Collagen Induction Therapy
We live in a time when more people are living to a greater age than ever before. At the same time, there is an accent on youth such that our patients are asking us to make them look as young as possible. This quest for younger-looking skin has spawned many different topical techniques that share the same principle of damaging the skin to cause fibrosis. The fibrosis then causes tightening of the skin. Among them Collagen Induction Therapy is the most popular.
Historically, skin peels were the first method of skin rejuvenation. The principle of peeling is to destroy the epidermis partially or almost completely to damage the fibroblasts and dermal structures. This damage then sets up an inflammatory response proportional to the damage, which results in the deposition of collagen. The proponents of peeling looked only at the increase of collagen in the papillary and reticular dermis but did not pay any attention to the epidermis. The epidermis suffered by becoming less undulating due to the destruction of the dermal papillae and subsequent impaired nourishment and, in turn resulted in a thinner epidermis with fewer cells in the stratum spinosum than before treatment. The stratum corneum is then less likely to act as an efficient barrier, so it is not surprising that many patients feel that their skin is too dry for years after the treatment. Consequently, hydration of the dermis also is affected.
Smoothing skin is still most effectively done by CO2 laser through the aggressive heat damage that is caused. No other technique can match it, but at the same time, CO2 laser causes the most complications. A significant problem is that deep treatments like this stimulate fibrosis rather than new, naturally oriented collagen formation. This fibrosis may result in a much whiter reflectance from the dermis, giving the skin an unnatural pallor. The sad fact is that several years after the treatment, the collagen will be resorbed—as all scar collagen is—and fine wrinkles will start to show as a result of the thin epidermis with no dermal papillae. The impaired hydration of the skin means that it is not as plump as it could be and can look atrophic due to this excessive destruction. To rejuvenate facial skin and really look young, we need a perfect epidermis with natural dermal papillae, good hydration, normal color, and normal resilience.
The idea of needling may have been around for hundreds, even thousands of years, starting with ancient Chinese, Indian and Egyptian health practices. However, cosmetic and medical needling as it is known today is a relatively new concept. Modern day micro needling consists of piercing the skin multiple times with very thin needles to deliver light trauma, thereby inducing an immune response. This is one of the approaches to something known as “fractional rejuvenation”.Various terms are used to describe collagen induction therapy terms included ‘skin needling’, ‘microneedling’, ‘needle dermabrasion’, ‘tattooing without pigment’, ‘dry tattooing’, ‘percutaneous collagen induction therapy’, and ‘dermaroller’ and the latest addition derma pen.
The advantages of micro needling were first observed by Dr. Andre Camirand, following his efforts to camouflage hypertrophic scars on several of his patients by tattooing pigment into their skin.Following Dr Camirand’s development, Dr. Des Fernandes introduced his own needling device: a small needle stamp that he used regularly in his surgical practice to induce collagen production. He delivered his first paper on skin needling of the upper lips at the ISAPS congress in Taipei in 1996.
In 2004, the first needle roller was introduced. A dermal roller is a small rolling pin, which, oddly enough, rolls across to skin’s surface, leaving behind a trail of microscopic punctures. This starts up an aseptic inflammation process, which will result in collagen production. The number of punctures caused by dermal rollers is much greater than the number of punctures created by a tattoo gun or any previously used method, but the roller presented many limitations. Different regions on the face and body require different depth of penetration, hence multiple single use rollers are required for a single patient. The roller is also unable to treat some of the harder to reach areas, such as those around the eyes and nose. The rolling action of the dermal roller also creates surface tears in the skin and causes unnecessary pain and discomfort for the patient during the procedure.
Mechanism of action Collagen Induction Therapy
Phase I: Initial injury
The inflammation phase starts when the needles prick the skin and rupture blood vessels and blood cells and serum gets into the surrounding tissue . Platelets are important in causing clotting and releasing chemotactic factors, which cause an invasion of other platelets, leucocytes, and fibroblasts .The leucocytes, particularly neutrophils, then act on the damaged tissue to remove debris and kill bacteria. After the platelets have been activated by exposure to thrombin and collagen, they release numerous cytokines.
