1. © COPYRIGHT 2013 BELLUS MEDICAL LLC. ALL RIGHTS RESERVED. Advanced Microneedling Training

2. How Does Medical Needling Work? 0.5mm – 3.0mm Uses very fine, surgical stainless steel needles to make channels into the epidermis and dermis to release growth factors Promotes scarless healing and deposition of normal woven collagen rather than scar collagen Similar to Fraxel, without the negative loss of dermal papillae, potential destruction of melanocytes, abnormal collagen, coagulated growth factors Allows 80% more product into the skin (compared to 7-10% normally) 1.15

3. 1.10 Collagen Induction Therapy *Fernandes, D. OralL Maxillofacial Surg Clin 2005; 17:51-63 Microinjuries allow for release of serum containing cytokines and growth factor*

4. 1.19 Phases of Wound Repair

5. Wrinkles Thin skin Hyperpigmentation Rosacea Loss of Resiliency Premature aging Scars Epidermal density and strength Lax skin UV damage Stretch marks Hair restoration Most Effective Uses of Dermal Needling 1.16

6. Features of Healthy Skin  Soft, compact stratum corneum, with strong skin barrier  Dense spinosum layer with consistent, strong cell-to-cell adhesion  Even color, with melanocytes that distribute melanin uniformly  Resilience  Dermis rich with collagen and elastin fibers  Good dermal and epidermal hydration: Extracellular matrix rich with glycosaminoglycans 1.3

7. The Three Layers of the Skin 1.4

8. Optimizing the Keratinocytes  Basic epidermal topical requirements:  Omega 3  Omega 6  Ceramide  Squalenes  Sphingolipid  Phospholipid 1.7

9. Epidermal Cell Requirements Omega 3 Kiwifuit seed oil Lecithin Hemp see oil Flax seed oil Camelina oil Omega 6 Hemp seed oil Borage oil Evening Primrose oil Rice bran oil Ceramide Yeast (pichia anomala extract) Wheat extracts Squalenes Rice bran oil Olive oil Sphingolipid Yeast (pichia anamola extract) Phospholipid Lecithin

10. Optimizing the Melanocyte Unfortunately, melanocytes lie between most anti-aging treatment modalities and the targeted fibroblasts, and are often sacrificed in overzealous attempts to obtain greater injury through aggressive injury.

11. Optimizing the Melanocyte 1.9

12. Optimizing the Melanocyte 5 intervention points: Block UV radiation Block Melanin Stimulating Hormone (MSH) before it stimulates the keratinocytes and melanocytes Inhibit tyrosinase, the enzyme needed to form melanin in the melanosome Interfere with L-Dopa, the building blocks for pigment in the melanosomes Interfere with transfer of pigment from the melanosome to the keratinocyte 1.8

13. Product Ingredients Affecting Melanogenesis* Active IngredientMSHTyrosinasePigment Granule Melanosome Transfer Magnesium ascorbyl phosphate  Ascorbyl tetra isopalmitate  Niacinamide  Arbutin  Azelaic acid  Paper mulberry  Aloesin  Glabridin  Glucosamine  Ascorbic acid *Florence Barrett-Hill. Secretions. Cosmetic Chemistry. 

14. Compounds Affecting Melanogenesis* CompoundsMSHTyrosinasePigment Granule Melanosome Transfer Lumixyl  Melanostat  Sulforawhite  Whitesphere  Lightocean  *Florence Barrett-Hill. Secretions. Cosmetic Chemistry.

15. Ingredients TO AVOID* with microneedling SubstanceMSHTyrosinasePigment Granule Melanosome Transfer Kojic Acid**  Hydroquinone***  *Florence Barrett-Hill. Secretions. Cosmetic Chemistry. **Banned in some countries. May cause dermatitis long term. ***Banned is some countries. Potential carcinogenic effect.

16. Medical Needling eliminates the risk of melanocyte heat injury and actually optimizes cell function, making it the ideal treatment for all skin types. Lance Setterfield, Dermal Needling, Medical Edition, 2010

17. Optimizing the Fibroblast Requires injury to stimulate: chemical peels Levulan and photodynamic therapy IPL Thermage Fraxel CO2 Laser

18. Ingredients for Optimal Fibroblast Function Aids in Collagen Synthesis Aids in GAG Synthesis Prevents Oxidative Stress Prevents Lipid Peroxidation Growth Factors  Magnesium ascorbyl phosphate  Ascorbyl tetra isopalmitate  Retinyl palmitate  Retinol  Copper peptides  Beta-carotene  DMAE  Hyaluronic Acid *Florence Barrett Hill. Secretions, Cosmetic Chemistry 2009 **all above have antioxidant and anti-inflammatory properties and can be used on compromised and high-risk skins excepts retinol. 

