An Axisymmetric Computational Model of Skin Expansion and Growth

Skin expansion is the principal technique used in plastic surgery to repair large cutaneous defects, typically after tumour removal, burn care, craniofacial surgery and post-mastectomy breast reconstruction. It allows a gain of new tissue by means of gradual expansion of a prosthesis, surgically implanted beneath the patient’s skin. Nevertheless, wide clinical use is not supported by a deep quantitative knowledge of the phenomena occurring during the expansion. A finite element model of the skin expansion was developed to evaluate the stresses and the strains of the skin due to the expander inflation and validated by proper in vitro experiments; furthermore, a growth model based on the mechanical stimulus was implemented to estimate the skin area gain. The developed computational approach, composed of the skin expansion model interaction and the growth law, proved its validity to investigate skin expansion phenomena: its use suggests a new predictive tool to optimize clinical procedures and the expander devices’ design.     

Increased survival and vascularity of random-pattern skin flaps elevated in controlled, expanded skin

Controlled clinical tissue expansion, a new technique of providing donor tissue, results in an increase in surface area of expanded skin. The aim of the present study was to determine the effect of controlled tissue expansion on the surviving lengths of random-pattern skin flaps elevated in expanded tissue. In five pigs the surviving lengths of flaps raised in skin expanded for 5 weeks using a 250-cc rectangular Radovan-type tissue expander were compared with the survival lengths of flaps elevated in tissue in which a similar prosthesis was not expanded, bipedicle flaps delayed for 5 weeks, and control acutely raised random-pattern flaps. The expanded flaps had a mean increase in surviving length of 117 percent over control flaps, which was statistically significant. The delay flaps had an increase in survival of 73 percent over control flaps, which was also statistically significant. There was no significant difference in survival between expanded flaps and delayed flaps. Morphologic studies using radiographic techniques on one pig demonstrated increased vascularity with tissue expansion. The results of this work demonstrate that in addition to providing increased surface area with controlled expansion, flaps raised in expanded skin have a significantly augmented surviving length. The mechanism for this increased vascularity with expansion is not known at this time, but it may be due to physical forces associated with expansion acting as a stimulus for angiogenesis.     

Continuous versus intraoperative expansion in the pig model.

Continuous tissue expansion utilizing a continuous infusion device that maintains a constant expander pressure was previously demonstrated to be feasible and successful in obtaining rapid tissue expansion in a canine model. Intraoperative tissue expansion has been described and has gained some clinical acceptance as a method to gain rapid expansion. We compared the efficacy of continuous tissue expansion versus intraoperative tissue expansion in a piglet model. After completing a pilot study, continuous tissue expansion was performed in six pigs (14.5 to 20 kg) on one flank over a 3-day period utilizing an improved prototype device; at the termination of continuous tissue expansion, intraoperative tissue expansion was performed on the opposite flank. There were no complications or continuous tissue expansion device malfunctions. Intraoperative tissue expansion gave a true gain in area of 7.4 percent, while continuous tissue expansion produced a 22 percent gain (p < 0.02). When the effects of both recruitment and expansion were added, continuous tissue expansion gave a dividend of 286 percent versus 192 percent for intraoperative tissue expansion (p < 0.01). Biomechanically, intraoperative tissue expansion skin showed few differences from unexpanded skin, while continuous tissue expansion skin showed a significant increase in stress relaxation (47.78 versus 38.74) and decrease in breaking strength. Histologic analysis revealed some epidermal hyperplasia and inflammation surrounding the continuous tissue expansion expander and some vascular congestion over the intraoperative tissue expansion expander. We conclude that continuous tissue expansion is superior to intraoperative tissue expansion and that the prototype device may be useful clinically.     

