Article

Nonsurgical Breast Enlargement Using an External Soft-Tissue Expansion System

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Abstract

Less than 1 percent of the women interested in having larger breasts elect to have surgical augmentation mammaplasty with insertion of breast implants. The purpose of this report is to describe and test the efficacy of a nonsurgical method for breast enlargement that is based on the ability of tissues to grow when subjected to controlled distractive mechanical forces. Seventeen healthy women (aged 18 to 40 years) who were motivated to achieve breast enlargement were enrolled in a single-group study. The participants were asked to wear a brassiere-like system that applies a 20-mmHg vacuum distraction force to each breast for 10 to 12 hours/day over a 10-week period. Breast size was measured by three separate methods at regular intervals during and after treatment. Breast tissue water density and architecture were visualized before and after treatment by magnetic resonance imaging scans obtained in the same phase of the menstrual cycle. Twelve subjects completed the study; five withdrawals occurred due to protocol noncompliance. Breast size increased in all women over the 10-week treatment course and peaked at week 10 (final treatment); the average increase per woman was 98 +/- 67 percent over starting size. Partial recoil was seen in the first week after terminating treatment, with no significant further size reduction after up to 30 weeks of follow-up. The stable long-term increase in breast size was 55 percent (range, 15 to 115 percent). Magnetic resonance images showed no edema and confirmed the proportionate enlargement of both adipose and fibroglandular tissue components. A statistically significant decrease in body weight occurred during the course of the study, and scores on the self-esteem questionnaire improved significantly. All participants were very pleased with the outcome and reported that the device was comfortable to wear. No adverse events were recorded during the use of the device or after treatment. We conclude that true breast enlargement can be achieved with the daily use of an appropriately designed external expansion system. This nonsurgical and noninvasive alternative for breast enlargement is effective and well tolerated.

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... NUMBER 1. JANUARY 2022 along with economic growth [7]. However, the ongoing crisis of breast implant-associated anaplastic large cell lymphoma has led to growing concerns for patient safety, which in turn have prompted increasing interest in non-surgical breast augmentation [8]. ...
... Since cyclic stimulation is inherently more effective than constant stimulation, our team focused on intense cyclic stimulation for breast augmentation rather than long continuous stimulation [16]. According to a previous study, participants who used settings of 20 mmHg for 10-12 hours a day during an average of 14.7 weeks showed about a 55% increase in volume after 4 weeks of application [8]. ...
... Sustaining the volume increase is another important issue that needs to be addressed. Studies have shown that volume recoil occurs approximately 1 week after the protocol and that only half of the volume gain remains in the long term after applying 20 mmHg of pressure for 10-12 hours a day, for an average of 14.7 weeks of application of an external breast expander [8]. Participants in our study were asked to visit the clinic for breast volume measurements 4 weeks after cessation of device usage, which is when recoil stops and volume is sustained according to a previous study. ...
Article
Background Various types of external breast tissue expanders have been found to be effective for aesthetic breast augmentation. However, their use has been limited when compared with implant-based breast augmentation due to the burdensome nature of their application. This article reports the possibility that external breast tissue expanders may be applied safely and effectively with higher pressure and shorter application time.Methods The participants comprised patients who desired breast augmentation using the EVERA-RAPHA device between January 2020 and March 2020. A double-blinded prospective study was conducted on two groups of eight patients each, with either 60 mmHg or 100 mmHg of pressure applied. Standardized photographs were taken and blinded measurements of volume and circumference were made. The Mann-Whitney and paired t-tests were conducted.Results Sixteen patients were evaluated after 1 month of treatment. The women in groups 1 and 2 (60 mmHg and 100 mmHg, respectively) used EVERA-RAPHA for 15.400± 0.704 and 15.300±0.477 minutes per day, respectively. The mean volume increases in groups 1 and 2 were 39.000±42.526 cc and 27.700±20.260 cc, respectively. No patients dropped out of the study. All patients reported that the device was tolerable. Mild bruising was found in 62.5% of the patients in group 2.Conclusions Breast augmentation using external tissue expanders can be a safe, effective, and practical option. Pressures of 60 mmHg or 100 mmHg can be safely applied for a shorter duration. Larger studies are needed to further confirm our findings.
... 11,12,14 Brava system was used with a wide range of pressure values. Although some of the studies did not explicitly report on the pressure applied, we hypothesize that they used the device as initially described by Khouri et al. 12,[18][19][20]22,23 (˗15 to ˗25 mm Hg). Kosowski et al. ...
... Finally, Del Vecchio and Bucky 17 stated that expansion programs were individualized for each patient based on lifestyle analysis and psychological compliance testing, with a negative pressure, which in 1 of his studies was ranging from ˗1 to ˗3 inches of mercury (˗25.4 to ˗76.2 mm Hg). 15 Four studies reported the use of cyclical pressure, 14,18,21,24 whereas the remaining studies did not report on whether the device was used with continuous or cycling power, yet we believe that it was continuous as initially described. 22 Regarding different time and durations of preexpansion, patients started their treatment with the external expansion device up to 4 weeks before autologous fat transfer for 10-24 h/d. 2,7,11,12,[14][15][16][17][18][19] Postoperatively, the Brava system was worn for 5 days to 4 weeks, with the duration of application ranging from 10 to 24 h/d, only at night or for as many hours per day as tolerated. ...
... However, after the enthusiasm generated by this first investigations, following researches outlined the limitations of the procedure: only small breast-size enlargement (1 cup) possible, high patient compliance required, patient social life restriction and drop out rates around 25%, 50% of the volume increase only due to swelling at 10 weeks with the suggestion to wear the device for 16-20 weeks. 12,22,[35][36][37][38] Despite the consequent modest success as nonsurgical breast augmentation procedure, the ability of Brava to determine a marked temporary increase in breast size with the creation of a very large fibrovascular scaffold induced several authors to investigate its potential as device to prepare the recipient site in fat grafting procedures. 12 These studies reduced the duration of the original protocol, with external volume expansion evolving from 2 to 3 months of static low pressure to 3 weeks individualized programs. ...
Article
Full-text available
Background:. The fat grafting process includes the 4 phases of tissue harvesting, processing, recipient-site preparation, and reinjection. Among them, the preparation of the recipient site has never been exhaustively reviewed. We aim to provide a comprehensive overview of the methods to prepare the recipient site through external expansion with the resulting outcomes. Methods:. PubMed/Medline database was searched for studies on fat grafting recipient site preparation by applying the following algorithm: ((fat grafting) OR (lipofilling) OR (lipograft) AND (recipient site)). A priori criteria were used to review the resulting articles and identify those dealing with external expansion. Results:. Fourteen studies published from 2008 through 2016 met inclusion criteria (4 case reports, 6 retrospective, and 4 prospective studies), representing 1,274 treated patients. Two devices for preexpansion were used with different protocols: BRAVA system and Kiwi VAC-6000M with a PalmPump. The 13 studies that applied the BRAVA system reported large fat volume transplantation to the breast (average > 200 cc). The most common complications were localized edema (14.2%), temporary bruising, and superficial skin blisters (11.3%), while the most serious was pneumothorax (0.5%). The majority of the studies reported enhancement of fat graft survival, which ranged between 53% and 82% at 6 months to 1 year follow-up, and high satisfaction of patients and surgeon. Conclusions:. External expansion and fat grafting is a promising technique for breast reconstruction and augmentation. However, due to the overall low level of evidence of the available studies, further research is needed to validate the procedure.
... 1,2 These methods, however, have limitations, including donor-site morbidity, unpredictable absorption rate, and rejection reactions, respectively. [3][4][5] Induction of in situ tissue regeneration may overcome these limitations. ...
... 6 This method yielded good results when utilized clinically to breast enlargement. 4 In animal models, application of an external vacuum to skin increased tissue vascularity and induced adipose tissue growth in the expanded prefabricated adipose tissue (EPAT), resulting in soft tissue enlargement. 7 However, it is not fully clear how EVE induces regeneration of neoadipose tissue. ...
Article
External volume expansion (EVE) is an effective method of adipose tissue regeneration. However, it remains unclear how EVE induces adipose tissue regeneration. In this study, we developed EVE devices to generate expanded prefabricated adipose tissue (EPAT) in rats and investigated cell proliferation, adipogenesis, and the expression of extracellular matrix (ECM) proteins during the 12 weeks suction. In addition, EPAT-generated decellularized adipose tissue (DAT) was used to assess the role of ECM proteins in cell proliferation and differentiation. Matrix deposition was significantly increased after EVE suction, with fibronectin and laminin showing the most dramatic changes. Fibronectin expression peaked during weeks 1-4, when Ki67 cells in EPAT peaked. Laminin expression peaked during weeks 8-12, when peroxisome proliferator-activated receptor-γ expression also peaked. In vitro, adipose-derived stem cells (ASCs) displayed a higher proliferation rate in week 1 DAT, when fibronectin expression was highest, whereas ASC adipogenesis was significantly higher on week 12 DAT, when laminin expression was abundant. These results showed that EVE device enhanced ECM deposition, which is closely related to cell proliferation and differentiation. Impact Statement Large soft tissue defects caused by cancer, trauma, or deformity remain a major challenge for reconstructive surgery. External volume expansion (EVE) successfully induces adipose tissue regeneration and shows great therapeutic potential in correction for soft tissue defect. This study showed that EVE enhanced the secretion of extracellular matrix (ECM) proteins and regulated ASC proliferation and differentiation through shifting matrix synthesis from fibronectin to laminin. These findings revealed the relation between ECM modulation and ASC behavior, indicating that EVE can induce adipose regeneration by regulating matrix synthesis.
... A minimally invasive breast augmentation device (Brava, Biomecanica, Inc., Miami, FL) uses low-level suction to increase adipose and fibroglandular tissue without changing the breast architecture. 10 The vacuum suction during cryolipolysis may trigger adipose growth in susceptible patients with "firm" adipose. With inadequate tissue draw, the cold temperature may be unable to incite a cold panniculitis or trigger apoptosis, instead of allowing the effects of suction to trigger tissue expansion. ...
Article
Cryolipolysis, an aesthetic procedure that reduces adipose tissue by exposure to cold temperature, is generally well tolerated with mild side effects including temporary numbness, erythema, and tenderness. However, as cryolipolysis is gaining popularity and more treatments are being performed, reports of rare adverse events including delayed onset pain and paradoxical adipose hyperplasia (PAH) have been described. Recent studies have suggested that PAH can be more common than expected and have a predilection for males, as a disproportionate number of the cases reported in the literature have occurred in men despite the fact that fewer men are likely to be treated with cryolipolysis. Sexual dimorphism in adipose anatomy may provide insight into the increased susceptibility of men to PAH. Careful patient selection avoiding men with visceral abdominal adipose and firm, nondistensible, fibrous fat may be important to minimize the risk of PAH.
... When solid tissue pieces such as muscle were implanted into the chamber they did not survive but regularly the dead tissue induced endogenous fat replacement. 166 Khouri et al. 167 designed a tissue-engineering chamber (BRAVA ® ) to induce fat growth for breast tissue replacement. It consists of a suction device applied to the external surface of the breast which, when worn regularly for prolonged periods, pulls the tissue away from the chest wall, creating tissue injury, inflammation, and a potential space. ...
