Skin Regeneration Symposium Cambridge, 12-13 April 2016 Part 3

The Annual Skin Regeneration Symposium, held in Cambridge, UK, 12-13 April 2016, explored the latest advancements in skin repair, regeneration and restoration, and the impact this has on patients. With over 140 delegates from the disciplines of burn and trauma care, chronic wounds and esthetic medicine, the Symposium sparked lively debate and the sharing of results from interesting case studies, clinical trials and basic research to support the use of a Regenerative Epithelial Suspension produced using the ReCell® technology. Furthermore, it enabled delegates and speakers alike to share ideas and discuss how to improve the quality of care for patients.

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May 27, 2016
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RESTORE: PLASTICS AND ESTHETICS

An experience using ReNovaCell

In the second keynote presentation of day 2, Dr Jean Michel Rives (Clinique Esthetique Elysee Montaigne and Clinique Sainte Isabelle, France) presented his experience with ReNovaCell™, which has been available in France since 2006. The occipital scalp area has the highest concentrations of stem cells, keratinocytes and melanocytes. From this area, Dr Rives takes a full-thickness sample, the length of which varies according to number of kits used. This area will generally heal quickly without hypertrophic scarring, and any surgical scarring will be hidden by hair regrowth. Dr Rives often uses multiple devices to generate large amounts of concentrated cell suspension, which he feels results in a higher basal cell ratio. He has found that this improves the rate of healing and quality of results. Dr Rives prepares the patients’ wounds using a classical surgical dermabrasion with a diamond burr. When treating hypertrophic scarring he uses more aggressive dermabrasion. Once Dr Rives has applied the cell suspension he uses a biological dressing (Biobrane®, Smith and Nephew), which he believes optimizes the wound environment for RES. This is then covered using conventional secondary dressings using two layers of sterile gauze. The first postoperative dressing change after ReNovaCell™ application is always done under the surgeon’s supervision at 2-5 days post-surgery, depending on size and location. Biobrane® is kept in situ. Vaseline gauze with topical HA (Ialuset®, Genevrier) is applied on top of Biobrane®. Following the initial twice-weekly dressing change, patients are seen in the outpatient setting. Gradually the Biobrane® will unstick and should be tailored until it is completely healed. Ialuset® is applied to the wound to reinforce skin quality and healing. Dr Rives uses ReCell® for a number of indications, including vitiligo, hyperpigmentation, rhinophyma, facial acne sequelae and hypertrophic scarring. In future Dr Rives also believes there could be an indication in cosmetic surgery for facial skin rejuvenation owing to stem cell potential.

In burns in particular, ReCell® presents a good opportunity for surgeons, and is a useful technique for quick and fast closure. It gives stable coverage even on infected areas, good functional outcomes and acceptable cosmetic results.

Combination of needling and ReCell® – a new promising approach

Dr Matthias Aust (Malteser Hospital, Germany) discussed the use of needling in combination with the cell suspension produced using the ReNovaCell™ device. With acute and chronic wounds there is an existing wound bed, but if it is a closed surface (intact skin) such as in vitiligo, hypertrophic scarring, or photoaging, the skin must be prepared to provide a wound bed with pin-point bleeding to receive the cells. When reviewing the literature, all techniques for the preparation of the wound bed work by removing the epidermis to varying degrees, and depth of this removal depends on the technique and the user. This carries risks such as dyspigmentation, scarring, delayed wound healing, prolonged downtime for the patient and potential infection of the open wound. Dr Aust suggests that instead of removing the epidermis, such as using an ablative laser, the skin should be wounded to stimulate the body’s own repair mechanisms and remodeling of matrix proteins. Dr Aust uses a 3-mm needling device, which is rolled vertically, horizontally and diagonally across the surface of the scar creating microtrauma. In turn, this regenerates and thickens the epidermis [15]. However, needling alone does not achieve repigmentation, so Dr Aust and colleagues tested the combination of needling and skin cell suspensions produced using ReNovaCell™ [16].

Twenty patients with a mean age of 33 years (6-60 years) with scars from deep second- and third-degree burns have been treated. The average treated surface area was 94cm² (15-250cm²) and was focused on prominent areas such as the face, neck, chest and arms. The noncultured autologous skin cell suspension was produced using the ReNovaCell™ Autologous Cell Harvesting Device and applied to the scars, which had been prepared by microneedling as previously described. Control areas included microneedling only and a reference no treatment (microneedling or RES) in each patient. Dr Aust followed the patients for 12 months postoperatively. Pigmentation changes were measured objectively using a Mexameter® (Courage + Khazaka electronic GmbH) to quantify the presence of melanin in the skin at baseline, 3, 6, 9 and 12 months, together with assessments using the Patient and Observer Scar Assessment Scale (POSAS).

