Cosmetic Breast Augmentation with Autologous Ex Vivo-Expanded Adipose-Derived Mesenchymal Stem/Stromal Cell (Stemform®)-Enriched Fat Grafts: A Study of the First Twenty-Two Real-World Patients.

BACKGROUND: Fat grafting is commonly utilized in breast surgery, and since it was first described, clinicians and researchers have stridden towards improvement of graft retention. Current advancements include adding adipose-derived mesenchymal stem/stromal cells (MSC(AT)s), which have demonstrated promise for improved graft retention. OBJECTIVES: This study reports outcomes for the first twenty-two patients undergoing breast augmentation (Stemform BA) or artificial implant replacement (Stemform AIR) with MSC(AT)-enriched fat in a real-world setting. METHODS: Autologous MSC(AT)s were isolated and expanded ex vivo, then mixed with lipoaspirate and injected as enriched fat for Stemform BA and AIR. The breast volume was measured preoperatively and at 3 and 12 months postoperative using a 3D Infinity Dual-Lens Camera and LifeVizApp software. Additionally, independent plastic surgeons evaluated clinical images, and patient satisfaction was obtained at equal time points. RESULTS: Twenty-two patients were included. All completed 3 and 12 months clinical follow-up and 3 months volume measurements. Nineteen patients completed 12 months volume measurements. The median fat graft retention at 12 months was 95.7% (IQR = 82.44-103.12%) for Stemform BA patients and 113.0% (IQR = 94.8-131.2%) for Stemform AIR patients. The Stemform BA patients had a median breast enlargement of 172.0% (IQR = 156.7-241.0%). The implant replacement volume of Stemform AIR patients was 102% (IQR = 85.1-130.3%). The patient reported 92.8% and 100% would elect to repeat treatment if they had the opportunity for Stemform BA and Stemform AIR, respectively. CONCLUSION: Breast augmentation and breast implant replacement patients receiving ex vivo-expanded MSC(AT)-enriched fat grafts had high graft retention and patient satisfaction scores. The paper confirms the clinical efficacy of using ex vivo-expanded MSC(AT)s. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Comparison of two devices for the treatment of keloid scars with the use of intralesional cryotherapy: An experimental study.

BACKGROUND: Intralesional (IL) cryotherapy is a new technique for the treatment of keloid scars, in which the scar is frozen from inside. Two cryodevices are available, which were recently evaluated. Both devices showed promising results, but differed in clinical outcome. To explain these differences, more understanding of the working mechanism of both devices is required. OBJECTIVE: This experimental study was designed to investigate and compare the thermal behavior of an argon gas- and a liquid nitrogen-based device. Thermal behavior constitutes: (1) minimum tissue temperature (°C), (2) the freezing rate (°C/min). The thermal behavior was measured inside and on the outer surface of the scar. Both devices were tested ex vivo and in vivo. RESULTS: Ex vivo, when determining the maximum freezing capacity, the argon gas device showed a higher end temperature compared to the liquid nitrogen device (argon gas: -120°C, liquid nitrogen: -140°C) and a faster freezing rate (argon gas: -1300°C/min, liquid nitrogen: -145°C/min). In vivo, measured inside the keloid, the argon gas device showed a lower end temperature than the liquid nitrogen device (argon gas: -36.4°C, liquid nitrogen: -8.1°C) and a faster freezing rate (argon gas: -14.7°C/min, liquid nitrogen: -5°C/min). The outer surface of the scar reached temperatures below -20°C with both devices as measured with the thermal camera. CONCLUSION: In conclusion, the argon gas device displayed a lower end temperature and a faster freezing rate in vivo compared to the liquid nitrogen device. Although this resulted in lower recurrence rates for the argon gas device, more hypopigmentation was seen compared to the liquid nitrogen device following treatment. Finally, the low outer surface temperatures measured with both devices, suggest that some hypopigmentation following treatment is inevitable.

Lab-scale fermentation tests of microchip with integrated electrochemical sensors for pH, temperature, dissolved oxygen and viable biomass concentration.

This article shows the development and testing of a microchip with integrated electrochemical sensors for measurement of pH, temperature, dissolved oxygen and viable biomass concentration under yeast cultivation conditions. Measurements were done both under dynamic batch conditions as well as under prolonged continuous cultivation conditions. The response of the sensors compared well with conventional measurement techniques. The biomass sensor was based on impedance spectroscopy. The results of the biomass sensor matched very well with dry weight measurements and showed a limit of detection of approximately 1 g/L. The dissolved oxygen concentration was monitored amperometrically using an ultra-microelectrode array, which showed an accuracy of approximately 0.2 mg/L and negligible drift. pH was monitored using an ISFET with an accuracy well below 0.1 pH unit. The platinum thin-film temperature resistor followed temperature changes with approximately 0.1 degrees C accuracy. The dimensions of the multi sensor chip are chosen as such that it is compatible with the 96-well plate format.