... Reproduced with permission from Coleman (2001) Since then, many theories have evolved; however, superiority has never been proven. In 2014, Austen et al. from the Massachusetts General Hospital proved that there are no differences in the number of stem cells isolated, comparing centrifugation with mesh filtering, and that the concentration efficacy of mesh/gauze is equivalent to centrifugation at 1200 × g, with equivalent in vivo outcomes (Khouri et al. 2000). In 2015, Cleveland et al. from New York University failed to find compelling evidence to advocate a single technique as the superior method for processing lipoaspirate in preparation for autologous fat grafting. ...
Chapter
Full-text available
Fat transfer to the breast is used for filling soft tissue and removing contour defects. Its increasing popularity can be attributed to its low cost, easy surgical technique, and its autologous nature. As with every novelty, the safety of fat transplantation was questioned; however, this has been proven. What began as a simple technique of suctioning fat and inserting it into the breast has developed into a number of different surgical techniques and diverse technologies. Nowadays, we can state that with a good harvesting, processing, and surgical technique fat transfer to the breast is a totally effective choice and that no other device is needed to achieve success.
... Aesthetic Surgery Journal 40 (2) graft volumes without much fat necrosis objectively demonstrates some superiority of the technique. ...
... Studies have shown that it can induce adipogenesis, enhance tissue vascularity, and increase recipient capacity and mechanical compliance, thereby priming the recipient site for a large volume fat transfer. [36][37][38][39][40] Harvesting, Processing, and Delivery ...
Article
Autologous fat transplantation has become increasingly popular in recent years. Its biocompatable properties and availability made it a widely used treatment modality for soft tissue augmentation and volume replacement in both reconstructive and aesthetic plastic surgery. Multiple protocols and clinical applications have been described in the literature, with wide variations in the harvesting, processing, and injection techniques. In this review, the authors will discuss the basic principles and clinical applications of fat grafting in plastic and reconstructive surgery. The article will then conclude with a discussion of fat grafting limitations as well as potential future applications, giving the reader a well-rounded understanding of autologous fat transfer.
... [44][45][46][47][48] Furthermore, reports have shown that an external breast tissue expander, Brava (Brava LLC, Miami, FL), can effectively cause the augmentation of the breast volume without necessarily recurring to breast surgery. 49 Adipogenesis was frequently induced by external tissue expanders, but they required a dome to support the tensile force. 45 Another application of this kind of device is the temporary stimulation of breast expansion followed by fat grafting. ...
Article
Full-text available
Background Tissue expanders are widely utilized in plastic surgery. Traditional expanders usually are “inflatable balloons,” which are planned to grow additional skin and/or to create space to be filled, for example, with an implant. In very recent years, reports suggest that negative pressure created by an external device (ie, Brava) induces both skin expansion and adipogenesis. Objectives The authors evaluated and assessed the adipogenetic potential of a novel internal tissue expander in an in vivo animal model. Methods New Zealand female rabbits were enrolled in the study. A prototype spiral inner tissue expander was employed. It consisted of a-dynamic conic expander (DCE) with a valve at the end: when empty, it is flat (Archimedean spiral), whereas when filled with a fluid, it takes a conic shape. Inside the conic spiral, a negative pressure is therefore created. DCE is implanted flat under the latissimus dorsi muscle in experimental animals (rabbit) and then filled to reach the conical shape. Animals were investigated with magnetic resonance imaging, histology, and transmission electronic microscopy at 3, 6, and 12 months. Results Magnetic resonance imaging revealed a marked increase in newly formed adipose tissue, reaching its highest amount at 12 months after the DCE implantation. Histology confirmed the existence of new adipocytes, whereas transmission electronic microscopy ultrastructure confirmed that most of these new cells were mature adipocytes. Conclusions Tensile stress, associated with negative-pressure expanders, generated newly white subcutaneous adipose tissue.
... 14 Different fat graft harvesting techniques place different amounts of mechanical stress on adipocytes, and studies have demonstrated differences in cell viability and adipocyte functionality between techniques. 4 Physical interactions with the extracellular matrix of adipose tissue can also influence stem cell behavior, and external tissue expansion has been shown experimentally to stimulate adipogenesis, resulting in a reversible enlargement of adipose tissue. 14,17,19 Graft Survival Currently, three theories have been put forth describing how fat grafts survive after avascular surgical implantation, and research suggests that each theory may play a role in the survival process. 7 The theories are called the graft survival theory, the graft replacement theory, and the host cell replacement theory. ...
Article
Autologous fat grafting has become a popular and well-established technique used by plastic surgeons in a variety of aesthetic and reconstructive procedures. An understanding of the basic science principles underlying fat grafting is crucial to explaining its extensive utility for soft tissue rejuvenation, volume augmentation, and body contouring—and the unpredictable fat resorption rates after grafting that pose a significant challenge for plastic surgeons. While the scientific principles of fat grafting can theoretically be exploited to optimize fat grafting techniques and increase fat tissue survival, a consensus has yet been established as to the best practices for this procedure. This review discusses the biology of adipose tissue and the scientific principles behind its behavior and survival in autologous fat grafting.
... 5 The system stimulates the growth of breast tissue by applying distracting force and was first used in breast augmentation in 1999. [6][7][8][9] However, its underlying mechanism is unclear. ...
Article
Full-text available
Large soft-tissue defects are challenging to reconstruct surgically. Expansion of soft tissue using an external volume expansion (EVE) device is a noninvasive method to improve such reconstruction; however, the underlying mechanism is unclear. In this study, we created fat flaps in Sprague-Dawley rats, applied an external force of 3 or 6 kPa using an EVE device, and investigated the migration and differentiation of adipose-derived stem/progenitor cells (ASCs). In addition, we performed finite element analysis to explore the stiffness of adipose tissue. An external force of 3 kPa promoted the migration and adipogenic differentiation of ASCs. By comparison, an external force of 6 kPa had a larger effect on migration of ASCs, but a smaller effect on adipogenic differentiation of ASCs. External force affected adipose tissue stiffness. In conclusion, external force generated by an EVE device increases the stiffness of adipose tissue, which influences the migration and differentiation of ASCs. The size of the external force can be altered according to the tissue stiffness required at particular time points to promote long-term adipose tissue regeneration.
... In 1999, an external breast tissue expander was introduced as a nonsurgical alternative to breast augmentation when used consistently for 10 hours a day for a minimum of 10 weeks [9]. ...
... 5.6 External volume expansion (EVE) can enhance tissue vascularity, induce matrix deposition, and increase the stiffness of adipose ECM, which recruits circulating mesenchymal stromal cells (Heit et al., 2012;Lancerotto et al., 2013;Chin et al., 2016). In addition, EVE can regulate ASC proliferation and differentiation via shifting ECM synthesis from fibronectin to laminin, thereby priming the recipient site for autologous fat transfer (Khouri et al., 2000;Zhang et al., 2020). 5.7 Oil cysts filled with necrotic material result in persistent inflammation, and calcification continues to develop over time, with these progressive changes persisting Shida et al., 2017). ...
Article
Full-text available
Remodeling of the extracellular matrix (ECM), which provides structural and biochemical support for surrounding cells, is vital for adipose tissue regeneration after autologous fat grafting. Rapid and high-quality ECM remodeling can improve the retention rate after fat grafting by promoting neovascularization, regulating stem cells differentiation, and suppressing chronic inflammation. The degradation and deposition of ECM are regulated by various factors, including hypoxia, blood supply, inflammation, and stem cells. By contrast, ECM remodeling alters these regulatory factors, resulting in a dynamic relationship between them. Although researchers have attempted to identify the cellular sources of factors associated with tissue regeneration and regulation of the microenvironment, the factors and mechanisms that affect adipose tissue ECM remodeling remain incompletely understood. This review describes the process of adipose ECM remodeling after grafting and summarizes the factors that affect ECM reconstruction. Also, this review provides an overview of the clinical methods to avoid poor ECM remodeling. These findings may provide new ideas for improving the retention of adipose tissue after fat transplantation.
... Overall, dynamic mechanical loads such as cyclic stretching at physiological rates characterizing physical exercise were found to suppress adipogenesis and to decrease fat mass. Sustained mechanical stretching, however, characterizing chronic static loading in weight-bearing tissues during prolonged sitting or lying, was found to have the opposite effect, that is, it promoted and accelerated adipogenesis (Case et al. 2013;Kato et al. 2010;Khouri et al. 2000;Krishnamoorthy et al. 2016;Levy et al. 2012;Li et al. 2013aLi et al. , 2015Luu et al. 2009;Rubin et al. 2007;Shoham and Gefen 2012b;Shoham et al. 2012Shoham et al. , 2015aTanabe et al. 2004;Turner et al. 2008;Yang et al. 2012). Cell culture studies have specifically demonstrated that deformations applied to the plasma membrane (PM) in adipocytes activate signaling pathways that regulate adipogenesis such as the MEK or the TGFβ/Smad pathways (Levy et al. 2012;Shoham and Gefen 2012b;Shoham et al. 2012;Tanabe et al. 2004;Turner et al. 2008). ...
Article
Full-text available
An inactive sedentary lifestyle is a common risk factor contributing to sarcopenic obesity. At the cell scale, sustained mechanical deformations of the plasma membrane (PM) in adipocytes, characterizing chronic static loading in weight-bearing tissues during prolonged sitting or lying, were found to promote adipogenesis. Taking a mechanobiological perspective, we correlated here the macroscale mechanical deformations of weight-bearing adipose tissues (subcutaneous and intramuscular) with mechanical strains developing in the PMs of differentiating adipocytes. An innovative multiscale modeling framework for adipose tissues was developed for this purpose, where the buttocks, adipose tissues, adipocytes and the subcellular components: intracytoplasmic nucleus and lipid droplets as well as the PMs of the cells, were all represented. We found that a positive feedback loop very likely exists and is involved in the onset and progression of sarcopenic obesity, as follows. Adipogenesis in statically deformed adipocytes results in gaining more macroscopic subcutaneous and intramuscular fat mass, which then increases fat deformations macroscopically and microscopically, and hence triggers additional adipogenesis, and so on. Our present study is highly relevant in research of sarcopenic obesity and other adipose-related diseases such as diabetes, since mechanical distortion of adipocytes promotes adipogenesis and fat gain at the different dimensional scales.
... In this approach, an external tissue-expanding device applies a gentle vacuum distraction force for 10-12 h/day to the breast tissue. It was stated that after a 10 week period of EVE, the stable long-term increase in breast size was 55% (Khouri et al., 2000). However, in subsequent publications, the authors described the permanent breast augmentation after Brava therapy to be only modest and this technique was adjusted. ...
Article
Background: The reconstruction of gluteal deformities remains a major challenge. The aim of this article is to provide a systematic review of the literature concerned, and to present a case series with representative defects from various zones. Methods: A review of the literature was performed using PubMed, EMBASE, and The Cochrane Library, in accordance with the PRISMA statement. Quality of evidence was rated according to GRADE. Patients with various buttock deformities were included and, depending on the defect, the reconstructive techniques applied consisted of lipoinjection, local fasciocutaneous flap, or pedicled gracilis muscle flap. Complications, patient’s pain assessment, impairment in everyday-life activities, aesthetic outcome, objective assessment of sensitivity, and recurrence were considered. Results: A total of 498 records were identified in the literature search. Of those, 12 studies met the PICOS (participants, interventions, comparators, outcomes, and study design) criteria. Overall, 41 patients were analysed, the evidence of which was of low quality. In this study, four patients (three female and one male) with a mean age of 44 ± 15 years were operated on between 2010–2014. The mean operation time was 83 ± 30 minutes. One patient required revision due to persistent seroma and recurrence, and one patient required neurolysis and gracilis denervation due to neuroma and scarring. After a mean follow-up of 40 ± 21 months, the results were functionally and cosmetically satisfactory. Conclusions: Reconstruction of buttock deformities using an integrated approach can lead to a long-lasting, functionally and aesthetically satisfactory result. However, evidence is limited due to the lack of good-quality studies.
