The relationship between light and health has been observed for millennia: Hippocrates often advised his patients to expose themselves to sunlight to treat a variety of ailments. Herodot, a citizen of ancient Cairo, opined that the strength of the human skull was related to amount of sunlight to which a person was exposed (vitamin D?) In more recent times, light (or rather lack of it) has been recognized as causative in seasonal affective disorder (SAD), a depressive condition in which lack of light upon the retina decreases CNS secretion of melatonin and serotonin.
Phototherapy for elevated bilirubin in newborn
Light has found a home in medicine for more than a century. It was first employed as a skin treatment in 1895 when a carbon arc light source was used to treat a patient with lupus vulgaris. Ultraviolet phototherapy has been a recognized treatment for a number of skin conditions for decades, psoriasis, eczema, and pityriasis rosea among them. Neonatal jaundice has long been treated using artificial blue light. It has been used to treat acnes since 1978 and SAD since the 1980’s.
Light, in numerous manifestations, found a home in aesthetics years ago. It is one of the most widely used forms of energy in skincare with new modalities constantly evolving. Let’s take a look at the role of light in aesthetics – how it’s used and what benefits it offers.
The Miracle of Lasers
The word laser is an acronym for Light Amplification by the Stimulated Emission of Radiation. The light emitted is profoundly different from sun light, or light emitted by common artificial light sources. Laser light can be immensely intense, powerful enough to cut through steel or destroy a rocket in mid-flight. It can also be incredibly precise and delicate, even used to cauterize tiny bleeding vessels in the retina of the eye. Lasers are now everywhere: office copiers, surveying equipment, computer mice, industrial measurements, even “pointers” to direct an audience’s attention to PowerPoint slides.
The laser was invented in 1957 by a graduate student in physics at Columbia University. He devised a cylinder with mirrors at both ends facing inwards, with one of the mirrors being slightly less reflective than the other. His theory was that when a light source was introduced, the light source within the cylinder would bounce back and forth, gaining energy to the point that some of the light would emerge through the less reflective mirror. He was right, although now lasers have two highly reflective surfaces with one of them having a small transparent window to allow light to emerge. In more technical terms:
“A laser is an optical oscillator, which is made out of a solid, liquid or gas with mirrors at both ends. To make the laser work, the material is excited or “pumped,” with light or electricity. The pumping excites the electrons in the atoms, causing them to jump to higher orbits, creating a “population inversion.” A few of the electrons drop back to lower energy levels spontaneously, releasing a photon (quantum of light). The photons stimulate other excited electrons to emit more photons with the same energy and thus the same wavelength as the original. The light waves build in strength as they pass through the laser medium, and the mirrors at both ends keep reflecting the light back and forth creating a chain reaction and causing the laser to “lase.”
The combination of spontaneous emission first, and then stimulated emission, causes the laser to “lase,” which means it generates a coherent beam of light at a single frequency. The wave length of the light emitted is dependent upon the substance being used to generate the photons within the laser. Wavelengths are measured in nm (nanometers) and lasers in medicine have particular clinical applications that are best treated using machines with certain wavelengths.
Lasers in Aesthetic Medicine
The unique ability of optical technologies to target specific structures and layers in tissues to cause chemical, mechanical, or thermal changes makes them a powerful tool in cutaneous rejuvenation, hair removal, fat removal, and 
treatment of vascular lesions such as port-wine stains, among many other procedures. With the development of epidermal cooling, lasers and optical technologies have become more versatile and safe. They are constantly being improved to provide safer, easier, more quantifiable, and more individualized therapy.
Lasers have become particularly useful in the management of photoaging, with protocols involving single or combination systems depending on degree of skin damage. Treatments can be aggressive with extensive tissue damage, significant healing “downtime”, and increased risks of untoward pigmentation and scarring, or superficial and subtle, sometimes requiring multiple treatments to achieve desired results. In recent years, there has been a trend toward less invasive or minimally invasive treatments, with the aim of reducing the risk of side effects, complications, and downtime.
A compromise treatment utilizes fractional resurfacing or photothermolyis, where the laser injuries are tiny and performed in a grid-like pattern, leaving large percentages of undisturbed skin.. These are less aggressive than CO2 resurfacing and result in much less patient down-time. The physician tailors the skin resurfacing procedure to each person’s unique needs. The technology can be used on light, medium and deep settings depending on the amount of improvement and the number of days for complete rehabilitation along with the number of treatments desired. It does not have the previous CO2′s high risk of discoloration, long healing times and prolonged erythema.