Of special interest in understanding the action of Collagen Induction Therapy are the following:
- Fibroblast growth factor: promotes not only fibroblast proliferation but also epidermal proliferation and stimulates the production of new blood vessels. Vitamin A is an essential regulator of differentiation of fibroblasts and keratinocytes so adequate doses in the tissues are required at this stage. In anticipation of the interrupted blood supply, it should be ensuredthat the highest-possible normal levels of vitamin A are stored in the skin before Collagen Induction Therapy.
- Platelet-derived growth factor: chemotactic for fibroblasts and promotes their proliferation, meaning that more collagen and elastin will be made. The need for vitamin C at this stage becomes crucial because without adequate levels of this vitamin, proline and lysine cannot be incorporated into collagen and the strands will then be defective.
- Transforming growth factor a (TGF-a): facilitates re-epithelialization. In the case of Collagen Induction Therapy, re-epithelialization is not an important action.
- Transforming growth factor b (TGF-b): a powerful chemotactic agent for fibroblasts that migrate into the wound about 48 hours after injury and start producing collagen types I and III, elastin, glycoseaminoglycans, and proteoglycans. Collagen type III is the dominant form of collagen in the early wound-healing phase. Again, this action is heavily dependent on adequate doses of vitamin C. At the same time, TGF-b inhibits proteases that break down the intercellular matrix.
- Connective tissue activating peptide III: also promotes the production of intercellular matrix. Fibroblasts migrate into the area, and this surge of activity inevitably leads to the production of more collagen and more elastin. Vitamin A and C again are important mediators of this action. Neutrophil activating peptide-2: has a chemotactic effect for neutrophils that then migrate into the wounded area. Neutrophils are important for killing bacteria and helping to debride tissue but, in the case of Collagen Induction Therapy, their main action is the release of cytokines that enhance the effects of the platelet cytokines (eg, platelet derived growth factor and connective tissue growth factor).
Phase II: The period for tissue proliferation
As time passes, probably about 5 days in the case of Collagen Induction Therapy, neutrophils are replaced by monocytes . The monocytes differentiate into macrophages and phagocytose the decaying neutrophils. They are very important for the later healing phases because they remove cellular debris and release several growth factors including platelet-derived growth factor, fibroblast growth factor, TGF-b, and TGF-a, which stimulate the migration and proliferation of fibroblasts and the production and modulation of extracellular matrix. With Collagen Induction Therapy, there is only extravasated blood and very little connective tissue damage to be dealt with.
Bacterial infection is rare, but it has been noticed that when the needled area gets infected, greater smoothing of skin may occur, probably due to a heightened growth factor response. In standard wounds, the inflammatory phase ends after about 5 to 6 days, as proliferation and tissue formation ensue. In these cases, the main cell is the keratinocyte. Keratinocytes change in morphology and become mobile to cover the gap in the basement membrane. The changes include retraction of tonofilaments and the dissolution of desmosomes and hemidesmosomes so that the cells can migrate. Peripheral cytoplasmic actin filaments also are developed that ‘‘pull’’ keratinocytes together to close the wound. These actin filaments, however, are not an important factor in Collagen Induction Therapy because re-epithelialization, or the closure of the needle holes, occurs within a few hours after needling because the gap is so small.Disruption of the basement membrane by Collagen Induction Therapy destroys the lamina lucida and brings basal keratinocytes into direct contact with the underlying collagen, which inactivates laminin and stimulates keratinocyte migration. When the keratinocytes have joined together, they start producing all the components to re-establish the basement membrane with laminin and collagen types IVand VII.