Article
Background: Multiple studies have demonstrated that mechanical forces promote the growth of adipose tissue. However, the mechanism of adipose tissue regeneration induced by mechanical forces remains unclear. Methods: In an experiment using rats, prefabricated adipose tissue with a vessel pedicle was expanded using an external volume expansion (EVE) device. The volume of fat flaps was tested at different time points. Cell proliferation and angiogenesis were analyzed using immunofluorescence. The expression of adipogenic genes and inflammatory cytokines were evaluated using real-time polymerase chain reaction analysis and enzyme-linked immunosorbent assay, respectively. Results: There were more CD31+ cells and Ki67/CD34+ cells in the experimental group than in the control group. The number of Ki67/CD34+ cells peaked at 1-4 weeks. However, the expression levels of PPARγ and CEBPβ were highest from 4-12 weeks in the experimental group. Compared with the control group, the experimental group showed more pro-inflammatory cytokines: IL-1β, IL-6, TNF-α, and macrophage migration inhibitory factor (MIF). Conclusions: The construction of expanded prefabricated adipose tissue by mechanical forces is a dynamic and complex process. Mechanical forces promoted cell proliferation and angiogenesis in the early stage of adipose tissue regeneration (before 4 weeks) and induced adipogenic differentiation at a later stage (after 4 weeks) through upregulation of MIF, which provided an adipogenic inductive microenvironment.
Article
Background: Fat grafting has variable and sometimes poor outcomes, and therefore new methods are needed. Multiple studies have demonstrated the excellent performance of external volume expansion and focused only on preexpansion with emphasis on the recipient. Methods: Two mouse models (a suction model and a fat-exchange transplantation model) were established to investigate changes in the origins and biological behaviors of regeneration-related cells in grafted fat under daily suction provided by external volume expansion. Results: Blood supply increased from new host-derived capillaries or macrophage infiltration under suction. CD34-positive cells showed increased migration from the host into the grafts under suction. At week 12, nearly half of the mature adipocytes regenerated in the grafts in the suction group were derived from the host. Peroxisome proliferator-activated receptor γ expression of the suction group was significantly higher than that of controls at weeks 2 and 4 during adipogenesis. The normalized sample weight of the grafted fat was significantly greater than that of controls at 1 (0.081 ± 0.001 versus 0.072 ± 0.005; p < 0.001), 4 (0.060 ± 0.002 versus 0.048 ± 0.001; p = 0.002), 8 (0.060 ± 0.001 versus 0.046 ± 0.001; p < 0.001), and 12 weeks (0.060 ± 0.001 versus 0.046 ± 0.001; p = 0.002). Conclusions: The mechanical effect of daily suction provided by external volume expansion favors the regeneration of grafted fat and improves retention by promoting the migration of regeneration-related cells and the differentiation of adipocytes. Thus, more mature fat tissue with a well-organized structure was formed under suction.
Chapter
Insufficient donor tissue availability and significant donor-site morbidity are two major barriers to autologous breast reconstruction that could be addressed through the development of tissue engineered breast reconstruction. A brief review of the adipose tissue engineering literature was performed before our own experience with developing and up-scaling murine and rat adipose tissue engineering chamber models to produce a large animal model for large volume vascularized adipose tissue production is discussed. Discussion: Taking a microenvironmental approach, it was possible to upscale small animal models for adipose tissue engineering into a large animal model to produce a clinically relevant volume of new tissue. Non-invasive monitoring of tissue growth and vascularization within the chambers was possible as a prelude to human trials. Conclusions: The production of clinically relevant volumes of vascularized adipose tissue is possible in large animal models using a technique that can be translated into human trials but whether such an approach will be universally effective in humans of different ages and regenerative capacities is yet to be seen.
Article
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Background: Noninvasive external volume expansion device has been applied to stimulate nonsurgical breast enlargement in clinical settings. Although previous results demonstrate the capacity of external volume expansion to increase the number of adipocytes, this strategy alone is insuffcient to reconstruct soft-tissue defects or increase breast mass. The authors combined a minimally invasive tissue dissection method with external volume expansion to generate large volumes of adipose tissue. Method: In vitro, various densities of adipose-derived stem cells were prepared to evaluate relations between cell contacts and cell proliferation. In vivo, dorsal adipose tissue of rabbits was thoroughly dissected and the external volume expansion device was applied to maintain the released state. External volume expansion without tissue dissection served as the control. Results: In the dissection group, the generated adipose tissue volume was much larger than that in the control group at all time points. A larger number of proliferating cells appeared in the dissection samples than in the control samples at the early stage after tissue dissection. At low cell density, adiposederived stem cells displayed an increasing proliferation rate compared to high cell density. Protein expression analysis revealed that cell proliferation was mediated by a similar mechanism both in vivo and in vitro, involving the release of cell contact inhibition and Hippo/Yes-associated protein pathway activation. Conclusions: Adipose tissue dissection releases cell-to-cell contacts and induces adipose-derived stem cell proliferation. Preexpanded adipose-derived stem cells undergo adipogenesis under the adipogenic environment created by external volume expansion, leading to better adipose regeneration compared with the control.
Article
This article is a review of fat grafting for breast reconstruction. The use of small volume fat grafting for the correction of step-off deformities, intrinsic deformities, and extrinsic deformities of the breast, and the uses of large volume fat grafting for total breast reconstruction, correction of implant complications with simultaneous implant exchange with fat, and correction of noncancer chest wall deformities is reviewed. Cancer monitoring and the risks of cancer recurrence following fat-grafting to the breast is also reviewed.
Article
Background: External volume expansion (EVE) has been effectively applied as an assistance to fat transplantation on breast plastic surgery. Many indicators and refinements have been made in clinical practice; meanwhile, the related mechanism and more optimized preclinical model also have been explored in experimental studies. Methods: A literature search was conducted using PubMed with the keywords: EVE, negative pressure, breast enlargement, breast augmentation, breast reconstruction, breast plastic surgery and breast aesthetic surgery. Studies dealing with the clinical and preclinical aspects of the subject and also in vitro experiments related to a certain period of negative pressure and adipose-derived cells were selected, and those only focused on negative pressure were excluded. Results: The indications, contraindications, complications and treatments of EVE in clinical practice were summarized. The experimental studies were mainly classified into two groups (mechanical and translational) according to their contents. Mechanical studies were further divided into inference experimental validation phase studies. For the experimental validation phase, EVE was verified to promote angiogenesis, while it still remained controversial whether it would enhance adipogenesis and cell proliferation. Conclusion: Clinically, our experience is on the stage of exploration, and there is a lack of standardized guidelines on its clinical application. Experimentally, the previous studies showed some subtly different views on the functional mechanisms. However, it is not enough to regulate the clinical practice yet. Therefore, related basic studies and long-term clinical follow-up are needed. Level of evidence iv: 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 .
Chapter
Lipoinjection is a good alternative procedure for breast augmentation, as autologous tissue is employed, which is a great advantage, avoiding rejection and capsular contracture as it may happen when silicone implants are used. It is biocompatible and in some cases, it is abundantly available, can be easily harvested and processed, and can be injected in controlled amounts. The fat can be harvested from a number of areas including the abdomen, medial, lateral or anterior thighs, flank, lower and upper back, and knees. For young patients, the inferior abdomen is the best donor area; for older patients the flank is better. This difference is not well established in other areas. It can be performed in association with liposuction, a very common surgical procedure in plastic surgery, used to achieve a better body contour. However, to achieve good results in breast augmentation with lipoinjection, at least 300 mL should be used in each breast.
Article
Background: The treatment of a tuberous breast deformity has changed over the years, with a large variety of procedures described. However, maintaining a long-lasting breast contour is an ongoing challenge. The aim of this study was to evaluate the long-term results of tuberous breast corrections, focusing on the incidence of secondary procedures and patient satisfaction. Materials and methods: Forty-six patients who underwent correction of a tuberous breast deformity from 2000 through 2013 were considered. Age, degree of deformity, asymmetry, BMI, pregnancy, first surgical technique used, complications and further surgical procedures were evaluated. Statistical analysis was conducted to identify predicting factors for multiple procedures. Patient satisfaction was evaluated with BREAST-Q. Results: Eighty-eight breasts were treated: 57 breasts underwent implant-based corrections, whereas 31 breasts underwent autologous procedures. A multi-step procedure was initially planned in 7 breasts only, and 41 breasts underwent secondary procedures: 33 out of 53 breasts (62.3%) were re-operated in the implant-based group, whereas 8 out of 28 breasts (28.6%) were re-operated in the autologous group. Statistical analysis showed a correlation between the number of procedures and young age (P = 0.0253) and between the number of procedures and the primary surgical technique (P = 0.0132). The BREAST-Q evaluation suggested that patient satisfaction was comparable. Conclusions: The question of time is one of the main issues in breast surgery. The management of tuberous breast deformities requires a customized strategy considering all parameters to improve the longevity of the result in the long term. Level of evidence iv: 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 .
Article
Background: Fat grafting has been demonstrated as a means of reconstructing breast conservation therapy defects. However, there is continued uncertainty regarding its clinical efficacy and oncologic safety. Furthermore, the role of external preexpansion (i.e., with the Brava device) remains unclear in this setting. The purpose of this study was to examine the safety and clinical outcomes of Brava/fat grafting following breast conservation therapy. Methods: A retrospective chart review was performed on all patients undergoing fat grafting following breast conservation therapy. Complications were defined as either a clinically palpable oil cyst/area of fat necrosis or infection. The mean time of follow-up was 2.3 years. Results: A total of 27 fat grafting sessions were performed on 20 patients, with an overall complication rate of 25 percent. The mean interval from completion of radiation therapy to fat grafting was 7 years and was not a significant predictor for complications (p = 0.46). Among those who underwent repeated grafting, there was no difference in the complication rates between their first and second encounters (p = 0.56). There was no difference in complication rates between patients with Brava preexpansion and those without preexpansion. Patients undergoing Brava preexpansion had a significantly higher initial fill volume in comparison with those who did not (219 cc versus 51 cc; p = 0.0017). There were no cases of locoregional cancer recurrence following fat grafting. Conclusion: Brava preexpansion was associated with higher initial fill volume in the setting of breast conservation therapy defects.
Article
We hypothesized that use of a composite three-dimensionally (3D) printed scaffold with electrospun nanofibers in conjunction with recipient-site preconditioning with an external volume expansion (EVE) device would enable successful dermal tissue regeneration of a synthetic polymer scaffold. Cell viability, cell infiltration, extracellular matrix deposition, scaffold contraction, and mRNA expression by dermal fibroblasts cultured on three different scaffolds, namely, 3D-printed scaffold with a collagen coating, 3D-printed scaffold with an electrospun polycaprolactone nanofiber and collagen coating, and 3D-printed scaffold with an electrospun polycaprolactone/collagen nanofiber, were measured. Before scaffold implantation, rats were treated for 2 h with an EVE device to evaluate the effect of this device on the recipient site. Cell proliferation rates were significantly higher on the 3D-printed scaffold with electrospun polycaprolactone nanofiber and collagen coating than on the other scaffolds. In cell invasion studies, the 3D-printed scaffold with electrospun polycaprolactone nanofiber and collagen coating showed better cell integration than the other scaffolds. Under stereomicroscopy, fibroblasts adhered tightly to the electrospun area, and the fibroblasts effectively produced both collagen and elastin. Rat skin treated with an EVE device exhibited increased HIF-1α protein expression and capillary neoformation compared with control skin. Invasion of CD8+ cytotoxic lymphocytes surrounding the scaffold decreased when the recipient site was preconditioned with the EVE device. The composite 3D printed scaffold with electrospun nanofibers provided a favorable environment for proliferation, migration, and extracellular matrix synthesis by fibroblasts. Recipient-site preconditioning with an EVE device allowed for scaffold incorporation with less inflammation due to improved angiogenesis.
