The practice of medicine is experiencing a massive renewal equal in significance to the great Medicine Renaissance of the 15th Century. In many ways, aesthetics is leading the charge as more people desire natural anti-aging therapies rather than chemical-based treatments or other substances foreign to their bodies.
With regenerative aesthetics, the body’s ability to heal is enhanced via therapies that incorporate the patient’s own tissue, platelet-rich plasma (PRP), stem cells, growth factors, peptides and other biocellular-based resources extracted from blood and tissue.
According to Ryan Welter, MD, PhD, CEO and medical director of Regeneris Medical (Attleboro, Mass.), the fundamental driving force behind this regenerative movement is the desire to reverse and slow the aging process. “There are a lot of emerging therapies that are showing up in both the biological scientific/experimental world, and lately in the clinical world. It started with PRP use in aesthetics and transitioned into other kinds of cell treatments that are being developed into more powerful clinical approaches,” he said.
When Gregory Chernoff, MD, a facial plastic and reconstructive surgeon in Beverly Hills, Calif., started talking about cellular medicine 20 years ago, “it was considered science fiction. People wondered what planet I was from. Today, the entire field of medicine is interested in it,” he noted.
With regenerative aesthetics, the biggest challenge confronting physicians is how to treat the patient’s overall wellness holistically, rather than looking at them for one-off treatments.
“If someone is coming in to an aesthetic practice, it is because they are interested in looking good,” stated Kristin Comella, PhD, chief scientific officer of U.S. Stem Cell (Sunrise, Fla.). “Nonetheless, while they are worried about some sagging skin or wrinkles, they are also thinking that their knee hurts. So, if the physician can provide a stem cell injection in their knee while they are getting a stem cell facelift, they are addressing the whole person.”
Most regenerative aesthetics-based procedures center on the use of fat transfer in combination with other modalities to treat the skin and add volume. “Fat is liquid gold,” Dr. Comella stated. “When undergoing cosmetic procedures, patients have an opportunity to also con- sider the health benefits of regenerative medicine. Instead of just throwing the fat away, they can opt to isolate those cells for use in treating a variety of different conditions,” she said.
Resizing fat – including the use of micronized and nano-fat – is a growing trend in regenerative aesthetics, noted Gregory Laurence, MD, a cosmetic, plastic and reconstructive surgeon in Germantown, Tenn. “I also consider PDO threads and the collagen stimulating fillers, such as Bellafill (Suneva) and Sculptra (Galderma), as part of the regenerative space. We can connect all of the avail- able technologies to work together, from lasers and other energy-based modalities to stem cells, growth factors and other bio-cellular approaches.”
Combination therapies are dominating, Dr. Welter echoed. “Regenerative medicine is not comprised by just one technology. It is many technologies that are generally very safe and effective, and combining them only makes sense. For instance, the use of energy-based devices to stimulate stem cells that are combined with PRP and growth factors, has shown tremendous results on the skin, which has been well studied. We can also use amniotic tissue. Intravenous stem cell deployment into the body is becoming popular, as well.”
“We have a procedure that combines energy-based technology with PRP, as well as adipose derived stem cells,” said Tess Mauricio, MD, a cosmetic dermatologist with practices in San Diego and Beverly Hills, Calif.
“Multiple areas are treated with a single harvest of the patient’s fat, and then parts of that will go into the scalp for hair rejuvenation. We then re-volumize the eyes and face with micronized fat, after which we do a skin resurfacing combination therapy,” she elaborated. “Patients can also get an IV-based regenerative stem cell therapy. And, we can perform vaginal rejuvenation, in which we combine CO2 laser treatment with injected PRP and micronized fat. All of this in one day.”
Some of the more cutting-edge developments in regenerative therapies come from the work of biohackers. There are people that specialize in applying the tech-hacker philosophy to biology, where in small labs and at some universities, scientists and researchers explore biology “hacks” intended to improve quality of life via experimental biologics.
Aside from these unorthodox approaches, most regenerative-style combination treatments currently used in practices involve PRP and, to a lesser degree, stem cells. According to Warren B. Seiler, III, MD, a cosmetic surgeon and medical director at Seiler Skin (Homewood, Ala.), “The main difference between PRP and stem cells is that stem cells have not been designated as one type of cell. They can differentiate themselves as new tissue structures, cartilage, skin, etc. PRP is simply the part of the patient’s blood that contains healing elements, growth factors, cytokines and stimulators that aid the healing response.”
A relative of PRP, platelet-rich fibrin matrix (PRFM) is popular as well, Dr. Laurence noted. “Physicians will inject the fibrin matrix into a patient’s tissue, where it acts as a scaffold for the PRP to take hold and secrete its growth factors,” he explained. “We have been achieving really great results with the PRP and PRFM combination in hair restoration. It does not magically grow hair, but when you inject it into the scalp, it decreases shedding for people who are prone to alopecia, and it dramatically increases the diameter of the hair follicles,” he said.
Dr. Seiler utilizes PRP and its variants post-surgery to help in wound healing. “It is great for anti-aging in general, but especially for treating scars,” he stated. “We draw blood and spin out the red blood cells in an FDA- approved process using a centrifuge, and then reinject the PRP back into the patient, whether it is in the face or other body areas. You can do it via needle injection or microneedling. It is safe and, if done correctly, is very beneficial for the patient.”
As these treatments grow more sophisticated, so does the hardware and processing technologies that provide better quality PRP yields. For instance, RegenLab® (New York City, N.Y.) offers a line of expertly designed medical devices manufactured in Switzerland, including the RegenKit®-BCT product family for the preparation of leukocyte poor PRP; RegenKit-BCT-1 Plus for the use of autologous PRP and autologous thrombin serum; and the RegenTHT kit, which produces PRP enriched in MNC (lymphocytes and monocytes), but poor in granulocytes. The low blood volume requirement allows for physician ease- of-use and a positive patient experience.
