Percutaneous collagen induction. Scarless skin rejuvenation: fact or fiction?

Photoageing is generally treated by ablative procedures that injure the epidermis and basement membrane, and lead to fibrosis of the dermis. Percutaneous collagen induction (PCI) therapy is an alternative treatment for photoaged skin that does not result in clinical signs of dermal fibrosis. In this study, the immediate effects of PCI on the skin were assessed, including the systemic inflammatory response and the production and gene expression of transforming growth factor (TGF) isoforms beta1, beta2 and beta3. Eighty rats were split into four groups: group 1 (n = 24; PCI plus skin care); group 2 (n = 24; skin care only); group 3 (n = 24; PCI only) and group 4 (n = 8; controls). Microarray analysis showed that TGF-beta3, an essential marker for preventing scarring, was upregulated and expressed for 2 weeks postoperatively. PCI might offer a regenerative therapy to improve skin appearance and quality and to improve or even prevent scarring.

Insight in human skin microcirculation using in vivo reflectance-mode confocal laser scanning microscopy.

Reflectance-mode confocal laser scanning microscopy allows in vivo imaging of the human skin. We hypothesized that this high-resolution technique enables observation of dynamic changes of the cutaneous microcirculation. Twenty-two volunteers were randomly divided in two groups. Group 1 was exposed to local heating and group 2 to local cold stress. Confocal microscopy was performed prior t (0) (control), directly t (1) and 5 min t (2) after local temperature changes to evaluate quantitative blood cell flow, capillary loop diameter, and density of dermal capillaries. In group 1, blood flow increased at t (1) (75.82 +/- 2.86/min) and further at t (2) (84.09 +/- 3.39/min) compared to the control (61.09 +/- 3.21/min). The control capillary size was 9.59 +/- 0.25 microm, increased to 11.16 +/- 0.21 microm (t (1)) and 11.57 +/- 0.24 microm (t (2)). The dermal capillary density increased in t (1) (7.26 +/- 0.76/mm(2)) and t (2) (8.16 +/- 0.52/mm(2)), compared to the control (7.04 +/- 0.62/mm(2)). In group 2, blood flow decreased at t (1) (41.73 +/- 2.61/min) and increased at t (2) (83.27 +/- 3.29/min) compared to the control (60.73 +/- 2.90/min). The control capillary size was 9.55 +/- 0.25 microm, decreased at t (1) (7.78 +/- 0.26 microm) and increased at t (2) (11.38 +/- 0.26 microm). Capillary density decreased at t (1) (5.01 +/- 0.49/mm(2)) and increased at t (2) (7.28 +/- 0.53/mm(2)) compared to the control (7.01 +/- 0.52/mm(2)). Confocal microscopy is a sensitive and noninvasive imaging tool for characterizing and quantifying dynamic changes of cutaneous microcirculation on a histomorphological level.

Is superficial burn caused by ultraviolet radiation (sunburn) comparable to superficial burn caused by heat--a histomorphological comparison by in vivo Reflectance-Mode-Confocal Microscopy.

BACKGROUND: Regardless of the underlying cause, both sunburn and superficial thermal injuries are classified as first-degree burns, since data on morphological differences are scarce. Reflectance-Mode-Confocal Microscopy (RMCM) enables high-resolution non-invasive investigation of the human skin. OBJECTIVE: We studied in vivo histomorphological alterations in both sunburn and superficial thermal injuries using RMCM. METHODS: Ten patients (6 female, 4 male; aged 28.4 +/- 10.6 years) with first-degree thermal-contact Injuries (TI group), and 9 sunburned patients (SB group; 7 female, 2 male; aged 30.2 +/- 16.4 years), to a maximum extent of 10% of the body surface were evaluated 24 h after burn injury using RMCM. The following parameters were obtained using RMCM: stratum corneum thickness, epidermal thickness, basal layer thickness, granular cell size. RESULTS: Compared to the controls (12.8 +/- 2.5 microm), stratum corneum thickness decreased significantly to 10.6 +/- 2.1 microm in the TI group, whereas it increased significantly to 16.4 +/- 3.1 microm in the SB group. The epidermal thickness did not differ significantly in the TI group (47.9 +/- 2.3 microm) and SB group (49.1 +/- 3.5 microm); however, both increased significantly compared to their respective controls (41.8 +/- 1.4 microm). The basal layer thickness increased more in the SB group compared to the TI group (17.9 +/- 1.4 microm vs. 15.6 +/- 1.1 microm). Both differed also significantly compared to their controls (13.8 +/- 0.9 microm). The granular cell size increased significantly in both groups compared to the controls (731 +/- 42 microm); however, a significantly higher increase was observed in the TI group (852 +/- 58 microm) compared to the SB group (784 +/- 61 microm). CONCLUSIONS: Ultraviolet radiation seems to influence predominantly deeper epidermal layers, whereas heat-induced burns affect more superficial epidermal layers. The term 'First-degree burn' should not be used synonymously for sunburn and superficial thermal burn injuries. Conflicts of interest None declared.

