Cosmetic Dermatology – Skin Therapy Letter https://www.skintherapyletter.com Written by Dermatologists for Dermatologists Tue, 18 Jul 2023 16:04:08 +0000 en-US hourly 1 https://wordpress.org/?v=6.8.1 DaxibotulinumtoxinA-lanm (Daxxify™): A Comprehensive Overview https://www.skintherapyletter.com/cosmetic-dermatology/daxibotulinumtoxina-lanm-daxxify/ Wed, 12 Jul 2023 23:43:14 +0000 https://www.skintherapyletter.com/?p=14587 Nicole Salame, MD1; Ariel E. Eber, MD2; Jeffrey Dover, MD, FRCPC2,3

1Department of Dermatology, Emory University School of Medicine, Atlanta, GA, USA
2SkinCare Physicians, Chestnut Hill, MA, USA
3Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA

Conflict of interest: Nicole Salame and Ariel Eber have no conflicts to disclose.
Jeffrey Dover has served as an investigator in the SAKURA trials and advises for Revance Therapeutics.

Abstract:
Botulinum toxin A (BoNTA) is produced by Clostridium botulinum and widely used for aesthetic indications requiring neuromuscular blockade. For dynamic facial lines, BoNTA is effective and safe, but also temporary, requiring repeat injections approximately every 3-4 months for maintenance of effects. There is a desire by both patients and providers for a longer-lasting neurotoxin to prevent periods of suboptimal correction. Approved by the US Food and Drug Administration (FDA) in September 2022, daxibotulinumtoxinA for injection (DAXI or Daxxify™) is the first long-lasting BoNTA formulated with a 150-kDa BoNTA (RTT150) and proprietary stabilizing excipient peptide (RTP004) in place of human serum albumin. DAXI is approved for treatment of moderate to severe glabellar lines. The median duration of effect was 6 months and results lasted as long as 9 months in some patients. Its unique formulation and prolonged effectiveness positions DAXI as a safe, novel BoNTA for improved durability and patient satisfaction.

Keywords: neuromodulator, neurotoxin, botulinum toxin, daxibotulinumtoxinA, rhytids, glabellar lines, forehead lines, lateral canthal lines, aesthetics, dermatology


Introduction

Botulinum toxin type A (BoNTA) is derived from Clostridium botulinum and has a variety of medical and aesthetic indications. BoNTA has been widely used in the United States (US) and Canada for the treatment of dynamic rhytids since its initial Food and Drug Administration (FDA) approval for glabellar lines in 1989. BoNTA inhibits muscle contraction by blocking neurotransmitter release in the neuromuscular junction, preventing formation of deep facial lines. This blockade is not permanent, necessitating repeat injections every 3-4 months to maintain the aesthetic benefit. Patient surveys have identified a desire for longer-lasting neuromodulators to reduce periods of suboptimal correction.1

DaxibotulinumtoxinA-lanm for intramuscular use (DAXI or Daxxify™) is a novel peptide-formulated BoNTA engineered with a proprietary stabilizing excipient peptide (RTP004) in place of human serum albumin (HSA). On September 8, 2022, the US FDA approved DAXI as the first and only long-acting neuromodulator for the treatment of glabellar lines with a median duration of 6 months and up to 9 months for some patients.2 Its innovative formulation, prolonged durability, and overall performance has caused excitement among early practitioners for DAXI’s potential in the realm of BoNTA treatment.

The Novelty of DAXI

While DAXI shares similarities with other BoNTA formulations approved in the US, it has important characteristic differences [Table 1]. DAXI is the first BoNTA entirely produced and formulated in the US. Its biochemical structure is unique; containing a highly purified 150-kDa core BoNTA (daxibotulinumtoxinA, or RTT150), a proprietary synthetic stabilizing peptide (RTP004), and other excipients including a surfactant (polysorbate-20), buffers, and sugar.1 Importantly, DAXI’s unit definition is based on testing of biologic activity of the proprietary product with an individualized patented reference standard, rendering unit conversion to other BoNTA formulations impossible.

Table 1. Comparison of characteristics of BoNTA used for aesthetic injection in the United States.

Injectable Cosmetic Neuromodulators
Generic name DaxibotulinumtoxinA OnabotulinumtoxinA AbobotulinumtoxinA IncobotulinumtoxinA PrabotulinumtoxinA
Brand name Daxi, Daxxify Botox Dysport Xeomin Jeuveau
Manufacturer Revance Therapeutics Allergan Pharmaceuticals Ipsen Biopharm Merz Pharma Evolus
Packaging (U/vial) 100 100 500 100 100
Constituents and excipients
  • RTP004
  • Polysorbate-20
  • Sugar
  • Buffer
  • Hemaglutinin and nonhemaglutin proteins
  • HSA, 500 μg
  • Saccharose
  • NaCl
  • Hemaglutinin and nonhemaglutin proteins
  • HSA, 125 μg
  • Lactose
  • HSA, 1 mg
  • Saccharose
  • HSA
  • NaCl
Molecular weight, kDa 150 900 500-900 150 900
Preparation Lyophilized Vacuum-drying Lyophilized Lyophilized Vacuum-drying
Storage prior to reconstitution Room temperature 2°C to 8°C 2°C to 8°C Room temperature 2°C to 8°C
Shelf-life once reconstituted 72 hours 36 hours 24 hours 36 hours 24 hours
Median duration 6 months 3-4 months 4 months 3 months 1 month
U, units; HSA, human serum albumin; kDa, kilodalton; NaCL, sodium chloride; RTP004, stabilizing excipient 35 peptide

DAXI’s unique proprietary excipient, RTP004, is a 35-amino highly positively charged peptide in place of HSA. While other neurotoxin products require HSA to prevent BoNTA from aggregating and/or adsorbing to glass surfaces, RTP004 fulfills this role by stabilizing daxibotulinumtoxinA via strong electrostatic bonds. RT004’s core domain consists of 15 lysine residues flanked on each side by a protein transduction domain (PTD). Positively charged amino acids in the PTD region form non-covalent, electrostatic interactions with negatively charged surface of the core BoNTA, preventing aggregation and defeating the need for HSA. The absence of HSA also allows DAXI to remain stable at room temperature for up to 3 years before reconstitution.

