Biophysical properties of Striae Distensae evaluated in vivo using non-invasive assays.

BACKGROUND: Striae Distensae (SD) or stretch marks are manifestations of epidermal atrophy that occurs after tissue tearing due to rapid growth or over-stretching and are characterized by distinct microstructural features. The objective of this in vivo study was to investigate the biophysical properties of SD lesions, including skin barrier function, skin surface hydration, mechanical properties, and chromophore concentrations, compared to normal adjacent skin. METHODS: Non-invasive methods were used on 29 volunteers with SD to characterize: (i) visual appearance (visual assessment and clinical imaging), (ii) skin barrier function by measuring transepidermal water loss, (iii) skin surface hydration using corneometry (skin capacitance), (iv) mechanical properties measuring skin elasticity under vacuum and surface propagation of a sonic wave, (v) the presence of erythema and pigmentation using diffuse reflectance spectroscopy, and (vi) the levels of interleukin-1α on the skin surface. RESULTS: No difference was observed in skin barrier function and a slight difference in skin hydration between the striae and adjacent uninvolved skin. Viscoelasticity measurements showed that SD lesions were significantly less firm, less elastic, and less deformable than normal skin (P < 0.05). Mechanical anisotropy was increased in SD compared to normal skin, reflecting the skin surface anisotropy reported previously. Diffuse reflectance spectroscopy showed no differences in the apparent hemoglobin concentrations between SD and control. Skin pigmentation and light scattering values were significantly lower in SD (P < 0.001) compared to adjacent skin and there was no correlation between them indicating independent causes: lower melanin production for pigmentation and altered collagen fiber structure in the dermis for light scattering. CONCLUSIONS: Based on these results, the distinct microstructural features characterizing SD lesions are accompanied by changes in the mechanical and optical properties. These changes however do not seem to affect the skin barrier and moisturization properties.

Age-dependent changes in stratum corneum barrier function.

BACKGROUND/PURPOSE: The Stratum Corneum (SC) barrier function mainly depends on the SC structure at the tissue level, its composition, and the organization of intercellular lipidic cement at the molecular level. The goal of this study was to assess the age-dependent changes of the SC barrier function and the associated physiological parameters. METHODS: This study was conducted on 40 French women divided into four groups of age. Measurements were done on three sites: cheek, protected, and exposed arm sites. SC composition (water, lipid/protein ratio, cholesterol, and ceramides) was measured using Raman confocal microspectroscopy, skin surface hydration using skin conductance, and barrier function through transepidermal water loss (TEWL) measurements. RESULTS: Transepidermal water loss decreases slightly with age, which is partially explained by the age-dependent increase in SC thickness. This decrease is faster for the face compared to both arm sites. The lipid to protein ratio and lipid compactness decrease significantly with age only for the arm sites. Water concentration profiles only decrease very close to the skin surface. At all ages tested, the SC on the cheek showed significantly higher TEWL, water and lipid content and less thickness compared to the arm sites. Comparison of the exposed to unexposed arm site showed difference only for the lipid compactness at the older group studied. CONCLUSION: Skin aging, body site and environmental exposure can affect the SC barrier function, its structure, and its lipid content. The thickening of the SC with age compensates for the decrease of the quantity and ordering of the lipidic cement.

Striae distensae are characterized by distinct microstructural features as measured by non-invasive methods in vivo.

BACKGROUND: Stretch marks or striae distensae (SD) are characterized by epidermal atrophy following repeated over-stretching of the skin tissue. The objective of this study was to investigate the skin texture and microstructure of SD lesions compared to those of normal adjacent skin in vivo using non-invasive methods. METHODS: A population of 26 women and 3 men with SD were examined after giving written informed consent. Following clinical grading, skin replicas were collected, confocal microscopy was performed on SD lesions and healthy neighboring skin. Skin surface texture parameters were calculated using 3D image analysis of the skin replicas and epidermal and dermal microstructure were evaluated by analysis of the confocal images. In a parallel study, histological analysis was performed on 6 skin biopsies taken from abdominal reduction surgeries in areas where skin exhibited SD. RESULTS: Analysis of the skin surface texture showed that the SD area was more anisotropic and with higher skin roughness than the adjacent skin in terms of directions of skin microglyphics. Confocal microscopy demonstrated that SD were characterized by shallower dermal papillae (P < 0.05) and that dermal papillae height inversely correlated to the intensity of collagen alignment on the SD sites (P < 0.05). The histology findings confirmed the in vivo confocal microscopy findings. CONCLUSIONS: The skin structure of SD is qualitatively and quantitatively different compared to healthy skin. Altered skin relief reflects structural modifications in the dermis. Flattening of the dermal-epidermal junction maybe functionally related to the observed collagen fiber alignment. Observations by non-invasive methods were in line with the histological findings and therefore relevant in studies assessing the efficacy of SD treatment options.

