In JoVE (1)

Other Publications (12)

Articles by Adrian Buganza Tepole in JoVE

 JoVE Bioengineering

Quantification of Strain in a Porcine Model of Skin Expansion Using Multi-View Stereo and Isogeometric Kinematics

1Mechanical Engineering, Purdue University, 2Division of Plastic Surgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, 3Mechanical Engineering, Bioengineering, Cardiothoracic Surgery, Stanford University

JoVE 55052

Other articles by Adrian Buganza Tepole on PubMed

Growing Skin: A Computational Model for Skin Expansion in Reconstructive Surgery

Journal of the Mechanics and Physics of Solids. Oct, 2011  |  Pubmed ID: 22081726

The goal of this manuscript is to establish a novel computational model for stretch-induced skin growth during tissue expansion. Tissue expansion is a common surgical procedure to grow extra skin for reconstructing birth defects, burn injuries, or cancerous breasts. To model skin growth within the framework of nonlinear continuum mechanics, we adopt the multiplicative decomposition of the deformation gradient into an elastic and a growth part. Within this concept, we characterize growth as an irreversible, stretch-driven, transversely isotropic process parameterized in terms of a single scalar-valued growth multiplier, the in-plane area growth. To discretize its evolution in time, we apply an unconditionally stable, implicit Euler backward scheme. To discretize it in space, we utilize the finite element method. For maximum algorithmic efficiency and optimal convergence, we suggest an inner Newton iteration to locally update the growth multiplier at each integration point. This iteration is embedded within an outer Newton iteration to globally update the deformation at each finite element node. To demonstrate the characteristic features of skin growth, we simulate the process of gradual tissue expander inflation. To visualize growth-induced residual stresses, we simulate a subsequent tissue expander deflation. In particular, we compare the spatio-temporal evolution of area growth, elastic strains, and residual stresses for four commonly available tissue expander geometries. We believe that predictive computational modeling can open new avenues in reconstructive surgery to rationalize and standardize clinical process parameters such as expander geometry, expander size, expander placement, and inflation timing.

Growing Skin: Tissue Expansion in Pediatric Forehead Reconstruction

Biomechanics and Modeling in Mechanobiology. Jul, 2012  |  Pubmed ID: 22052000

Tissue expansion is a common surgical procedure to grow extra skin through controlled mechanical over-stretch. It creates skin that matches the color, texture, and thickness of the surrounding tissue, while minimizing scars and risk of rejection. Despite intense research in tissue expansion and skin growth, there is a clear knowledge gap between heuristic observation and mechanistic understanding of the key phenomena that drive the growth process. Here, we show that a continuum mechanics approach, embedded in a custom-designed finite element model, informed by medical imaging, provides valuable insight into the biomechanics of skin growth. In particular, we model skin growth using the concept of an incompatible growth configuration. We characterize its evolution in time using a second-order growth tensor parameterized in terms of a scalar-valued internal variable, the in-plane area growth. When stretched beyond the physiological level, new skin is created, and the in-plane area growth increases. For the first time, we simulate tissue expansion on a patient-specific geometric model, and predict stress, strain, and area gain at three expanded locations in a pediatric skull: in the scalp, in the forehead, and in the cheek. Our results may help the surgeon to prevent tissue over-stretch and make informed decisions about expander geometry, size, placement, and inflation. We anticipate our study to open new avenues in reconstructive surgery and enhance treatment for patients with birth defects, burn injuries, or breast tumor removal.