[Vascular interventions and reconstructive plastic surgery. Optimizing the treatment of chronic wounds]. / Gefässchirurgische Interventionen und plastisch-rekonstruktive Chirurgie. Ergebnisoptimierung in der Behandlung chronischer Wunden.

Despite the high prevalence of arterial occlusive disease, only a few studies have investigated the benefit of interventions to recanalize extremity arteries prior to plastic operations to close chronic wounds. The purpose of this study was to investigate the correlation of simple clinical examinations and apparative diagnostics of arterial occlusive disease of the lower extremity in patients with chronic wounds and to evaluate the benefit of vascular procedures to optimize wound perfusion before surgical closure. A total of 150 individuals with chronic wounds were included in this retrospective study. All patients underwent palpation of their foot pulses, Doppler sonography, and measurement of occlusive pressure. Positive results were tested by angiography. All patients with peripheral extremity vessel occlusion underwent vascular interventions prior to plastic operations for definitive wound closure. In all 34 patients with missing foot pulses, the clinical diagnosis of arterial occlusion could be confirmed by angiography. Peripheral recanalization and improved wound perfusion could be achieved in all patients. Arterial insufficiency could be diagnosed rapidly and safely using simple clinical examination such as palpation of foot pulses or measurement of occlusive pressures combined with Doppler sonography. Thus this simple and straightforward algorithm helped to secure the success of surgical therapy by shortening the time until wound-healing and reducing the psychosocial burden on the patient and financial costs to the health care system.

[Autologous Skin Cell Transplantation and Medical Needling for Repigmentation of Depigmented Burn Scars on UV-protected and UV-exposed Skin]. / Autologe Hautzelltransplantation und Medical Needling zur Repigmentierung von depigmentierten Verbrennungsnarben an UV-exponierter und -geschützter Haut.

Background: Burn scars remain a serious physical and psychological problem for the affected people. Both clinical studies and basic scientific research have shown that medical needling can significantly increase the quality of burn scars with comparatively low risk and stress for the patient related to skin elasticity, moisture, erythema and transepidermal water loss. However, medical needling does not influence repigmentation of large hypopigmented scars. Objective: The goal is to evaluate whether both established methods - needling (improvement of scar quality) and non-cultured autologous skin cell suspension (NCASCS) "ReNovaCell" (repigmentation) - can be combined. So far, 20 patients with mean age of 33 years (6-60 years) with deep second and third degree burn scars have been treated. The average treated tissue surface was 94 cm² (15-250 cm²) and was focused on areas like face, neck, chest and arm. Methods: Medical needling is performed using a roller covered with 3 mm long needles. The roller is vertically, horizontally and diagonally rolled over the scar, inducing microtrauma. Then, NCASCS is applied, according to the known protocol. The patients have been followed up for 15 months postoperatively. The scars were subdivided into "UV-exposed" and "UV-protected" to discover whether the improved repigmentation is due to transfer of melanocytes or to reactivation of existing melanocytes after exposure to UV or the sun. Results: The objective measures show improved pigmentation in both UV-exposed and UV-protected groups. Melanin increases 1 year after NCASCS treatment in the UV-protected group are statistically significant. Conclusion: Medical needling in combination with NCASCS shows promise for repigmentation of burn scars, even in sun protected scars.