In addition to replacing HSA, RTP004 also contributes to DAXI’s efficacy and durability. RTP004’s strong electrostatic interaction and stabilization of core neurotoxin permits DAXI’s effect with a similar or lesser amount of product compared to other BoNTA preparations. RTP004’s positive charge also allows DAXI to bind to negative neurons and extracellular matrix proteins, facilitating localization of product and reduced diffusion from injection sites. Lastly, RTP004’s positive charge facilitates DAXI’s high-affinity binding to negatively-charge presynaptic nerve terminals, allowing for increased neurotoxin uptake into the neuron and prolonged efficacy.

DAXI in Clinical Trials

Glabellar Lines

Studies from the DAXI Glabellar Lines Clinical Program recruited 2994 subjects who underwent a total of 4444 DAXI treatments. The program included a phase 1/2 dose-escalation study,3 the Belmont phase 2 dose-ranging study (NCT02303002) comparing DAXI (20U, 40U, 60U) to onabotulinumtoxinA (20U) or placebo,4,5 two phase 3 pivotal trials (SAKURA 1, NCT03014622 and SAKURA 2, NCT03014635)6,7 and one large, phase 3 open-label safety (OLS) study (SAKURA 3, NCT03004248) evaluating the safety and efficacy of DAXI 40U.2,8

Results supported DAXI’s safety, improved efficacy, and prolonged sustained duration of up to 24 weeks before returning to none or mild glabellar line (GL) severity and 28 weeks before returning to baseline. Results were consistent between studies and upon repeat-dosing in the OLS. A subgroup analysis comparing those who had prior BoNTA treatments (treatment-experiences) to those who had not (treatment-naïve) found similar response, duration, and tolerance to DAXI.9 Data also revealed greater efficacy with DAXI 40U as compared to onabotulinumtoxinA 20U, despite similar mass of core neurotoxin (each 0.18 ng),2 suggesting that the aforementioned effects of RTP004 peptide and absence of HAS permitted increased efficacy for a similar given amount of core neurotoxin.

Forehead Lines, Eyebrow Positioning and Lateral Canthal Lines

Promising results from the Glabellar Lines Clinical Program prompted studies evaluating DAXI for treatment of forehead lines (FHL) and eyebrow position. An open-label, dose-escalating phase 2 trial evaluated treatment of FHL after GL treatment found that 86%, 87%, 94%, and 100% of patients had none or mild FHL severity by investigator assessment with 12U, 18U, 24U, and 30U doses, respectively.10 Mean time to loss of none or mild line severity by both investigator and patient assessments was 20 weeks for 18U, 24U, and 30U dose.10

A post-hoc analysis of the phase 2 FHL dose-escalating study and the SAKURA 3 OLS study found that adults receiving DAXI 40U for GL also experienced reductions in FHL and either positive or no impact on eyebrow position.11 A separate post-hoc analysis of the phase 2 FHL dose-escalation study found that precise injection of DAXI 40U to the corrugator supercilii and procerus muscles with avoidance of the frontalis can achieve aesthetically pleasing eyebrow position with prolonged duration.12

Because the upper facial lines are often treated together in real-world practice to improve outcomes and patient satisfaction, a separate phase 2 study was conducted to evaluate the simultaneous treatment of GL, FHL, and lateral canthal lines (LCL) with DAXI.13 DAXI was found to be safe and effective for simultaneous treatment of upper facial lines with no differences in response rates for GL, FHL, or LCL.13 Mean time to loss of none or mild upper facial line severity was 25 weeks for GL, 24 weeks for FHL, and about 28 weeks for LCL.13 Optimal DAXI doses of 18U and 24U allowed for effective duration while ensuring some movement remains in the upper facial lines;13 at 30U, patients can achieve no forehead line movement. To achieve a patient’s desired aesthetic outcome, DAXI dose may be selected along a range of 18U-30U based on patient preferences for sustained movement.13

Adverse Events

Adverse events from daxibotulinumtoxinA studies were mild and included erythema, facial discomfort, and headache. In studies involving FHL,13 no cases of eyelid or eyebrow ptosis were observed. Similarly, in dose escalation studies, no patients experienced eyelid ptosis with DAXI 40U for GL,4 30U for FHL,10 or 48U for LCL.14 In the large, phase 3 OLS study of repeated DAXI 40U dosing for GL, eyelid ptosis was seen in only 0.9% of treatments.8

Immunogenicity

Although DAXI lacks HSA, the presence of RTP004 excipient has potential implications on immunogenicity. Data from SAKURA 1, 2 and 3 found presence of anti-daxibotulinumtoxinA binding antibodies in 0.8% of subjects without evidence of neutralizing antibodies.15 Anti-RTP004 antibodies were found in 1.3% of subjects with low titer (<1:200) transient neutralizing antibodies.15 No patients had antibodies to both daxibotulinumtoxinA and RTP004.15 Presence of either antibody did not impact DAXI efficacy, and no patients reported immune-related adverse effects.15

Conclusion & Future Considerations

DAXI’s unique biochemical formulation with novel excipient peptide RTP004 in place of HSA, improved efficacy, safety, and prolonged duration utilizing a similar or potentially lower amount of core neurotoxin, supports DAXI’s role as a novel, pioneering BoNTA for treatment of dynamic facial lines. Future studies may focus on expanding DAXI for other cosmetic indications, including lower facial lines, neck lines, and in combination with other BoNTA and its use for functional disorders.