Obviously, lasers and light-based treatments alone might not be sufficient to control all aging symptoms. For this reason, many other treatments (botulinum toxin, dermal filling agents, chemical peels, systemic and topic Improved therapeutic results. Overall, there is a transition in antiaging aesthetics from aggressive surgical interventions like facelifts, to more natural looking and subtle changes.
Most Common Lasers Used in Medical Aesthetics
Carbon Dioxide (CO2) Laser
The CO2 laser system works on 10600 nm wavelength and can be used in several ways: “focused” for cutting skin without bleeding; “defocused” for superficially vaporizing skin; and “ultra pulsed” for facial resurfacing. By delivering very powerful, rapid pulsing or scanning of the latest generation of CO2 lasers, laser surgeons are able to resurface the skin for cosmetic improvement. This technique removes fine lines and wrinkles of the face, smoothes acne scars, and rejuvenates aging and sun-damaged skin as it contours the skin surface. When the CO2 laser’s energy is defocused and not continuous (pulsed), the dermasurgeon can treat warts, shallow tumors and certain precancerous conditions. When the CO2 laser energy is continuous and focused into a small spot of light, the beam is able to cut the skin. It is used in this way to remove skin cancers, to treat a variety of non-vascular and pigmented lesions and for eyelid operations. This technique is also used to remove warts and for some surgical incisions.
Erbium (Er:YAG) Laser
One of the latest tools available for the treatment of wrinkles, acne scars, aged and sun-damaged skin, the Erbium is a cool light laser that resurfaces the skin. This method results in less post-procedure redness, less swelling and faster healing time and much less risk of side effect than with other strong laser skin resurfacing methods. The Erbium laser can be used on the face, neck, chest and hands. The erbium:YAG 2940 nm (Er:YAG) laser produces energy in a wavelength that gently penetrates the skin, is readily absorbed by water and scatters the heat effects of the laser light. These properties enable laser doctors to remove thin layers of aged and sun-damaged skin tissue with exquisite precision while protecting healthy surrounding tissue. The Er:YAG laser is commonly used for skin resurfacing to improve moderate facial wrinkles, mild surface scars or splotchy skin discolorations. Newer Er:YAG lasers have an extended pulse duration that allows them to act in a similar manner to the CO2 laser.
Yellow Light Laser
Through the use of an organic dye, short pulses of yellow-colored light (578 nm) are produced. A popular yellow light laser is the pulsed dye laser. Because yellow light is more precisely absorbed by the hemoglobin than other colors, these lasers are effective in the treatment of blood vessel disorders, such as port wine stains, red birthmarks, enlarged blood vessels, rosacea, hemangiomas and red-nose syndrome. Certain yellow light lasers may also be used to treat stretch marks and are safe and effective for infants and children.
Green Light Laser
The green light (511 nm), in contrast, is used for the treatment of benign brown pigmented lesions, such as café-au-lait spots, the “old age” spots commonly found on the backs of the hands and lentigines or freckles. Green light lasers are also used for the treatment of small blood vessels on the face and legs.
Red Light Laser
The red light spectrum produced by the ruby or alexandrite light laser is emitted in extremely short, high-energy pulses due to a technique known as Q-switching. The Q-switched ruby or alexandrite laser systems were initially used to remove tattoos, but are now commonly used to treat many brown pigmented lesions, such as freckles or café-au-lait spots.
When the pulse duration of the ruby or alexandrite lasers is lengthened, it is effective in removing unwanted hair for long periods of time, sometimes even permanently.
Q-Switched Neodymium YAG (Nd:YAG)
Delivering infrared light, it is used to remove tattoos and deep dermal pigmented lesions, such as nevus of Ota. This laser can also be tuned to produce a green light for the treatment of superficial pigmented lesions like brown spots, as well as orange-red tattoos.
KTP
The KTP emits a green light and is capable of treating certain red and brown pigmented lesions. When the pulse duration is lengthened, the Nd:YAG laser is also effective in removing hair and an inflammatory condition termed pseudofolliculitis barbae for months and sometimes permanently. This is particularly useful in the treatment of dark-skinned patients.