On the Biomechanics and Mechanobiology of Growing Skin

Journal of Theoretical Biology. Mar, 2012  |  Pubmed ID: 22227432

Skin displays an impressive functional plasticity, which allows it to adapt gradually to environmental changes. Tissue expansion takes advantage of this adaptation, and induces a controlled in situ skin growth for defect correction in plastic and reconstructive surgery. Stretches beyond the skin's physiological limit invoke several mechanotransduction pathways, which increase mitotic activity and collagen synthesis, ultimately resulting in a net gain in skin surface area. However, the interplay between mechanics and biology during tissue expansion remains unquantified. Here, we present a continuum model for skin growth that summarizes the underlying mechanotransduction pathways collectively in a single phenomenological variable, the strain-driven area growth. We illustrate the governing equations for growing biological membranes, and demonstrate their computational solution within a nonlinear finite element setting. In displacement-controlled equi-biaxial extension tests, the model accurately predicts the experimentally observed histological, mechanical, and structural features of growing skin, both qualitatively and quantitatively. Acute and chronic elastic uniaxial stretches are 25% and 10%, compared to 36% and 10% reported in the literature. Acute and chronic thickness changes are -28% and -12%, compared to -22% and -7% reported in the literature. Chronic fractional weight gain is 3.3, compared to 2.7 for wet weight and 3.3 for dry weight reported in the literature. In two clinical cases of skin expansion in pediatric forehead reconstruction, the model captures the clinically observed mechanical and structural responses, both acutely and chronically. Our results demonstrate that the field theories of continuum mechanics can reliably predict the mechanical manipulation of thin biological membranes by controlling their mechanotransduction pathways through mechanical overstretch. We anticipate that the proposed skin growth model can be generalized to arbitrary biological membranes, and that it can serve as a valuable tool to virtually manipulate living tissues, simply by means of changes in the mechanical environment.

Stretching Skin: The Physiological Limit and Beyond

International Journal of Non-linear Mechanics. Oct, 2012  |  Pubmed ID: 23459410

The goal of this manuscript is to establish a novel computational model for skin to characterize its constitutive behavior when stretched within and beyond its physiological limits. Within the physiological regime, skin displays a reversible, highly nonlinear, stretch locking, and anisotropic behavior. We model these characteristics using a transversely isotropic chain network model composed of eight wormlike chains. Beyond the physiological limit, skin undergoes an irreversible area growth triggered through mechanical stretch. We model skin growth as a transversely isotropic process characterized through a single internal variable, the scalar-valued growth multiplier. To discretize the evolution of growth in time, we apply an unconditionally stable, implicit Euler backward scheme. To discretize it in space, we utilize the finite element method. For maximum algorithmic efficiency and optimal convergence, we suggest an inner Newton iteration to locally update the growth multiplier at each integration point. This iteration is embedded within an outer Newton iteration to globally update the deformation at each finite element node. To illustrate the characteristic features of skin growth, we first compare the two simple model problems of displacement- and force-driven growth. Then, we model the process of stretch-induced skin growth during tissue expansion. In particular, we compare the spatio-temporal evolution of stress, strain, and area gain for four commonly available tissue expander geometries. We believe that the proposed model has the potential to open new avenues in reconstructive surgery and rationalize critical process parameters in tissue expansion, such as expander geometry, expander size, expander placement, and inflation timing.

Systems-based Approaches Toward Wound Healing

Pediatric Research. Apr, 2013  |  Pubmed ID: 23314298

Wound healing in the pediatric patient is of utmost clinical and social importance because hypertrophic scarring can have aesthetic and psychological sequelae, from early childhood to late adolescence. Wound healing is a well-orchestrated reparative response affecting the damaged tissue at the cellular, tissue, organ, and system scales. Although tremendous progress has been made toward understanding wound healing at the individual temporal and spatial scales, its effects across the scales remain severely understudied and poorly understood. Here, we discuss the critical need for systems-based computational modeling of wound healing across the scales, from short-term to long-term and from small to large. We illustrate the state of the art in systems modeling by means of three key signaling mechanisms: oxygen tension-regulating angiogenesis and revascularization; transforming growth factor-β (TGF-β) kinetics controlling collagen deposition; and mechanical stretch stimulating cellular mitosis and extracellular matrix (ECM) remodeling. The complex network of biochemical and biomechanical signaling mechanisms and the multiscale character of the healing process make systems modeling an integral tool in exploring personalized strategies for wound repair. A better mechanistic understanding of wound healing in the pediatric patient could open new avenues in treating children with skin disorders such as birth defects, skin cancer, wounds, and burn injuries.