A day or two after Collagen Induction Therapy, the keratinocytes start proliferating and act more in thickening the epidermis than in closing the defect. Initially after Collagen Induction Therapy, the disruption of the blood vessels causes a moderate amount of hypoxia. The low oxygen tension stimulates the fibroblast to produce more TGF-b, platelet-derived growth factor, and endothelial growth factor. Procollagen mRNA also is upregulated, but this cannot cause collagen formation because oxygen is required (which only occurs when re-vascularization occurs). Collagen type III is the dominant form of collagen in the early wound-healing phase and becomes maximal 5 to 7 days after injury. The longer the initial phase, the greater the production of collagen type III.
If the injury extends deeper than the adnexal structures, then myofibroblasts may contract the wound considerably. Although the injury in skin needling extends deeper than the adnexal structures, because the epithelial wounds are simply cleft, myofibroblast wound contraction may not play a part in the healing. A number of proteins and enzymes are important for fibroplasia and angiogenesis that develop at the same time. Anoxia, TGF-b, and fibroblast growth factor and other growth factors play an important part in angiogenesis. Fibroblasts release insulin like growth factor that is an important stimulant for proliferation of fibroblasts themselves and endothelial cells. Insulinlike growth factor is essential in neovascularisation. Insulin like growth factor or somatomedin-C also is one of the main active agents for growth hormone. Integrins facilitate the interaction of the fibroblasts,endothelial cells, and keratinocytes.
Phase III – The process of tissue remodeling
Tissue remodeling continues for months after the injury and is mainly done by the fibroblasts. By the fifth day after injury, the fibronectin matrix is laid down along the axis in which fibroblasts are aligned and in which collagen will be laid down.
TGF-b and other growth factors play an important part in the formation of this matrix. Collagen type II is laid down in the upper dermis just below the basal layer of the epidermis. Collagen type III is gradually replaced by collagen type I over a period of a year or more, which gives increased tensile strength. The matrix metalloproteinases (MMPs) are essential for the conversion process. The various MMPs are generally classed as MMP-1 (collagenases), MMP-2 (gelatinases), and MMP-3 (stromelysins).
Indications for percutaneous Collagen Induction Therapy
- To restore skin tightness in the early stages of facial aging. This procedure is relatively minor and can safely be recommended. Some patients who are worried about cosmetic surgery may be satisfied with simple Collagen Induction Therapy. The neck, arms,abdomen, thighs, and areas between the breasts and buttocks also can be treated. Upper-lip creases can respond very well to needling but may give an even better result when combined with fat grafts.
- Fine wrinkles are an excellent indication for needling of the skin.
- Acne scarring—the skin becomes thicker and the results are superior to dermabrasion.
- To tighten skin after liposuction.
- Stretch marks.
- Lax skin on the arms and abdomen.
- Scars—if they are white, then they can become more skin colored.
- Hypertrophic burn scars—Collagen Induction Therapycan safely be used in children and may avoid procedures to release contractures.
Contraindications for percutaneous Collagen Induction Therapy
- Patients who have not pretreated their skin with vitamin A.
- Presence of skin cancers, warts, solar keratoses, or any skin infection. The needles may disseminate abnormal cells by implantation.
- Active acne or herpes labialis infections in the face or impetigo lesions anywhere on the body.
- Patients on any anticoagulant therapy like warfarin, heparin, and other oral anticoagulants. The presence of these drugs may cause excessive, uncontrolled bleeding. Patients previously on such treatment should have their coagulation status checked before the treatment to confirm that they have a normal clotting/bleeding profile.
- Many patients take aspirin daily for medical or health reasons. The aspirin should be stopped at least 3 days before the procedure.
- Allergy to local anesthetic agents or general anesthesia. These patients should be assessed by a specialist anesthetist before treatment.
- Patients on chemotherapy, high doses of corticosteroids, or radiotherapy.
- Patients with uncontrolled diabetes mellitus.
- Patients with an extremely rare but severe form of keloid scarring in which virtually every pinprick becomes a keloid. Patients often have keloids on the palms of the hands or soles of the feet.
