Amer H. Nassar1, Andrew S. Dorizas2, and Neil S. Sadick3,4 1 Division of Plastic Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA 2 Department of Dermatology, University of Miami, Miami, FL, USA 3 Sadick Dermatology, New York, NY, USA 4 Department of Dermatology, Weill Medical College of Cornell University, New York, NY, USA Dermal fillers have been utilized for decades, and recently their demand in cosmetic purposes has increased significantly. Although the desired outcome remains the same, the materials used to achieve facial contouring and correct volume loss have changed dramatically. The recent introduction of autologous dermal fillers in the field of cosmetic dermatology has shifted the focus into yet a new direction, one that possibly enhances many of the desired effects, while abolishing the adverse ones. Although autologous fillers are new and have a promising future, they are yet to be studied on a large scale. Platelets were first described by Max Schulze in the mid‐1800s, and their role in coagulation and blood clotting was discovered a short while later when Giulio Bizzozero noted the relationship between their adhesion, aggregation, and the subsequent fibrin deposition [1]. The wide role platelets play in a multitude of other processes have since been described, one of which is the healing process. Platelets release a number of growth factors (Table 47.1) including transforming growth factor beta (TGF) and platelet‐derived growth factor (PDGF), both closely involved in wound healing and the repair and regeneration of tissues. Platelet‐rich plasma (PRP) is a concentrated source of autologous platelets, prepared from whole blood, containing roughly five times the amount of platelets as the baseline blood platelet count. These features make PRP a great source of growth factors, and its capabilities in assisting in wound healing and tissue regeneration has attracted considerable interest from the medical community [6]. Recently, the dermatological possibilities of PRP for skin rejuvenation were recognized, and its ability to serve as an autologous dermal filler was comprehended. The cocktail of growth factors released from the α‐granules of platelets, serve to regulate cell migration and proliferation as well as the promotion of extracellular matrix (ECM) accumulation. This eventually led to angiogenesis stimulation which promoted activation of regional fibroblasts, thus inducing the synthesis of collagen, leading to skin rejuvenation [6]. Although robust evidence exists for the use of PRP in the fields of odontology, orthopedics, and traumatology, it was only recently that positive effects have been apparent in cosmetic dermatology. Sclafani has shown that as little as a single treatment with autologous platelet rich fibrin matrix (a similar product to PRP), has positive outcomes on deep nasolabial folds (NLF). In the past several years, PRP has received wide attention and considerable homage as an autologous filler not only for the treatment of deep NLF’s, but also facial rhytids, dermal depressions, and scars [7]. Results from clinical trials have shown that one to three monthly injections can improve skin quality, fine lines, and the signs of photoaging [8–10]. Aside from monotherapy it has been increasingly used in combination with traditional modalities for treating aesthetic indications. For example, PRP and subcision showed greater improvement postacne scars as compared to subcision alone [11]. Moreover, combination of PRP with lipofilling or biostimulatory fillers (hyaluronic acid, poly‐L‐lactic acid) has been shown to not only volumize the face but also enhance skin texture, sagging, and firmness [2, 3]. Table 47.1 Growth factors released from platelets during PRP treatment. Moreover, PRP therapy, as a possible treatment for hair loss has also been researched extensively, and it appears that fibroblast growth factor combined with other cytokines released from activated platelets plays a role as a potent stimuli for hair growth. Results appear promising for both androgenetic alopecia as well as alopecia areata [4, 5,12–21]. The preparation of PRP is a relatively simple and quick task, usually occurring without any complications with a wide variety of preassembled PRP preparation kits are available in the market (Figure 47.1). Initially, approximately 9 cc of blood is collected into a tube containing an anticoagulant, most commonly citrate dextrose‐A. After collection of the whole blood, either a single centrifugation or a two‐step centrifugation process follows. Although both processes are capable of producing PRP, the two‐step centrifugation process allows for a higher concentration of platelets and is therefore preferable. The initial step will separate the plasma containing the buffy coat from the red blood cells beneath. The second round of centrifugation accumulates the platelets at the bottom, which are used to create the PRP [6, 22]. Figure 47.1 Platelet‐rich plasma kit from Regen Lab containing three vacuum tubes, using a thixotropic gel for cell separation and sodium citrate as an anticoagulant. Before injection, the PRP can be activated using either thrombin or calcium chloride. This will allow exocytosis and the release of growth factors from α‐granules, and facilitate the processes which will eventually lead to tissue regeneration [23]. It is important to mention that injection techniques vary between physicians. A local anesthetic either in the form of a topical anesthetic cream or simple topical ice should be used to minimize discomfort and pain. Alternatively, for correction of deep NLFs, infraorbital nerve blockade could be utilized for further pain control. All injections should be done using a 27 or 30‐gauge needle. For NLF injections, a linear threading technique has proven most successful with correction performed from the alar crease to the level of the oral commissure, in the subdermal or intradermal plane. Intradermal injections should be used for fine rhytids, whereas a subscision followed by a subdermal injection using the “abundant ponfi” technique are best for treating acne scars [23, 24]. Other methods of injection include the “micro ponfi” technique in the forehead and neck and the “linear retrograde technique” in the cheek area [24]. Sclafani has contemplated that initial overcorrection of the dermal defects is desirable when using PRP, as much of the filler is plasma volume, which is quickly absorbed within the first 3–12 hours after the procedure [25]. As with any medical intervention, adverse reactions should always be acknowledged, and the risk minimized, when performing a procedure. Prior to the use of autologous fillers, injectable dermal fillers posed a risk of immunogenetic hypersensitivity reactions, as well as granuloma formation or chronic infections when using permanent fillers [23, 25]. Since PRP is prepared from the patient’s own blood, the aforementioned adverse reactions have been eliminated. The most observed side effects observed after PRP injections were mild and transient in nature. Mild bruising was experienced by most patients, which lasted between 1 and 3 days. In a minority of patients, bruising lasted considerably longer, up to 14 days, usually with injections in the periorbital area. There have been no reports of other adverse reactions from the use of PRP as an autologous dermal filler. Redaelli et al. have reported that in a group of 23 patients, none experienced any serious side effects including infections and hematomas [24]. This similar lack of adverse reactions was mentioned in another study of 15 patients by Sclafani [23].
CHAPTER 47
Autologous Skin Fillers
Introduction
Platelet‐rich plasma
Introduction
Growth factor name
Effect
Platelet‐derived growth factor – AA, AB, BB (PDGF)
Transforming growth factor – β 1,2 (TGF)
Vascular endothelial growth factor (VEGF)
Insulin‐like growth factor 1
Basic‐fibroblast growth factor (bFGF)
Epidermal growth factor (EGF)
Platelet factor‐4
Preparation of platelet‐rich plasma
Techniques for PRP injection
Adverse reactions
Autologous fibroblast cell therapy
Introduction
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