Rapid preparation of a noncultured skin cell suspension that promotes wound healing

Autologous skin cell suspensions have been used for wound healing in patients with burns and against normal pigmentation in vitiligo. To separate cells and the extracellular matrix from skin tissue, most researchers use enzymatic digestion. Therefore, this process is difficult to perform during a routine surgical procedure. We aimed to prepare a suspension of noncultured autologous skin cells (NCSCs) using a tissue homogenizer as a new method instead of harsh biochemical reagents. The potential clinical applicability of NCSCs was analyzed using a nude-rat model of burn healing. After optimization of the homogenizer settings, cell viability ranged from 52 to 89%. Scanning electron microscopy showed evidence of keratinocyte-like cell morphology, and several growth factors, including epidermal growth factor and basic fibroblast growth factor, were present in the NCSCs. The rat model revealed that NCSCs accelerated skin regeneration. NCSCs could be generated using a tissue homogenizer for enhancement of wound healing in vivo. In the NCSC group of wounds, on day 7 of epithelialization, granulation was observed, whereas on day 14, there was a significant increase in skin adnexa regeneration as compared to the control group (PBS treatment; p < 0.05). This study suggests that the proposed process is rapid and does not require the use of biochemical agents. Thus, we recommend a combination of surgical treatment with the new therapy for a burn as an effective method.     

The CCN1 (CYR61) protein promotes skin growth by enhancing epithelial‐mesenchymal transition during skin expansion

The skin expansion technique is widely used to induce skin growth for large‐scale skin deformity reconstruction. However, the capacity for skin expansion is limited and searching for ways to improve the expansion efficiency is a challenge. In this study, we aimed to explore the possible mechanism of skin expansion and to find a potential therapeutic target on promoting skin growth. We conducted weighted gene coexpression network analysis (WGCNA) of microarray data generated from rat skin expansion and found CCN1 (CYR61) to be the central hub gene related to epithelial‐mesenchymal transition (EMT). CCN1 up‐regulation was confirmed in human and rat expanded skin and also in mechanically stretched rat keratinocytes, together with acquired mesenchymal phenotype. After CCN1 stimulation on keratinocytes, cell proliferation was promoted and partial EMT was induced by activating β‐catenin pathway. Treatment of CCN1 protein could significantly increase the flap thickness, improve the blood supply and restore the structure in a rat model of skin expansion, whereas inhibition of CCN1 through shRNA interference could dramatically reduce the efficiency of skin expansion. Our findings demonstrate that CCN1 plays a crucial role in skin expansion and that CCN1 may serve as a potential therapeutic target to promote skin growth and improve the efficiency of skin expansion.     

Tanshinon IIA Injection Accelerates Tissue Expansion by Reducing the Formation of the Fibrous Capsule

The tissue expansion technique has been applied to obtain new skin tissue to repair large defects in clinical practice. The implantation of tissue expander could initiate a host response to foreign body (FBR), which leads to fibrotic encapsulation around the expander and prolongs the period of tissue expansion. Tanshinon IIA (Tan IIA) has been shown to have anti-inflammation and immunoregulation effect. The rat tissue expansion model was used in this study to observe whether Tan IIA injection systematically could inhibit the FBR to reduce fibrous capsule formation and accelerate the process of tissue expansion. Forty-eight rats were randomly divided into the Tan IIA group and control group with 24 rats in each group. The expansion was conducted twice a week to maintain a capsule pressure of 60 mmHg. The expansion volume and expanded area were measured. The expanded tissue in the two groups was harvested, and histological staining was performed; proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) and transforming growth factor-β (TGF-β) were examined. The expansion volume and the expanded area in the Tan IIA group were greater than that of the control group. The thickness of the fibrous capsule in the Tan IIA group was reduced with no influence on the normal skin regeneration. Decreased infiltration of macrophages, lower level of TNF-α, IL-6, IL-1β and TGF-β, less proliferating myofibroblasts and enhanced neovascularization were observed in the Tan IIA group. Our findings indicated that the Tan IIA injection reduced the formation of the fibrous capsule and accelerated the process of tissue expansion by inhibiting the FBR.     

A morphoelastic model for dermal wound closure

We develop a model of wound healing in the framework of finite elasticity, focussing our attention on the processes of growth and contraction in the dermal layer of the skin. The dermal tissue is treated as a hyperelastic cylinder that surrounds the wound and is subject to symmetric deformations. By considering the initial recoil that is observed upon the application of a circular wound, we estimate the degree of residual tension in the skin and build an evolution law for mechanosensitive growth of the dermal tissue. Contraction of the wound is governed by a phenomenological law in which radial pressure is prescribed at the wound edge. The model reproduces three main phases of the healing process. Initially, the wound recoils due to residual stress in the surrounding tissue; the wound then heals as a result of contraction and growth; and finally, healing slows as contraction and growth decrease. Over a longer time period, the surrounding tissue remodels, returning to the residually stressed state. We identify the steady state growth profile associated with this remodelled state. The model is then used to predict the outcome of rewounding experiments designed to quantify the amount of stress in the tissue, and also to simulate the application of pressure treatments.     