19. Ingredients for Optimal Fibroblast Function Aids in Collagen Synthesis Aids in GAG Synthesis Prevents Oxidative Stress Prevents Lipid Peroxidation Glucosamine  Super dismutase oxide  Resveratrol (Bioflavanoid)  Matrixyl®  Amino acid Proline  Amino acid Lysine  Ascorbic acid  Zinc  Calcium  *Florence Barrett Hill. Secretions, Cosmetic Chemistry 2009

20. Preserve the Epidermis Epidermis is complex, highly specialized organ 0.2mm thick Only protection from the environment

21. Preserve the Epidermis Traditional Ablative Therapies Damage the skin to cause fibrosis of the papillary dermis Epidermis thinned Dermal papillae destroyed Severe changes in dermis

22. Preserve the Epidermis Resultant Collagen from Ablative Therapies: Parallel (scar) orientation rather than normal, lattice network Scar collagen will be resorbed by the body over time – all scar collagen is Fine wrinkles will be visible due to thinned epidermis and lack of dermal papillae

23. 1.12 Collagen Induction Therapy CIT Promotes deposition of fresh new collagen without scar formation* Left, before CIT. Right, six months after CIT, more collagen (pink) and elastin (brown) can be detected. Estimated > 400% more collagen and improved epidermal/dermal thickness *Fernandes, D. OralLMaxillofacial Surg Clin 2005; 17:51-63

24. Preserve the dermal papillae Exchanges oxygen, nutrients, and waste products between the epidermis and dermis Provides strength between the epidermis and dermis to prevent the deterioration and separation of the dermal/epidermal junction, which presents as wrinkles

25. Break Down Scar Tissue Allows the epidermis to lift and lay flat, eliminating any shadowing

26. Induce Regenerative Healing Collagen forms from the base upwards Opposite of Regenerative Healing is “Cicatricial healing”: leaves a scar when the formation of new connecting tissue overlies a wound

27. Microneedling Meets All Goals Optimize cell function Preserve integrity of the epidermis Strengthen dermal/epidermal junction Preserve dermal papillae Break down scar tissue Release epidermal growth factors Increase natural collagen: transforming growth factor ß3 (TGF-ß3) Induce regenerative healing 1.10

28. Ablative vs. Non-Ablative Treatments 1.1 1

29. Comparison with Other Treatments 1.20

30. Introducing SkinPen 2013: SkinPen modernizes microneedling Stainless steel, cordless design Single, use disposable Advanced Microneedle Cartridge Minimizes epidermal destruction while delivering over 1400 microchannels per second Ideal for clinical practice  Fine lines or moderate wrinkles  Diminished skin texture, tone and color 1.8  Atrophic acne scars  Stretch marks  Traumatic scars  Photo aging

32. Dr. Des Fernandes – Topical A & C Pre-treats patients with topical A and C three weeks to three month prior to needling. Vitamin A is essential for the normal physiology of the skin and for collagen preservation; maximizes collagen production and the skin will heal as rapidly as possible Vitamin C needs to replaced daily to ensure for natural protection and repair of DNA; essential for the production of normal collagen

33. Microchannel Formation 1.15 *Figure from: The AAPS Journal, Vol. 13, No. 3, September 2011 For dermal rollers, the number of microchannels increases as a function of the number of passes made 1 pass3 passes5 passes10 passes15 passes

34. Microchannel Formation *Needles are ~1 mm apart (1000 microns) and the cartridge head has a diameter of 3.5 mm For SkinPen, the number of microchannels depends on how quickly you move the SkinPen across the surface of the skin. ► Needles cycle at 142 Hz or 142 “stamps”/second, potentially creating 1704 microchannels/second when moving the skin pen ► Slower movement at a rate of 1 cm/second, you can create roughly 4858 microchannels/ cm2 of skin* ► Faster movement at a rate of 3 cm/second, you can create roughly 1621 microchannels/ cm2 of skin* ► The SkinPen produces significantly more microchannels with one pass than created by a dermal rollers after many passes! 1.16