Early inflammatory processes in the skin.

Skin is considered as the border defining the limits of the body from the external world and functions as a barrier between the two. In this capacity, it has evolved to be an integral part of the innate and adaptive immune system. Although many reviews have described skin inflammation and processes that lead to its clinical manifestations, we are not aware of any reviews that have focused on immunologic activity occurring in the absence of any visual inflammatory cues. In this review, we discuss the importance of subclinical inflammation in human skin and its relevance to innate immune surveillance under physiologic conditions. Reactive oxygen species generated by metabolic processes, ultraviolet radiation or oxidizers may damage cells, initiating proinflammatory cascades. In addition to serving as structural skin components, keratinocytes have significant immunologic activity: they secrete proinflammatory cytokines and mediators, including interleukin (IL)-1α, IL-6, IL-10, tumor necrosis factor-α and granulocyte-macrophage colony-stimulating factor. Infant skin is particularly susceptible to irritation, inflammation and infection, since skin barrier function is not fully developed after birth and continues to mature throughout the first few years of life. Non-invasive methods such as fluorescence spectroscopy, spectral imaging and diffuse reflectance spectroscopy, as well as minimally invasive tape stripping, can be used to assess subclinical inflammatory markers in vivo, including erythema, epidermal cell proliferation rate and cytokine concentrations. Appropriately formulated skin care products may help maintain skin barrier integrity and enhance its capacity. In the future, assessment of subclinical inflammation may help clinicians prevent acute or chronic inflammatory conditions of the skin.

Infant skin physiology and development during the first years of life: a review of recent findings based on in vivo studies.

Infant skin is often presented as the cosmetic ideal for adults. However, compared to adult skin it seems to be more prone to develop certain pathological conditions, such as atopic dermatitis and irritant contact dermatitis. Therefore, understanding the physiology of healthy infant skin as a point of reference is of interest both from the cosmetic as well as from the clinical point of view. Clinical research on healthy infants is, however, limited because of ethical considerations of using invasive methods and therefore until recently data has been scarce. Technical innovations and the availability of non-invasive in vivo techniques, such as evaporimetry, electrical impedance measurement, in vivo video and confocal microscopy, and in vivo fibre-optic based spectroscopy, opened up the field of in vivo infant skin physiology research. Studies incorporating such methods have demonstrated that compared to adult, infant skin continues to develop during the first years of life. Specifically, infant skin appears to have thinner epidermis and stratum corneum (SC) as well as smaller corneocytes at least until the second year of life. The water-handling properties are not fully developed before the end of the first year and infant SC contains more water and less amounts of natural moisturizing factors. Such findings re-evaluate the old notions that skin is fully matured at birth. Armed with this knowledge, we are in a position not only to better understand infant dermatological conditions but also to design better skin care products respecting the distinct qualities of infant skin.

Development and validation of a photonumeric grading scale for assessing lip volume and thickness.

BACKGROUND: Currently, there is the need of a validated grading scale for assessing lip volume/thickness. OBJECTIVE: The aim of this study was to assist clinicians in managing individuals seeking lip rejuvenation and to provide an objective method for evaluating the efficacy and longevity of such treatments. METHODS: Using accepted criteria for the development of dermatological grading scales, we have developed and validated a photographic grading scale for assessing lip volume and thickness based on digital parallel-polarized light imaging. RESULTS: The photographic grading scale was shown to be a valid and reliable instrument for assessing lip volume and thickness, with good inter- and intra-grader consistency. The validity of the scale was demonstrated by its correlation with clinical evaluation and 3-dimensional measurements. CONCLUSIONS: This validated lip-volume/thickness grading scale should prove helpful in clinical trial settings to standardize clinical evaluations and to quantify results and measure the longevity of dermal fillers and other procedures for lip rejuvenation.

Antiaging action of retinol: from molecular to clinical.