Article
Objective: To review the application progress, mechanism, application points, limitations, and oncological safety of external volume expansion (EVE) assisted autologous fat grafting for breast reconstruction and provide a reference for optimizing the design of EVE. Methods: Based on the latest relevant articles, the basic experiments and clinical applications of EVE were summarized. Results: EVE can reduce interstitial fluid pressure, increase blood supply, and promote adipogenic differentiation, thereby benefiting the survival of transplanted fat. EVE assisted autologous fat grafting in clinical practice can improve the retention rate of breast volume and the outcome of breast reconstruction, meanwhile it doesn't increase the risk of local recurrence. But there is no standard parameters for application, and there are many complications and limitations. Conclusion: EVE improves the survival of transplanted fat, but its complications and poor compliance are obvious, so it is urgent to further investigate customized products for breast reconstruction after breast cancer and establish relevant application guidelines.
Article
Background Autologous fat grafting has recently gained popularity in breast and reconstructive procedures. Objectives The authors adopted a tri-composite tuberous breast reconstruction using matrix dissociation through an extensive tunnelization, tissue recruitment using loops and autologous fat transfer. This principle is called “Matrix Modeling” and is applied using the Power-assisted Liposuction Loops and Lipofilling (P.A.L.L.L.) technique. This will expand the lower pole, reshape breast and increase its volume. Methods Between 2014 and 2020, a total of 47 patients underwent tuberous breast correction by combined lipofilling and the use breast loops. Patient population included patients with unilateral or bilateral tuberous breasts of any stage. Patients who were active smokers, lean, or who desired large breasts, were excluded from the study. Results Of the 47 patients, 31 had bilateral malformations. The mean age was 26 years. The mean recruited flap volume was 212 mL. A single session (mean transfer volume, 163 ml) was required in 34 cases (72%). A second session (mean transfer volume, 182 mL) was necessary in the remaining of 28% of cases. Patients were very satisfied in 93% of cases and satisfied in 7% of cases. One infection was observed. The mean operative time was 67 minutes. Imaging performed preoperatively and 1 year postoperatively did not reveal any anomalies other than oil cysts (4%). Conclusions Tri-composite breast reconstruction using P.A.L.L.L. is a novel, simple, safe and alternative technique for tuberous breast correction by remodeling the matrix. The aesthetic outcome is natural, implant free, and long lasting.
Article
Background External volume expander (EVE)-assisted autologous fat grafting is suitable for breast augmentation, but no large sample study in Asia confirms this method. Objectives In this study, we report our experience and outcomes in augmentation mammoplasty with EVE-assisted autologous fat grafting. Methods A retrospective study was conducted in 305 female patients who underwent augmentation mammoplasty with EVE-assisted fat grafting between September 2012 and December 2020. Doctors used Crisalix for 3D imaging acquisition to measure the increase in breast volume to evaluate doctor satisfaction. The Preoperative Satisfaction with Breast and BREAST-Q questionnaires were used to assess patients’ preoperative and postoperative satisfaction, respectively. Results The 305 female patients were aged between 18 and 50 (mean, 35.9). Among them, 68.52% were “very satisfied”, 18.69% were “somewhat satisfied”, 11.15% were “somewhat dissatisfied”, and 1.64% were “very dissatisfied” based on BREAST-Q analysis, whereas 100% were dissatisfied according to the Preoperative Satisfaction with Breast questionnaire. Doctors used Crisalix to measure the increase in breast volume to evaluate doctor satisfaction. The results showed 76.01% had an increase in breast volume of 150–250 mL or over 250 mL and were “satisfied” and “very satisfied”, respectively, 21.64% had an increase of 50–149 mL and were “somewhat satisfied”, and 2.30% had an increase of less than 50 mL and were “dissatisfied”. There were no complications, such as obvious fat liquefaction, infection or fat embolism. Conclusions Augmentation mammoplasty with EVE-assisted fat grafting is effective and satisfying in China. Crisalix for 3D imaging acquisition is convenient and effective in measuring breast volume.
Article
Background: The autologous fat grafting is commonly used for reconstructive or aesthetic purpose. However, due to the huge variation in methods, its retention rate varies a lot. External Volume Expansion (EVE) has been used to treat recipient sites of fat grafting. Concerns have raised regarding its effectiveness and safety. Methods: We have searched the PubMed, EMBASE, and the Cochrane Library for studies on EVE-assisted fat grafting published from 2000 to 2020. A meta-analysis was conducted to pool the retention rate. The incidence of complications was assessed for reconstructive or aesthetic purpose. Results: The 11 included studies involved 1152 patients with operations on 1794 breasts. Four studies were included in the meta-analysis. The pooled retention rate was 65% (95%CI 49-79). Eight studies reported the complications. The total complication incidence was 34%, which is 35% for aesthetic group and 33% for reconstructive group. The complication rate was not obviously different between two groups. Conclusions: The study demonstrates that the EVE-assisted fat grafting has better retention rate than traditional fat grafting. However, the data showed that the complication rate was much higher in the EVE-assisted group. Level of Evidence: The author assigned a level of evidence to each article according to Oxford Center for Evidence-based medicine guidelines. Six studies were level Ⅲ and five studies were level Ⅳ.
Article
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This report provides a simplified insight into the previously unexplained physical mechanism of the origin of local positive tissue pressure during negative-pressure wound therapy (NPWT). A chain of 2 spring model could be used to show the biomechanical interaction between the NPWT dressing and the adjacent body tissues. It is important to assume that the application of NPWT dressing to the body surface creates a new closed compartmentalized volume. Air suction generates local positive pressure within the dressing due to unopposed atmospheric load, which in turn leads to compression of the adjacent tissues and induction of positive pressure there. Analysis of the biomechanical events during NPWT implies the possibility of tissue injury by positive pressure and suggests clinical alertness in regard to the balance between the size of the NPWT dressing and suction pressure as well as further related research.
Chapter
Autologous fat transplantation has revolutionized soft tissue reconstruction, but conventional methods remain unpredictable as graft resorption rates are high due to lack of vascularization. The advent of adipose-derived stem cells (ASCs) has led to improvement of fat grafting outcomes, in part to their ability to undergo facile differentiation into adipose tissue, their angiogenic properties, and their ability to express and secrete multiple growth factors. This chapter discusses the isolation and characterization of human ASCs, its expansion in vitro, and relevant in vivo models for adipose tissue engineering.
Chapter
Tissue expansion enables soft tissue coverage of large defects secondary to burns, trauma, congenital malformations and cancer excision. It involves the insertion of an implant adjacent to a wound or defect that needs to be resurfaced. The chapter discusses the pathophysiology, surgical technique and complications of tissue expansion as well as recent developments such as external tissue expansion and needleless expansion with the AeroForm expander. Tissue expansion remains a powerful tool in the reconstructive ladder and the armamentarium of plastic surgeons.
Article
The reconstruction of large-volume soft tissue defects is a major problem in plastic surgery. Many plastic surgeons have focused on external volume expansion (EVE) because of its capacity to promote regeneration of soft tissues, including breast, subcutaneous fat, and skin. EVE is a minimally invasive and less costly tissue engineering approach that has shown great clinical potential. However, many challenges still need to be addressed before such technology can become a common clinical practice. Basic in vivo and in vitro studies have been performed to determine the possible mechanisms by which EVE promotes tissue regeneration and to design optimized animal models. EVE application was found to facilitate cell proliferation and migration, enhance adipogenesis, improve angiogenesis, and provide available space for soft tissue growth. Understanding the mechanical and chemical signals associated with EVE during tissue regeneration may enable the clinical adaptation of this technology. This article reviews the clinical application of EVE techniques, describes preclinical animal models, and evaluates the possible mechanisms by which EVE induces tissue regeneration.
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"Francisco Villegas, especializado en la Universidad Nacional de Colombia, eligió Tuluá para su ejercicio profesional, una pequeña ciudad del Valle del Cauca, y la eligió porque allí lo necesitaban, mucho, y allí y desde allí ha servido en todos los frentes de la cirugía plástica, trabajando, enseñando y publicando por casi veinte años. Ahora, en buena hora, teniendo más que decir, ha decidido, ampliar el auditorio y con el serio respaldo editorial de la Corporación para Investigaciones Biológicas (CIB), nos brinda ésta muy trabajada obra producto de su experiencia, estudio, y reflexión. No es un catálogo de nuevos inventos, no es un muestrario para esnobistas. Es más bien un inventario, una guía para quienes de una u otra manera se interesen por la capacidad reconstructiva y modeladora de la cirugía. Su vocación universitaria, su verdad, utilidad y síntesis, más que la extensión, miden su importancia. Definición, glosario, cicatrización, heridas, reparación, quirófano, urgencias, quemaduras, tumores, mano, microcirugía, malformaciones, maxilofacial, estética, innovaciones, mama, cara, recuperación, enfermedades. Diecinueve temas, diecinueve títulos, diecinueve capítulos bien referenciados, ilustrados, indexados, y escritos en llano lenguaje científico si cabe, hacen la consulta expedita y la lectura fácil." Dra María del Mar Vaquero
Chapter
The use of autologous fat grafting (AFG) is widely used in plastic surgery for both reconstructive and aesthetic indications, in particular for breast and buttock augmentation and facial rejuvenation. AFG is a simple and effective procedure presenting several advantages. Among them, the possibility of combining liposuction of areas with unpleasant accumulation with volumetric enhancement and reshaping of anatomical regions where augmentation is sought. Moreover, regeneration capacity is recognized to the graft, as a copious literature has investigated the role of adipose-derived stem cells contained in its stromal vascular fraction. Importantly, this potential has encouraged its clinical application for the therapy of scars, scar-related conditions, and burns.
Chapter
Breast reconstruction with fat grafting is very useful for correcting and modifying size and symmetry [1], but reconstructing a breast with fat alone is difficult because the shape obtained is flat rather than rounded. In this chapter, we describe our technique for breast reconstruction using fat grafting alone in patients with flaccid, elastic skin, via multiple injections of fat tissue [2].
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The role of fat grafting to the breasts has evolved in the recent past, gaining several new applications within both reconstructive and aesthetic surgery. Initially used for reconstructive purposes to fill lumpectomy defects or to correct residual contour deformities after breast reconstruction, it has since made its way into cosmetic breast surgery and has grown to encompass a wide variety of new indications. Fat grafting in aesthetic breast surgery may be performed as a form of primary autologous breast augmentation or as an adjunct to implant-based breast augmentation to disguise implant edges. It may also be used to provide added volume after explant surgery or to provide improvements in breast contour alongside mastopexy techniques. In this article, we will review the current applications of fat grafting in aesthetic breast surgery and provide an up-to-date summary of its reported outcomes, safety, and complications.