Acknowledegment

The authors gratefully acknowledge Revance Therapeutics for providing data in preparing this manuscript.

References



  1. Solish N, Carruthers J, Kaufman J, et al. Overview of daxibotulinumtoxinA for injection: a novel formulation of botulinum toxin type A. Drugs. 2021 Dec;81(18):2091-101.

  2. Fabi SG, Cohen JL, Green LJ, et al. DaxibotulinumtoxinA for injection for the treatment of glabellar lines: efficacy results from SAKURA 3, a large, openlabel, phase 3 safety study. Dermatol Surg. 2021 Jan;47(1):48-54.

  3. Garcia-Murray E, Velasco Villasenor ML, et al. Safety and efficacy of RT002, an inject- able botulinum toxin type A, for treating glabellar lines: results of a phase 1/2, open-label, sequential dose-escalation study. Dermatol Surg. 2015 Jan;41(Suppl 1):S47-55.

  4. Carruthers J, Solish N, Shannon H, et al. Injectable daxibotulinumtoxinA for the treatment of glabellar lines: a phase 2, randomized, dose-ranging, double-blind, multicenter comparison with onabotulinumtoxinA and placebo. Dermatol Surg. 2017 Nov;43(11):1321-31.

  5. Bertucci V, Humphrey S, Carruthers J, et al. Comparing injectable daxibotulinumtoxinA and onabotulinumtoxinA in moderate and severe glabellar lines: additional analyses from a phase 2, randomized, dose-ranging, double-blind, multicenter study. Dermatol Surg. 2017 Dec;43:S262–73.

  6. Bertucci V, Solish N, Kaufman-Janette J, et al. DaxibotulinumtoxinA for injection has a prolonged duration of response in the treatment of glabellar lines: pooled data from two multicenter, randomized double-blind, placebocontrolled, phase 3 studies (SAKURA 1 and SAKURA 2). J Am Acad Dermatol. 2020 Apr;82(4):838-45.

  7. Carruthers JD, Fagien S, Joseph JH, et al; SAKURA 1 and SAKURA 2 Investigator Group. DaxibotulinumtoxinA for injection for the treatment of glabellar lines: results from each of two multicenter, randomized, doubleblind, placebo-controlled, phase 3 studies (SAKURA 1 and SAKURA 2). Plast Reconstr Surg. 2020 Jan;145(1):45-58.

  8. Green JB, Mariwalla K, Coleman K, et al. A large, open-label, phase 3 safety study of daxibotulinumtoxinA for injection in glabellar lines: a focus on safety from the SAKURA 3 study. Dermatol Surg. 2021 Jan;47(1):42-6.

  9. Cohen JL, Green LJ, Beer KR, et al. Prior botulinum toxin treatment does not impact efficacy or safety in clinical trials: analysis of daxibotulinumtoxinA for injection in the SAKURA program. Dermatol Surg. 2021 Apr 1; 47(4):511-5.

  10. Solish N, Green JB, Fagien S, et al. A phase 2a dose-escalation study to evaluate the efficacy and safety of daxibotulinumtoxinA for injection for the treatment of dynamic forehead lines following glabellar line injections: an interim analysis. Poster presented at the 16th annual Maui Derm for Dermatologists 2020; January 25-29, 2020; Maui, HI.

  11. Solish N, Kane MAC, Biesman BS, et al. Impact of daxibotulinumtoxinA for injection on brow position and frontalis muscle activity following treatment of glabellar lines. Aesthet Surg J. 2022 Sep 12:sjab362. doi: 10.1093/asj/sjab362. Epub ahead of print. PMID: 36095026.

  12. Bertucci V, Green JB, Fezza JP, et al. Impact of glabellar injection technique with daxibotulinumtoxinA for injection on brow position. Aesthet Surg J. 2022 Nov 2:sjac002. doi: 10.1093/asj/sjac002. Epub ahead of print. Erratum in: Aesthet Surg J. 2022 Dec 30; PMID: 36322141.

  13. Dover JS, Humphrey SD, Lorenc ZP, et al. Treatment of upper facial lines with daxibotulinumtoxinA for injection: results from an open-label phase 2 study. Dermatol Surg. 2023 Jan 1;49(1):60-5.

  14. Keany T, Bhatia A, Fezza J, et al. DaxibotulinumtoxinA for injection for lateral canthal lines: 4-week interim analysis of a phase 2a study. Presented at American Society for Dermatologic Surgery (ASDS) 2020 virtual annual meeting; October 8-11, 2020.

  15. Gallagher CJ, Bowsher RR, Clancy A, et al. Clinical immunogenicity of daxibotulinumtoxina for injection in glabellar lines: pooled data from the SAKURA phase 3 trials. Toxins (Basel) 2023 Jan 10;15(1):60.


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Platelet-Rich Plasma (PRP): Current Applications in Dermatology https://www.skintherapyletter.com/acne/platelet-rich-plasma-prp/ Tue, 01 Oct 2019 22:00:54 +0000 https://www.skintherapyletter.com/?p=10762 Jason Emer, MD
Dr. Jason Emer, West Hollywood, CA, USA

Conflict of interest:
Dr. Emer has been a consultant for Regen Lab and Eclipse.