Bulk elastic properties of chicken embryos during somitogenesis

We present measurements of the bulk Young's moduli of early chick embryos at Hamburger-Hamilton stage 10. Using a micropipette probe with a force constant k ~0.025 N/m, we applied a known force in the plane of the embryo in the anterior-posterior direction and imaged the resulting tissue displacements. We used a two-dimensional finite-element simulation method to model the embryo as four concentric elliptical elastic regions with dimensions matching the embryo's morphology. By correlating the measured tissue displacements to the displacements calculated from the in-plane force and the model, we obtained the approximate short time linear-elastic Young's moduli: 2.4 ± 0.1 kPa for the midline structures (notocord, neural tube, and somites), 1.3 ± 0.1 kPa for the intermediate nearly acellular region between the somites and area pellucida, 2.1 ± 0.1 kPa for the area pellucida, and 11.9 ± 0.8 kPa for the area opaca.     

油菜绿色面积指数动态模拟模型

准确模拟绿色面积指数是作物生长模拟模型可靠预测作物生长和产量的关键。该研究的目的是以生理生态过程为基础,构建油菜(Brassica napus)叶面积指数和角果面积指数变化动态的模拟模型。油菜叶面积指数模型综合考虑了库或源限制下的叶面积增长模式,其中库限制下叶面积指数的增长呈指数方程,且受到温度、水分和氮素因子的影响;源限制下叶面积指数增长用比叶面积法来模拟。油菜角果面积指数由比角果面积和角果干物重来决定。比叶面积和比角果面积均为生理发育时间的函数。利用不同类型品种的播期试验及氮肥试验资料分别对模型进行了校正和检验,结果表明模型能较好地模拟不同条件下油菜叶面积指数和角果面积指数。     

Tissue interactions and antlerogenesis: new findings revealed by a xenograft approach.

Tissue interactions play a pivotal role in organogenesis. Here we describe a xenograft approach to investigate how heterotypic tissue interactions control antler formation in deer. Deciduous antlers grow from the apices of permanent protuberances, called pedicles. Histogenesis of pedicles depends on the antlerogenic periosteum (AP). Pedicles and growing antlers are made up of interior osseocartilage (a mixture of bone and cartilaginous tissue) and exterior skin. In a previous study we hypothesised that pedicle growth may result from mechanical interactions between the interior and exterior components whereas antler generation from a pedicle would involve molecules communicating between the interior and exterior components. To test this hypothesis, we subcutaneously transplanted AP of red deer (Cervus elaphus), either alone or with future pedicle skin, onto nude mice. The results showed that under the nude mouse skin, subcutaneously xenografted AP alone not only could form pedicle-shaped protuberances but also could differentiate into well-organised pedicle-like structures. The overlying mouse skin accommodated the expansion of the grafted AP by initial mechanical stretching and subsequent formation of new skin. Nude mouse skin was not capable of participating in antler tissue formation. However, grafted deer skin together with AP may have successfully rescued this failure after wounding, which highlights the necessity of the specificity of the overlying skin for antler tissue generation. Therefore, we conclude that it is the interaction between the antlerogenic tissue and the overlying skin that results in antlerogenesis: reciprocal mechanical interactions cause pedicle formation, whereas reciprocal instructive interactions induce first antler generation.     

Co-Ordination of Cell Division and Tissue Expansion in Sunflower, Tobacco, and Pea Leaves: Dependence or Independence of Both Processes?