Technique of percutaneous Collagen Induction Therapy
The skin is routinely prepared by using topical vitamin A and C and antioxidants for at least 3 weeks, but preferably for 3 months if the skin is very sun damaged. If the stratum corneum is thickened and rough, a series of mild TCA peels (2.5%–5% TCA in a special gel formulation) will get the surface of the skin prepared for needling and maximize the result. Under topical, local, or general anesthesia, the skin is closely punctured with the special tool that consists of a rolling barrel with needles at regular intervals. By rolling backward and forward with some pressure in various directions one can achieve an even distribution of the holes. The skin should be needled as densely as possible. Usually, as the needle holes get too close to each other, the needle ‘‘slips’’ into an established hole and so it seems impossible to over treat the skin.
The needles penetrate through the epidermis but do not remove it, so the epidermis is only punctured and will rapidly heal. The needle seems to divide cells from each other rather than cutting through the cells so that many cells are spared. Because the needles are set in a roller, the needle initially penetrates at an angle and then goes deeper as the roller turns. Finally the needle is extracted at the converse angle and therefore the tracts are curved,reflecting the path of the needle as it rolls into and then out of the skin. The epidermis and particularly the stratum corneum remain intact, except for these tiny holes, which are about four cells in diameter. The needles penetrate about 1.5 to 2 mm into the dermis . Naturally, the skin bleeds for a short time, but that soon stops. The skin develops multiple microbruises in the dermis that initiate the complex cascade of growth factors that eventually results in collagen production. After the bleeding stops, there is a serous ooze that has to be removed from the surface of the skin. Wet gauze swabs soak up most of the serous ooze. As the skin swells, the holes are closed, the edges of the epidermis areapproximated, and the ooze stops. Noxious chemicals, however, may still penetrate the skin, so only safe molecules should be used topically.After this serous leak has stopped, the skin is washed thoroughly and then covered with vitamin A, C, and E oil or cream. Alternatively recombinant Beta fibroblast growth factor( BFGF) and Super oxide dismutase may be used which decreases the erythema and improves the pigmentation and healing process.
Care of the skin after percutaneous Collagen Induction Therapy
Immediately after the treatment, the skin looks bruised, but bleeding is minimal and there is only a small ooze of serum that soon stops. We recommends soaking the skin with saline swabs for an hour or two and then cleaning the skin thoroughly with a Tea Tree Oil–based cleanser. The patient is encouraged to use topical vitamin A and vitamin C as a cream or an oil to promote better healing and greater production of collagen. The addition of peptides like palmitoyl pentapeptide could possibly ensure even better results.
At home, the patient should stand under a shower for a long time, allowing the water to soak into the surface of the skin. Patients should be reminded to use only tepid water because the skin will be more sensitive to heat. While the water is running over the face or body, the patient should gently massage the treated skin until all serum, blood, or oil is removed. The importance of a thorough but gentle washing of the skin, a few hours after the procedure, cannot be stressed enough. The skin will feel tight and may look uncomfortable in a few cases. Most patients say that the skin is a little sensitive but the major complaint is about the bruising and swelling.
The following day, the skin looks less dramatic and by day 4 or 5, the skin has returned to a moderate pink flush, which caneasily be concealed with makeup . Men usually seem to heal faster and are less bruised than women. From day 3 or 4 onward, iontophoresis and low-frequency sonophoresis of vitamin A and C could maximize the induction of healthy collagen.Iontophoresis also tends to reduce the swelling of the skin, which also helps the patient look better sooner.Low-frequency sonophoresis can be used alone without iontophoresis to enhance penetration of palmitoyl pentapeptide or other peptides (eg, palmitoyl hexapeptide, copper peptides, and so forth), which also may increase the creation of healthy collagen and elastin. After the skin has been needled, it becomes easier to penetrate, and much higher doses of vitamin A become available in the depth of the skin. Higher doses of vitamin A may cause a retinoid reaction even though the milder forms of vitamin A (eg,retinyl palmitate) are being used. This reaction will aggravate the pink flush of the skin and also cause dry, flaky skin. Needling may cause some slight roughness of the skin surface for a few days, and this condition is definitely worse when topical vitamin A is used. The clinician should ignore this and urge the patient to continue using the topical vitamin A. Patients usually anticipate that their skin will get red and do not complain much about that but become concerned about the dryness. It should be remembered that the skin has lost the important barrier function of keeping the water inside the skin. Until this barrier function is restored completely after a few days, the skin will feel dry. A hydrating cream or even petrolatum can be used to soothe the dry sensation. When the patient has not cleaned the skin thoroughly, a fine scab may form on the surface. The formation of scabs should be discouraged because they may cause obstruction and the development of simple milia or tiny pustules. Milia are uncommon but when they occur, they should be treated by pricking and draining. Tiny pustules are more common and usually found in patients treated for acne scars. It is important to open them early and make sure that the skin has been cleaned thoroughly and that there is no serous residue on the surface. When the pustules are allowed to dry on the skin, they will form thin scabs that effectively prevent the penetration of the vitamins necessary for a successful treatment.