Non-Ablative Lasers and Light Sources (IPL)
Instead of heating and removing the top skin tissue, non-ablative (non-wounding) lasers work beneath the surface skin layer to improve skin tone and texture and minimize fine lines with few side effects and a speedy recovery. Light-based devices that produce a broad spectrum of light (wavelengths) with computer-controlled parameters of energy delivery (Intense Pulsed Light, or IPL) can be adjusted according to a patient’s skin type and condition. This technology is primarily used for the treatment of benign red and brown lesions, hair removal and facial skin rejuvenation.
Results Can Indeed be Impressive
Cautions and Contra-indications
Certain skin conditions, health irregularities, and medications can impact whether it is safe for a person to receive a light based treatment. This list applies to both IPL and conventional laser treatments.
- Recent use of depilatory creams or sprays
- Recent waxing, tweezing, or sugaring
- Contagious skin diseases: not always contraindicated but requires special preparation
- Herpes I and II in the area to be treated: not always contraindicated but requires special preparation
- Skin trauma, lesions, sores or open wounds
- Keloid or hypertrophic scarring
- Moles or skin cancer: treatment can blanch skin marks, making melanoma difficult to detect
- Sunburn
- Suntan, real or fake: hyperstimulates melanin in skin which provides a confusing target for light
- Epilepsy or other seizures potentially caused by flashing light
- Polycystic Ovarian Syndrome (PCOS): condition needs to be normalised with medication before treatment
- Hyperthyroidism: condition needs to be normalised with medication before treatment
- Breastfeeding and pregnancy: increased hormone levels greatly decrease treatment efficacyHirsutism: not contraindicated but will require a greater number of treatments]
- Tattoos or permanent makeup in area to be treated
- Photo-sensitising topical creams or medication: Tetracycline, Minomycin, Doxycycline, St John’s Wort, any citrus essential oils
- Black garments: can singe or combust if struck directly by the light flash
- Pain during treatment: if a person feels more than mild discomfort during treatment, the machine settings are wrong
- According to Remington, manufacturer of an IPL hair remover, all IPL and laser devices should only be used on light to medium skin tones, and work best on darker hair.
Hi, doctors!
It’s been such a pleaure browsing through your blog and now, having done so, mind stimulated and funny bone tickled, I’m left with two and half questions (presented in order of priority):
1) Will you marry me?
2) Where can I find, and how can I acquire the products your company makes?
Thank you for answers past and pending!
Sheryl, thanks for taking the time to poke around here at BFT. It is a labor of love as we try to entertain while we educate and spark the occasional incendiary debate. As far as getting married on such short notice, no can do. Drjohn and drgeorge can be considered “old married farts” with many decades of marital bliss between us. (For me, drgeorge, my wife would agree the name sometimes fits…she never did think “Dutch ovens” were all that funny and banned them long ago.
To find and acquire our products, stop by AnteAGE.com. We’d love to hear from you, and, more importantly, prove to your our science does make a difference in skincare.
Darn! All the ‘good ones’ are already married aren’t they??? Anyhoo, here is a product being offered on ULTA’s website for $29.99. What say you concerning the claims in light of (sorry, couldn’t resist) your above information of some laser lights being beneficial? Thanks!
Details-
The skin around the eyes is delicate so it is often that area that shows the first signs of age. Skin cell turnover is a key to young looking skin. As we age, skin cell turnover slows down. Red light therapy safely penetrates skin tissue, and the light energy activates an enzyme called ATP, a skin cell power booster which stimulates turnover and repair. This regeneration increases circulation which leads to collagen and elastin production resulting in firmer, smoother skin and more even tone. Infrared light penetrates even more deeply to rejuvenate dermal and epidermal cells reducing fine lines and wrinkles.
With IlluMask you can expect:
Fewer fine lines, wrinkles and crow’s feet.
Hydrated and firm skin around the eyes.
Smoother texture of skin around eyes.
Eye area appears brighter, more radiant and makes you seem more awake.
Reduces the skelital appearance of sunken eyes.
No damging UV lights – safe for all skin types and tones and sensitive skin.
Gentle on the delicate skin aroudn the eyes.
I thought it was really interesting that the one before and after photograph you have above (the lady with the longer blond hair) also appears on the website of a skin care line (http://mindfulminerals.com/anti-aging/). They don’t specifically say that this lady used their product but the implication is very blatant. Do you know if this is a standard stock image that can be purchased somewhere? Since I retail this particular line in my spa, it makes me question their authenticity….