Application of Finite Element Modeling to Optimize Flap Design with Tissue Expansion

Plastic and Reconstructive Surgery. Oct, 2014  |  Pubmed ID: 24945952

Tissue expansion is a widely used technique to create skin flaps for the correction of sizable defects in reconstructive plastic surgery. Major complications following the inset of expanded flaps include breakdown and uncontrolled scarring secondary to excessive tissue tension. Although it is recognized that mechanical forces may significantly impact the success of defect repair with tissue expansion, a mechanical analysis of tissue stresses has not previously been attempted. Such analyses have the potential to optimize flap design preoperatively.

Characterization of Living Skin Using Multi-view Stereo and Isogeometric Analysis

Acta Biomaterialia. Nov, 2014  |  Pubmed ID: 25016279

Skin is our interface with the outside world. In its natural environment, it displays unique mechanical characteristics, such as prestretch and growth. While there is a general agreement on the physiological importance of these features, they remain poorly characterized, mainly because they are difficult to access with standard laboratory techniques. Here we present a new, inexpensive technique to characterize living skin using multi-view stereo and isogeometric analysis. Based on easy-to-create hand-held camera images, we quantify prestretch, deformation and growth in a controlled porcine model of chronic skin expansion. Over a period of 5 weeks, we gradually inflate an implanted tissue expander, take weekly photographs of the experimental scene, reconstruct the geometry from a tattooed surface grid and create parametric representations of the skin surface. After 5 weeks of expansion, our method reveals an average area prestretch of 1.44, an average area stretch of 1.87 and an average area growth of 2.25. Area prestretch is maximal in the ventral region with a value of 2.37, whereas area stretch and area growth are maximal above the center of the expander, with values of 4.05 and 4.81, respectively. Our study has immediate impact on understanding living skin to optimize treatment planning and decision making in plastic and reconstructive surgery. Beyond these direct implications, our experimental design has broad applications in clinical research and basic sciences: it serves as a simple, robust, low cost, easy-to-use tool to reconstruct living membranes, which are difficult to characterize in a conventional laboratory setup.

Computational Modeling of Skin: Using Stress Profiles As Predictor for Tissue Necrosis in Reconstructive Surgery

Computers & Structures. Sep, 2014  |  Pubmed ID: 25225454

Local skin flaps have revolutionized reconstructive surgery. Mechanical loading is critical for flap survival: Excessive tissue tension reduces blood supply and induces tissue necrosis. However, skin flaps have never been analyzed mechanically. Here we explore the stress profiles of two common flap designs, direct advancement flaps and double back-cut flaps. Our simulations predict a direct correlation between regions of maximum stress and tissue necrosis. This suggests that elevated stress could serve as predictor for flap failure. Our model is a promising step towards computer-guided reconstructive surgery with the goal to minimize stress, accelerate healing, minimize scarring, and optimize tissue use.

Multi-view Stereo Analysis Reveals Anisotropy of Prestrain, Deformation, and Growth in Living Skin

Biomechanics and Modeling in Mechanobiology. Oct, 2015  |  Pubmed ID: 25634600

Skin expansion delivers newly grown skin that maintains histological and mechanical features of the original tissue. Although it is the gold standard for cutaneous defect correction today, the underlying mechanisms remain poorly understood. Here we present a novel technique to quantify anisotropic prestrain, deformation, and growth in a porcine skin expansion model. Building on our recently proposed method, we combine two novel technologies, multi-view stereo and isogeometric analysis, to characterize skin kinematics: Upon explantation, a unit square retracts ex vivo to a square of average dimensions of [Formula: see text]. Upon expansion, the unit square deforms in vivo into a rectangle of average dimensions of [Formula: see text]. Deformations are larger parallel than perpendicular to the dorsal midline suggesting that skin responds anisotropically with smaller deformations along the skin tension lines. Upon expansion, the patch grows in vivo by [Formula: see text] with respect to the explanted, unexpanded state. Growth is larger parallel than perpendicular to the midline, suggesting that elevated stretch activates mechanotransduction pathways to stimulate tissue growth. The proposed method provides a powerful tool to characterize the kinematics of living skin. Our results shed light on the mechanobiology of skin and help us to better understand and optimize clinically relevant procedures in plastic and reconstructive surgery.