The patient should avoid direct sun exposure for at least 10 days if possible and use a broad-brimmed hat or scarf to protect the facial skin. Patients may shocked when they look in the mirror, but this procedure is a far less shocking experience than laser resurfacing. The treatment can be repeated a month later, but the best interval between treatments is presently unknown. If a clinician intends to achieve a smoothing comparable to a laser resurfacing, then depending on the original state, a patient may require three or even four treatments. The results that are achieved are not temporary but endure for many years. Again, it should be emphasized that this progress is utterly dependent on adequate nutrition for the skin.
Predicted appearance after percutaneous Collagen Induction Therapy
- Immediately after procedure: bleeding and bruising
- Five to 20 minutes after procedure: bleeding stops quickly; serum oozes from the skin
- Day 1: bruised and dark purple-red appearance in light skin; puffy facial appearance; some bruising, especially close to eyes and in thinskinned areas
- Day 2: red-purple hue on light skin like a moderate sun burn; bruising, if any, starts to lighten; swelling may be worse on the second day in many people, and most people are not ready to be seen in public at this stage
- Day 3: appearance still pink, with bruising getting steadily lighter; swelling reduced; some people ready to appear in public but could be conspicuous
- Day 4 to 6: minimal swelling; bruising will take a few days to disappear; can use makeup; patient can appear in public with confidence with the use of makeup
- Day 7: in most patients, very few signs are visible of the procedure. Most patients should be advised to stay off work for between 5 and10 days if they deal with people at work and are sensitive about their own appearance
Derma pen vs. Fractional Laser
Derma pen Treatments are one example of what is known as “fractional rejuvenation”, a term which gets its name from fractional lasers, the technology closest to Derma pen in theory and results. Fractional lasers use heat to systematically ablate “fractions” of the skin’s surface, while leaving surrounding areas in tact, essentially “drilling holes” in the skin to produce a wound healing response. The unaffected tissue around the holes acts as a reservoir for fibroblasts and stem cells needed for regeneration of affected segments. Fractional radio frequency devices work on a similar principle and have many of the same side effects as fractional lasers. Lasers use light to either char and obliterate the epidermis, or “denature” the collagen, depending on the laser type and manufacturer. Derma pen on the other hand, creates reproducible and consistent micro-punctures in the skin without the damaging side effects of heat.
Derma pens mode of action limits the occurrence of side effects specific to fractional lasers, such as:
- Pain; higher in dark skinned patients.
- Persistent erythema.
- Infections (viral and bacterial). Facial herpes reported in 10.6% of patients in spite of antiviral prophylaxis.
- Post-inflammatory hyper-pigmentation in up to 18%
- Post-inflammatory hypo-pigmentation – seen in patients up to two years after a laser treatment. Occurs in up to 20% of patients with photo-aged skin.
Light-based therapy is not for all skin types. The indications for use cleared by the FDA may put limits on the skin types that can be treated with a fractional laser, as is often seen with Fitzpatrick skin types 4, 5 and 6 (darker skin colors). The fractional holes “drilled” by the laser are affected by skin type, skin thickness, and vascularity. Alternatively, the Derma pen is “color-blind” and is therefore safe for virtually all skin types.