Intralesional Cryotherapy for the Treatment of Keloid Scars: Evaluating Effectiveness.

BACKGROUND: Intralesional (IL) cryotherapy is a novel treatment technique for keloid scars, in which the scar is frozen from inside. Over the past decade, several studies have been published with varying outcomes. A critical analysis of the current literature is, therefore, warranted to determine whether IL cryotherapy is an alternative to established keloid scar treatments. METHODS: A comprehensive review was performed, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. PubMed and EMBASE were searched from inception. Studies and level of recommendation were graded according to the American Society of Plastic Surgeons criteria. RESULTS: Eight studies meeting the inclusion criteria were selected. The average scar volume decrease ranged from 51% to 63%, but no complete scar eradication was achieved on average. Scar recurrence ranged from 0% to 24%. Hypopigmentation posttreatment was seen mostly in Fitzpatrick 4-6 skin type patients. Finally, complaints of pain and pruritus decreased significantly in most studies. CONCLUSIONS: IL cryotherapy for the treatment of keloid scars shows favorable results in terms of volume reduction and alleviated complaints of pain and pruritus. However, no complete scar eradication is established, and recurrences are seen. Also, persistent hypopigmentation proved a problem in Fitzpatrick 4-6 skin type patients. Summarized, the evidence proved limited and inconsistent resulting in an American Society of Plastic Surgeons grade C recommendation for this type of treatment of keloid scars.

Intralesional cryotherapy for treatment of keloid scars: a prospective study.

BACKGROUND: Intralesional cryotherapy is a novel treatment for keloid scars in which the scar is frozen from inside. Published results are promising, but the treatment has only been tested in a Caucasian patient population. Therefore, the authors evaluated intralesional cryotherapy in a patient population including different Fitzpatrick skin types (I through VI). METHODS: This prospective multicenter study with a 1-year follow-up included 27 patients with 29 keloid scars. Intralesional cryotherapy was administered with a disposable liquid nitrogen-based device called CryoShape. Scar assessment was performed using the Patient and Observer Scar Assessment Scale and four objective devices to determine scar color, scar elasticity, scar volume, and patient skin type. RESULTS: Keloid scars showed an average volume decrease of 63 percent (range, 16 to 100 percent) after 12 months, compared with baseline (p < 0.01). Recurrence was seen in seven keloids (24 percent) and hypopigmentation recovered in 69 percent of all keloid scars within 12 months. Scar assessment with the Patient and Observer Scar Assessment Scale showed an overall improvement according to both doctors and patients. In addition, complaints of pain and itching were reduced. When analyzing the results per Fitzpatrick skin type, African American patients showed a higher incidence of persistent hypopigmentation (p = 0.02). CONCLUSIONS: Intralesional cryotherapy for the treatment of keloid scars shows favorable results in terms of reduction of volume and complaints of pain and pruritus. However, no complete eradication was obtained in some cases and recurring scars were seen. In addition, persistent hypopigmentation proved a problem in non-Caucasian patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Surgical Excision with Adjuvant Irradiation for Treatment of Keloid Scars: A Systematic Review.

BACKGROUND: Excision followed by adjuvant irradiation is considered safe and most efficacious for treatment of keloid scars. Recently, different authors published successful treatment protocols and recommended the following: (1) the use of high-dose-rate brachytherapy instead of low-dose-rate brachytherapy or external radiation; (2) a short-time interval between operation and irradiation; (3) single fraction instead of multifraction irradiation; and (4) a minimum of 12- to 24-month follow-up post treatment. METHODS: This study evaluates the above recommendations with a systematic review of the English-language literature, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Both PubMed and EMBASE were searched. Studies were graded according to the American Society of Plastic Surgeons Rating Levels of Evidence. RESULTS: Thirty-three studies were selected. Six studies were graded as level of evidence type II studies and 27 as type III. High-dose-rate brachytherapy showed lower recurrence rates compared with low-dose-rate brachytherapy and external radiation. A short-time (<7 hours) interval between scar excision and irradiation results in a lower recurrence rate compared with long-time intervals (>24 hours). Single-fraction irradiation showed promising results in terms of recurrence rate and patient convenience. Finally, scar recurrences were seen between 2 and 36 months, with a mean of 15 months. CONCLUSIONS: Based on this systematic review of the literature, the evidence confirms the recommendations stated by authors in the recent years. However, due to the lack of high-quality randomized studies, the quality of this evidence is limited. More randomized studies will generate stronger recommendations.

A new argon gas-based device for the treatment of keloid scars with the use of intralesional cryotherapy.

