The skin is the largest organ of the body and experiences both intrinsic and extrinsic ageing factors (Skowron et al, 2021). Skin ageing is characterised by features such as wrinkling, loss of elasticity, laxity and rough-textured appearance. The ageing process is accompanied by phenotypic changes in cutaneous cells, as well as structural and functional changes in extracellular matrix components, such as collagen and elastin (Zhang et al, 2018). In this article, the author will discuss skin ageing and the use of platelet-rich plasma for skin rejuvenation.
Ageing skin
Skin is a barrier that protects the body from water loss and micro-organism infection. It is thought that it also has an important cosmetic role, as a youthful and beautiful appearance may have a positive influence on a person's social behaviour and reproductive status (Blanpain et al, 2006).
The ageing process of the body's organs begins from the time of birth, and this also includes the skin. As the most voluminous organ of the body, the skin shows obvious and visible signs of ageing. For many people, especially women, a considerable amount of money is spent on cosmetics and treatments in an attempt to delay or reverse the skin's signs of ageing (Kazanci et al, 2016).
Cutaneous ageing is caused by both intrinsic and extrinsic factors. Intrinsic ageing is an inevitable physiological process that results in thin, dry skin, fine wrinkles and gradual dermal atrophy, while extrinsic ageing is caused by external environmental factors, such as air pollution, smoking, poor nutrition and sun exposure, which result in coarse wrinkles, loss of elasticity, laxity and a rough-textured appearance (Blanpain et al 2006; Kazanci et al 2016).
The skin is constantly exposed directly to the air and is not only subject to intrinsic ageing, but also superimposed by extrinsic ageing. These ageing processes are accompanied by phenotypic changes in cutaneous cells, as well as structural and functional changes in extracellular matrix components, such as collagens, elastin and proteoglycans, that are required to provide tensile strength, elasticity and hydration to the skin (Kazanci et al, 2016).
It is widely documented that sun damage is the primary cause of ageing. In the author's experience, patients tend to look after their face and neck but neglect their hands, despite them being the most visible area of the body, other than the face (WebMD, 2021). The skin on the face is affected by both intrinsic and extrinsic ageing factors, leading progressively to a loss of structural integrity and physiological function. Intrinsic ageing of the skin occurs as a natural consequence of physiological changes over time at variable, yet genetically determined, rates. Intrinsic ageing affects the deeper soft tissue, decreasing skin elasticity, volume and dermal vascularity. This can result in wrinkles and thinner and lax skin (Farage et al, 2008).
Extrinsic factors are, to varying degrees, controllable and, for the face, include exposure to sunlight, pollution or nicotine, which damage skin by discolouring it, and miscellaneous lifestyle components, such as diet and overall health (Farage et al, 2008; WebMD, 2021). Extrinsic ageing affects the epidermal and dermal layers following exposure to the sun, hyperpigmentation, chemicals and smoking, which can cause actinic keratosis, solar lentigines, hypopigmentation and solar purpura (Farage et al, 2008).
Platelet-rich plasma can be combined with other procedures, such as dermal fillers, microneedling, mesotherapy and chemical peels
Changes in intrinsic ageing
Intrinsic skin ageing is a process of chronologically physiological change. The ageing of photo-protected areas (for example, the inner side of the upper arm) is mainly due to intrinsic genetic or metabolic factors, whereas exposed skin areas are additionally influenced by extrinsic factors, especially solar ultraviolet (UV) radiation (Mancini et al, 2014).
Intrinsically aged skin changes occur in the basal cell layer. Research has found that, as a person ages, the proliferation of cells in the basal layer reduces. The epidermis then becomes thinner, and the contact surface area between the dermis and the epidermis decreases. This results in a smaller exchange surface for nutrition supply to the epidermis, which further weakens the ability of basal cell proliferation (Moragas et al, 1993; Makrantonaki and Zouboulis, 2007). This process of decreased proliferative cell ability, including keratinocytes, fibroblasts and melanocytes, is called cellular senescence. In addition to this, the dermis of photo-protected aged skin shows not only fewer mast cells and fibroblasts than photo-protected young skin, but also rarefied collagen and elastic fibres (Kohl et al, 2011).
The evidence suggests that, in intrinsically aged skin, fibrous extracellular matrix components, including elastin, fibrillin, and collagens, and oligosaccharide are degenerated, which, in turn, influences the skin's ability to retain bound water (Naylor, 2011).