Hi Michelle, that is not a stock image. It was supplied by our friends at Lasering USA who sell the MixTo CO2 laser, and the picture credit is Jannine Kafford, a physician who uses the MixTo and got these results. It is not uncommon for companies to purloin images from the internet and claim them as their own. Dead Sea, or Dead Conscience? I think is is copyrighted, so with your permission I will report the infringers to the copyright owner. Let’s see how fast it comes down. May I suggest a new line?
Hi, I realize I’m a bit late to this thread, but I had some questions.
I was wondering if you could provide the common names for these lasers that doctors use. For instance, I recently had what was termed a v-beam treatment, and I can’t tell which of the above lasers this one is.
Is one of the above lasers the new Pico laser, which is supposed to provide superior rejuvenation results?
Lastly and most importantly, what about the issue that some or all of these lasers cause fat atrophy?
I appreciate your work here, thank you!
Mary
Mary, thanks for your question.
Soon after discovery, lasers found a place in medical care. Lasers provide easily focused controllable energy capable of use to shape, cut, vaporize, heat, melt, and coagulate different types of tissues, both external and internal. The key to appropriate application is proper selection of the wave length of the light beam being utilized. Different wave lengths make it possible to control depth of penetration, preferentially select lipid or water in tissues, and treat structures of specific color, most notably red (blood) or brown (melanin.) A perfect example is the eye, where laser of one type can be used to coagulate leaking blood vessels in the retina, and another can reshape the surface (cornea) of the eye to change the refractive index and make vision clearer.
There are lasers in the ultraviolet, visible, and infrared spectra, the light beam produced depending on the substrate being utilized to generate the radiation wave length. The V Beam laser is used to treat red colored structures such as the dilated vessels seen in rosacea. It is also a pulsed laser, one that is on, then off, to prevent overheating of tissues. Because the transmitted energy is concentrated in hemoglobin, surrounding tissue is spared and the intermittent nature of the beam enables treatment without the need for anesthesia in most applications. The V Beam laser is a pulsed dye laser, one that can be “tuned” by varying the color of the dye used to produce the light beam. It is used to treat vascular lesions of several types.
The “pico” laser refers to a type of powerful beam laser that is emitted in ultra-short duration pulses, i.e. picosecond bursts. It can be used to remove tattoos. Lasers in general have variable settings that permit one to control pulse length duration. As a rule, darker skin types require greater caution as to pulse lenght since pigmentation results in larger amounts of energy being transformed into heat. High intensity is required to “shatter” the ink particles yet very short duration is needed to prevent excess heating of surrounding tissue.
As to fat atrophy being a side effect of laser treatment, that is not a major concern for superficial treatments as the energy cannot penetrate to subcutaneous depths. Laser, however, has found a home in fat removal and is used in some liposuction technologies and to vaporize fatty deposits within the lumen of blood vessels. I can think of no energy modality that has found so many disparate and varied uses in medicine.
Thanks for such a thorough and comprehensible reply! As to the last point, can one safely assume that the margin between a superficial treatment and one that vaporizes fatty deposits is wide enough to allay concerns (yes, I’m paranoid!)?
I really appreciate your willingness to engage on these topics.
Yes, there is a good margin. By measuring skin temperature, you can pretty much control that variable.
I absolutely love your website/articles and information. I’d love to hear your opinion about Tria laser (for anti aging – not the hair removal device).
Thanks,
Brandy
Overpromised, underpowered. In short, we are underwhelmed.
I’ve had the Tria since February and while I do agree it’s underpowered (I do double sessions on the highest setting), it’s still slowly transforming my skin. I recently started using Anteage serum and accelerator after using the Tria and the result from that is brilliant. The Tria has been a great solution for people like me who don’t have a week or more to recover from a proper fraxel treatment, and after adding the Anteage, I could not be happier.
We are delighted to hear of your good results. While we have tested AnteAge in combination with lasers of various sorts, microneedling, RF, fractional RF, etc. we have not yet tested with a non-ablative laser technology. Perhaps Tria lasering is to resurfacing with CO2 lasers what cosmetic needling is to medical needling? If so we would expect stellar results. Please send any pictures you may have taken long the way – others might benefit from your experience. Thanks.