Combination of medical needling and non-cultured autologous skin cell transplantation (renovacell) for repigmentation of hypopigmented burn scars in children and young people.

Burn scars remain a serious physical and psychological problem for the affected. Clinical studies as well as basic scientific research have shown that Medical Needling can significantly increase the quality of burn scars with comparatively low risk and stress for the patient with regards to skin elasticity, moisture, erythema and transepidermal water loss. However, Medical Needling has no influence on repigmentation of large hypopigmented scars. The goal is to evaluate whether both established methods - Needling (improvement of scar quality) and ReNovaCell (repigmentation) - can be combined. So far, eight patients with mean age of 20 years (6-28 years) with deep second and third degree burn scars have been treated. The average treated tissue surface was 76cm² (15-250cm²) and was focused on areas like face, neck, chest and arm. Medical Needling is performed using a roller covered with 3mm long needles. The roller is vertically, horizontally and diagonally rolled over the scar, inducing microtrauma. Then, non-cultured autologous skin cell suspension (ReNovaCell) is applied, according to the known protocol. The patients were followed 12 months postoperatively. Pigmentation changes were measured objectively, and with patient and observer ratings. Patient satisfaction/preference was also obtained. We present the final study results. Taken together, pigmentation ratings and objective measures indicate improvement in six of the study participants. Melanin increase seen 12 months after ReNovaCell treatment in the study group as a whole is notable. Medical Needling in combination with ReNovaCell shows promise for repigmentation of burn scars.

Les séquelles de brûlures demeurent un problème physique et psychologique pour les victimes. Les études cliniques, ainsi que les recherches scientifiques ont montré que l'Aiguilletage médical peut améliorer de façon significative la qualité des cicatrices de brûlures avec un risque faible et un retentissement psychologique mineur chez les patients et ceci vis-à-vis de l'élasticité cutanée, l'hydratation, l'érythème et la déperdition hydrique trans épidermique. Cependant l'Aiguilletage médical n'a pas d'influence sur la repigmentation des vastes cicatrices hypo pigmentées. Le but est d'apprécier la possible association des deux méthodes: Aiguilletage (amélioration de la cicatrice) et ReNovaCell (re pigmentation). Ainsi 8 patients avec une moyenne d'age de 20 ans (6-28 ans) présentant des cicatrices de brûlures du 2e degré profond et 3e degré ont été traités. La moyenne de surface traitée était de 76cms carrés (15-20cms carrés) et les zones choisies furent la face, le cou, le thorax et les bras. L'Aiguilletage médical était réalisé avec un rouleau couvert d'aiguilles de 3mm de long. Le rouleau est manié verticalement, horizontalement et en diagonale sur la cicatrice provoquant un microtraumatisme. Puis, les cellules cutanées autologues non cultivées en suspension (ReNovaCell) sont appliquées suivant le protocole connu. Les patients furent suivis pendant 12 mois après le traitement. Les changements de pigmentation étaient mesurés de façon objective par le patient et évalués suivant une grille. La satisfaction du patient et son avis étaient alors notés. Nous présentons les résultats de la fin de notre étude. Prenant en compte les taux de repigmentation et les mesures objectives, l'amélioration fut constatée chez 6 de nos patients. L'augmentation de la mélanine fut observée 12 mois après le traitement par ReNovaCell dans l'ensemble du groupe de façon notable. L'association « Aiguilletage médical +ReNovaCell ¼ est riche de promesse pour la repigmentation des cicatrices de brûlures.

Combination of medical needling and non-cultured autologous skin cell transplantation (ReNovaCell) for repigmentation of hypopigmented burn scars.