Abstract Temporal analyses of cell division and tissue expansion in pea, tobacco, and sunflower leaves reveal that both processes follow similar patterns during leaf development. Relative cell division and relative tissue expansion rates are maximal and constant during early leaf development, but they decline later. In contrast, relative cell expansion rate follows a bell-shaped curve during leaf growth. Cell division and tissue expansion have common responses to temperature, intercepted radiation, and water deficit. As a consequence, final leaf area and cell number remain highly correlated throughout a large range of environmental conditions for these different plant species, indicating that cell division and tissue expansion are co-ordinated during leaf development. This co-ordination between processes has long been explained by dependence between both processes. Most studies on dicotyledonous leaf development indicate that leaf expansion rate depends on the number of cells in the leaf. We tested this hypothesis with a large range of environmental conditions and different plant species. Accordingly, we found a strong correlation between both absolute leaf expansion rate and leaf cell number. However, we showed that this relationship is not necessarily causal because it can be simulated by the hypothesis of independence between cell division and tissue expansion according to Green's theory of growth (1976). Received 23 February 2000; accepted 3 March 2000     

Development of a method for assessing micronucleus induction in a 3D human skin model (EpiDerm)

To meet the requirements of the EU 7th Amendment to the Cosmetics Directive, manufacturers of cosmetics products will need to ascertain the safety of ingredients using non-animal methods. Starting in 2009, in vivo genotoxicity tests for cosmetics ingredients will not be allowed. Skin is a target area of interest for many cosmetic products because of its relatively high exposure. Therefore, it would be beneficial to have a non-animal, skin-based genotoxicity assay, especially one that utilized human skin in vitro. In this paper, we describe the development of a reproducible micronucleus assay that uses EpiDerm engineered human skin constructs (MatTek Corp., Ashland, MA). We describe methods for isolating single cells from the 3D skin model and for processing the cells for microscopic analysis of micronuclei (MN). In addition, since little was known about the kinetics of the dividing keratinocytes in the EpiDerm model, we evaluated whether cytochalasin B (Cyt-B) could be used to distinguish the population of dividing cells allowing the development of a micronucleus assay in binucleated cells. We found that the frequency of binucleated cells increased both with time and with increasing concentration of Cyt-B. After a 48-h exposure, 30-50% binucleated cells were reproducibly obtained. Finally, we evaluated micronucleus induction using the model genotoxicants mitomycin C (MMC) and vinblastine sulfate (VB). The background frequency of MN is very low and reproducible in this model, and statistically significant increases in the frequency of micronucleated cells were induced by both MMC and VB. These are initial steps in developing a routine "in vivo-like" assay for chromosomal damage in human tissue. It is hoped that other investigators utilize these methods to further the understanding of this potentially valuable new non-animal method.     

胸三角皮瓣并自体脂肪移植修复颌面部大面积缺损畸形

目的：探讨颌面部皮肤软组织大面积缺损凹陷的理想修复方法。方法：本组6例均为爆炸伤后颌面部皮肤软组织缺损及严重凹陷畸形,采用胸三角皮肤扩张形成带蒂皮瓣修复上述皮肤缺损及自体脂肪移植纠正残存凹陷畸形。手术分五步进行：1．胸三角深筋膜浅层埋植500mL-800mL皮肤扩张器并注水扩张3个月。2井艮据面颈部预计皮肤缺损大小及形状作皮瓣预制并面部局部皮瓣纠正器官移位。3．带蒂皮瓣转移修复颌面部缺损。4．蒂部延迟及断蒂微整形。5．自体脂肪移植。结果：所有皮瓣成活良好,皮瓣色质接近面颈部周围正常皮肤,缺损畸形修复,外观形态好,供区直接缝合无需植皮,取得了较好的面部改观效果。结论：对于面部大面积皮肤软组织缺损,合并面部凹陷、面部器官缺损及移位,采取胸三角扩张延迟预制皮瓣并自体脂肪移植修复可取得良好的整复效果,为颌面部战创伤畸形提供了理想的修复方法。     

Development of the Mouse Dermal Adipose Layer Occurs Independently of Subcutaneous Adipose Tissue and Is Marked by Restricted Early Expression of FABP4