Dr Aust’s data demonstrated significant repigmentation and improvements in skin quality in the areas of the hypertrophic scar receiving microneedling and RES. There were no improvements in pigmentation in the control areas. Only three of the patients failed to respond and Dr Aust attributed this to less effective cleaning of the microneedled wound and serous fluid plugging of the needle channels.

Dr Aust’s results show a marked subjective and objective improvement in pigmentation. Both medical needling and RES preserve the epidermis, which results in a reduced risk of new scarring or dyspigmentation. Considering all factors, he concluded that the combination of medical needling and RES is a promising approach to repigment large hypopigmented burn scars.

ReCell® in vitiligo and piebaldism patients: preliminary data of a randomized controlled study on the recipient site preparation

Vitiligo is a common pigmentation skin disorder, with no discrimination between gender, ethnicity, skin type or where it appears on the body. Patients often find their disease distressing, especially when it occurs on visible areas such as the face, hands or legs. This can have a significant impact on QoL. Nonsegmented vitiligo is the most common type of the disease and is considered a progressive autoimmune disease. Segmented vitiligo is less common but usually more stable after the first depigmentation, and a good patient group when investigating new pigmentation techniques. Dr Annelies Lommerts (Netherlands Institute of Pigment Disorders) and colleagues undertook a study of the use of ReNovaCell™ in congenital segmented vitiligo of the lower legs, forehead and trunk. The patient-controlled prospective study (n=10 patients) was designed to investigate the effectiveness of RES in combination with ablative CO2 laser preparation techniques. Dr Lommerts demonstrated the areas of depigmented skin that were treated with the ablative laser and RES repigmented (78% of patients), while those treated with laser alone or untreated areas did not repigment (Figure 5) [17].

Figure 5. More than 75% repigmentation was seen in patients treated with ablative CO2 laser in combination with RES, (a) before treatment and (b) after treatment. i. fractional laser alone; ii. Control group; iii. CO2 200mJ plus RES; iv. CO2 150mj plus RES

Dr Lommerts also presented a preview of a newer study, which focuses on recipient site preparation. The team at the Netherlands Institute of Pigment Disorders is using RES in combination with fractional CO2 laser and a more superficial setting of CO2 laser, as well as repeating the deeper ablative CO2 treatment of the previous study. The hypothesis is that the fractional or more superficial settings may reduce patient discomfort during skin preparation and reduce risk of scarring while still achieving good repigmentation. As before, ten patients have received RES in combination with fractional, deep or superficial ablative CO2 laser settings, plus an untreated control area and are followed for 6 months and pigmentation assessed. Following wound bed preparation, RES was applied to each test area and to the donor sites. Following treatment, systemic antibiotics were prescribed for 1 week in addition to wound dressings, and UVA light was applied twice per week for 2-4 months postoperatively. To date all patients have been enrolled and are now being followed up for 6 months. The study has yet to complete, but results are promising. Of particular note is that in the patients who have completed so far, the superficial and deeper ablative laser methods with RES yield similar results; a very good repigmentation was seen in 60% of patients and in fact, a number of the study patients have requested full treatment of their depigmented patches at the study end. The use of RES in combination with CO2 laser preparation at the Netherlands Institute of Pigment Disorders has been found to be an effective treatment for segmental vitiligo.

RES transplantation with the ReCell® device for vitiligo: the therapeutic protocol

The goal of any vitiligo treatment is to replace damaged melanocytes or replace those destroyed by disease. Topical therapies are often the first-line therapy, followed by phototherapy. Surgical intervention is the last resort, with two options available – transplantation or grafting. The usual ratio of donor site to transplant site is 1:1, so this can be a time-consuming treatment. Associate Professor Ang Zeng and Professor Zhifei Liu (both Peking Union Medical College Hospital, China) use cell suspensions produced using ReNovaCell™, and see it as an effective approach. They formed their own technical protocol and applied it as a treatment in a number of hospitals. The protocol comprised three actions: criteria for patient participation; the procedure; and postoperative management and follow-up to gather data. Inclusion criteria were no spreading of disease for at least 1 year, and a treatment area that is easy to mobilize and bandage. Optimal candidates had spotted repigmentation and a good response to blister therapy. Patients were also counselled on realistic expectations on the extent of pigmentation any treatment might restore, and so it was imperative that the patients understood that any improvement would be gradual. Patients also needed to comply with treatment. Other exclusion criteria were uncontrolled diabetes, smoking, pregnancy and keloid scarring. Before surgery, patients had a detailed consultation to provide treatment information and discuss medical history. Photographs were taken before treatment to track any changes. The procedure was performed in an outpatient clinic under local anesthesia. After cell treatment patients received UV phototherapy, which was monitored for hyperpigmentation.