Abstract
Platelet-rich plasma (PRP) is an autologous serum containing high concentrations of platelets and growth factors. PRP continues to evolve as an important treatment modality with many applications in dermatology, particularly in the areas of hair restoration, skin rejuvenation, acne scars, dermal augmentation, and striae distensae. Furthermore, combining PRP with laser therapies, microneedling, dermal fillers, and autologous fat grafting produces synergistic effects, leading to improved aesthetic results. Future studies should standardize PRP treatment protocols for specific indications. PRP holds considerable promise in dermatology with therapeutic applications continuing to expand.

Key Words:
acne scars, aesthetic, androgenic alopecia, autologous fat grafting, cosmetic, dermal fillers, dermatology, facial rejuvenation, fractional laser resurfacing, hair restoration, microneedling, platelet rich plasma, PRP, rhytids

Introduction

Platelet-rich plasma (PRP) is an ever-expanding treatment modality that continues to demonstrate considerable promise in the field of dermatology. PRP has long been used in the medical fields of cardiac surgery, oral surgery, orthopedics, and facial plastic surgery, and it continues to develop as a versatile therapy in dermatology. PRP is an autologous serum containing high concentrations of platelets and growth factors.1 Alpha granules within the platelets are responsible for promoting stem cell regeneration and soft tissue remodeling.2 Many fundamental growth factors are contained within the PRP alpha granules, such as platelet-derived growth factors (aa, bb, ab), vascular endothelial growth factor, epithelial growth factor, transforming growth factor beta, and insulin-like growth factor.3 Mitogenesis and differentiation of monocytes, fibroblasts, stem cells, keratinocytes, and endothelial cells occur as a result of PRP alpha granule growth factors.2 These growth factors are also known to induce cell proliferation, angiogenesis, and chemotaxis, as well as contain serotonin, dopamine, histamine, adenosine, and calcium, which increase membrane permeability.2-4

Chart of Platelet-rich plasma applications in dermatology and corresponding protocols.
Table 1: Platelet-rich plasma applications in dermatology and corresponding protocols. PRP = platelet-rich plasma; L-PRP = leukocyte platelet-rich plasma; PRFM = platelet-rich fibrin matrix
Click here to enlarge table.

The use of PRP results in improved cosmetic dermatologic outcomes through angiogenesis, neocollagenesis, and adipogenesis.2 Applications for hair restoration and skin rejuvenation remain the most highly-supported indications for PRP in aesthetic dermatology (Table 1). Moreover, the use of PRP when combined with other treatment modalities, such dermal fillers, lasers, and other devices demonstrates significant improvements in skin appearance, texture, and tone. There is also emerging potential for the use of PRP with augmented fat injections to enhance fat survival (Figure 1). Although few clinical trials have been performed on the numerous above-mentioned therapeutic options, physicians note enhanced results with treatments combined with PRP versus solo treatment. PRP shows promising uses in the field of dermatology, and more studies are needed to test its validity alone or in combinations for enhancing outcomes.

Before and after Image of male buttock augmentation
Figure 1A: Buttock augmentation with PRP/ACell®-enriched autologous fat grafting, male.
Before and after image of female buttock augmentation
Figure 1B: Buttock augmentation with PRP/ACell®-enriched autologous fat grafting, female.

Harvesting Platelet-Rich Plasma

There are many commercially available PRP systems and kits, and protocols vary according to brand name and treatment indication (Table 2). Traditionally accepted preparations involve initial venipuncture to obtain 10 to 22 mL of whole blood, which is combined with an anticoagulant agent. Centrifugation then separates the whole blood sample into three layers: red blood cells (RBCs), platelet-poor plasma (PPP), and the of-interest PRP layer. Subsequent centrifugations isolate and harvest the PRP layer, while discarding the RBCs and PPP. The now concentrated PRP pellet may be treated with calcium chloride or thrombin to activate the platelets (many harvesting systems do not require activation), releasing alpha granules and growth factors. For the most common dermatological uses, activation is not required, as a more viscous substance (once activated) is better suited for wound healing, post-surgical healing, and orthopedic uses. Activation of growth factors occurs within 10 minutes, with nearly 100% activation occurring within 1 hour.5 Some cosmeceutical brands have started to create “customized” skin care products that allow patients’ PRP to be added to a base formulation to complete a bespoke growth factor anti-aging skin care product. However, it is not yet known for how long the activated growth factors remain viable. It is thought that changes in pH and temperature may affect the viability of PRP within a few hours after collection. Current US Food and Drug Administration (FDA) guidelines also indicate that platelets should not be used beyond 5 days after collection, due to bacterial contamination during venipuncture. Nevertheless, patient demand for such autologous customized skin care products remains high.


Commercially Available PRP Harvesting Systems

Eclipse PRP® (Eclipse)
Blood Volume Draw (mL): 11 – 22
Platelet Concentration Above Baseline: 1.8 – 4x
Regulatory Status: FDA Cleared 510(k)

Magellan® (Isto Biologics)
Blood Volume Draw (mL): 30 – 80
Platelet Concentration Above Baseline: Up to 14x
Regulatory Status: FDA Cleared 510(k)

PurePRP® (EmCyte)
Blood Volume Draw (mL): 25 – 50
Platelet Concentration Above Baseline: 4 – 7x
Regulatory Status: FDA Cleared 510(k)

RegenKit® (Regen Lab)
Blood Volume Draw (mL): 10
Platelet Concentration Above Baseline: 1.6x
Regulatory Status: FDA Cleared 510(k)

Selphyl® PRFM (UBS Aesthetics)
Blood Volume Draw (mL): 9
Platelet Concentration Above Baseline: Less than 2x
Regulatory Status: FDA Cleared 510(k)

Table 2: Commercially available platelet-rich plasma harvesting systems commonly used in dermatology.