How would you compare microneedling vs laser treatments? Specifically:
1. “spider veins” (dilated capillaries) can definitely be addressed by lasers, but the more credible sources on microneedling seem to say that microneedling is at best unlikely to address it. What other kinds of skin damage are similarly better addressed with lasers?
2. is there any form of laser treatment that replicates the ability of microneedling to get cosmeceuticals into deeper layers of skin? Fractional resurfacing seems to have the same concept of grid-like damage to stimulate healing.
Thanks in advance docs, really enjoying your in-depth takes on various topics.
Hi Charles.
Lasers and microneedling definitely compete for the same indications. Both cause microwounds, but in different ways. Lasers create multiple tiny wounds with areas of healthy tissue in between. So does microneedling. But the difference is that lasers heat up the tissue, destroying some cells around the boundary of the light itself, and also coagulating the tissue to create eschar. Like charring a steak on the BBQ. This has advantages for things like spider veins, where coagulation causes the veins to regress – sort of like pruning. It also controls bleeding. Microneedling causes wounds without heating. They are wider, but fewer cells are damaged or killed, leaving more surrounding tissue intact. Lasers interact with chromophores (pigment in the skin), and therefore varies between people of different skin colors. Microneedling does not. Microneedling produces channels which are also portals of entry, whereas lasers tend to seal the tiny holes through coagulation. These channels can be used for good (infuse human cytokines and growth factors) or evil (infuse snail and other proteins foreign to humans leading to granulomas). Both modalities can be used selectively to improve sun damaged and aged skin, wrinkles, scars, and stretch marks. Both can be used for problems involving pigmentation, but it is trickier with laser, for reasons cited above. Microneedling equipment costs a lot less, and treatments are generally less expensive. They can also be used together. And there are new machines out there that combine microneedling with RF pulses that sort of blend all this together and blur the boundaries.
How are lasers any different from getting a sunburn? Lasers cause damage and inflammation to the skin and underlying tissues for a temporary? plumping affect. Isn’t it causing more damage in the long term? Isn’t it like tanning…Sure, it may look nice now…but 20 years down the road the “effects” show up –wrinkled, sagging skin and face! Cancer, even.
Can you explain how lasers are NOT a temporary “fix” that comes crashing back to bite you later on? I would like someone to explain how it is not damaging to skin and tissues. Are you suggesting that inflammation is good for us? Because that’s what lasers do–they inflame, wound, and damage. You’re saying this doesn’t have consequences beyond the near term “plumping” effect everyone is chasing after? It builds collagen, does it? Or does it inflame tissues so that they swell in reaction? If it truly builds collagen instead of ultimately tearing it down, why haven’t doctors used laser to rebuild collagen in joints for those with real medical issues, such as arthritis?
Is there any scientific explanation WHY damaging the tissues with inflammation doesn’t ultimately degrade and harm collagen? Lasers are the exception to the Inflammation Is Bad for Skin and Health credo?
Funny how no one ever brings this up. I would appreciate it if you could bring clarity to this.
Thank You
Jane, thank you for a very good question. We’ll discuss inflammation next; let’s first speak to how light wavelength and intensity affect the skin and the injuries it causes– first from sunlight, then from lasers.
Sunlight is comprised of visible and invisible light. When it comes to skin damage it is the UV light that is the culprit. There are three classes, UVA, UVB, and UVC, which are defined by the wavelength with UVC being the shortest, UVB next shortest, and UVA the longest. The shorter the wavelength, the more damage it can cause.
UVC is, thankfully, completely filtered out by the atmosphere, either by dioxygen (100-200 nm) or by ozone (200-280 nm). It is so lethal, it is used purposefully in machines intended to sterilize equipment and surfaces.
Medium-wavelength UVB is very biologically active but cannot penetrate beyond the superficial skin layers. It is responsible for delayed tanning and burning; in addition to these short-term effects it enhances skin ageing and significantly promotes the development of skin cancer. Most solar UVB is filtered by the atmosphere. Only about 5% of the UV light reaching the earth’s surface is UVB.
The relatively long-wavelength UVA accounts for approximately 95 per cent of the UV radiation reaching the Earth’s surface. It can penetrate into the deeper layers of the skin and is responsible for the immediate tanning effect. Furthermore, it also contributes to skin ageing and wrinkling. For a long time, it was thought that UVA could not cause any lasting damage. Recent studies strongly suggest that it may also enhance the development of skin cancers.