The antiaging efficacy of retinol (ROL) has been explored mainly clinically in photoprotected skin sites and for high doses of ROL (0.4-1.6%). The objective of the study was to demonstrate the antiaging action of a low and tolerable dose of ROL (0.1%) ex vivo by measuring the expression of cellular retinoic-acid-binding protein II (CRABP2) and heparin-binding epidermal growth factor (HBEGF) by a histological evaluation of the epidermis and in vivo by assessing major aging signs and performing three-dimensional profilometry and digital imaging during a 9-month double-blind placebo-controlled study involving 48 volunteers. Finally, epidermal cell proliferation was evaluated using tryptophan fluorescence spectroscopy. Our results demonstrate that 0.1% ROL induced CRABP2 and HBEGF gene expression and increased keratinocyte proliferation and epidermal thickness. In human volunteers, topical application of a ROL-containing product improved all major aging signs assessed in our study (wrinkles under the eyes, fine lines and tone evenness). Moreover, tryptophan fluorescence increased in the active-agent-treated group and not in the placebo-treated group, indicating that cell proliferation was accelerated in vivo. These data demonstrate that a product containing a low dose (0.1%) of ROL promotes keratinocyte proliferation ex vivo and in vivo, induces epidermal thickening ex vivo and alleviates skin aging signs, without any significant adverse reaction.

Development and validation of a three-dimensional finite element model of the face.

A detailed three-dimensional finite element model of the face is presented in this paper. Bones, muscles, skin, fat, and superficial muscoloaponeurotic system were reconstructed from magnetic resonance images and modeled according to anatomical, plastic, and reconstructive surgery literature. The finite element mesh, composed of hexahedron elements, was generated through a semi-automatic procedure with an effective compromise between the detailed representation of anatomical parts and the limitation of the computational time. Nonlinear constitutive equations are implemented in the finite element model. The corresponding model parameters were selected according to previous work with mechanical measurements on soft facial tissue, or based on reasonable assumptions. Model assumptions concerning tissue geometry, interactions, mechanical properties, and the boundary conditions were validated through comparison with experiments. The calculated response of facial tissues to gravity loads, to the application of a pressure inside the oral cavity and to the application of an imposed displacement was shown to be in good agreement with the data from corresponding magnetic resonance images and holographic measurements. As a first application, gravimetric soft tissue descent was calculated from the long time action of gravity on the face in the erect position, with tissue aging leading to a loss of stiffness. Aging predictions are compared with the observations from an "aging database" with frontal photos of volunteers at different age ranges (i.e., 20-40 years and 50-70 years).

Influence of facial skin attributes on the perceived age of Caucasian women.

BACKGROUND AND OBJECTIVE: The facial appearance of a person does not always reflect the chronological age; some people look younger or older than they really are. Many studies have described the changes in skin properties (colour, wrinkles, sagging, micro relief, etc.) with age, but few of them have analysed their influence on the perceived age. The primary objective of this study was to assess the contribution of individual skin attributes of the face on the perceived age of Caucasian women. Secondary objectives were to assess the influence of age and gender of graders with regard to the age perception. SUBJECTS AND METHOD: A random sample of 173 subjects of 20 to 74 years of age was taken from a database of more than 5000 healthy Caucasian women. A trained grader performed visual assessment of facial skin attributes (using a visual analogue scale), and a front face photograph was taken from each subject. Photographs were shown to 48 graders (20 men and 28 women, aged 22-64 years) who were asked to estimate the age of the subjects. Graders were classified as young (less than 35 years), middle age (35-50 years) and seniors (older than 50 years). Partial Least Square regression models were built to predict the chronological and the perceived age from the measured facial individual attributes. The contribution of each attribute within the regression model enabled to measure the relevance of this attribute with regards to age prediction. RESULTS: The eye area and the skin colour uniformity were the main attributes related to perceived age. For age prediction, older graders' estimations were more driven by lips border definition shape and eyes opening, whereas younger graders' (older than 50 years) estimations were more driven by dark circles, nasolabial fold and brown spots. There were statistically significant differences in graders' age perception between gender and among age ranges. Our findings suggest that female graders are more accurate than male, and younger graders (under 35 years) are more accurate than older (over 50 years) to predict Caucasian women age from facial photographs. CONCLUSIONS: Different skin attributes influence the estimation of age. These attributes have a different weight in the evaluation of the perceived age, depending on the age and of the observer. The most important attributes to estimate age are eyes, lips and skin colour uniformity.

In vivo measurement of skin erythema and pigmentation: new means of implementation of diffuse reflectance spectroscopy with a commercial instrument.