Burn scars remain a serious physical and psychological problem for the affected people. Clinical studies as well as basic scientific research have shown that medical needling can significantly increase the quality of burn scars with comparatively low risk and stress for the patient with regards to skin elasticity, moisture, erythema and transepidermal water loss. However, medical needling has no influence on repigmentation of large hypopigmented scars. The goal of this study is to evaluate whether two established methods - needling (for improvement of scar quality) and non-cultured autologous skin cell suspension (for repigmentation) - can be successfully combined. Twenty subjects with 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 arm. Percutaneous collagen induction or "medical needling" was performed using a roller covered with 3mm long needles. The roller is vertically, horizontally and diagonally rolled over the scar, inducing microtrauma. Then, non-cultured autologous skin cell suspension (NCASCS) was produced and applied using the ReNovaCell Autologous Cell Harvesting Device (Avita Medical), according to the manufacturer's instructions. The patients were followed 12 months postoperatively. Pigmentation changes were measured objectively, as well as with patient and observer ratings. Patient satisfaction/preference was also obtained. Taken together, the pigmentation ratings and objective measures indicate individual improvement in 17 of the study participants. The melanin increases seen 12 months after NCASCS treatment are statistically significant. Medical needling in combination with NCASCS shows promise for repigmentation of burn cars.

Microneedling: matching the results of medical needling and repetitive treatments to maximize potential for skin regeneration.

The benefits and risks of singular and repetitive microneedling (1 mm) have not been thoroughly investigated. The aim of this study was to evaluate the benefits and risks of singular and repetitive skin needling with a microneedling device in an animal model with and without skincare. 30 Sprague Dawley rats were randomized to five groups: control, skin-care only (Vitamin A & C), 1× needling 1 mm, 4× needling 1 mm, 4× needling 1 mm with skin-care. All animals were euthanized after 10 weeks. Skin specimens were stained with HE and Masson's trichrome. Additionally, gene expression analysis with microarray technique for various growth factors (TGFß1-3, FGF, EGF, VEGF, TNF-α) and real time reverse transcription PCR for collagen I & III were conducted. We showed that singular microneedling matches and repetitive microneedling sessions superposition epidermal and dermal benefits such as an increase of epidermal thickness (up to 658% increase, p value 0.0008) and dermal connective tissue--even more so when combined with skin-care with vitamin A and C. Juvenile collagen I showed itself up-regulated in all groups, while collagen III was down-regulated. Singular and repetitive PCI with a microneedling device can achieve and supersede the results already shown with medical needling.

Percutaneous collagen induction-regeneration in place of cicatrisation?

BACKGROUND: Ablative procedures that are used for the improvement of a degenerative process that leads to a loss of skin elasticity and integrity, injure or destroy the epidermis and its basement membrane and lead to fibrosis of the papillary dermis. It was recently shown in clinical and laboratory trials that percutaneous collagen induction (PCI) by multiple needle application is a method for safely treating wrinkles and scars and smoothening the skin without the risk of dyspigmentation. In our study, we describe the effect of PCI on epidermal thickness and the induction of genes relevant for regenerative processes in the skin in a small animal model. METHODS: The purpose of this study in a rat model was to determine the effects of PCI on the skin both qualitatively and quantitatively. The epidermal and dermal changes were observed by histology and immunofluorescence. The changes in gene expression were measured by array analysis for cytokines, such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-7, epidermal growth factor (EGF) and extracellular matrix molecules such as collagen type I and type III. RESULTS: The present study showed that PCI with topical vitamins resulted in a 140% increase in epidermal thickness; an increase in gene and protein expression of collagen I, glycosaminoglycans (GAGs) and growth factors such as VEGF, EGF and FGF7. The collagen fibre bundles were increased, thickened, and more loosely woven in both the papillary and reticular dermis. CONCLUSION: We were able to show that PCI modulates gene expression in skin of those genes that are relevant for extracellular matrix remodelling.

In vivo reflectance-mode confocal microscopy provides insights in human skin microcirculation and histomorphology.