Isogeometric Kirchhoff-Love Shell Formulations for Biological Membranes

Computer Methods in Applied Mechanics and Engineering. Aug, 2015  |  Pubmed ID: 26251556

Computational modeling of thin biological membranes can aid the design of better medical devices. Remarkable biological membranes include skin, alveoli, blood vessels, and heart valves. Isogeometric analysis is ideally suited for biological membranes since it inherently satisfies the C(1)-requirement for Kirchhoff-Love kinematics. Yet, current isogeometric shell formulations are mainly focused on linear isotropic materials, while biological tissues are characterized by a nonlinear anisotropic stress-strain response. Here we present a thin shell formulation for thin biological membranes. We derive the equilibrium equations using curvilinear convective coordinates on NURBS tensor product surface patches. We linearize the weak form of the generic linear momentum balance without a particular choice of a constitutive law. We then incorporate the constitutive equations that have been designed specifically for collagenous tissues. We explore three common anisotropic material models: Mooney-Rivlin, May Newmann-Yin, and Gasser-Ogden-Holzapfel. Our work will allow scientists in biomechanics and mechanobiology to adopt the constitutive equations that have been developed for solid three-dimensional soft tissues within the framework of isogeometric thin shell analysis.

The Incompatibility of Living Systems: Characterizing Growth-Induced Incompatibilities in Expanded Skin

Annals of Biomedical Engineering. May, 2016  |  Pubmed ID: 26416721

Skin expansion is a common surgical technique to correct large cutaneous defects. Selecting a successful expansion protocol is solely based on the experience and personal preference of the operating surgeon. Skin expansion could be improved by predictive computational simulations. Towards this goal, we model skin expansion using the continuum framework of finite growth. This approach crucially relies on the concept of incompatible configurations. However, aside from the classical opening angle experiment, our current understanding of growth-induced incompatibilities remains rather vague. Here we visualize and characterize incompatibilities in living systems using skin expansion in a porcine model: We implanted and inflated two expanders, crescent, and spherical, and filled them to 225 cc throughout a period of 21 days. To quantify the residual strains developed during this period, we excised the expanded skin patches and subdivided them into smaller pieces. Skin growth averaged 1.17 times the original area for the spherical and 1.10 for the crescent expander, and displayed significant regional variations. When subdivided into smaller pieces, the grown skin patches retracted heterogeneously and confirmed the existence of incompatibilities. Understanding skin growth through mechanical stretch will allow surgeons to improve-and ultimately personalize-preoperative treatment planning in plastic and reconstructive surgery.

A Finite Element Model for Mixed Porohyperelasticity with Transport, Swelling, and Growth

PloS One. 2016  |  Pubmed ID: 27078495

The purpose of this manuscript is to establish a unified theory of porohyperelasticity with transport and growth and to demonstrate the capability of this theory using a finite element model developed in MATLAB. We combine the theories of volumetric growth and mixed porohyperelasticity with transport and swelling (MPHETS) to derive a new method that models growth of biological soft tissues. The conservation equations and constitutive equations are developed for both solid-only growth and solid/fluid growth. An axisymmetric finite element framework is introduced for the new theory of growing MPHETS (GMPHETS). To illustrate the capabilities of this model, several example finite element test problems are considered using model geometry and material parameters based on experimental data from a porcine coronary artery. Multiple growth laws are considered, including time-driven, concentration-driven, and stress-driven growth. Time-driven growth is compared against an exact analytical solution to validate the model. For concentration-dependent growth, changing the diffusivity (representing a change in drug) fundamentally changes growth behavior. We further demonstrate that for stress-dependent, solid-only growth of an artery, growth of an MPHETS model results in a more uniform hoop stress than growth in a hyperelastic model for the same amount of growth time using the same growth law. This may have implications in the context of developing residual stresses in soft tissues under intraluminal pressure. To our knowledge, this manuscript provides the first full description of an MPHETS model with growth. The developed computational framework can be used in concert with novel in-vitro and in-vivo experimental approaches to identify the governing growth laws for various soft tissues.

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