BACKGROUND: Various physical, chemical and biological insults, including exposure to ultraviolet (UV) radiation, cause erythema and change in pigmentation in human skin. These reactions provide an important measure of the cutaneous response to the insult. OBJECTIVES: To present a new implementation of a method for objective in vivo measurement of erythema and pigmentation. METHODS: The method is based on acquisition of reflectance spectra in the visible range using a commercially available spectrophotometer. The probe of this instrument incorporates an integrating sphere that captures the light remitted from the skin in a wide range of angles. We corrected the acquired reflectance spectra for the contribution of specular reflections by an amount given by the Fresnel equation and verified this correction experimentally. This correction is particularly important when measurements are performed on heavily pigmented skin. The corrected reflectance spectra are then transformed into absorbance spectra. To analyse these spectra, we developed an algorithm which can be used to calculate apparent concentrations of oxyhaemoglobin, deoxyhaemoglobin and melanin. This method was tested in clinical studies of skin reactions induced by exposure to UV radiation. These experiments involved three groups of subjects with progressively darker complexion (constitutive pigmentation). Each group consisted of 10 subjects. Erythema was measured 1 day after UV exposure, and pigmentation (melanin content) 1 week later. Results Distinct apparent absorbance spectra were obtained for dark, intermediate and fair skin. There was good agreement between reconstructed spectra and experimental data at relevant wavelengths. Difference absorption spectra were able to show the dose dependence of UV-induced responses, and erythema and pigmentation values obtained by the spectroscopic method showed good correlation with those derived by subjective visual grading. CONCLUSIONS: The results demonstrate that the presented methodology provides an objective noninvasive way of measuring UV-induced reactions independently of the level of constitutive pigmentation.

Combined retinol-lactose-glycolic acid effects on photoaged skin: a double-blind placebo-controlled study.

The objective of this study was to assess the efficacy of the combination of retinol, lactose and glycolic acid applied topically on photodamaged skin. Forty female volunteers were enrolled in a double-blind, randomized placebo-controlled clinical study. A cream containing retinol, lactose and glycolic acid was applied on one side of the face and a placebo cream on the other side, twice daily for 12 weeks. Skin photoageing signs were assessed clinically, whereas skin microrelief and moisturization were measured instrumentally. Both the clinical assessment and the objective instrumental measurements revealed that the active-treated side was significantly improved at the end of the study compared with baseline and control-treated side. In conclusion, our results demonstrate that topical application of a combination of retinol, lactose and glycolic acid has significantly improved the appearance of photodamaged skin.

Skin viscoelasticity displays site- and age-dependent angular anisotropy.

One of the dominant characteristics of skin aging is loss of elasticity. Although the changes in the mechanical properties of the skin over several decades of life are substantial, objective measurements have failed to capture their magnitude thus far. Moreover, the mechanical properties of the skin are not uniform in all directions, and there is a need to understand this angular anisotropy. In this work we present a methodology of documenting the angular anisotropy of skin elasticity with high sensitivity and dynamic range using the Reviscometer RVM 600 (Courage & Khazaka Electronic GmbH, Cologne, Germany). The method is based on determining the directional dependence of the speed of an acoustic shear wave on the skin surface at intervals of 3 degrees . Based on the angular distribution of the resonance running time, we define two parameters: the anisotropy and the angular dispersion width. We find that with increasing age the anisotropy increases, while the angular dispersion width decreases. The ratio of these values provides a sensitive parameter for the assessment of the directional behavior of the skin mechanical properties. This parameter provides a large effective dynamic range capable of demonstrating close to an order of magnitude differences in skin viscoelasticity from infants up to adults 75 years of age. Furthermore, we show that the direction of the angular anisotropy relates to the direction of the dermal cleavage lines as defined by Langer, indicating that the anisotropy of the mechanical properties of skin stems from structural parameters. Based on these results, we conclude that the proposed methodology is able to capture accurately the age-dependent changes of the mechanical properties of the skin and to demonstrate a structure-function relationship.

Facial skin fluorescence as a marker of the skin's response to chronic environmental insults and its dependence on age.