PURPOSE: Various approaches are used to study microcirculation, however, no modality evaluates microcirculation and histomorphology on cellular levels. We hypothesized that reflectance-mode confocal microscopy (RCM) enables simultaneous evaluation in vivo of both microcirculation and histomorphology. PRINCIPALS: The forearm of 20 volunteers was exposed to either local heat stress (HS-group), or to local cold stress (CS-group). RCM was performed prior and after temperature stress to evaluate quantitative blood-cell flow, capillary loop diameter, granular cell size, and basal layer thickness. RESULTS: In the HS-group, we observed significant increase in capillary loop diameter and increased blood-cell flow after heat stress. In the CS-group, significant decreases of capillary loop diameter and in blood-cell flow were determined following cold stress. Granular cell size and basal layer thickness differed insignificantly prior and after local temperature stress. CONCLUSIONS: RCM provides real-time and in vivo high resolution imaging of temperature-dependent changes in the human skin microcirculation and histomorphology on cellular levels.

[Dermal subsitute with the collagen-elastin matrix Matriderm in burn injuries: a comprehensive review]. / Aktuelle Ubersicht zum Dermisersatz mit Kollagen-Elastin-Matrix Matriderm bei Brandverletzungen.

Matriderm is a dermal substitute consisting of a native (non-cross-linked) collagen matrix supplemented by a elastin hydrolysate. It is available in sheets of 1 mm and 2 mm thickness, and may be covered in a single step procedure with immediate split thickness skin grafting. Duration of the surgical procedures are only marginally increased. There is no diminished take of split thickness graft and only marginally prolonged healing time compared with the split thickness graft only. In experimental models the matrix reduces wound contracture, histologically collagen bundles in the scar are more randomly orientated. Clinical trials with a long-term clinical evaluation showed no difference in scar elasticity between the described dermal substitute and split thickness grafts alone. There is a lack of clinical data on the development of wound contracture.

Lower limb revascularisation preceding surgical wound coverage - an interdisciplinary algorithm for chronic wound closure.

BACKGROUND: Chronic wounds may occur or persist due to arterial insufficiency. Despite the high prevalence of arterial occlusive disease, a search of the literature has yielded a paucity of data on the benefit of interventions to recanalise lower extremity arteries prior to surgical closure of chronic wounds. OBJECTIVE: To investigate the correlation of simple clinical examinations and apparative diagnostics for the detection of arterial occlusive disease of the lower extremity in patients with chronic wounds, and to evaluate the benefit of vascular procedures to optimise wound perfusion before surgical closure. PATIENTS AND METHODS: During a 6-year period, 150 patients with chronic lower extremity wounds (no healing for more than 30 days) were included into this prospective study. All patients underwent palpation of foot pulses, Doppler sonography and measurement of occlusive pressures. Positive clinical findings were re-evaluated by angiography. All patients with peripheral extremity vessel occlusions underwent vascular interventions (percutaneous transluminal angioplasty with stenting, open thrombectomy or vascular bypass surgery) prior to surgical wound closure. RESULTS: In all 34 patients (21%) with missing foot pulses, suspicious Doppler signals or pathological occlusive pressure measurements, the clinical diagnosis of arterial occlusion was confirmed by angiography. An arterial pathology had previously been diagnosed in merely two of those patients. Nineteen patients underwent percutaneous transluminal angioplasty and 21 stents were implanted; in 10 cases, open thrombectomy or vascular bypasses were performed. In all 34 patients, sufficient peripheral recanalisation and improved wound perfusion were successfully achieved. For definitive wound closure, microsurgical tissue transplantation was performed in 15 patients. Angiography was performed prior to surgery. In 11 patients, regional or local flaps were used. Six patients received split skin grafting only; two wounds healed conservatively following vascular intervention. Vacuum-assisted closure (VAC) therapy was applied in 15 cases. Postoperatively, three cases of impaired wound healing and one infection occurred. CONCLUSIONS: Arterial insufficiency can be diagnosed safely by simple clinical examination. All clinically pathological results were successfully confirmed by angiography, allowing for a targeted peripheral vessel reopening to improve wound perfusion before surgery. This straightforward algorithm helped to improve the success of surgical therapy of chronic lower extremity wounds.

Lipomas after blunt soft tissue trauma: are they real? Analysis of 31 cases.