Patients completed a questionnaire for patient-reported outcomes, and the clinicians completed an assessment of adverse events and an esthetic evaluation. After treating 100 patients the team feels they have an effective protocol incorporating ReNovaCell™ for the treatment of vitiligo, and this is now being used in a number of hospitals in China.

ReCell®: an Australian case series

Dr Shobhan Manoharan (Brisbane Skin and Westside Dermatology, Australia) is a recent convert to the use of cell suspensions and has been using ReNovaCell™ in his clinic for the past 6 months. He described how he has incorporated ReNovaCell™ into his skin clinic and shared some preliminary results. Dr Manoharan focused on hypopigmented scar treatment in combination with techniques including ablative and fractional laser. Dr Manoharan has been using fractional lasers for a number of years, with topical hydroquinone and corticosteroids to reduce scarring. Fractional laser treatments have many benefits, including that they can be used in darker skin types, and cause less discomfort and downtime. In the three cases Dr Manaharan has completed with ReNovaCell™, he can already see improvements in scar quality and restoration of pigmentation. It is early days and the treated areas continue to improve. Dr Manaharan will continual to monitor these patients for the next year and treat additional patients with a view to presenting his results in a peer-reviewed journal.

Pretibial laceration treatment in the outpatient department with autologous noncultured cell therapy

Pretibial lacerations are a significant injury to the aging population and account for approximately 50 in every 1000 attendances in the emergency department. There is currently no guidance on the management of these injuries in the UK. Mr Robert Manton (St Mary’s Hospital, London, UK) presented a case example of an 85-year-old with significant comorbidities, who was usually very independent and mobile. The patient presented acutely to the emergency department at King’s College Hospital (KCH), London, and was later admitted to the orthopedic team for formal wound debridement. The patient was seen by plastic surgeons at KCH, discharged and seen 1-week postoperatively. There was no evidence of granulation tissue at that time, so RES was applied following debridement under local anesthetic. The patient was discharged with a regular dressing and gauze. The team monitored the patient closely and by 3 weeks post-treatment the wound area had decreased 25%, and 75% at 5 weeks. The wound was healed by 3 months without complication, good-quality skin formed and her donor site healed without complication. Mr Manton explained that they had found using RES in an outpatient setting advantageous to both patient and surgeon. The patient only required a local anesthetic, a small donor site and did not require hospital admittance. This enabled her to remain independent, mobile and with considerable cost savings to the NHS Trust. The team is now continuing to treat these injuries with RES and is gathering further data for publication.

ReCell surgical treatment for large area vitiligo

Dr Meng Zhongping (Borun Group, China) explained that vitiligo is common among the Chinese population, but there is a limited number of hospitals that specialize in treatment for the condition. The Borun Group is a specialized group of 23 hospitals focusing on the treatment of vitiligo, which was established in 2010, with more than 100 vitiligo experts employed. They have applied both traditional Chinese medicine and modern Western medicine to treat the condition. They have been using ReNovaCell™ since 2014, and more than 50 patients have benefited from the treatment. There are three kinds of surgical therapies for vitiligo treatment – suction blister, particle pigmentation and ReNovaCell™ surgical treatments. Dr Zhongping explained that the attraction of the ReNovaCell™ procedure is its simplicity and that it can treat large areas of affected skin. As previously described, a protocol was developed by Professors Liu and Zeng, and this is now in use across the Borun Group Hospitals to make the ReNovaCell™ procedure available to the wider population.

Peculiar scars that require multi-modalities

The final presentation of the Symposium was presented by Dr Jeremy Rawlins in which he discussed staged scar revision. Dr Rawlins discussed his “tool-box” of procedures and how he has incorporated ReNovaCell™ into his practice as an adjunct to treatments to improve scar quality and pigmentation.

Of particular note was the work Mr Rawlins has completed for rhinophyma. Rhinophyma can be difficult to treat as the patient is often left with a raw wound on the nose for many weeks. Dr Rawlins supports using Versajet® in this treatment modality as it allows the physician to reduce the amount of sebaceous tissue and keep the area clean. He then applied RES. Mr Rawlins explained the wound re-epithelialized rapidly and good quality skin was formed, far superior than that achieved with standard scalpel excisions.

In patients presenting with significant scar tissue, Mr Rawlins explained that it is essential to stimulate collagen and break up the scar. In a similar application to Dr Aust’s, Dermaroller and microneedling techniques in combination with ReNovaCell™ have been very effective to restore pigmentation to hypopigmented darker skin.