BACKGROUND: Throughout life facial skin is exposed to a variety of adverse environmental conditions and is constantly required to repair itself. The rate of epidermal cell proliferation is indicative of the skin's repair rate and can be monitored noninvasively in vivo using skin intrinsic fluorescence markers. OBJECTIVES: The goal of the present study was to assess the effects of ageing, geographical region, ethnic origin and season on the ability of facial skin to repair itself in the presence of chronic environmental insults using in vivo fluorescence spectroscopy. METHODS: Skin fluorescence emission was measured on the cheeks of 522 individuals in winter and repeated in summer in five different geographical locations in the Asia-Pacific region. Fluorescence emission was also measured from 80 caucasians of fair complexion in the United States (New Jersey area) on the face and on a relatively protected area (upper inner arm). The age range of the participants was 14-75 years. RESULTS: We found that epidermal proliferation rates decrease monotonically with age, while the fluorescence of collagen and elastin cross-links increases with age indicating accumulation of advanced glycation end-products. These trends were independent of geographical region, ethnic origin and season of measurement. Epidermal proliferation rates of facial skin were higher than those of unexposed sites; they may be 10 times higher in younger (second decade) than in older (seventh decade) individuals, and they decrease with age at rates 10 times faster compared with those of unexposed sites. CONCLUSIONS: This is the first time that epidermal proliferation and its dependence on ageing have been measured noninvasively on the human face. The higher tryptophan fluorescence values on the face vs. the protected site are indicative of accelerated rates of epidermal proliferation in the presence of chronic environmental insults. The repair potential of facial skin, i.e. its ability to maintain high proliferation rates, is maximal in younger populations and gradually decreases with age.

Suppression of UVB-induced cutaneous erythema by a previous UVB exposure.

People who vacation in sunny places are exposed to the sun on multiple occasions at least on a daily basis. The clinical assessment of sun exposure is erythema in the first 48 h after exposure and pigmentation at times greater than 3-5 days. The purpose of this investigations was to determine the extent to which consecutive erythemogenic exposures result in additive erythema responses. Studies were conducted in which volunteers were first exposed to a graded series of fluences of UVB radiation and then on subsequent days (1-3 days) the same sites along with the surrounding unexposed skin were challenged with varying fluences of UVB radiation. The erythema reactions were assessed clinically and were objectively documented with diffuse reflectance spectroscopy. The sites that received two exposures always showed a reduced erythema response compared to a single erythemogenic exposure. The suppression of erythema was more pronounced when the second exposure was given 48 h after the first. The erythema suppression was maximal when the first exposure was at 1.3 minimum erythema dose (MED). The pigment response to the first exposure was completely suppressed for fluences less than 1.5 MED. We thus provide evidence for a decoupling of the classical sequence of erythema-pigmentation response. We also show that the erythema induced by a second exposure may be substantially suppressed by an earlier exposure, and that this cannot be due to melanin photoprotection or due to substantial thickening of the stratum corneum. We propose that the cause may be some diffusible element of yet unknown origin.

Rapid flow-induced responses in endothelial cells.

Endothelial cells alter their morphology, growth rate, and metabolism in response to fluid shear stress. To study rapid flow-induced responses in the 3D endothelial cell morphology and calcium distribution, coupled fluorescence microscopy with optical sectioning, digital imaging, and numerical deconvolution techniques have been utilized. Results demonstrate that within the first minutes of flow application nuclear calcium is increasing. In the same time frame whole cell height and nuclear height are reduced by about 1 microm. Whole cell height changes may facilitate reduction of shear stress gradients on the luminal surface, whereas nuclear structural changes may be important for modulating endothelial growth rate and metabolism. To study the role of the cytoskeleton in these responses, endothelial cells have been treated with specific disrupters (acrylamide, cytochalasin D, and colchicine) of each of the cytoskeleton elements (intermediate filaments, microfilaments, and microtubules, respectively). None of these compounds had any effect on the shear-induced calcium response. Cytochalasin D and acrylamide did not affect the shear-induced nuclear morphology changes. Colchicine, however, completely abrogated the response, indicating that microtubules may be implicated in force transmission from the plasma membrane to the nucleus. A pedagogical model based on tensegrity theory principles is presented that is consistent with the results on the 3D endothelial morphology.

Controlled release of transforming growth factor beta1 from biodegradable polymer microparticles.