BACKGROUND: Soft tissue trauma and lipomas are common occurrences in surgical practice. Lipomas are defined as benign tumours of adipose tissue with so far unexplained pathogenesis and aetiology. A link between preceding blunt soft tissue trauma at the site of the tumour and the formation of lipomas has been described earlier. These soft tissue tumours have been named 'post-traumatic lipomas'. OBJECTIVES: In a retrospective review, to analyse all patients with benign adipose tissue tumours treated at our institution between August 2001 and January 2007. METHODS: All cases were reviewed regarding medical history, magnetic resonance imaging findings, intraoperative findings, clinical chemistry and histology. RESULTS: In 170 patients presenting with lipomas, 34 lipomas in 31 patients were identified as post-traumatic. The mean +/- SD age of the patients with post-traumatic lipomas was 52 +/- 14.5 years. The mean time elapsed between soft tissue trauma and lipoma formation was 2.0 years (range 0.5-5). Twenty-five of the 31 patients reported an extensive and slowly resolving haematoma after blunt tissue trauma at the site of lipoma formation. The mean +/- SD body mass index was 29.0 +/- 7.6 kg m(-2). Fourteen of 31 patients presented with an elevated partial thromboplastin time. Eleven of 34 lipomas were found on the upper extremities, five on the lower extremities, 13 on the trunk, and two on the face. All tumours were located subcutaneously, superficial to the musculofascial system. Thirty-three lipomas were removed by surgical excision and one by liposuction following an incisional biopsy. Histological examination revealed capsulated and noncapsulated benign adipose tissue in all 34 tumours. CONCLUSIONS: The existence of a pathogenic link between blunt soft tissue trauma and the formation of post-traumatic lipomas is still controversial. Two potential mechanisms are discussed. Firstly, the formation of so-called post-traumatic 'pseudolipomas' may result from a prolapse of adipose tissue through fascia induced by direct impact. Alternatively, lipoma formation may be explained as a result of preadipocyte differentiation and proliferation mediated by cytokine release following soft tissue damage after blunt trauma and haematoma formation.

[Diagnosis and treatment of posttraumatic pseudolipomas. A retrospective analysis]. / Diagnostik und Therapie posttraumatischer Pseudolipome. Eine retrospektive Analyse.

BACKGROUND: Both trauma and lipomas are frequently encountered in day-to-day clinical practice. Although lipomas are defined both clinically and pathologically as benign fatty tissue tumours, their aetiology is still not clear. METHODS: In this study 19 patients with 23 posttraumatic lipomas were analysed retrospectively with reference to ultrasound and MRI diagnosis, history, laboratory results and histopathological investigations. RESULTS: The mean age of the patients was 50.5 years (+/-15.5). The causative soft tissue trauma dated back an average of 2.6 years. When the histories were taken, 16 of the 19 patients reported vast, slow-resorbing posttraumatic haematomas. Nine of the 23 lipomas were sited in the upper extremity, 3 in the lower extremity, 9 in the trunk and 2 in the face. All were located epifascially. In 22 cases the lipomas were excised, and in 1 case the lipoma was removed by liposuction. Histological examination demonstrated capsulated benign fatty tissue tumours in 19 cases and uncapsulated benign fatty tissue tumours in 4. The average body mass index (BMI) was 29 kg/m(2). Removal of the tumour resulted in a good aesthetic result in all patients. CONCLUSIONS: The link between a blunt soft tissue injury and the development of a posttraumatic lipoma is still the subject of controversy; there are two mechanisms that seem more likely than any others proposed: (1) the "pseudolipoma" as the result of a prolapse of fatty tissue as an immediate result of trauma and (2) the development of a lipoma by way of differentiation of pre-adipocytes mediated by cytokines released by a posttraumatic haematoma. There appears to be a correlation between an increased partial thromboplastin time (PTT) and the development of posttraumatic lipomas. The generalised increase in the volume of body fat documented by the elevated BMI supports the idea that lipomas arise from the prolapse of adipose tissue. However, there is no single mechanistic explanation for the development of posttraumatic lipomas. They are probably caused by multiple factors and not by isolated pathological mechanisms.