Everyone is familiar with the term SPF which refers to the multiple amount of time one can spend in the sun without burning with and without sunscreen protection. The higher the SPF, the more UV energy is blocked or absorbed by the sunscreen.
Lasers are a different concept although wavelength does again enter into their utility and ability to penetrate the skin. Again, shorter wavelengths have less ability to penetrate the skin. Lasers may employ invisible (i.e. UV and infrared) or visible light. The UV lasers have shallow penetration and longer wavelengths, i.e. blue, green, or red lasers, penetrate more deeply. There are literally thousands of lasers with light of all wavelengths possible. Types include gas, chemical, dye, metal-vapor, solid-state, and semi-conductor lasers. Medicine utilizes a handful of wavelengths; industry has an almost inexhaustible number of uses for lasers, from ultra-precise measurements to cutting steel.
Another consideration in laser selection is for what purpose is the laser being used. Brown (melanin) and red (blood vessels) lesions in the skin will absorb different wavelengths to different degrees. New, state-of-the-art lasers have revolutionized the treatment of skin disorders including pigmentation, freckles, brown spots and tattoos. Lasers are often the treatment of choice to treat ‘broken blood vessels’, spider veins, leg veins, and port wine stain birthmarks as well as redness within hypertrophic scars and stretch marks. All of these lesions can be treated with various lasers which either target pigment or hemoglobin (a component of blood).
Depending on the purpose of the laser treatment, a variety of choices exist. For skin rejuvenation, carbon dioxide gas lasers are commonly used. They produce infrared wavelengths which is absorbed by water extremely well. Whereas they were originally used in a “continuous” mode, they are now used in a “fractional” mode that allows varying amounts of surface area to be ablated i.e. vaporized. The length of time they are on, the “dot” size, and the spacing of the injuries allows specific percentages of surface area to be treated. Adjustment of power, dwell (on/off) time, and spot size also determines how deep the individual burn injuries penetrate into the skin.
About inflammation: our bodies are programmed to initiate the healing process with a few days of acute inflammation. In the very old days, this may have been lifesaving when an animal bite or scrape against a dirty rock could lead to a fatal infection. With sterile surgery, and modern hygiene, the need is less or non-existent, yet we still inflame. When excessive or chronic, inflammation can lead to unpleasant aesthetic results – excess pigment, fibrosis (scarring), wrinkles, a variety of skin lesions, including cancers.
BFT readers know we are all about minimizing inflammation as the key to improving aesthetics in the skin, either acutely or chronically. Sun worshipers create a state of chronic inflammation is the skin and we all know where that leads. In the case of iatrogenic (doctor-caused) skin damage, such as laser resurfacing, we are huge proponents of exiting the inflammatory phase as quickly as possible to get on with the process of healing and avoiding pigment and fibrosis issues.
(WARNING – ANOTHER HORN TOOT!)
Our AnteAGE MD products are routinely used by some of the largest laser clinics in the U.S. and Canada during the acute recovery phase after laser resurfacing, precisely because they quench the fires of inflammation, speeding recovery and improving outcomes.
Hi Drs, have you heard of a home device called Mykinbuddy (see myskinbuddy.com) that uses ultrasonic vibration, ion care, LED and thermal heat therapy. It can be used to cleanse, tone and moisturize. It claims to enhance product penetration, reduce redness and inflammation, stimulate collagen, reduce appearance of fine lines and kill P. acnes bacteria. I’m not convinced using LED light for less than 10 minutes would be very helpful for wrinkles/acne. I’m not too familiar with the other technologies. Would buying this device be a worthwhile investment in your opinion? Your input is much appreciated!
It tries to do too many things at once. And wrong settings. Iontophoresis is a good modality for penetration, but not at those levels. Similar problem with ultrasonic vibration, the mhz setting is too high.LED has weak evidence.
Hi drjohn: what sort of levels for iontophoresis/ good mhz for product penetration would you say are a good rule of thumb to look for? Thank you! (sorry I may have posted this as a stand alone comment rather than a reply!)
US 20 khz, IP 0.27-0.33 mA/cm2
Han T, Das DB. Potential of combined ultrasound and microneedles for enhanced transdermal drug permeation: a review. Eur J Pharm Biopharm. 2015;89:312–328.