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The authors report targeted muscle reinnervation (TMR) in an 11-year-old male who sustained a trans-radial amputation of the right upper extremity in an ATV accident. A combination of targeted muscle reinnervation, external tissue expansion, and free muscle transfer allowed us to preserve elbow function, prevent neuroma formation, and allow for the future use of a myoelectric prosthetic. The use of TMR in pediatrics leverages the enhanced cortical plasticity of younger patients to improve outcomes and quality of life following traumatic injury, limiting the otherwise significant financial and psychosocial impact of amputation. This report offers the first account of TMR performed on a pediatric patient with no neuroma formation or phantom limb pain.
Chapter
Transplantation of autologous adipose tissue as per Coleman can be subdivided into three phases: harvesting using a blunt, 11G needle, the processing and centrifuging and the return of the fat suspension. Alternate methods of fat transplantation include phase separation through sterile compression and filter-base systems. Those named here include the Shippert process, LipiVage and Revolve System. Systems for enrichment of stroma and stem cells include, amongst other things, the Celution System. Apart from this, the pre-expansion through the external under-pressure expander BRAVA has been described. The BEAULI Protocol serves for the harvesting of large volumes and is mainly based on suctioning using a water jet equipment (“body-jet”).
Chapter
Oncoplastic surgery was incorporated into the primary treatment of breast cancer to prevent the damaging consequences of this treatment and produce a significant benefit both aesthetically and psychologically without altering the oncological safety. In the conservative treatment, although there are many reconstructive techniques to prevent sequelae, for different reasons there are a number of patients with unsatisfactory results magnified by the effects of radiotherapy. Traditionally, aggressive techniques with high rates of complication (autologous tissue, prosthetic) and unstable results were used for the reconstruction of these defects; however, in recent years the introduction of lipotransference opened up a promising new stage, achieving results in many cases that are highly satisfactory, stable, and with lower morbidity.
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Cells are exposed during their lifetimes to an array of physical forces ranging from those generated by association with other cells and extracellular matrices to the constant forces placed on cells by gravity. Alterations in these forces, either with differentiation and development or changes in activity or behavior, result in modifications in the biochemistry and adaptation in structure and function of cells. Also, a variety of differentiated cells have unique shapes that relate to extremely specialized functions, with structure and function emerging concurrently. These observations lead to the concept that the forces perceived by cells may dictate their shape, and the combined effects of external physical stimuli and internal forces responsible for maintaining cell shape may stimulate alterations in cellular biochemistry. This review examines the state of our knowledge concerning the mechanisms through which physical forces are converted to biochemical signals (mechanotransduction), and speculates on the molecular structures that may be involved in mechanotransduction.
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Treatment of wounds with pharmacologic doses of the BB homodimeric form of recombinant PDGF (rPDGF-BB) induces the recruitment, activation, and proliferation of mesenchymal cells, resulting in the deposition of provisional, and subsequently collagen-containing extracellular matrix. In preliminary experiments with an in vitro growth chamber model in the rat consisting of a silicone shell containing a dissected femoral vascular bundle, we found that rPDGF-BB incorporated into a rapidly dissolving collagen type I film induces the generation of a marked, but transient amount of de novo tissue around the femoral vascular bundle. In the present studies, the new tissue generated around the femoral vascular bundle was wrapped with a full thickness syngeneic skin graft to determine if functional support of the graft would lead to sustained maintenance of the underlying generated tissue and create an epithelialized soft tissue appendage. The tissue generated after a single application of rPDGF-BB was skin grafted on the 10th day, exteriorized 20 d later, and observed for an additional month. This led to the formation of soft tissue appendages which demonstrated marked neovascularization, fibroblast migration and proliferation, and increased glycosaminoglycan, fibronectin, and collagen fibril deposition, now leading to preservation of the newly generated tissue. In contrast, minimal new tissue was generated in control-treated vascular bundles or bundles treated with inactive PDGF-BB, and grafting with skin failed to sustain the underlying tissue. Thus, rPDGF-BB coupled with skin grafting induced the formation of functional large soft tissue appendages which are potentially useful clinically to fill tissue defects or to serve as a cell delivery system for transfected genes.
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The effect of cyclic mechanical strain on growth of neonatal rat vascular smooth muscle (VSM) cells were examined. Cells were grown on silicone elastomer plates subjected to cyclic strain (60 cycle/min) by application of a vacuum under the plates. A 48 h exposure to mechanical strain increased the basal rate of thymidine incorporation by threefold and increased cell number by 40% compared with cells grown on stationary rubber plates. Strain also increased the rate of thymidine incorporation in response to alpha-thrombin (from 15- to 33-fold), but not to PDGF. As determined by thymidine autoradiography, strain alone induced a fourfold increase in labeled nuclei at the periphery of dishes, where strain is maximal, and a 2-3-fold increase at the center of dishes. Strain appeared to induce the production of an autocrine growth factor(s), since conditioned medium from cells subjected to strain induced a fourfold increase in DNA synthesis in control cells. Western blots of medium conditioned on the cells subjected to strain indicate that the cells secrete both AA and BB forms of PDGF in response to strain. Northern blots of total cell RNA from cells exposed to strain for 24 h show increased steady-state level of mRNA for PDGF-A. Lastly, polyclonal antibodies to the AA form of PDGF reduced by 75% the mitogenic effect of strain and polyclonal antibodies to AB-PDGF reduced mitogenicity by 50%. Antibodies to bFGF did not significantly reduce the strain-induced thymidine incorporation. Thus, the mechanism of strain-induced growth appears to involve the intermediary action of secreted PDGF.
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Human and bovine capillary endothelial cells were switched from growth to apoptosis by using micropatterned substrates that contained extracellular matrix-coated adhesive islands of decreasing size to progressively restrict cell extension. Cell spreading also was varied while maintaining the total cell-matrix contact area constant by changing the spacing between multiple focal adhesion-sized islands. Cell shape was found to govern whether individual cells grow or die, regardless of the type of matrix protein or antibody to integrin used to mediate adhesion. Local geometric control of cell growth and viability may therefore represent a fundamental mechanism for developmental regulation within the tissue microenvironment.
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Our long-term medical, biologic, and engineering basic science research has led to the discovery of a general biologic law governing the stimulation of tissue growth and regeneration: the law of tensionstress. We have learned that gradual traction on living tissues creates stresses that can stimulate and maintain the regeneration of active growth of certain tissues. Slow, steady traction of tissues causes them to become metabolically activated, resulting in an increase in the proliferative and biosynthetic functions. These processes are dependent upon the adequacy of the blood supply to the tissues being elongated and the stimulating effect of weight-bearing and functional use.
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The current strategy for breast cancer treatment involves early detection of the neoplasm before it has metasta-sized outside the breast, and surgical treatment of the lesion that minimizes deformity. Conventional methods of diagnostic imaging of the breast, including mammogra-phy, sonography, and galactography, do not adequately address clinical needs with regard to lesion characterization and staging. Magnetic resonance (MR) imaging has been proposed as a modality that may address these needs. The potential clinical uses of MR imaging are defined in terms of clinical needs and technologic requirements. Applications of MR imaging in detection of breast lesions can be divided into two major approaches based on the clinical questions to be answered: (a) improved specificity and (b) improved sensitivity. These approaches are defined by specific sets of clinical needs and have substantially different technologic requirements. The specificity approach is used to reduce the number of biopsies performed to confirm false-positive mammo-graphic findings. The MR imaging device that is used to improve specificity must visualize only the lesions that are seen mammographically. The sensitivity approach requires the visualization of lesions not identified at mammography, so that breast disease can be more effectively staged for treatment. The technologic requirements for the sensitivity approach are considerably more rigorous, because all lesions must be identified. The advantages and disadvantages of each of these approaches and the potential clinical ramifications are described.
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[[HN1]][1] The shape of a cell within its tissue is determined by a fibrous network called the extracellular matrix. In this issue, [ Chen et al .][2] manipulate the shapes of cells with microfabricated patterns of extracellular matrix dots and show that cells grow better when they are stretched and flattened than when they are plump and round. In his Perspective, Ruoslahti explains how cell surface molecules, the integrins, may participate in this effect and what this means for tissue repair and regulation. [1]: http://www.sciencemag.org#note1 [2]: http://www.sciencemag.org/cgi/content/short/276/5317/1425
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Endothelial cells (ECs) may behave as hemodynamic sensors, translating mechanical information from the blood flow into biochemical signals, which may then be transmitted to underlying smooth muscle cells. The extracellular matrix (ECM), which provides adherence and integrity for the endothelium, may serve an important signaling function in vascular diseases such as atherogenesis, which has been shown to be promoted by low and oscillating shear stresses. In this study, confluent bovine aortic ECs (BAECs) were exposed to an oscillatory shear stress or to a hydrostatic pressure of 40 mmHg for time periods of 12 to 48 h. Parallel control cultures were maintained in static condition. Although ECs exposed to hydrostatic pressure or to oscillatory flow had a polygonal morphology similar to that of control cultures, these cells possessed more numerous central stress fibers and exhibited a partial loss of peripheral bands of actin, in comparison to static cells. In EC cultures exposed to oscillatory flow or hydrostatic pressure, extracellular fibronectin (Fn) fibrils were more numerous than in static cultures. Concomitantly, a dramatic clustering ofα 5β1 Fn receptors and of the focal contact-associated proteins vinculin and talin occurred. Laminin (Ln) and collagen type IV formed a network of thin fibrils in static cultures, which condensed into thicker fibers when BAECs were exposed to oscillatory shear stress or hydrostatic pressure. The ECM-associated levels of Fn and Ln were found to be from 1.5-to 5-fold greater in cultures exposed to oscillatory shear stress or pressure for 12 and 48 h, than in static cultures. The changes in the organization and composition of ECM and focal contacts reported here suggest that ECs exposed to oscillatory shear stress or hydrostatic pressure may have different functional characteristics from cells in static culture, even though ECs in either environment exhibit a similar morphology.
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Ureteral augmentation is an effective method of bladder reconstruction using the native urothelium of a megaureter. Clinically this procedure is contingent on the presence of an enlarged ureter. We have iatrogenically produced a segmental megaureter, while preserving renal function in a pig model. The urothelium of the enlarged ureter was then used for augmentation cystoplasty. A tissue expander suitable for insertion into the lumen of the ureter was constructed. The tissue expander was passed antegrade through a flank incision of 8 pigs, and a separate nephrostomy tube was left in place. During the ensuing 1 to 4 weeks the pigs underwent daily dilation of the tissue expander without anesthesia. After dilation the pigs underwent ureteral augmentation of the bladder. The segment of expanded ureter was isolated from the native ureter, opened and anastomosed to the bladder. The continuity of the left ureter was restored by primary ureteroureterostomy. The animals underwent cystograms at 1 and 4 weeks and were sacrificed 4 weeks after augmentation. Tissue was harvested for gross and microscopic histology. Of the 8 pigs starting the protocol 5 underwent successful ureteral tissue expansion followed by bladder augmentation. Tissue expansion was performed from 1 to 4 weeks, and volumes of 150 to 1,000 cc were obtained. Two to 3 weeks of dilation was optimal to achieve ease of dilation, and no animal showed evidence of discomfort or failure to thrive. All 5 animals underwent successful ureteral augmentation with primary ureteroureterostomy. Tissue expansion volumes of approximately 250 cc were optimal for tissue management and ease of augmentation. Cystograms of all augmented animals showed increased bladder capacity with filling of the ureteral segment. Histological examination of the ureteral augmentation revealed preservation and regeneration of the urothelial mucosa. The use of a tissue expander in the lumen of the ureter is a novel method of generating urothelium for use in bladder augmentation. It may provide an alternative to bowel in patients who require bladder augmentation. Long-term studies are currently under way.