Management of patient expectations is extremely important and it is essential to include the patients in discussions to determine the best treatment modalities. Mr Rawlins concluded that there is a diverse set of tools available for scar revision and that ReNovaCell™ presents a beneficial adjunct to treatment.

References

1. Trim JE, Quick A. Regenerative Epithelial Suspension. Avita Medical, May 2015

2. Duke J, Wood F, Semmens J, et al. Rates of hospitalisations and mortality of older adults admitted with burn injuries in Western Australian from 1983 to 2008. Australas J Ageing. 2012;31(2):83–9

3. Graves C, Saffle J, Cochran A. Actual burn nutrition care practices: an update. J Burn Care Res. 2009;30(1):77-82

4. Lawrence A, Faraklas I, Watkins H, et al. Colloid administration normalizes resuscitation ratio and ameliorates "fluid creep". J Burn Care Res. 2010; 31(1):40-7

5. Hettiaratchy S, Dziewulski P. ABC of burns. Introduction. BMJ. 2004;328(7452):1366-8

6. Barrow RE, Spies M, Barrow LN, Herndon DN. Influence of demographics and inhalation injury on burn mortality in children. Burns. 2004;30:72–7

7. Bergan JJ, Schmid-Schönbein GW, Smith PD, Nicolaides AN, Boisseau MR, Eklof B. Chronic venous disease. N Engl J Med. 2006;355(5):488–498

8. Moffatt CJ, Franks PJ, Doherty DC, Martin R, Blewett R, Ross F. Prevalence of leg ulceration in a London population. QJM. 2004;97(7):431–437

9. Heit JA. Venous thromboembolism epidemiology: implications for prevention and management. Semin Thromb Hemost. 2002;28(suppl 2):3–13

10. Kurz N, Kahn SR, Abenhaim L, et al., eds. VEINES Task Force Report, The management of chronic venous disorders of the leg (CVDL): an evidence based report of an international task force. McGill University. Sir Mortimer B. Davis-Jewish General Hospital. Summary reports in: Angiology. 1997;48(1):59–66; and Int Angiol. 1999;18(2):83–102.

11. Smith JJ, Guest MG, Greenhalgh RM, Davies AH. Measuring the quality of life in patients with venous ulcers. J Vasc Surg. 2000; 31(4): 642-9

12. NICE. Diabetic foot problems: prevention and management. 2015 https://www.nice.org.uk/guidance/ng19/chapter/Introduction

13. Jackson PC, Wilks D, Rawlins J, Matteucci PL. Combined use of hyperbaric oxygen and sprayed keratinocyte suspension to tackle a difficult wound. Ann R Coll Surg Engl. 2014;96(6):e20-2

14. Enoch S, Leaper D. Basic science of wound healing. J Investigative Dermatology. 2007;27:514-525

15. Aust MC, Fernandes D, Kolokythas P, Kaplan HM, Vogt PM. Percutaneous collagen induction therapy: an alternative treatment for scars, wrinkles, and skin laxity. Plast Reconstr Surg. 2008; 121(4): 1421-9

16. Busch KH, Bender R, Walezko N, Aziz H, Altintas MA, Aust MC. Combination of medical needling and non-cultured autologous skin cell transplantation (ReNovaCell) for repigmentation of hypopigmented burn scars. Burns. 2016; [Epub ahead of print]

17. Komen L, Vrijman C, Tjin EPM, et al. Autologous cell suspension transplantation using a cell extraction device in segmental vitiligo and piebaldism patients: a randomized controlled pilot study. J Am Acad Dermatol. 2015;73(1):170-2

To catch up on this event, please find part 1 of the conference report here and part 2 of the conference report here.

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Regenerative Medicine

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Regenerative Medicine is an award-winning peer-reviewed journal, in print and web formats. The journal provides a forum to address the important challenges and advances in stem cell research and regenerative medicine, delivering this essential information in concise, clear and attractive article formats. Among other indexing services Regenerative Medicine is listed by MEDLINE/Index Medicus, EMBASE/Excerpta Medica, Chemical Abstracts, Science Citation Index Expanded™ (SciSearch®), Emcare, Biological Abstracts, BIOSIS Previews, Biotechnology Citation Index®, Journal Citation Reports/Science Edition®, Scopus® with an Impact Factor of 2.786 (2014). Each issue contains expertly drafted Reviews, Original Research articles, Perspectives, Editorials, topical insight from international leaders in their field, and additional added-value content. The Senior Editor of the journal is Professor Chris Mason, University College London. You can find out more about Regenerative Medicine at our website (www.future-science-group.com/journalprofile/regenerative-medicine/), where you can find the aims and scope of the journal and details of our international editorial board.
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