The laboratory mouse is a key animal model for studies of adipose biology, metabolism and disease, yet the developmental changes that occur in tissues and cells that become the adipose layer in mouse skin have received little attention. Moreover, the terminology around this adipose body is often confusing, as frequently no distinction is made between adipose tissue within the skin, and so called subcutaneous fat. Here adipocyte development in mouse dorsal skin was investigated from before birth to the end of the first hair follicle growth cycle. Using Oil Red O staining, immunohistochemistry, quantitative RT-PCR and TUNEL staining we confirmed previous observations of a close spatio-temporal link between hair follicle development and the process of adipogenesis. However, unlike previous studies, we observed that the skin adipose layer was created from cells within the lower dermis. By day 16 of embryonic development (e16) the lower dermis was demarcated from the upper dermal layer, and commitment to adipogenesis in the lower dermis was signalled by expression of FABP4, a marker of adipocyte differentiation. In mature mice the skin adipose layer is separated from underlying subcutaneous adipose tissue by the panniculus carnosus. We observed that the skin adipose tissue did not combine or intermix with subcutaneous adipose tissue at any developmental time point. By transplanting skin isolated from e14.5 mice (prior to the start of adipogenesis), under the kidney capsule of adult mice, we showed that skin adipose tissue develops independently and without influence from subcutaneous depots. This study has reinforced the developmental link between hair follicles and skin adipocyte biology. We argue that because skin adipocytes develop from cells within the dermis and independently from subcutaneous adipose tissue, that it is accurately termed dermal adipose tissue and that, in laboratory mice at least, it represents a separate adipose depot.     

Leaf expansion – an integrating plant behaviour

Leaves expand to intercept light for photosynthesis, to take up carbon dioxide, and to transpire water for cooling and circulation. The extent to which they expand is determined partly by genetic constraints, and partly by environmental conditions signalling the plant to expand more or less leaf surface area. Leaves have evolved sophisticated sensory mechanisms for detecting these cues and responding with their own growth and function as well as influencing a variety of whole-plant behaviours. Leaf expansion itself is an integrating behaviour that ultimately determines canopy development and function, allocation of materials determining relative shoot : root volume, and the onset of reproduction. To understand leaf development, and in particular, how leaf expansion is regulated, we must know at the molecular level which biochemical processes accomplish cell growth. Physiological experimentation focusing on ion fluxes across the plasmamembrane is providing new molecular information on how light stimulates cell expansion in some dicotyledonous species. Genetic analyses in Arabidopsis, corn, and other species are rapidly generating a list of mutations and enzyme activities associated with leaf development and expansion. Combination of these approaches, using informed physiological interpretations of phenotypic variation will allow us in the future to identify genes encoding both the processes causing cell expansion, and the regulators of these events.     

Effects of fibroin microcarriers on inflammation and regeneration of deep skin wounds in mice

The process of tissue regeneration following damage takes place with direct participation of the immune system. The use of biomaterials as scaffolds to facilitate healing of skin wounds is a new and interesting area of regenerative medicine and biomedical research. In many ways, the regenerative potential of biological material is related to its ability to modulate the inflammatory response. At the same time, all foreign materials, once implanted into a living tissue, to varying degree cause an immune reaction. The modern approach to the development of bioengineered structures for applications in regenerative medicine should be directed toward using the properties of the inflammatory response that improve healing, but do not lead to negative chronic manifestations. In this work, we studied the effect of microcarriers comprised of either fibroin or fibroin supplemented with gelatin on the dynamics of the healing, as well as inflammation, during regeneration of deep skin wounds in mice. We found that subcutaneous administration of microcarriers to the wound area resulted in uniform contraction of the wounds in mice in our experimental model, and microcarrier particles induced the infiltration of immune cells. This was associated with increased expression of proinflammatory cytokines TNF, IL-6, IL-1β, and chemokines CXCL1 and CXCL2, which contributed to full functional recovery of the injured area and the absence of fibrosis as compared to the control group.     