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Breast volume measurements were made on 47 adult subjects using a casting method. After drying, fast-setting plaster casts were filled with sand of known density to a level approximating the curvature of the chest wall. The reliability of both sand filling and casting proved to be high, r = 0.97, and r = 0.99, respectively. The total variable error was 10.2%. The effects of position (standing versus lying) was investigated in a separate sample of 15 subjects. No significant difference (P less than 0.05) was found between methods. The relationship between breast volume, girths, skinfolds, and body density was reported to be low.
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There are ion channels in the cell membrane that are sensitive to stress in the membrane cytoskeleton. Some channels turn on with stress, others turn off. In specialized receptors such as those involved in hearing, touch, etc. the role of the channels is clear. However, virtually all cells have these channels, and we don't yet know the physiological role of the channels although it is reasonable to suppose that they are involved in the control of cell size, either acutely as in volume regulation, or trophically as in the control of cell division.
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Lengthening of the mandible by gradual distraction was performed on four young patients (average age 78 months). The amount of mandibular bone lengthening ranged from 18 to 24 mm; one patient with Nager's syndrome underwent bilateral mandibular expansion. Following the period of expansion, the patients were maintained in external fixation for an average of 9 weeks to allow ossification. The patients were followed for a minimum of 11 months to a maximum of 20 months with clinical and dental examinations as well as photographic and radiographic documentation. The technique holds promise for early reconstruction of craniofacial skeletal defects without the need for bone grafts, blood transfusion, or intermaxillary fixation.
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Endothelial cells (EC) mediate many of the organ responses to shock. Much of our knowledge of EC are obtained from cell culture studies. However, compared to the dynamic milieu in vivo, the stationary environment for large-vessel EC may be artificial and inappropriate. In this study, the morphology, growth rate, and production of prostacyclin (PGI2) by EC obtained from different vascular beds under stationary and dynamic conditions were examined. EC were harvested from the thoracic aorta (Ao), pulmonary artery (PA), and vena cava (VC) of the same calves and exposed to 0.5 sec 24% deformation alternating with 0.5 sec relaxation (i.e., 60 cycles/min). Our results show that in response to the cyclic regimen, VCEC were elongated perpendicular to the force vector and their actin filaments aligned in the same direction, while AoEC and PAEC did not exhibit any morphological changes. The growth rate of AoEC (but not PAEC or VCEC) was significantly enhanced when stimulated by cyclic stretch. In addition, AoEC demonstrated an increased PGI2 synthetic activity with cyclic stretch, while PAEC and VCEC were unaltered. We conclude that the maintenance of EC phenotype and function is dependent on the hemodynamic milieu in vivo and may be influenced by the vascular origin of the cultured EC.
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Bra cup size and handedness were studied as possible risk factors for breast cancer. Data for 3918 cases and 11,712 controls from 7 centres were used to examine the association of handedness with laterality of breast cancer; data for 2325 cases and 7008 controls from 4 centres were used to assess the relation of bra cup size to breast cancer risk. There was a suggestive (P about 0.10) association of handedness with breast cancer laterality: odds ratio of a left-handed (or ambidextrous) woman having a left-sided cancer 1.22 (95% CI 0.96-1.56). Handedness may affect the lateral occurrence of breast cancer, although this tumour is in general more common in the left breast, possibly because this breast is usually slightly larger. Premenopausal women who do not wear bras had half the risk of breast cancer compared with bra users (P about 0.09), possibly because they are thinner and likely to have smaller breasts. Among bra users, larger cup size was associated with an increased risk of breast cancer (P about 0.026), although the association was found only among postmenopausal women and was accounted for, in part, by obesity. These data suggest that bra cup size (and conceivably mammary gland size) may be a risk factor for breast cancer.
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Two measures are being advocated to evaluate physiologic changes associated with compression of skin: transcutaneous oxygen tension (tcO2) and laser-Doppler blood flow. This study asked: 1) What changes occur in tcO2 and laser-Doppler blood flow with increasing compressive weight; and 2) do these measures respond differently to increasing weight? An indenter was used to apply incremental weight to the trochanter of healthy volunteers. During the first session, tcO2 was measured, and laser-Doppler blood flow was measured during the second session. The mean values of tcO2 and laser-Doppler blood flow were analyzed for significant changes over the range of applied weight. If significant change occurred, the polynomial that best described the data was determined. Mean values for tcO2 showed a significant decrease with increasing compressive weight. Its decrease was described by a second degree polynomial (quadratic). The weight that resulted in the tcO2 reaching zero for individual subjects ranged from 400-1000. Mean values for laser-Doppler blood flow showed a significant decrease with increased weight. The decrease was best described by a first degree polynomial (line), which is a different pattern from the tcO2. Laser-Doppler blood flow continued to decline with increasing weight beyond the point where tcO2 reached zero. During low-flow states, tissue oxygen utilization may exceed oxygen delivery and lead to ischemia even though capillary closure has not occurred.
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A recent resurgence of interest in mechanical forces and cell shape as biological regulators has revealed extracellular matrix as the site at which forces are transmitted both to and from cells. at the same time, great advances have been made in terms of defining cell-surface integrin receptors as transmembrane molecules that mediate cell attachment and physically interlink extracellular matrix with the intracellular cytoskeleton. Convergence of these two lines of research has begun to elucidate the molecular mechanism by which cells sense physical forces and transduce mechanical signals into a biochemical response.
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Bone lengthening was achieved on rabbit tibias by means of callus distraction (callota- sis) using a dynamic external fixator. The periosteum and the muscle fascia were labeled with metal markers; changes in position of these markers during slow progressive distraction were monitored by soft radiography. During the waiting period before commencing distraction, the periosteal markers around the osteotomy site were elevated from the bone surface by newly formed external callus. There was an apparent lag period until the periosteal reaction occurred after osteotomy. Subperiosteal callus was first formed in an uncalcified state and subsequently became calcified. As distraction began, longitudinal migration of the periosteal markers was observed. It appears that the periosteum slides over the bone cortex, mitigating local stretching of the muscle around osteotomy site. The elongation of muscle occurs throughout the muscle substance and not simply at the site of osteotomy.
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Soft-tissue expansion is most often used to correct a preexisting deformity or tissue deficit. More recently, tissue expansion has been used prior to creation of the tissue defect to facilitate closure of large defects with better cosmetic results, e.g., free-flap donor sites. Surgical excision of some malignant skin lesions results in difficult-to-close skin defects. Can a soft-tissue expander be used directly beneath a tumor prior to excision? If so, what effect does the tissue expansion have on tumor growth? To study this in the experimental animal, Fischer rats were injected intradermally with 13762 mammary carcinoma cells and assigned at random to one of four groups: group I (n = 24), nonoperated control; group II (n = 22), creation of a sham pocket beneath the tumor, group III (n = 21), expander placed beneath the tumor bed, unexpanded; and group IV (n = 22), a tissue expander placed beneath the tumor bed, expanded. Three weeks following injection, the tumors were excised and weighed, and animals were sacrificed and autopsied. Tumor weights in various groups were as follows: group I, 8.73 ± 1.2 gm; group II, 9.51 ± 1.3 gm; group III, 1.91 ± 0.4 gm; and group IV, 0.83 ± 0.2 gm. The tumor weight of the control (group I) and sham (group II) animals was greater than in the nonexpanded (group III) and expanded (group IV) animals (p < 0.0001). Thirteen of 24 animals (54 percent) in group I, 9 of 22 (41 percent) in group II, 5 of 21 (24 percent) in group III, and 2 of 22 (9 percent) in group IV demonstrated visceral metastases. We conclude that growth of the intradermal 13762 breast tumor in Fischer rats is substantially retarded by placement of a tissue expander beneath the tumor, and this is further diminished by tissue expansion. The tissue expander, in addition, acts as a barrier to visceral spread.
Article
Breast reconstruction using inflatable expanders has become an established and preferred technique. Although our knowledge of the biomechanical changes occurring in expanded skin has increased greatly, little information is available regarding average aesthetic results achieved with this technique. In order to eliminate the bias of best case selection reports, this study of 60 consecutive patients undergoing skin-expansion breast reconstruction was undertaken. Results of the study demonstrated a significant frequency and diversity of complications. In particular, immediate breast reconstruction with skin expanders was identified as a high-risk procedure because of its association with skin necrosis and delayed wound healing. Although two procedures--insertion and replacement--had been anticipated, patients from both the Boston and New York groups required approximately three operations to complete the expansion process. Average aesthetic results, often characterized by problems of symmetry, ptosis, and contour, need to be recognized and improved.
Article
The history of tissue expansion, technique, indications, and complications are reviewed. A detailed review of delayed tissue expansion's histologic, biochemical, biomechanical, and physiologic changes in the skin is given. There is a net gain in epidermal tissue during delayed expansion. Recent experimental and clinical experience suggests that expansion for 1 to 2 weeks is just as effective as longer delayed expansion for 6 to 8 weeks. A new deviation from standard technique, intraoperative tissue expansion, may have significant implications for dermatologic surgery. Intraoperative tissue expansion is explored in relation to other commonly used techniques of intraoperative load cycling.
Article
For 40 years, the author has been developing a system of orthopedics, traumatology, and limb lengthening using a circular transfixion-wire external skeletal fixator, often in combination with biomechanic methods of stimulating the formation of new osseous tissue within a widening osteotomy distraction site. The factors important for neoosteogenesis after osteotomy include: maximum preservation of extraosseous and medullary blood supply; stable external fixation; a delay prior to distraction; a distraction rate of 1 mm per day in frequent small steps; a period of stable neutral fixation after lengthening; and physiologic use of the elongating limb. For a successful fixator application, the apparatus must be applied with consideration given to the number, size, and location of the rings, the placement and tension on the wires, the technique of wire insertion, the effect of soft-tissue transfixion on limb use, and the prevention of bone and joint deformities caused by countertension in soft tissues. Clinical application of the author's techniques permits stature increase in certain forms of dwarfism, correction of deformities and limb-length inequalities, and stump elongation. For many of these applications, motorized distraction can provide continuous limb lengthening while the apparatus is on the patient.
Article
Several types of cells' skeletal, muscle, nerve, epithelia, and heart have been shown to contain ion channels which are sensitive to membrane tension. In chick skeletal muscle, the transduction persists in excised patches and involves no chemical messengers. Quantitative analysis of single channel records reveals that the sensitivity to stretch can be described by a linear four state model with three closed (C) and one open (O) state: (Formula: see text). Only the rate constant k12 is sensitive to tension (and membrane potential) following the law: k12 = kO12 exp/(theta T2 + alpha V) where theta is a constant describing the sensitivity to tension, T, and alpha is a constant describing the sensitivity to voltage, V, and kO12 is a constant. The form of the tension sensitivity can be accounted for by a model in which strain energy is used to gate the channel. Analysis of strain sensitivity, theta, indicates that the channel must concentrate energy from a large (ca. 500-nm diameter) area of membrane which suggests that the channel is in series with a component of the cytoskeleton. Treatment with cytochalasins suggests that actin is mechanically in parallel with the channel. When a channel with the above properties is incorporated into a simple model of mechanical transduction in hair cells, the resulting model is capable of explaining the kinetic features and the sensitivity found in the cochlear-vestibular system. The proposed gating mechanism of mechanical transduction appears to be general and can account for existing data on a variety of systems.
