play an important role in skin care
The water content of the stratum corneum and skin surface is important in the appearance and function of skin(Cheng et al, 2007). Moisturisers reduce the loss of skin humidity and increase hydration to make it moist, smooth and soft (Kim et al, 2018). For a long time it was believed that the large molecular structure of beta-glucans would prevent it from effectively penetrating the skin. This all changed following a clinical study(Pillai et al, 2005)which evaluated the effects of beta-glucan in the reduction of wrinkle depth and height. The researchers applied beta-glucan to skin samples and left it to absorb for 8 hours before examining the samples and finding that it was able to enter the stratum corneum and epidermis and penetrate into the dermis. It’s also interesting to note that beta-glucan does not penetrate the skin by moving through individual cells, but instead passes in the spaces between cells.
Ongoing application of TR Pro+® can reduce wrinkles and fine lines
Wrinkle formation is one of the main signs of ageing and the major cause of fine wrinkles is the loss of structural protein, or collagen, in the dermal layer of skin. Collagen makes up 70-80% of the dry weight of skin (Du et al 2014) and the amount of collagen varies from person to person. In a study published in the International Journal of Cosmetic Science (Pillai et al, 2005), 27 people were tested to evaluate the effects of beta-glucan on facial fine lines and wrinkles. After twice daily use over 8 weeks, they found that there was a reduction in all wrinkles (including deep wrinkles) as well reductions in the average peak and roughness. A further by study by Wu et al (2022) showed that the TR Pro+® hydrogel was able to reduce wrinkling and improve elastosis in skin that had been resurfaced using a CO2 laser.
Beta-glucans like Glucoprime® have also been shown to have potent antioxidant properties. Given that oxidative stress from free radicals is a major cause of skin ageing, these antioxidant properties are also beneficial in combating the ageing effects of sunlight and pollutants (Majtan and Jesenak 2018).
TR Pro+ can reduce skin irritation and redness
TR Pro+® protects the skin from external stressors and irritation by increasing your skin’s natural barrier function and preventing harmful bacteria or pollution from making their way into your skin. It aids in providing relief from excessive sun exposure, rashes and mild burns. Glucoprime® provides a film-forming linear polymer, which means that it links together to form a thin, undetectable barrier that enhances the natural protecting properties of the skin layer. Its ability to penetrate deep into the skin serves to immediately calm down redness and irritation caused after cosmetic treatments.
TR Pro+® is specifically designed to support the skin’s natural barrier function and works to diminish the appearance of redness. Gentle enough for dry and sensitive skin types, use it once daily or as needed, massaging a small amount onto the affected areas.
TR Pro+® containing beta-glucan, is fragrance-free and suitable for most skin types. This oil-free gel works to instantly boost skin’s hydration, giving you a healthy supple complexion.
The science behind TR Pro+®
TR Pro+® is supported by a comprehensive body of scientific and clinical research which sets it apart it from other aftercare products that heal skin. The information that underpins TR Pro+® and its active ingredient, Glucoprime®, has enabled inclusion on the Australian Register of Therapeutic Goods (ARTG). This signifies Tissue Repairs commitment to adhering to stringent regulatory requirements, and to meeting the highest standards in relation to product safety, efficacy and quality. TR Pro+® is manufactured in a GMP accredited facility that complies with internationally recogised standards for medicines manufacture.
Ridder, W.E.Study Number 500663 (2008)
In a Goettingen mini-pig model, histological examination of comparisons between TR Pro+® gel and placebo demonstrated that the most marked increase in epidermal thickness occurred at the TR Pro+® test sites after daily administration for 5 days. Microscopically, the primary effects of the TR Pro+® therapy were enhanced migration of macrophages and neutrophils into the wound space, followed by earlier onset of all aspects of the healing cascade. Histological examination of the punch biopsy samples showed significant cellular changes with regenerative processes commencing sooner at sites where the active treatment had been applied, based on changes in the stratum lucidum and stratum corneum.
Roy S, et al. Particulate beta–glucan induces TNF-α production in wound macrophages via a redox-sensitive NF-κβ-dependent pathway. Wound Repair Regen. 2011 May-Jun;19(3):411-9.
In this study, the hypothesis that TR Pro+® regulates wound macrophage function was tested. TR Pro+® induced tumor necrosis factor (TNF) α transcription in macrophages isolated from murine wound sites. Multiplex assay identified interleukin (IL)-10 and TNFα as two cytokines that are induced by TR Pro+® in human blood monocyte-derived macrophages. TR Pro+® -induced TNFα production was observed to be mediated via the TLR-2 and dectin-1 receptors, receptor tyrosine kinases and NFκB activation. Consistently, TR Pro+® induced TNFα expression in wound-site macrophages isolated from two patients with chronic wounds. These observations establish the translational significance of the net findings of this study. Activation of wound macrophages by TR Pro+® represents one of the potential mechanisms by which this beta-glucan may benefit chronic wounds where inefficient inflammatory response is one of the underlying causes of impaired healing.