Changes in extrinsic ageing
Kligman et al (1969) proposed that, besides intrinsic factors, sun exposure leads to skin ageing. Exposure to UV radiation is thought to be the primary factor of extrinsic skin ageing. It accounts for roughly 80% of facial ageing (Friedman, 2005). Furthermore, in contrast to the thinner epidermis in intrinsically aged skin, UV-radiated epidermis skin thickens (Kligman et al, 1989). Studies have found that collagen type I diminishes in photoaged skin due to increased collagen degradation. In photoaged skin, a striking characteristic is the accumulation of abnormal elastic tissue deep in the dermis (Bonta et al, 2013), which is a pathologic phenotype called solar elastosis.
Platelet-rich plasma
Platelet-rich plasma (PRP) is considered a growing modality for tissue regeneration (Elnehrawy et al, 2017). PRP injection treatment provides supraphysiological concentrations of growth factors that may help in accelerated tissue remodelling and regeneration. PRP is currently used in dermatology, plastic surgery and aesthetic medicine, wound care, sports medicine, orthopaedics, trauma surgery and oral surgery and dentistry (Mehryan, 2014).
» The growth factors are released following endogenous or exogenous activation of the platelets, which have a chemotactic effect and act directly and indirectly to regenerate the tissue. Some of the platelets are activated by mechanical influences during centrifugation «
PRP has emerged as a promising autologous biological treatment modality in aesthetic and regenerative medicine over the past few years. PRP is a high concentration of platelets derived from whole blood that is isolated by centrifugation to separate and concentrate platelet-containing plasma from red blood cells (Dhurat, 2014). PRP comprises hundreds of bioactive proteins, including growth factors, peptides and cytokines, that stimulate healing of skin and soft tissues. Due to the unique biological features of this whole blood-derived biological agent, multiple clinical uses for PRP exist in aesthetic and regenerative medicine (Samadi et al, 2019).
What platelet-rich plasma is
PRP is a concentrated preparation of the patient's own platelets from centrifugation of blood and extraction of the separated platelet-rich layer. Platelets contain numerous growth factors, such as platelet-derived epithelial growth factor and vascular endothelial growth factor, which modulate cell proliferation, tissue remodelling, angiogenesis and inflammatory responses. According to Marx (2001), PRP is autologous plasma with an increased platelet concentration, compared to the whole blood (baseline).
PRP contains numerous growth factors that are responsible for its effectiveness (Dhurat, 2014). The growth factors are released following endogenous or exogenous activation of the platelets, which have a chemotactic effect and act directly and indirectly to regenerate the tissue. Some of the platelets are activated by mechanical influences during centrifugation. Collagen activates the platelets endogenously in vivo, while needle-induced bleeding from the injection may also contribute to the clotting. Exogenous activation by means of adding calcium has become less popular in recent years (Delong et al, 2011). The author believes that one of the main reasons for this is that there are many PRP kits available on the market, and some kits do not have calcium to activate the platelets. Many practitioners are not aware that calcium activates the platelets prior to injection.
What platelet-rich plasma does
PRP allows the body to heal faster and more efficiently by stimulating DNA repair, which can heal scars and make dry, lacklustre skin look and feel younger (Cash et al, 1993).
Plasma, which comprises 55% blood fluid, is mostly water (90% by volume) and also contains dissolved proteins, glucose, mineral ions, hormones, carbon dioxide (plasma being the main medium for excretory product transportation), platelets and blood cells (Lachgar et al, 1996). As it is a concentration of platelets, it is also a concentration of the seven fundamental protein growth factors actively secreted by platelets to initiate all wound healing.
Platelets are the first responder to any trauma in the body, and so, by injecting the platelets directly to the site requiring treatment, the body responds as if a trauma has occurred, and the growth factors will start to work immediately to stimulate and rejuvenate (Cash et al, 1993).
Contraindications
While PRP is considered safe for most people, it is not recommended for anyone who has any of the following medical conditions:
- Hepatitis C
- Human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
- Any type of blood cancer
- Cardiovascular disease that requires taking a blood thinner
- Skin cancer in the area to be treated.
These conditions affect platelets and make them unable to deliver the expected results (Hersant et al, 2017; Houghton, 2018).
Study one
A study by Elnehrawy et al (2017) aimed to evaluate the efficacy and safety of a single autologous PRP intradermal injection for facial rejuvenation and the treatment of facial wrinkles. It included 20 patients with various degrees of facial wrinkles in the study. All patients received a single PRP intradermal injection and were all clinically assessed before and after treatment, up to 8 weeks post procedure. The authors used the Wrinkle Severity Rating Scale (WSRS), Skin Homogeneity and Texture (SHnT) scale, Physician Assessment Scale and Subject Satisfaction Scale.