Article
Biochemical, biomechanical, and physical changes occurring in the skin during tissue expansion have been studied using an animal model in which a Silastic expander was inserted into the peritoneal cavity. Forty-eight Sprague-Dawley rats were divided into four groups to be studied at 4, 8, 16 and 32 days after expansion. In the experimental animals (6 per group) the expander was inflated by a single injection of 120 ml of saline. Sixteen hours prior to sacrifice each animal received a single injection of tritiated proline. Sixteen days after expansion both the specific activity and the total content of hydroxyproline in the skin were significantly elevated in experimental animals. Intrinsic skin tension increased dramatically at the time of inflation but fell almost to control values at the end of 32 days. Skin thickness, initially decreased, returned to normal by the end of the experiment. There were no significant differences in breaking strengths between skin from experimental and control animals. Skin surface area, initially increased by stretching at the time of inflation, increased further between Days 0 and 8, possibly as a result of stress relaxation combined with enhanced remodelling of connective tissue macromolecules, and again from Days 24 to 32. We conclude that, during tissue expansion, there is a net accumulation of collagen in the skin and that this allows the local cellular environment to return to normal with respect to pressure and/or tension.
Article
Although laboratory studies have documented that externally applied pressure disrupts circulation, in clinical practice little is known about the characteristics of blood flow over bony prominences as a function of time. The purpose of this study was to describe the pattern of blood flow over the trochanter when subjected to a constant interface pressure for a prolonged period of time. A quasi-experimental design was used to measure skin blood flow over the left trochanter in a sample of 19 healthy adults. With the use of laser doppler flowmetry, the pattern of blood flow was monitored continuously while subjects lay on a supportive air mattress. Measurement of blood flow was described for three periods: preload with subjects supine, loading with subjects in the left lateral position and hyperemia after subjects returned to the supine position. Rate of blood flow under loading showed a gradual increase from preload. There was a marked initial increase in flow during hyperemia that gradually tapered off, but failed to reach preload levels within 30 min. Individual blood flow tracings revealed an inconsistent pattern of response to loading, suggesting the presence of a range of physiological response to compressive surface pressure. Given the individual variation in response to a common external pressure, further research is recommended to evaluate the pattern of blood flow over bony prominences subjected to known interface pressure.
Article
To evaluate the optimum conditions for osteogenesis during limb lengthening and to study the changes in soft tissues undergoing elongation, a series of experiments were performed on the canine tibia. The experiments used the transfixion-wire, Ilizarov circular external skeletal fixator in configurations of differing stability of fixation in combination with a second variable, i.e., preservation of the periosteum, bone marrow, and medullary blood supply. Both increased fixator stability, and maximum preservation of the periosseous and intraosseous soft tissues enhanced bone formation during limb lengthening. To assess the role that the direction of the elongation vector plays in osteogenesis, canine tibiae were widened rather than lengthened in a second series of experiments using an Ilizarov apparatus modified for lateral distraction. The new bone formed parallel to the tension vector even when perpendicular to the bone's mechanical axis. As in longitudinal lengthening, damage to the bone marrow inhibits osteogenesis occurring by the influence of a lateral tension-stress vector. In a third series of experiments, half- and full-circumference cortical defects were created in canine tibiae to study the osteogenic potential of the marrow. New bone formed rapidly, even when the marrow was separated from the surrounding periosseous soft tissues by a sheet of polyvinyl chloride, attesting to the importance of marrow element preservation during osteotomy for limb lengthening.
Article
Clinical tissue expansion has been quite successful but takes 2 to 3 months. This study compares the effects of a conventional tissue expansion regimen of 6 weeks with an accelerated regimen of 2 weeks in the dog model, which is biomechanically similar to the human. In 22 dogs, the skin expanded 34.4 percent in the 2-week and 35.8 percent in the 6-week protocol, excluding stretch and recruitment. There was thinning of the panniculus carnosus in the 6-week group and otherwise no significant decrease in dermal thickness in either group. The biomechanical properties of elasticity and creep did not differ in expanded skin from both groups, while stress/relaxation mildly decreased from a control value of 53.5 percent to 48.8 percent in the 6-week group (p less than 0.05). Collagen activity was increased in both the 6-week and the 2-week groups (p less than 0.001) over nonexpanded skin, and immunohistochemical staining with a monoclonal procollagen antibody demonstrated collagen synthesis by dermal fibroblasts in both groups. We conclude that rapid tissue expansion did not demonstrate any deleterious effects when compared with a conventional regimen.
Article
This paper presents a critical review of the results of tissue expansion in our clinical experience. Seventy-six expansions performed in 66 patients between 1981 and August 1986 are included in the study. Complications necessitating some revision in the original treatment plan were documented in 39% of cases. However, sufficient tissue was usually generated to complete the proposed reconstruction without compromising the final results. The complications of tissue expansion are further analysed in relation to their anatomical distribution, time of onset and ultimate consequences. Causative factors are identified and preventative measures are introduced.
Article
Breast reconstruction following mastectomy has previously relied on the insertion of a silicone gel implant or the use of a myocutaneous flap. We report the use of an innovation, the inflatable tissue expander, for both immediate and delayed breast reconstruction in 26 patients where soft tissue cover was inadequate to permit the use of the silicone implant. By serial inflation of the tissue expander with saline, sufficient tissue cover was achieved for a second operative placement of a silicone prosthesis of appropriate volume to match the normal breast. To date, 10 patients undergoing delayed reconstruction and 5 of 16 patients with immediate reconstruction have had their final prosthesis inserted, while 3 women are satisfied with the result of the expandable implant and desire no further surgery. Only two technical complications have arisen with loss of the expander in one patient who had had recent radiotherapy and in another the tissue expander was placed much too high on the chest wall. Mechanical failure occurred in three cases where disruption of the seam led to sudden deflation in two and a slow leak from the injection port developed in one. One patient also attempted self-inflation leading to deflation of the tissue expander. The cosmetic results were subjectively and objectively very good with capsular distortion present in only one case. We feel that the inflatable tissue expander is simple and safe to use, may be used for immediate reconstruction without compromising the ablative surgery and should be a choice available to general surgeons for providing safe and cosmetically acceptable reconstructive surgery.
Article
Immediate reconstruction of a breast removed for treatment of carcinoma can be accomplished without altering the cancer-ablative surgical procedure. The theoretical possibility that reconstruction might compromise the cure rate has tempered enthusiasm for this approach. To test this issue, the relapse-free survival of 101 patients who underwent breast reconstruction in the immediate postmastectomy period was compared with that of 377 patients with breast cancer who underwent mastectomy without immediate reconstruction. This comparison was accomplished using multivariable statistical techniques to correct for baseline inequalities between the patient groups. After adjustment for the relevant prognostic factors, no significant difference remained between the two groups. We conclude that immediate reconstruction has no discernible adverse influence on the natural history of surgically treated breast carcinoma.
Article
A method has been devised to calculate breast volumes from mammograms. This has been applied to mammograms from 42 women with breast cancer and 42 age-matched normal controls. No difference in breast volumes was noted. ImagesFig. 1
Article
With the exception of women with previous breast cancer and those with breast cancer in the immediate family, no particular group of women appears to require more surveillance than the average woman.
Article
Soft-tissue expansion complements existing reconstructive techniques and provides new vistas for the plastic surgeon. The technique finds use for overcoming a shortage of tissue, for obtaining skin with special desirable qualities, for creation of flaps otherwise not possible because of the resultant donor site or limited vascularity, for creation of flaps with functioning muscle and overlying soft tissue, and for minimizing flap donor-site problems. Careful planning should include patient counseling, optimum incision placement, and time for a leisurely, complete expansion. The surgery can often be performed under local anesthesia and expansion is tolerated well. Patients should be counseled that the incidence of major complications in an unselected series is 1 in 4 patients. Major complications, however, typically result in a delay in reconstruction and not tissue loss.
Article
An electron microscopic study of guinea pig skin and soft tissue after expansion by self-inflating silicone implant for periods of 7 weeks to 8 months revealed definite ultrastructural changes. In the epidermis, the cells of the malpighian layer contained larger groups of tonofilaments forming tonofibrils. Intercellular spaces in all layers of expanded epidermis were much more reduced than in normal epidermis. The basal lamina and the laminar surfaces of the basal cells demonstrated more undulation than those of the controls. The expanded dermis contained large bundles of compacted collagen fibers, as well as thin collagen fibers, active fibroblasts, and a few myofibroblasts. The subcutaneous tissue contained a paucity of adipose tissue and thickened collagen fibers in the interlobular spaces. The skeletal muscle showed larger amounts of sarcoplasm in relation to myofibrils. An increased number and size of mitochondria were found with sarcomeres abnormally arranged. The capsule around the implant was composed of active, elongated, and flattened fibroblasts and bundles of collagen fibers with variable fiber width. Intracellular collagen fibers were found in the cytoplasm of the fibroblasts. Myofibroblasts in the capsule were observed more often in early expanded tissue. Small blood vessels in the capsule showed multiplication of the basal lamina or were surrounded by a very wide, homogenous material. Inflammatory cells were not found in the capsule. Such findings are important in developing and evaluating future skin-expansion research in humans and animals.
Article
The effect of externally applied load on the partial pressure of oxygen in tissue, measured at the skin surface (PSO2) was examined by applying a load to a transcutaneous O2 monitor mounted on the skin of healthy subjects. The load was increased every 4 minutes, and the PSO2 was recorded at the end of the 4-minute period. Three sites were investigated: the sacrum, the greater trochanteric area, and the lateral aspect of the thigh. Mean initial values for the 3 sites were found to be 10.1, 11.1, and 10.1 kPa, respectively. On increasing the applied load, values were found to reduce gradually at first and then at an increasing rate to zero at the "cut-off" load. The mean cut-off pressure for the 3 areas was 15.2, 18.8, and 18.1 kPa.
Article
The authors have developed a simple, accurate, and inexpensive device for measuring the volume of the female breast. The concept is based on an adjustable geometrical conical form into which the breast is placed. The breast volume is then easily read from a graduated scale on the device. The device is available in sterile prepackaged form for intraoperative use. The various applications and advantages are described.
Article
In recent years, the universally used internal expansion by implanting a silicone elastomer balloon into the soft tissue under the skin has shown certain disadvantages, i.e., certain complications associated with the operation, high cost, and the fact that the materials cannot be recycled. That the materials are used only once adds to the operating cost. In view of these disadvantages, we have designed and developed a kind of mechanical external skin expander, which is composed of (1) an adjustable tractor, (2) preserving splints, and (3) a traction frame. The tractor is used to grip the contracted skin in order to make the soft tissue of the skin expand with the lapse of time and increase in traction weight. The external skin expansion has the following advantages compared with internal expansion: avoiding the complications caused by implanting the soft-tissue expander beneath the skin; simplicity and efficiency of operation; and the fact that the equipment can be reused, reducing the operating which is suitable for these basic units. The data of the expanded skin area can be calculated through the computer. Since June of 1993, a satisfactory curative effect has been obtained in 44 patients suffering from advanced postburn scars. Thirty-two patients among them were treated for more than half a year, with the scar becoming normal in both appearance and function. External skin expansion provides a new method for expansion of skin soft tissue. It has a bright future in its clinical application.