Platelet-Rich Plasma Subtype Families

Platelet concentrations vary per harvest protocol; a platelet count of 1 million/mL is widely accepted as the necessary PRP platelet concentration for therapeutic efficacy.6 Moreover, PRP contains plasma at concentrations 2 to 8 times greater than unaltered whole blood.2 PRP preparations have been classified into four subtypes: pure platelet-rich plasma (P-PRP), leukocyte platelet-rich plasma (L-PRP), pure platelet-rich fibrin matrix (P-PRFM), and Leukocyte and platelet-rich fibrin matrix (L-PRFM). Aesthetic dermatology indications predominantly use the pure PRP preparation with minimal leukocyte collection.3 The P-PRFM preparation has a lower platelet concentration and includes fibrin. The fibrin matrix created in P-PRFM binds and traps growth factors, releasing them more slowly over several days. This preparation may be used for fat grafting procedures, as it allows for sustained, prolonged release of growth factors within the grafted tissues.7

Hair Restoration

PRP has demonstrated significant improvements in hair growth when treating androgenic alopecia (AGA) (Figure 2). PRP growth factors promote hair regrowth by stimulating stem cell differentiation of hair follicles, inducing and prolonging the proliferative anagen phase of hair follicles, as well as activating anti-apoptotic pathways and promoting angiogenesis to increase perifollicular vascularization and the survival of dermal papilla fibroblasts.2,8-10

Before and after close up of male hairline from PRP/ACell injections
Figures 2A: Significant increased in hair density and color with six monthly injections of PRP/ACell®, male.
Before and after close up hair growth from PRP/ACell injections
Figures 2B: Significant increased in hair density and color with six monthly injections of PRP/ACell®, female.

A wide array of studies indicates that PRP is a promising treatment for thinning hair.2 Both male and female pattern hair loss, as well as alopecia areata, can be improved with PRP. Injections of PRP may be combined with progesterone, dalteparin microparticles, or CD34+ cells. PRP administered with progesterone naturally inhibits 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone (DHT). DHT damages hair follicles and is culpable in genetic hair loss. Progesterone inhibits 5-alpha reductase and thus DHT, which allows hair growth to recover. PRP with dalteparin induced significant increases in hair diameter and proliferation of collagen fibers and fibroblasts, along with thickened epithelium and hair follicles due to increased angiogenesis.11 Using CD34+ cells with PRP showed significant improvement in hair thickness and overall presentation.12

While some studies reveal minimal improvement in hair restoration, it is hypothesized that inadequate treatment protocols have been used. Studies using an insufficient number of treatments lacked substantial improvements.2 Multiple continued treatments with PRP is necessary for significant aesthetic improvement of increased hair density. It is thought that three injections per year is the minimum frequency in order to observe any clinically beneficial result. In clinical practice, most physicians commence with a series of monthly injections until improvement is seen, then continuing with maintenance therapies every 2 to 3 months indefinitely. More research is needed nevertheless to determine proper frequency, dosing, and maintenance. Furthermore, combining PRP injections with other hair restoration treatments, such as finasteride (male patients), minoxidil, low-level light therapy, and spironolactone (female patients), may enhance the overall efficacy. PRP injections may also improve the outcome of hair transplantation and may soon be part of the pre-treatment and post-treatment maintenance protocols. In clinical practice, the author (JE) has found substantial improvement with the use of ACell® (naturally-occurring urinary bladder matrix epithelial basement membrane; MicroMatrix®) and/or human exosomes (placental mesenchymal stem cell and amniotic fluid derived; Kimera Labs, Inc.) combined with PRP in patients with less than substantial improvement with PRP injections alone. Combined with hair transplantation, injectable regenerative therapies have shown improved outcomes in the author’s experience.

Skin Rejuvenation

Several reports demonstrate improvements in traumatic scars and acne scars with PRP treatment. Increases in collagen density and dermal elastic fibers are notable benefits when using PRP in aesthetic dermatology. When PRP is used in combination with other therapies, such as laser treatments, microneedling, and hyaluronic acid fillers, further improvements in skin appearance are achieved (Figure 3). Autologous fat grafting combined with PRP to enhance long-term fat survival has preliminarily shown positive results. Furthermore, cosmetic improvements in striae distensae have been noted when combining radiofrequency, laser, and ultrasound therapies with PRP.

Before and after image of full facial rejuvenation
Figure 3: Female full facial rejuvenation, notice the significant improvement in texture, color, and tone of the skin. Combination approach of: fillers to improve the lateral lateral cheeks, chin, and lips; internal radiofrequency (InMode FaceTite™) and liposuction to the lower face and neck; Botox® Cosmetic for chemical brow lifting (glabellar “11” lines) and eye wrinkles (crow’s feet); microneedling radiofrequency (InMode Fractora™) with PRP in a series of three treatments in a 12 month period.

Acne Scars & Traumatic Scars

Multiple studies indicate significant improvement in appearance of acne scars, as well as traumatic scars, when using PRP13,14 (Figure 4). Cutaneous injuries may result in scar tissue, presenting aesthetic and functional issues. Optical coherence tomography revealed improved acne scar depth when PRP was used with fractional laser therapy, compared to laser alone.3

A decrease in erythema and edema is observed when treating acne scars with PRP. Improved skin elasticity and increased collagen and fibroblasts are also noted when treating scars.15

Before and after of acne scar treatment.
Figure 4: Acne scar improvement, laser resurfacing plus topical PRP.