Mills, S, et al. Beta-Glucan Hydrogel (TR Pro+®) modulates inflammation, by controlling macrophage differentiation, to improve the rate of healing in murine excisional wounds. AWTRS Abstract October 2024.
C57BL/6 mice received 10mm circular wounds to their dorsum, which were treated at the time of wounding, with TR Pro+® hydrogel or hydrogel alone. Three time points were investigated including day 3, day 7 and day 14. At these time points wound measurements, collagen deposition, immune cell infiltrate, growth factor and cytokine expression were investigated.
The data showed that TR Pro+® treatment significantly reduced macroscopic wound gape and microscopic wound area and width at day 7, when compared to hydrogel treatment. The inflammatory profile, at day 7, showed a greater number of macrophages within the TR Pro+® treated wound site but the ratio of M1:M2 macrophages showed a greater proportion of M2 macrophages, when compared to the hydrogel control. This higher ratio of M2 macrophages indicates a resolution of inflammation and a progression in the wound healing process, which is beneficial for healing outcomes.
In summary, TR Pro+® hydrogel treatment increased the rate of wound closure by regulating macrophage differentiation. This modulated the immune response by limiting pro-inflammatory responses yet simultaneously promoting a wound resolving anti-inflammatory phenotype. This area of research is showing that beta-glucan therapy could hold promising therapeutic potential for wound healing
Two Phase 2 studies (GLYC-101-1a and GLYC-101-1b) were conducted to test TR Pro+® treatment after retro-auricular CO2 laser skin resurfacing (LSR) and CO2 laser skin resurfacing. Both studies demonstrated an acceptable safety profile when administering TR Pro+® . The studies demonstrated the time to healing was shorter (10.9 days) in the TR Pro+® group than in both the 1.0% Glucoprime® (13.1 days) and placebo (16.3 days) groups; the difference between TR Pro+® and placebo treatment was statistically significant (p=0.0062) (Angra et al. 2021).
Wu DC et al. A Novel Macrophage-Activating Gel Improves Healing and Skin Quality After CO2 Laser Resurfacing of the Chest. Dermatol Surg. 2022 Dec 1;48(12):1312-1316
A third study compared TR Pro+® against a placebo gel on 42 healthy subjects that had undergone fractionated CO2 laser resurfacing to the chest. Treatment occured once daily for 5 days with and assessment of skin quality made at 28 day. The study demonstrated that TR Pro+® treatment reduced redness, cutaneous wrinkling and improved elastosis, using the Fitzpatrick-Goldman Classification. With regard to wrinkling, 85% of responders achieved a ≥ 1-point improvement in scores between baseline and day 28 in the active group compared to only 50% in the placebo group, corresponding to an absolute improvement of 35% (p=0.04). For elastosis there were 75% of responders who achieved a ≥ 3-point improvement in scores between baseline and day 28 in the active group compared to 35% in the placebo group. This represents an absolute improvement of 40% (p=0.011). TR Pro+® can shorten downtime and reduce wrinkling due to an increased rate of physiologic dermal collagen production.
Patient Experiential Program, IQVIA, September 2022
A multi-clinic (n=12) real-world evidence study involving 48 patients who had undergone a range of aesthetic and medical procedures was undertaken to collect patient feedback following aftercare treatment with TR Pro+®. The feedback was collected anonymously via an online portal at days 6 and 28.
Patients overwhelmingly reported a reduction in itchiness and tingling following the application of TR Pro+®, as well as increased hydration. When patients were asked how they perceived their skin to be healing, 85% reported it as well/very well. When patients who had had prior procedures were asked how their healing with TR Pro+® compared to previous occasions, 100% reported that it was as good as, or better than previous.
It is likely that the ability of TR Pro+® to modulate post-procedure inflammation leads to reduced itchiness and tingling. The increased number of M2 macrophages made available by TR Pro+® are able to commence healing earlier and ensure superior skin quality.
Using TR Pro+™
TR Pro+® can be used with a range of aesthetic and medical procedures including:
Aesthetic
Medical
Detailed instructions for use are provided in the TR Pro+® Product Brochure.
In general, TR Pro+® can be applied directly after the procedure, and from then on in the evening and then left to absorb into the skin overnight. A loose dressing can be used to cover the area if necessary. The skin is gently cleansed the following morning, and if appropriate, moisturiser, makeup and/or sunscreen can be applied throughout the day. TR Pro+® is applied in the same way each evening for at least 5 days, and then every second evening afterwards as required or until the skin returns to normal.
There may be a brief mild stinging sensation before the cooling effect of the gel becomes apparent, at which time there may also be a feeling of skin tightening which is normal.
References