A major complication from light-based therapy includes Post-inflammatory Hyper-pigmentation (PIH) in Oriental, Mediterranean, and African skin types. PIH presents as symmetric hyper-pigmented macules and patches on the face, and is one of the most common and distressing pigmentary disorders seen in dermatology clinics. It is notably difficult to treat and may relapse. Micro-needling, for the most part, has not had reports of PIH complications and thus is much safer for darker skin types.
Derma pen vs. Dermal Rollers
Dermal rollers are simpler, less tech-savvy predecessors to the Derma pen. A dermal roller consists of a rolling pin covered with tiny needles. During a derma roller treatment, the roller is rolled across the skin, leaving behind a trail of microscopic punctures. While the needle roller is effective, the rolling action of the device pushes the skin into mounds, and causes the needles to enter AND exit the skin at an angle, creating lateral epidermal tears. The tearing is NOT due to the needles not being “properly anchored” in the skin, but the simple mechanics of angular needle entry. Whilst not detrimental to the results, this makes the treatment much more painful, and often causes a longer downtime for the patient.
The Derma pens needles enter the skin at a 90 degree angle, eliminating the pain and epidermal tearing associated with dermal rollers.The needle roller also makes it difficult to treat certain hard to reach areas, such as those around the eyes, nose and mouth.
The Derma pen tip has a much smaller surface area which comes in contact with the skin, which allows it to treat those hard to reach areas quickly, easily, and effectively. Even though it may seem that such a small contact surface would make the treatment much longer and much more tedious, the truth is to the contrary — because the needles vibrate at such a high oscillation rate, the Derma pen glides across the skin with ease, providing for quicker treatment times.
The different depths needed to treat various regions on the face and body presents another problem — the need for multiple depth rollers to treat just one patient. Some practitioners, due to the high cost of dermal rollers, choose to rely on variable pressure to treat different areas. This means that the practitioner never truly knows the depth of penetration they are achieving at any given point during the treatment.
The Derma pen features adjustable needle depth, making it easy for the practitioner to tailor the treatment perfectly to patients’ needs. Derma pen needles are made of surgical grade stainless steel, which means they retain their sharpness long after a typical Derma pen Treatment is completed. The needle tips are also the only disposable piece of the Derma pen device, which means not only low consumables cost in the long run, but also much less waste, making them a more environmentally-friendly choice.
The most important difference between dermal rollers and the Derma pen lies in the effectiveness of the two technologies. One thing has been repeatedly shown to be true — the more micro-punctures a device is able to achieve, the more dramatic the results will be. With the majority of dermal rollers, the maximum achievable number of holes is somewhere between 300 and 400 holes per second. While the number of micro-punctures created by the Derma pen. With its 12-tip needle head and a motor that produces close to 110 revolutions per second, the Derma pen is able to deliver an impressive 1,300 holes per second, ensuring the most dramatic results.
Types of microneedling devices
- DERMASTAMP – It is a miniature version of dermaroller. Needles are 2mm in length with a diameter of only 0.1mm. They are used for localized scars eg.post herpetic scars, varicella scars, post traumatic scars.
- HOME CARE DERMAROLLERS – They are less than 0.15 mm in length .Mainly used for transdermal delivery of substances like lipopeptides and other antiageing products.
- AUTOMATED ROLLERS – They are battery driven with disposable heads, can be used in more than one patient as disposable heads needs only to be changed. Pressure applied on scars here are uniform.
- Scalp roller: It uses titanium needles unlike steel needles used in other rollers, used to treat thinning hair
Collagen Induction Therapy is a simple technique and, with the right tool, can thoroughly puncture any skin easily and quickly. Although a single treatment may not give the smoothing that is seen with laser resurfacing, the epidermis remains virtually normal. When the result is not sufficient, treatment can be repeated. The technique can be used on areas that are not suitable for peeling or laser resurfacing.