Combination Therapies: Lasers & Microneedling

The use of PRP in conjunction with laser therapies and microneedling is increasingly popular in aesthetic dermatology. Fractional laser resurfacing and microneedling treatments create small holes in the skin, which act to enhance uptake and delivery of PRP.2 Combining PRP with laser therapies and microneedling procedures improves wound healing and shortens recovery times, as well as reduces erythema and melanin index of treated areas.14,16,20 Transepidermal water loss (TEWL) and inflammatory hyperpigmentation are also found to be significantly lower when combining PRP with device treatments. Patients treated with PRP after CO2 or erbium fractional resurfacing have improved skin elasticity, increased fibroblasts, and notably thicker collagen bundles when compared to laser treated sites without added PRP.20 Furthermore, there is anecdotal evidence of improved healing times with PRP combined with laser therapy, as well as earlier granulation, decreased erythema, and improved outcomes.

Dermal Augmentation

Combining PRP with hyaluronic acid-based fillers has been popular and widespread in cosmetic dermatology for several years. The “Vampire Facelift” was coined after combining PRP and dermal fillers; this technique has become well-known via social media. The numerous growth factors in PRP are thought to rejuvenate the skin, improving texture and smoothness, while also decreasing rhytids.22,23 Hyaluronic acid fillers or other dermal augmentation agents serve as a scaffold to which PRP can bind and enhance skin rejuvenation, as well as enhance soft tissue augmentation2 (Figure 5). Lasting cosmetic improvements are seen when treating nasolabial folds, horizontal neck bands, skin homogeneity and tonicity, and facial rhytids with dermal fillers combined with PRP. Studies have also indicated significant improvements in rhytids and skin tone in the infraorbital region.24

Before and after of facial skin texture and color.
Figure 5: Substantial improvements in texture and color of the skin along with dark circles and ocular hollows (i.e., tear troughs) with topical and injectable PRP combined with fractional CO2 laser resurfacing at 1 month.

Augmented Fat Injections

Combining PRP with autologous fat grafting is thought to bolster survival of the injected fat. Autologous fat injections have gained popularity for facial rejuvenation and dermal augmentation, as the fat grafts are deemed safe and free from potentially transmissible blood-borne pathogens due to the autologous origin of the fat. Pure PRP preparations with a fibrin matrix (P-PRFM) binds and traps growth factors contained within PRP, releasing them more slowly, ensuring prolonged survival of injected fat.7 Reports have indicated considerable potential for the use of PRP with augmented fat injections, while some investigations indicate no significant improvement was observed. Patients with HIV-associated facial fat atrophy treated with PRP fat grafting did not experience a significant difference in cosmetic appearance when compared to fat injections alone.17 However, results from other studies indicate PRP enhances volume retention of injected fat, maintains volume overtime, and reduces revision rates.7,18,19 In the author’s opinion (JE) there is a substantial improvement in fat viability and retention with the use of PRP in a high enough ratio of PRP to fat; although that “ratio” is not defined based on the current studies in the literature and in practice at least 4-8:1 (fat to PRP) is utilized for a noticeably improved long-term outcome.

Striae Distensae

Continuous stretching of the skin often leads to atrophic dermal scars, known as striae distensae. Reports indicate beneficial cosmetic outcomes when combining intradermal radiofrequency and ultrasound devices with PRP.21,25 Ultrasound therapies often follow radiofrequency treatments, as ultrasound assists in transepidermal penetration of PRP. Abdominal biopsies posttreatment have indicated increases in collagen density and elastic fibers, and the majority of patients report good or very good improvements in cosmetic appearance of their striae distensae.21

Conclusion

PRP continues to evolve as a consequential therapeutic tool in dermatology. Numerous growth factors contained within PRP promote neocollagenesis, angiogenesis, and overall proliferation of stem cells and soft tissue remodeling. PRP is easily harvested from patients’ own whole blood using numerous commercially available systems, making it a safe, in-office procedure. Top evidence-based dermatologic indications for PRP include hair restoration and skin rejuvenation, as well as improvements in acne scars. Moreover, combining PRP with other treatment modalities, such as laser therapies, microneedling, dermal fillers, and autologous fat injections has demonstrated synergistic effects, enhancing overall cosmetic outcomes. The dermatologic community stresses that more studies are needed to further standardize and define PRP protocols beyond anecdotal experience for specific indications.

Acknowledgement

The author gratefully acknowledges the editorial support from Bradford Ferrick in preparing this manuscript.

References



  1. Kang RS, Lee MK, Seth R, et al. Platelet-rich plasma in cosmetic surgery. Int J

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Fat Grafting: What is it? https://www.skintherapyletter.com/cosmetic-dermatology/fat-grafting/ Fri, 01 Jan 2016 16:50:22 +0000 https://www.skintherapyletter.com/?p=11580 Welcome to our comprehensive video guide to fat grafting.

Fat grafting is a popular and effective cosmetic procedure. At the same time, the procedure is not as well understood as other procedures like synthetic fillers, which are also used to add volume where it has been lost. In this video series, we interview renown plastic surgeon from Vancouver, Canada, Dr. Bryce Cowan, questions about fat grafting.

Fat grafting is the transplantation of fat cells from one location of the body to another. This procedure has a long history in both reconstruction and in cosmetic realms. Cosmetically, fat grafting helps to restore volume that has been lost with age. It has an excellent safety record, and with recent advancements and refinements in technique, almost all of the grafted fat survives at the new location. This allows for more precise transplantation, transferring fat at a close to 1 to 1 ratio. Fat grafting also has other side benefits as well, improving the quality of the skin overlying the grafted fat cells.