BACKGROUND: Intralesional (IL) cryotherapy is a new promising technique for the treatment of keloid scars, in which the scar is frozen from inside. Multiple devices are available, mostly based on a simple liquid nitrogen Dewar system, which have a limited freezing capacity. Argon gas-based systems ensure accurate and highly controlled freezing and have shown to be effective within the field of oncologic surgery. However, this technique has never been used for the treatment of keloid scars. OBJECTIVE: This prospective study evaluates an argon gas-based system for the treatment of keloids in a patient population including all Fitzpatrick skin types with a 1-year follow-up. METHODS: Twenty-five patients with 30 keloid scars were included and treated with a device called Seednet (Galil Medical, Yokneam, Israel). Scar quality and possible scar recurrence were assessed before treatment and post treatment (6 and 12 months) with objective devices determining scar color, scar elasticity, scar volume, and patient's skin type. In addition, scars were evaluated using the Patient and Observer Scar Assessment Scale. RESULTS: After 12 months, a significant volume reduction of 62% was obtained, p = 0.05. Moreover, complaints of pain and itching were alleviated and scar quality had improved according to the Patient and Observer Scar Assessment Scale. Scar pigmentation recovered in 62% of all keloid scars within 12 months. Five out of 30 (17%) scars recurred within 12 months, three of which had previously been treated with liquid nitrogen-based IL cryotherapy. Both recurrent and persistent hypopigmentation were mainly seen in Afro-American patients. CONCLUSIONS: IL cryotherapy with the use of an argon gas-based system proves to be effective in the treatment of keloid scars, yielding volume reduction and low recurrence rates. Although hypopigmentation recovered in most cases, it is strongly related to non-Caucasian patients. Finally, additional treatment of keloid scars previously unresponsive to IL cryotherapy is predisposed to a high recurrence rate. TRIAL NUMBER: NCT02063243.

High-dose-rate brachytherapy for the treatment of recalcitrant keloids: a unique, effective treatment protocol.

BACKGROUND: Keloids cause aesthetic disfigurement and physical complaints, mainly pain and pruritus. Treatment of these scars is difficult, with high recurrence rates forming the main issue. Surgical excision with adjuvant radiotherapy is considered the most efficacious treatment. At their institution, the authors have been treating keloids with a high-dose-rate brachytherapy procedure for over 10 years, using a protocol with the lowest total radiation dosage known in the literature. METHODS: This prospective study included 43 patients of all Fitzpatrick skin types, with 67 keloids in total. After extralesional excision, a radiation scheme of 2 × 6 Gy was administered in two fractions: the first within 4 hours after surgery and the second within 24 hours. Scars were measured and recurrence was judged. Scar appearance was evaluated using the Patient and Observer Scar Assessment Scale. RESULTS: The recurrence rate was 3.1 percent at a mean follow-up of 33.6 months. A significant average scar surface decrease of 56.7 percent was measured (p = 0.01). Complaints of pain and pruritus decreased by 82.9 and 87.2 percent, respectively. Patients were satisfied with the treatment in 88.6 percent of the cases and with the cosmetic result in 77.1 percent. Pigmentation problems were seen in 21.4 percent of the patients, mostly in Fitzpatrick type V and VI/African American individuals. CONCLUSIONS: The results of this prospective study show a good cosmetic outcome with a low recurrence rate. The unique radiation schedule proves the efficacy and safety of high-dose-rate brachytherapy and suggests the importance of immediate postoperative irradiation. In addition, only one outpatient treatment is required after surgery, enhancing patient convenience. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Could metabolic syndrome, lipodystrophy, and aging be mesenchymal stem cell exhaustion syndromes?

One of the most important and complex diseases of modern society is metabolic syndrome. This syndrome has not been completely understood, and therefore an effective treatment is not available yet. We propose a possible stem cell mechanism involved in the development of metabolic syndrome. This way of thinking lets us consider also other significant pathologies that could have similar etiopathogenic pathways, like lipodystrophic syndromes, progeria, and aging. All these clinical situations could be the consequence of a progressive and persistent stem cell exhaustion syndrome (SCES). The main outcome of this SCES would be an irreversible loss of the effective regenerative mesenchymal stem cells (MSCs) pools. In this way, the normal repairing capacities of the organism could become inefficient. Our point of view could open the possibility for a new strategy of treatment in metabolic syndrome, lipodystrophic syndromes, progeria, and even aging: stem cell therapies.

Dermal substitution in acute burns and reconstructive surgery: a 12-year follow-up.