Article
Increases in signal intensity enhancement were measured in defined regions of interest (ROIs) to allow distinction between malignant and benign tumors with dynamic gadolinium-enhanced magnetic resonance (MR) mammography. Twenty patients with palpable breast lesions (15 malignant, five benign) underwent MR mammography. The dynamic gradient-echo sequence was performed with intravenous bolus injection of gadopentetate dimeglumine and consisted of 25 images with a time resolution of 30 seconds. Contrast enhancement was calculated by comparing user-defined ROIs on pre- and postcontrast images. An increase in signal intensity of 70% or more on the 1-minute postcontrast image was used as the criterion of malignancy. MR mammographic results correlated with histopathologic findings in all patients when the defined ROI was in the most enhancing part of the tumor. For the ROI in areas of submaximal enhancement or when the ROI surrounded the whole lesion, only five and nine tumors, respectively, fulfilled the malignancy criterion. All malignant tumors showed large variations in signal intensity enhancement that depended on the position of the ROI in the tumor. Dynamic, gadolinium-enhanced MR mammography allows distinction of benign from malignant breast tumors when the selected ROI is in the most enhancing part of the lesion.
Article
Tissue expansion is a well established method for reconstructive surgery. As a complement, a new technique of skin extension has been developed, and tested clinically. The device consists of two holding bars with several straps placed between them, which usually is applied under local anaesthesia. It is an efficient, rapid, and inexpensive way of expanding skin before excision of skin defects. Thirty-two patients have been treated, three patients have had complications, and length of follow up ranged from 2-12 months.
Article
The effects of shear forces externally applied to the skin surface on the underlying tissues have been investigated. An analysis of the internal stresses and strains was conducted using a simplified model incorporating elasticity theory. Skin blood flow was measured using laser Doppler flowmetry while variable shear forces over a range of 0-250 g were applied to the skin surface. The theoretical model predicts that the application of surface shear forces alters the internal stress distribution and makes the shear and compressive components of stresses increase ahead of the surface force application point. The force resulting from concomitant application of shear and normal force determines the internal maximum stress and strain. Theoretically, the shear force should have the same effects on the underlying tissues as normal force. The experimental investigations revealed that the skin blood flow decreased roughly linearly with the increase of shear forces. When a shear force equal to the normal force was applied, the flux decreased by 45%, nearly equal to the increasing magnitude (41%) of resultant of normal and shear forces.
Article
To study the architecture and enhancement characteristics of breast lesions with magnetic resonance imaging. Forty-one patients with mammographic and/or palpable lesions were imaged. T1-weighted, fat-saturated T2-weighted fast spin-echo, and gadolinium-enhanced and -unenhanced fat-saturated spoiled gradient-echo images were obtained. All patients underwent excisional biopsy or cyst aspiration. Fifteen of 16 carcinomas were identified and exhibited at least partially irregular borders. T2-weighted signal intensity and contrast enhancement varied. Rim enhancement was seen in five lesions. Nine of 10 fibroadenomas were visualized and showed well-defined borders. T2-weighted signal intensity and contrast enhancement varied and correlated with histologic features. Internal septations were seen in five lesions. Time-intensity curves showed no statistically significant difference between fibroadenomas and cancers. There is an overlap in the signal intensity characteristics and enhancement profiles of benign and malignant lesions. However, border characteristics, internal architecture, enhancement characteristics, and the presence of multiple tiny associated cysts may be important clues to lesion identification.
Article
For the management of infants with the short-bowel syndrome, we developed a two-stage bowel elongation procedure based on experimental studies of what we term as an isolated bowel segment. The procedure consists of: (1) initial coaptation of the antimesenteric surface of a segment of bowel to host organs such as liver and abdominal wall, and (2) after collaterals have developed from these host organs, secondary longitudinal split of the bowel to provide two bowel loops, one from its antimesenteric half and the other from its mesenteric half. These are arranged in series by end-to-end anastomosis to double the original bowel length. The antimesenteric loop is totally free of its original mesenteric attachment but viable by vascular collaterals formed across the coaptation site. This procedure was successfully used for an infant who was born with 17 cm of duodenum and 17 cm of the distal colon from first trimester intrauterine midgut volvulus. At completion of the multistaged procedures at the age of 1 year when we reentered the abdomen for duodenoplasty, his small bowel measured 90 cm in length. He is currently taking 50% to 60% of required calories via the enteric route at 18 months of age. This procedure is suitable for elongating the duodenum of infants when other alternatives such as the Bianci procedure are not feasible because of mesenteric absence.
Article
An in vivo experimental model was introduced to determine whether the mitogenic effect of recombinant platelet-derived growth factor (rPDGF) could be used to generate potentially useful tissue. In Lewis rats, the extended femoral arteriovenous bundle was placed within silicone chambers containing collagen disks. The disks could deliver their content of rPDGF-BB (125 to 131 micrograms/disk) either as a rapid pulse or as a slow release. The time course of tissue generation was determined by harvesting the specimens at various postoperative days. The effect of continuous versus pulsed delivery was determined at 30 days. Analysis of the generated tissue was performed by use of histomorphometry. Pulsed delivery of rPDGF-BB induced the formation of a substantial amount of tissue that peaked at 10 to 15 days (145.9 +/- 13.8 vs 35.0 +/- 6.8 mm3, p < 0.0001); however, the generated tissue completely subsided by day 30. Sustained delivery of rPDGF-BB caused continuous growth of the tissue and was more effective than pulsed delivery. In an experimental model that approximates an in vivo tissue culture system, rPDGF-BB can induce a tenfold increase in tissue within the chamber. However, that tissue is labile and its survival necessitates continuous rPDGF-BB delivery. To become useful for reconstructive purposes, means to stabilize this new tissue growth are needed.
Article
Tissue expansion is one of the powerful tools for various reconstructive procedures and has proven to provide more available local tissues. However, limited attention has been given to the characteristics of expanded skeletal muscle. Using a rat model (n = 41), we expanded the rat gracilis muscle and investigated the histomorphologic changes in the expanded skeletal muscle. By expansion, the gracilis muscle after 3 weeks increased 50.4 to 58.4 percent in length and 60.5 percent in width and decreased 39.0 to 42.0 percent in thickness. Histologically, the expanded muscle demonstrated a normal striation and no signs of inflammation or necrosis. The cross-sectional areas of muscle fibers indicated that expanded muscle consisted of predominantly smaller fibers. Vasculature in the expanded muscle demonstrated a longer network of arteries and a more obvious and developed arterial arcade. The average number of sarcomeres in a fiber estimated from the sarcomere length and fiber length was significantly greater (46.5 percent) in the expanded muscle. These findings suggest that the expansion of skeletal muscle is not a "stretching" process of muscle but rather a growth process of the muscle accompanied by an increase in the number of sarcomeres per fiber. Furthermore, the expanded skeletal muscle appears to preserve normal skeletal muscle architecture, vasculature, and function while undergoing the ischemic stress of expansion.
Article
The incidence of postoperative wound complications and early cancer recurrence was studied in 289 patients who had mastectomy alone and in 113 patients who underwent immediate reconstruction following mastectomy. Patients undergoing immediate reconstruction were younger and had less advanced disease than patients who had mastectomy alone. The postoperative hospital stay was 3.8 days and 4.4 days (p < 0.05) in patients with and without reconstruction, respectively. The overall incidence of postoperative complications was similar in the two groups of patients: 31% and 28% in patients with and without reconstruction, respectively. The incidence of postoperative seroma was higher among patients with mastectomy alone (19% versus 3%, p < 0.05), whereas the incidence of other wound complications was similar in the two groups of patients. Prosthesis-specific complications occurred in 17%. Eight prostheses were removed because of complications. During the relatively short follow-up period (approximately 20 months), local recurrence was noted in 16 patients (6%) who had mastectomy alone and in 1 patient (1%) who had immediate reconstruction after mastectomy (p < 0.05). There was no significant difference in the incidence of distant metastases between the two groups of patients. The results suggest that immediate breast reconstruction can be performed following mastectomy for cancer without increased risk for overall postoperative complications, prolonged hospital stay, or local recurrence. However, patients who choose to have immediate reconstruction need to be informed about risks for specific complications associated with the procedure, especially if an implant is used.
Article
In 20 patients subjected to breast reconstruction by means of tissue expansion, a skin biopsy was obtained at the vertex of the breast before and the day after expansion. Samples were incubated in [3H]thymidine, and the number of labeled cells were counted. A statistically significant rise in the number of labeled basal and suprabasal keratinocytes was seen after expansion. The findings suggest a net gain of tissue not only by stretching but also by formation of new tissue generated by tissue expansion.
Article
The relationship between brassière size, as an indicator of breast size, and breast cancer risk was considered in a case--control study conducted between 1991 and 1994 in six Italian centres. Cases were 2,557 women, below age 75, with histologically confirmed breast cancer, and controls were 2,566 women admitted to hospital for a wide spectrum of acute, non-neoplastic, non-hormone-related diseases. Odds ratio (ORs) of breast cancer and their 95% confidence intervals (CIs) were obtained from multiple logistic regression equations including terms for study centre and age, as well as main breast cancer risk factors. A slight inverse relationship was observed between breast size and the risk of breast cancer, with an OR of 1.37 (95% CI 1.05-1.80) for the smallest brassière size compared with the largest; the increase in risk disappeared after adjustment for main recognized breast cancer risk factors, with an OR of 1.16 (95% CI 0.87-1.54) for brassière size < or = 1 compared with > or = 5. No significant heterogeneity in risk of breast cancer with breast size was found in strata of age at diagnosis, parity, age at first birth, age at menopause, family history of breast cancer, benign breast disease, ever use of oral contraceptives and/or hormone replacement therapy. Thus, this study, based on large number of caucasian women, provides conclusive evidence of a lack of appreciable association between breast size and breast cancer risk in this Italian population.
Article
Physical forces of gravity, hemodynamic stresses, and movement play a critical role in tissue development. Yet, little is known about how cells convert these mechanical signals into a chemical response. This review attempts to place the potential molecular mediators of mechanotransduction (e.g. stretch-sensitive ion channels, signaling molecules, cytoskeleton, integrins) within the context of the structural complexity of living cells. The model presented relies on recent experimental findings, which suggests that cells use tensegrity architecture for their organization. Tensegrity predicts that cells are hard-wired to respond immediately to mechanical stresses transmitted over cell surface receptors that physically couple the cytoskeleton to extracellular matrix (e.g. integrins) or to other cells (cadherins, selectins, CAMs). Many signal transducing molecules that are activated by cell binding to growth factors and extracellular matrix associate with cytoskeletal scaffolds within focal adhesion complexes. Mechanical signals, therefore, may be integrated with other environmental signals and transduced into a biochemical response through force-dependent changes in scaffold geometry or molecular mechanics. Tensegrity also provides a mechanism to focus mechanical energy on molecular transducers and to orchestrate and tune the cellular response.
Article
External load plays a critical role in determining muscle mass and its phenotype in cardiac myocytes. Cardiac myocytes have the ability to sense mechanical stretch and convert it into intracellular growth signals, which lead to hypertrophy. Mechanical stretch of cardiac myocytes in vitro causes activation of multiple second messenger systems that are very similar to growth factor-induced cell signaling systems. Stretch of neonatal rat cardiac myocytes stimulates a rapid secretion of angiotensin II which, together with other growth factors, mediates stretch-induced hypertrophic responses in vitro. In this review, various cell signaling mechanisms initiated by mechanical stress on cardiac myocytes are summarized with emphasis on potential mechanosensing mechanisms and the relationship between mechanical loading and the cardiac renin-angiotensin system.