In this video series Dr. Bryce Cowan discusses an important comparison between the use of synthetic hyaluronic acid fillers like Restylane and fat grafting. Both procedures are popular cosmetic options to address volume loss of the face, and many patients wonder about the pros and cons of these very different procedures. Both procedures have their appropriate uses. Injectable fillers are considered a “soft procedure” and is cheaper and more convenient. They start at several hundred dollars, and generally they require no downtime. On the other hand, these fillers are metabolized by the immune system over time, and generally only last several months. Fat grafts, when successfully grafted, can last a decade or more typically, and in theory, can last indefinitely. Dr. Cowan believes that younger patients who require very little filler and are using it for touch up and maintenance are likely good candidates for fillers, while older patients who may have more significant hollowing and loss of volume should consider opting for fat grafting. When larger volumes of filler are required, the costs also increase accordingly, and since they only last several months, the cost of maintenance can becomes significant. With fat grafting, the changes are far more lasting.

So, what is fat grafting?

In this first video of the series Dr. Bryce Cowan explains fat grafting – this important rejuvenating option that is used both in restorative surgery (after a trauma) and for cosmetic purposes.

Fat grafting is the transplantation of fat cells from one location of the body to another. This procedure has a long history in both reconstruction and in cosmetic realms. In cosmetics, fat grafting helps restore volume that has been lost with age.

In general, fat is lost with age, and to restore and rejuvenate, it’s necessary to add new fat cells that survive and thrive in the area where fat has been lost. In reconstruction, we know that fat grafting helps to add and restore volume where it has been lost, but as an additional benefit, it substantially improves scars, especially tight scars. The grafted fat cells also regrow collagen, improving the overlying skin quality as well.

Next Video

Fat Grafting and Volume Loss of the Face

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Fat Grafting and Volume Loss of the Face https://www.skintherapyletter.com/cosmetic-dermatology/fat-grafting-face-volume-loss/ Fri, 01 Jan 2016 16:48:22 +0000 https://www.skintherapyletter.com/?p=11604 At what age do we start losing volume in the face, and in what areas?

In our second video plastic surgeon Dr. Bryce Cowan explains the process of volume loss with age, and how it affects the overall appearance of the face, and how fat grafting can help combat these changes. Typically volume loss is most noticeable around the temples and the cheeks. It typically starts at around the 40s or 50s understanding that the timing can vary from person to person.

Fat grafting can help to restore fat and volume in these patients in a way that is long standing, as the grafted fat cells survive. Typical treatment areas include the temples, cheeks, smile lines and nasolabial folds, marionette lines. The chin and around the eye area are also areas that can be treated, and this is a small change in the way that we approach blepharoplasty in the last decade. Another non-facial area where fat grafting is often used effectively is on the back of the hands. A skeletonized tendony appearance on the back of the hands is one of the hallmarks of aging, and this can be dramatically improved with fat grafting.

Next Video

Improved Skin Quality with Fat Grafting

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Improved Skin Quality with Fat Grafting https://www.skintherapyletter.com/cosmetic-dermatology/improved-skin-quality-fat-grafting/ Fri, 01 Jan 2016 16:46:22 +0000 https://www.skintherapyletter.com/?p=11611 Fat grafting, the transplantation of fat cells from one site to another to restore volume where volume is lost, has an added rejuvenating benefit.

Grafted fat is transferred as whole cells which are believed to contain stem cells that release cytokines and growth factors. This promotes a rejuvenative process in the surrounding skin, and studies have shown that there is an increase in collagen production in the dermis where fat has been grafted. This improves the quality of the overlying skin as an additional benefit to volume restoration.

Next Video

The Process of Fat Grafting

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The Process of Fat Grafting https://www.skintherapyletter.com/cosmetic-dermatology/fat-grafting-process/ Fri, 01 Jan 2016 16:44:22 +0000 https://www.skintherapyletter.com/?p=11614 What is involved in the process of fat grafting exactly?

We ask plastic surgeon Dr. Bryce Cowan about what patients should expect on the day of the surgical procedure.

Fat grafting can be done under local anesthetic, or if it’s a larger procedure combined with other surgical treatments, general anesthetic (the kind that puts you to sleep) is used. Volume deficiency is first identified and marked, and harvest site is chosen, usually the abdomen or the flank. That area is then anesthetized or a tumescent solution is used if larger volumes of fat are required.

The surgeon makes a 3mm incision in the harvest site and using a suction based cannula system, harvest whole fat cells. These specialized cannulas avoid unnecessary damage to the fat cells. Once extracted, the fat cells are washed, processed, and then transferred to larger syringes. Then they are transferred to finer 1cc syringes for introduction.

At this stage, the surgeon uses a blunt tip cannula of appropriate shapes and sizes to reintroduce the fat cells to the new site. A 3mm incision is used, and multiple passes are made in different planes to add volume in a layered fashion. The blunt tipped cannulas minimize the risk of trauma to surrounding blood vessels and minimizes the chance of introducing fat into the vessels that can potentially cause fat emboli, a possible risk of the procedure. Once the fat is successfully introduced, a small suture is used to close the site and the area is allowed to heal with just a fine dressing.

Next Video

The History and Safety Record of Fat Grafting

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The History and Safety Record of Fat Grafting https://www.skintherapyletter.com/cosmetic-dermatology/fat-grafting-history-safety-record/ Fri, 01 Jan 2016 16:42:22 +0000 https://www.skintherapyletter.com/?p=11618 We ask plastic surgeon Dr. Bryce Cowan about the history of fat grafting, and the procedure’s safety profile. The last 2 to 3 decades have seen impressive improvements in the success rate of fat grafting, changing the landscape of the procedure.