Platelet-rich plasma is an effective treatment for skin revitalisation, scars (including acne scars) and stretch marks
The most significant outcome was seen with the younger patients, who had mild and moderate nasolabial fold wrinkles. Of 17 patients with nasolabial fold wrinkles, 14 showed more than a 25% improvement.
The authors concluded that a single PRP intradermal injection was capable of rejuvenating the face and producing a significant correction of wrinkles, especially the nasolabial fold (Elnehrawy et al, 2017).
Study two
A study by Abuaf et al (2016) was conducted to evaluate the efficacy and safety of intradermal PRP injection for facial rejuvenation. It was a prospective, single-centre, single-dose, open-label, non-randomised controlled clinical study. PRP was injected to the upper site of the right infra-auricular area and all of the face. Saline was injected to the left infra-auricular area. Histopathological examinations were performed before PRP treatment, 28 days after and on the saline (control) treatments.
The researchers enrolled 20 women aged 40–49 years in the study. The mean optical densities of collagen in the pre-treatment, control and PRP-treated area were measured. In the mean optical densities of PRP, an 89.05% improvement was found when it was compared with the mean optical densities of pre-treatment. The results showed that the mean optical densities of collagen fibres was highest on the PRP side. The PRP-to-saline improvement ratio was 1.93:1.
The authors concluded that PRP increased dermal collagen levels not only by growth factors, but also by skin needling (the mesotherapy technique used to deliver the PRP). Even a single PRP application could be considered as an effective and safe treatment for facial skin rejuvenation (Abuaf et al 2016).
Study three
In a clinical trial by Banihashemi et al (2014), 30 patients with a Glogau score of II and III volunteered to participate. The PRP treatment was conducted in two sessions, with a 3-month interval between each session. Subdermal and intradermal injections were i cc in the upper face, i cc in the cheeks and i cc in the lower face.
Digital photographs of all patients were taken before and after the treatment. Evaluation of wrinkle improvement was based on the personal judgement of the patient and a therapeutic physician and dermatologist, who observed before and after photographs and were not told which order the photographs were taken.
The results showed that, at the 3- and 6-month follow-ups, most of patients reported moderate-to-excellent improvement in periorbital darkness, periorbital wrinkles, nasolabial folds and skin rigidity. Most of the patients reported moderate-to-excellent improvement, and only 17% of patients reported no improvement or mild improvement.
In the therapeutic physician assessment at 3- and 6-month follow-ups, in most patients, mild-to-moderate improvement in periorbital wrinkle and dyschromia was reported. However, in the nasolabial fold assessment, most reported no improvement. In the second physician assessment, no improvement or mild improvement was observed in periorbital wrinkles at the 3- and 6-month follow-ups.
In conclusion to this study, the best effect of PRP was specified to be periorbital darkness improvement and a decrease in skin wrinkles (Banihashemi et al, 2014).
Conclusion
PRP is an effective treatment for skin ageing, whether as a standalone treatment or in combination with other treatment modalities. The results are dependent on the skin quality of the patient, compliance and aftercare. Other factors to consider include the PRP kits and centrifuge used, as well as whether the PRP is activated or not.
PRP is a generally safe procedure that gives natural results, and there is no risk of allergic reactions, as the patient cannot be allergic to their own blood, and their body will not reject it. Additionally, there is limited downtime associated with PRP treatment, and it can be combined (on the same day or at another time) with other procedures, such as dermal fillers, microneedling, mesotherapy and chemical peels.
PRP works especially well for the forehead, cheeks, neck, décolletage, knees, elbows and hands, and it is an effective treatment for skin revitalisation, scars (including acne scars) and stretch marks. It is also good for promoting hair growth and for non-healing wounds (Cash et al, 1993). PRP is very actively researched. New studies are being published on an almost daily basis, and the author found over 22 000 worldwide studies on PubMed and 33 000 on Wiley Online Library at the time of writing. These studies cover almost every field of medicine, including dental, orthopaedic, eye laser surgery, plastic surgery, cardiac surgery and, most commonly, treatment for sports injuries and hair loss.
While there are many research papers into the effectiveness of PRP, further research is required on the topic of treating indications such as facial rejuvenation and whether PRP requires activation prior to injection. Overall, the treatment speaks for itself. PRP is a procedure that heals and repairs the body.
Key points
- The skin is the largest organ of the body
- The skin on the face is affected by both intrinsic and extrinsic ageing factors
- Platelet-rich plasma is autologous plasma with an increased platelet concentration
- Platelets are the first responder to any trauma in the body.
CPD reflective questions
- In which layer of the skin does intrinsic skin ageing occur?
- What is the primary factor of extrinsic skin ageing?
- What are the contraindications of injecting platelet-rich plasma?