A meta-analysis of global urban land expansion

The conversion of Earth's land surface to urban uses is one of the most irreversible human impacts on the global biosphere. It drives the loss of farmland, affects local climate, fragments habitats, and threatens biodiversity. Here we present a meta-analysis of 326 studies that have used remotely sensed images to map urban land conversion. We report a worldwide observed increase in urban land area of 58,000 km(2) from 1970 to 2000. India, China, and Africa have experienced the highest rates of urban land expansion, and the largest change in total urban extent has occurred in North America. Across all regions and for all three decades, urban land expansion rates are higher than or equal to urban population growth rates, suggesting that urban growth is becoming more expansive than compact. Annual growth in GDP per capita drives approximately half of the observed urban land expansion in China but only moderately affects urban expansion in India and Africa, where urban land expansion is driven more by urban population growth. In high income countries, rates of urban land expansion are slower and increasingly related to GDP growth. However, in North America, population growth contributes more to urban expansion than it does in Europe. Much of the observed variation in urban expansion was not captured by either population, GDP, or other variables in the model. This suggests that contemporary urban expansion is related to a variety of factors difficult to observe comprehensively at the global level, including international capital flows, the informal economy, land use policy, and generalized transport costs. Using the results from the global model, we develop forecasts for new urban land cover using SRES Scenarios. Our results show that by 2030, global urban land cover will increase between 430,000 km(2) and 12,568,000 km(2), with an estimate of 1,527,000 km(2) more likely.     

Effect of Mixed Transplantation of Autologous and Allogeneic Microskin Grafts on Wound Healing in a Rat Model of Acute Skin Defect

The treatment of extensive thermal injuries with insufficient autologous skin remains a great challenge to burn surgeons. In this study, we investigated the influence of the ratio of autologous and allogeneic tissue in mixed microskin grafts on wound healing in order to develop an effective method for using limited donor skin to cover a large open wound. Four different mixtures were tested: autologous microskin at an area expansion ratio of 10∶1 with allogeneic microskin at an area expansion ratio of 10∶1 or 10∶3 and autologous microskin at an expansion ratio of 20∶1 with allogeneic microskin at an expansion ratio of 20∶3 or 20∶6. Wound healing, wound contraction, and integrin β1 expression were measured. Mixed microskin grafting facilitated wound healing substantially. The mixture of autologous microskin at an expansion ratio of 10∶1 with the same amount of allogeneic microskin achieved the most satisfactory wound healing among the 4 tested mixtures. Histological examination revealed the presence of obviously thickened epidermis and ectopic integrin β1 expression. Keratinocytes expressing integrin β1 were scattered in the suprabasal layer. Higher levels of integrin β1 expression were associated with faster wound healing, implying that ectopic expression of integrin β1 in keratinocytes may play a pivotal role in wound healing. In conclusion, this study proves that this new skin grafting technique may improve wound healing.     

Intraoperative tissue expansion in rhytidectomy revisited

Intraoperative tissue expansion is an adjunct that has been used during rhytidectomy to rejuvenate the face and neck. This technique has been thought to allow for additional skin resection and, thus, increased skin tightening during rhytidectomy. The stretch of the skin by expansion should allow for additional skin resection before closure. Also, when the force of the underlying expander is removed, the expanded skin would recoil and the advancement of the flap should become tighter, with improved results. The technique achieved some popularity a few years ago but has received little recent attention. In this study, the authors attempted to compare face-lift results of adjunctive intraoperative tissue expansion during rhytidectomy with similar techniques without intraoperative expansion. The results of 50 female patients who underwent rhytidectomy for midface rejuvenation by a single operating surgeon composed the study group. Twenty-five of the patients had undergone rhytidectomy that addressed the cheek, chin, and neck areas without expansion (nonexpanded rhytidectomy group). The other 25 patients (expanded rhytidectomy group) had adjunctive intraoperative tissue expansion performed with the rhytidectomy. A tissue expander was temporarily placed beneath the rhytidectomy flaps on each side and expanded in a standard manner before final skin resection and closure. Frontal and lateral photographs were evaluated by 54 examiners. Preoperative and postoperative photographs of the 50 patients were viewed side-by-side by the examiners. The patients were presented in blind fashion and random order. The examiners graded the results of each patient on a scale of improvement from 1 to 10, with 10 being the maximum level of improvement. The scores were recorded and statistically evaluated by using the two-sample test. Evaluation of the examiners' scores showed that the mean rating given to patients in the expanded rhytidectomy group was 5.07 (SD = 1.12). The mean rating for the nonexpanded rhytidectomy group was 5.27 (SD = 1.57). When the two groups were compared using the two-sample test, the difference between the two was not statistically significant (p = 0.6127). Intraoperative tissue expansion as an adjunct to rhytidectomy did not result in improved facial rejuvenation in this patient series. The authors' impression is that the benefits of tissue expansion do not justify the added expense, time, and risks associated with using tissue expansion during rhytidectomy.