In terms of history, fat grafting has been used in medical circles for almost a century. In recent decades, however, new research and innovations in technique have improved the success rate of fat grafting significantly. Harvesting, processing, application, and introduction of the harvested fat cells have all seen dramatic improvements, reducing errors and making for an optimized outcome.

In the past, many of the grafted fat cells were expected to die at the new site, meaning that more fat needs to be grafted than necessary to account for this. With new improvements, fat cells survive at a much higher rate, and now a surgeon uses near a 1 to 1 ratio, making the procedure more predictable and safe. These advances have allowed the procedure to be much more reliable cosmetically than in the past. Again, a major advantage of fat grafting is that the fat cells at the new site last for a very long time.

Fat grafting can be done under local anesthetic, or if it’s a larger procedure combined with other surgical treatments, general anesthetic (the kind that puts you to sleep) is used. Volume deficiency is first identified and marked, and harvest site is chosen, usually the abdomen or the flank. That area is then anesthetized or a tumescent solution is used if larger volumes of fat are required.

The surgeon makes a 3mm incision in the harvest site and using a suction based cannula system, harvest whole fat cells. These specialized cannulas avoid unnecessary damage to the fat cells. Once extracted, the fat cells are washed, processed, and then transferred to larger syringes. Then they are transferred to finer 1cc syringes for introduction.

At this stage, the surgeon uses a blunt tip cannula of appropriate shapes and sizes to reintroduce the fat cells to the new site. A 3mm incision is used, and multiple passes are made in different planes to add volume in a layered fashion. The blunt tipped cannulas minimize the risk of trauma to surrounding blood vessels and minimizes the chance of introducing fat into the vessels that can potentially cause fat emboli, a possible risk of the procedure. Once the fat is successfully introduced, a small suture is used to close the site and the area is allowed to heal with just a fine dressing.

Next Video

Fat Grafting vs Synthetic Fillers

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Fat Grafting vs Synthetic Fillers https://www.skintherapyletter.com/cosmetic-dermatology/fat-grafting-vs-synthetic-fillers/ Fri, 01 Jan 2016 16:40:22 +0000 https://www.skintherapyletter.com/?p=11623 Synthetic fillers like hyaluronic acid are now incredibly popular to restore lost volume, like fat grafting. We ask Dr. Bryce Cowan to compare the upsides and downsides of each procedure.

First, both synthetic fillers and fat grafting are used to treat volume loss but the procedures serve a very different need, and they both have an important place in the cosmetic marketplace. Cosmetic fillers are most commonly made of hyaluronic acid and are produced by strep bacteria and then chemically cross-linked to add additional stability and longevity. One of the advantages of fillers is that they are synthetic and available on the shelf so there is no donor site required, and therefore, the procedure has little down time. Synthetic fillers can be placed to fill in fine lines and wrinkles close to the surface in a concealed way. They are broken down by the immune system over time, however, and this is a major limitation as retreatment will be required to maintain the appearance. Another advantage of fillers is that the correction is reliable as fillers are used on a 1 to 1 basis, correcting what you see exactly. Finally, fillers can be reversed more readily using an enzyme called hyaluronidase, which resorps the filler, should the outcome not be satisfactory.

Fat grafting injects fat deeper into the skin and lasts far longer. Typically they can survive for a decade or longer, and in theory, indefinitely, far outlasting fillers which typically last 6 to 12 months. Fat grafts are usually used to fill in larger volumes. The procedure is more involved as a donor site is required, although most patients have some area where they don’t mind losing a bit of fat, like the abdomen. The recovery time is more significant, as bruising is more significant than they are with fillers. Again, both fillers and fat grafts have their proper place and uses.

Next Video

Risks Associated with Fat Grafting

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Risks Associated with Fat Grafting https://www.skintherapyletter.com/cosmetic-dermatology/fat-grafting-risks/ Fri, 01 Jan 2016 16:34:22 +0000 https://www.skintherapyletter.com/?p=11627 Plastic surgeon Dr. Bryce Cowan explains the risks associated with the fat grafting procedure that patients should be aware of before undergoing the procedure. Although serious complications are rare, it’s important to be aware of the various potential risks. Grafted fat cells need to survive in their new environment, and this doesn’t always happen, even though the survival rate is much higher in recent decades with improved technique. This is considered one of the risks of the procedure. When the fat is resorbed and die, multiple applications may be required.

Another risk is infection at the surgical site, or disruptions with the nerves. Bruising and hematoma clots are also another risk, although with the use of blunt tip cannula this risk is now very small. More serious risks include damage to the abdominal wall or internal organs during the harvesting process, although these cases are extremely rare. At the recipient site, with sensitive areas like the eyelids, damage can also occur.

As a whole these types of risks are extremely low in the hands of a skilled surgeon, however, it’s imperative to understand that risks are always present in any surgical procedure.

Next Video

What to Expect After a Fat Grafting Procedure

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What to Expect After a Fat Grafting Procedure https://www.skintherapyletter.com/cosmetic-dermatology/fat-grafting-expectations/ Fri, 01 Jan 2016 16:32:22 +0000 https://www.skintherapyletter.com/?p=11631 Dr. Bryce Cowan explains what the patient should expect after a fat grafting treatment in terms of results, as well as the side-effects that patients can expect following the procedure.

Patients should expect some swelling and bruising at the surgical sites for a could of days following the procedure. After this subsides, the patient should notice a volume increase at the surgical site. This will be monitored for several months to ensure that the grafted fat survives, and is not reabsorbed, which sometimes happen. In this case, a retreatment may be necessary. Once successful, however, the fat grafts are very long-lasting, far outlasting any synthetic filler that is currently available.

Next Video

How Long Do the Grafted Fats Last?

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