Sachin M. Shridharani, MD, a plastic surgeon in New York City, processes PRP using RegenLab products in combination with a variety of microneedling therapies, including scar treatments and hair restoration. “We needed an FDA- cleared product backed by good science and good data in order to optimize outcomes,” he said. “RegenLab had the right proprietary technology, which we found came with high predictability and high yields of good PRP.”
Another system, ProGen PRPTM Advantage from Bellus Medical (Dallas, Texas), is an easy-to-use, one spin system that features 15 mL and 30 mL tubes. This enables production of PRP in larger volumes, providing a low cost per mL of PRP and the flexibility of increasing PRP volume when needed. In addition, the company says that its ProGen PRPTM Versa system provides the greatest yields of platelets and a high return on investment per mL.
Along with PRP, other treatments and modalities are gaining a foothold in medical aesthetics. For example, Suneva Medical (Santa Barbara, Calif.) has begun marketing a triptych of products that support regenerative therapies, including its Bellafill long-lasting dermal filler combined with Puregraft® fat grafting products and Suneva HD PRP, a PRP processing system that features an innovative high platelet capture design. The company’s goal is to lead practices to adopt regenerative aesthetics utilizing its multi-modality kit.
Regenacell Therapy, Inc. (Castle Rock, Colo.), recently launched another system aimed at encouraging physicians to implement regenerative treatments. The Lipo-Pro System allows for the sourcing of adipose aspirate and subsequent graft processing at the point of care, from which the clinician can prepare a small volume of adipose tissue for use as a high-density fat graft.
As more regenerative therapies enter the marketplace, they are an easy sell to patients, Dr. Mauricio highlighted. “Especially if they have had experience with fillers, then they come in aware of a filler’s limitations. As a result, they are very open to getting fat transfer procedures instead. With regenerative aesthetics, we can also address all of their rejuvenation issues at a lower cost than with traditional cosmetic procedures.”
A relatively new element, exosomes, are now being deployed for regenerative work in scar therapy. Exosomes are lipid vesicles that carry proteins and genetic information among cells. “When you excise, for example, a keloid scar, and inject exosomes, you are creating a whole new capability for introducing new cells to reprogram the tissue in the affected area,” said Dr. Laurence.
Another growing area is the use of allografts and extra-cellular matrices to support fat grafting and facial volumization. Some of these bio-cellular products are sold directly to physicians by tissue banks. In addition, recent clinical studies offer evidence that the implantation of an allograft adipose matrix leads to safe, sustained volume retention in human tissue.
A recent product in this genre, Renuva from MTF Biologics (Edison, N.J.), is an all-natural extracellular injectable matrix that acts as a scaffold, allowing the body to recruit new fat cells that attach to it. Made from human allograft tissue and containing the same collagens, growth factors and proteins in its matrix as autologous fat, Renuva is a soft tissue injectable that is an alternative to fat grafting.
Practitioners have come up with novel uses for extra-cellular matrix products. As Dr. Chernoff reported, “I had a patient who was a smoker and got a facelift. She massaged the scabs and eventually got a large wound on her cheek. In the past, we would’ve had to rotate a flap or put a skin graft on the area. Instead, we took a relatively inexpensive sheet of placentallyderived extracellular membrane and laid that on her face with a couple of stitches to hold it in place. She totally re-epithelial-zed within a couple of weeks.”
There is more to regenerative medicine than the integration of stem cells, growth factors and other cell-based elements with traditional aesthetic approaches. Physicians must consider working in unfamiliar areas like hormone
optimization to address a patient’s well- rounded wellness regimen.
“Hormone optimization is not necessarily about treating a medical deficiency or abnormality; it is about optimization for anti-aging purposes,” Dr. Welter explained. “There are different sets of parameters and guidelines that we want to follow when we look at optimization versus treatment. Then we also look at vitamin levels. The patient’s B complex and vitamin D levels all have to be optimized in order to address bioidentical hormone deficiency.”
Additionally, topical products that avoid the use of chemical ingredients have become an essential adjunct to new holistic regenerative approaches. For instance, the innovative cell-based skin- care products from DefenAge (Carlsbad, Calif.), utilize defensins, which are naturally, occurring peptides that work to activate the body’s dormant reserve of LGR6-positive stem cells. Once activated, these stem cells “reprogram” the skin to become visibly younger and to help reverse visible signs of aging.
In spite of these advances, main- stream acceptance of beneficial cell- based approaches is slow because so few therapies are FDA-approved. In addition, the agency has pushed back strongly on some clinics that offer popular stem cell therapies. For instance, The Cell Surgical Network (CSN), in Rancho Mirage, Calif., which consists of a group of stem cell clinics in the U.S., were sued by the FDA and DOJ in May 2018. The suit sought a permanent injunction against the clinics’ marketing of adipose-derived stem cell procedures.
Additionally, U.S. Stem Cell recently lost a court case against the FDA after being prosecuted for marketing unapproved stem cell-based products and violating manufacturing requirements.
“As the adoption of regenerative aesthetics takes hold and regulatory issues get solved, we must consider that there is going to be fear about the widespread changes that are related to disruptive cell-based medicine,” said Dr. Laurence. “It is important for manufacturers, physicians and the FDA to be transparent for progress to be rapid. While I admire the FDA for its longstanding rules that relate to patient safety, I admire stakeholders like CSN and others for being advocates for change and pushing for regulatory guidance that makes sense.”