35. Recommended Needle Depth Needle depth is contingent on:  Thickness of dermis in area to be treated:  The dermis of the face is variable, typically no deeper than 1.5 mm  Dermis in other areas of the body may be thicker or thinner, with the dermis of the back typically the thickest (~3 mm)  Reason for Treatment:  Facial rejuvenation for improvement of skin texture of fine lines will require less penetration  Improvement of scar tissue will require a more aggressive treatment and therefore deeper penetration Fabbrocini G, et al.. J Dermatolog Treat. 2012 Dec 8. [Epub ahead of print]. 3.4

36. Recommended Needle Depth Plast Reconstr Surg. 2005 May;115(6):1769-73 Average Skin Thickness Measurements Site AVG ABC Upper lip Lower lip Philtrum Chin Upper eyelid Lower eyelid Forehead Right cheek 0.83 ± 0.17 0.82 ± 0.15 0.83 ± 0.10 1.15 ± 0.11 0.38 ± 0.09 0.82 ± 0.21 1.03 ± 0.15 1.07 ± 0.09 Site AVG ABC Left cheek Malar eminence Submental Nasal tip Nasal dorsum Right neck Left neck 1.17 ± 0.08 1.05 ± 0.45 0.89 ± 0.19 1.22 ± 0.15 1.15 ± 0.11 0.52 ± 0.23 0.54 ± 0.20 3.5

37. Why SkinPen? Stainless steel, cordless design The most advanced microneedle cartridge on the market:  Bio-Sleeve technology eliminates cross-contamination and protect the pen  12 medical grade steel, 32 gauge needles to reduce epidermal destruction for superior results and positive patient experience  Exhaust port to reduce suction and risk of broken capillaries

38. Treating Hyperpigmentation 5 intervention points: 1.Block UV radiation 2.Block Melanin Stimulating Hormone (MSH) before it stimulates the kertinocytes and melanocytes 3.Inhibit tyrosinase, the enzyme needed to form melanin in the melanosome 4.Interfere with L-Dopa, the building blocks for pigment in the melanosomes 5.Interfere with transfer of pigment from the melanosome to the keratinocyte 1.8

39. Topicals: Increase collagen synthesis Amino acids such as Proline and Lysine Copper peptides Peptides such as palmitoyl oligopeptide, Matrixyl 3000, palmitoyl tetrapeptide 7, kinetin Zinc Bioflavinoids: plant-derived antioxidants such as grape seed extract/resveratrol, green tea extract Stem cells Omega 3 & 6

40. 2.22 Clinical Study: Scars Microneedling offers a simple and safe modality to improve the appearance of acne scars without risk of dyspigmentation in patient of all skin types  60 patients of skin types phototype I to VI were treated with microneedling for treatment of acne scars  Three treatments at monthly intervals.  Evaluated by using a Global Aesthetic Improvement Scale (GAIS), and analyzed statistically by computerized image analysis of the patients’ photographs.  Average reduction of 31% of scarring.  No short- or long-term dyschromia was observed. Fabbrocini G, et al.. J Dermatolog Treat. 2012 Dec 8. [Epub ahead of print].

41. Stretch Marks Difficult to treat Epidermis is atrophied and support structure beneath it is compromised Melanocytes are sparse or absent, distance to cover is too great for migration Needling: Improves density of the epidermis through release of epidermal growth factor Considered to be the most effective solution for stretch marks Important to not overpromise and under-deliver results

42. Clinical Study: Stretch Marks Treatment of striae distensae using needling therapy: a pilot study. 16 Korean volunteers 3 microneedling treatments at 4-week intervals Assessed by pre and post-treatment clinical photographs, skin biopsies, and patient satisfaction scores. Dermatological Surgery 2012 Nov:38(11): 1823-8

43. Clinical Study: Stretch Marks Results: 7 patients (43.8%): marked to excellent improvement 9 patients: minimal to moderate improvement Patient Satisfaction Scores: 6 patients (37.5%): highly satisfied 8 patients (50%): somewhat satisfied 2 patients (12.5%): unsatisfied No significant side effects except mild pain, erythema, and spotty bleeding. Dermatological Surgery 2012 Nov:38(11): 1823-8

44. Rosacea Stimulates EGF (epidermal growth factor) to increase density of epidermis, lessening appearance of vessels under the skin and overall redness Strengthens collagen in vessel walls and connective tissue that supports the vessels Increases Platelet GF which attracts monocytes into the wound which release interleukin 10 (anti-inflammatory cytokine) Increases availability of cell nutrients and antioxidants