Recombinant human transforming growth factor beta1 (TGF-beta1) was incorporated into biodegradable microparticles of blends of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) at 6 ng/1 mg microparticles. Fluorescein isothiocynate labeled bovine serum albumin (FITC-BSA) was coencapsulated as a porogen at 4 microg/1 mg of microparticles. The effects of PEG content (0, 1, or 5 wt %) and buffer pH (3, 5, or 7.4) on the protein release kinetics and the degradation of PLGA were determined in vitro for up to 28 days. The entrapment yield of TGF-beta1 was 83.4 +/- 13.1 and 54.2 +/- 12.1% for PEG contents of 0 and 5%, respectively. The FITC-BSA and TGF-beta1 were both released in a multiphasic fashion including an initial burst effect. Increasing the PEG content resulted in the decreased cumulative mass of released proteins. By day 28, 3.8 +/- 0. 1 and 2.8 +/- 0.3 microg (based on 1 mg microparticles) of loaded FITC-BSA and 3.4 +/- 0.2 and 2.2 +/- 0.3 ng of loaded TGF-beta1 were released into pH 7.4 phosphate buffered saline (PBS) from microparticles with 0 and 5% PEG, respectively. Aggregation of FITC-BSA occurred at lower buffer pH, which led to decreased release rates of both proteins. For microparticles with 5% PEG, 2.3 +/- 0.1 microg of FITC-BSA and 2.0 +/- 0.2 ng of TGF-beta1 were released in pH 7.4 buffer after 28 days, while only 1.7 +/- 0.3 microg and 1.3 +/- 0.4 ng of the corresponding proteins were released in pH 3 buffer. The degradation of PLGA was also enhanced at 5% PEG content, which was significantly accelerated at acidic pH conditions. The calculated half-lives of PLGA were 20.3 +/- 0.9 and 15.9 +/- 1.2 days for PEG contents of 0 and 5%, respectively, in pH 7.4 PBS and 14.8 +/- 0.4 and 5.5 +/- 0.1 days for 5% PEG in pH 7.4 and 3 buffers, respectively. These results suggest that PLGA/PEG blend microparticles are useful as delivery vehicles for controlled release of growth factors.

Effects of transforming growth factor beta1 released from biodegradable polymer microparticles on marrow stromal osteoblasts cultured on poly(propylene fumarate) substrates.

Recombinant human transforming growth factor beta1 (TGF-beta1) was incorporated into microparticles of blends of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) to create a delivery vehicle for the growth factor. The entrapment efficiency of TGF-beta1 in the microparticles containing 5% PEG was 40.3 +/- 1.2% for a TGF-beta1 loading density of 6.0 ng/1 mg of microparticles. For the same loading, 17.9 +/- 0.6 and 32.1 +/- 2.5% of the loaded TGF-beta1 was released after 1 and 8 days, respectively, followed by a plateau for the remaining 3 weeks. Rat marrow stromal cells showed a dose response to TGF-beta1 released from the microparticles similar to that of added TGF-beta1, indicating the activity of TGF-beta1 was retained during microparticle fabrication and after TGF-beta1 release. An optimal TGF-beta1 dosage of 1.0 ng/mL was determined through a 3-day dose response study for maximal alkaline phosphatase (ALP) activity. The TGF-beta1 released from the microparticles loaded with 6.0 ng TGF-beta1/1 mg of microparticles for the optimal dosage of TGF-beta1 enhanced the proliferation and osteoblastic differentiation of marrow stromal cells cultured on poly(propylene fumarate) substrates. The cells showed significantly increased total cell number, ALP activity, and osteocalcin production with values reaching 138,700 +/- 3300 cells/cm(2), 22.8 +/- 1.5 x 10(-7) micromol/min/cell, and 15.9 +/- 1.5 x 10(-6) ng/cell, respectively, after 21 days as compared to cells cultured under control conditions without TGF-beta1. These results suggest that controlled release of TGF-beta1 from the PLGA/PEG blend microparticles may find applications in modulating cellular response during bone healing at a skeletal defect site.

Novel optical methodologies in studying mechanical signal transduction in mammalian cells.

For the last 3 decades evidence has been accumulating that some types of mammalian cells respond to their mechanically active environment by altering their morphology, growth rate, and metabolism. The study of such responses is very important in understanding, physiological and pathological conditions ranging from bone formation to atherosclerosis. Obtaining this knowledge has been the goal for an active research area in bioengineering termed cell mechanotransduction. The advancement of optical methodologies used in cell biology research has given the tools to elucidate cellular mechanisms that would otherwise be impossible to visualize. Combined with molecular biology techniques, they give engineers invaluable tools in understanding the chemical pathways involved in mechanotransduction. Herein we briefly review the current knowledge on mechanical signal transduction in mammalian cells, focusing on the application of novel optical techniques in the ongoing research.