BACKGROUND: Application of dermal substitutes has been reported to improve the outcome of burns. However, the long-term effectiveness of dermal substitutes has not been investigated objectively. The aim of this study was to evaluate long-term effectiveness of a collagen-elastin dermal substitute in acute and reconstructive burn surgery. METHODS: From 1996 to 1998, an intraindividual comparison was carried out between a dermal substitute with a split-skin graft and a split-skin graft alone in patients with acute and reconstructive wounds. In this follow-up, scar elasticity, vascularization, pigmentation, and surface roughness were determined objectively. In addition, a subjective scar assessment was performed. RESULTS: In 46 patients, 69 pairs of substituted and conventionally treated sites were measured, consisting of acute and reconstructive burn scars. In reconstructive scars, one surface roughness parameter was significantly better in substituted scars. Subjective assessment in acute and reconstructive burn scars showed several statistically significant differences in favor of substituted scars, such as pliability, relief, and the general observer score. Elasticity measurements showed higher scores for substituted scars, although the difference was not statistically significant. For the subcategory of scars treated with a largely expanded meshed skin graft, a significantly higher elasticity was found for the substituted area. CONCLUSION: In this first long-term and objective follow-up of dermal substitution, the authors found improved scar parameters in both acute and reconstructive wounds treated with the substitute, indicating a long-lasting effect on scar quality.

Aerobic batch cultivation in micro bioreactor with integrated electrochemical sensor array.

Aerobic batch cultivations of Candida utilis were carried out in two micro bioreactors with a working volume of 100 muL operated in parallel. The dimensions of the micro bioreactors were similar as the wells in a 96-well microtiter plate, to preserve compatibility with the current high-throughput cultivation systems. Each micro bioreactor was equipped with an electrochemical sensor array for the online measurement of temperature, pH, dissolved oxygen, and viable biomass concentration. Furthermore, the CO(2) production rate was obtained from the online measurement of cumulative CO(2) production during the cultivation. The online data obtained by the sensor array and the CO(2) production measurements appeared to be very reproducible for all batch cultivations performed and were highly comparable to measurement results obtained during a similar aerobic batch cultivation carried out in a conventional 4L bench-scale bioreactor. Although the sensor chip certainly needs further improvement on some points, this work clearly shows the applicability of electrochemical sensor arrays for the monitoring of parallel micro-scale fermentations, e.g. using the 96-well microtiterplate format.

Biological background of dermal substitutes.

Dermal substitutes are of major importance in treating full thickness skin defects, both in acute and chronic wounds. In this review we will outline specific requirements of three classes of dermal substitutes: Biological and clinical requirements will be translated to composition, physical structure, immunological properties and cell-matrix interactions of the various materials. Important properties like pore size, cell adhesion sites (e.g. RGD sequences), crosslinking, degradability and the presence of a basement membrane will be discussed for each of the different classes of materials.

Development of a system for the on-line measurement of carbon dioxide production in microbioreactors: application to aerobic batch cultivations of Candida utilis.

We developed and applied a conductometric method for the quantitative online measurement of the carbon dioxide (CO(2)) production during batch cultivations of Candida utilis on a 100-microL scale. The applied method for the CO(2) measurement consisted of absorption of the produced CO(2) from the exhaust gas of the microbioreactor in an alkali solution, of which the conductivity was measured on-line. The measured conductivity change of the alkali solution showed a linear relation with the total amount of CO(2) absorbed. After calibration of the CO(2) measurement system, it was connected to a well of a 96-well microtiter plate. The mixing in the well was achieved by a magnetic stirrer. Using online measurement of the CO(2) production during the cultivation, we show reproducible exponential batch growth of C. utilis on a 100-microL scale. The CO(2) production measurements obtained from the microcultivation were compared with the CO(2) production measurement in a 4-L bioreactor equipped with a conventional off-gas analyzer. The measurements showed that on-line measurement of the CO(2) production rate in microbioreactors can provide essential data for quantitative physiological studies and provide better understanding of microscale cultivations.

Quantitative determination of glucose transfer between concurrent laminar water streams in a H-shaped microchannel.

To explore the applicability of a laminar fluid diffusion interface (LFDI) for the controlled feeding of microbioreactors, glucose diffusion experiments were carried out in a rounded H-shaped microstructure etched in a glass substrate. The diffusion channel of the microstructure had a length of 4 mm and a depth of 50 microm with a trapezoidal cross section with a width of 100 microm at the bottom and 200 microm at the surface of the channel. The microchannel was operated at residence times of less than 1 s ensuring high-mass-transfer rates. It was confirmed, both by microscopic observations as well as computational fluid dynamics (CFD) studies that the flow characteristics in the microchannel were fully laminar. Special attention was paid to flow splitting at the end of the channel, because the CFD simulations indicated that the performance of the device was sensitive to unequal flow splitting. The difference in outflow volume of the two streams was measured to be small (1.25% +/- 0.6%). The measured glucose concentration in both exit ports at a fixed residence time was found to be stable in time and reproducible in multiple experiments. CFD simulation was shown to be a powerful tool for estimating the mass transfer in the LFDI, even at very short residence times. The results obtained in this work show the applicability of LFDI for the controlled diffusive supply of a solute to a water stream, with as possible application substrate and/or precursor feeding to microreactors.