Strength over time of a resorbable bioscaffold for body wall repair in a dog model

The change in strength over time of a biomaterial derived from the small intestinal submucosa (SIS) was determined in a dog model of body wall repair. Full-thickness body wall defects measuring 8 x 12 cm were surgically created and then repaired with a multilaminate eight-layer form of SIS in 40 dogs. Five dogs were sacrificed at each of the following time points: 1 day, 4 days, 7 days, 10 days, and 1, 3, 6, and 24 months. Ball burst tests that measured biaxial ultimate load-bearing capability were performed on the device prior to implantation and on the device/implant site at the time of sacrifice. The strength of the device at the time of implant was approximately 73 +/- 12 pounds. The strength of the implant site diminished to 40 +/- 18 pounds at 10 days, and then progressively increased to a value of 156 +/- 26 pounds at 24 months (P < 0.05). The clinical utility of a degradable biomaterial such as SIS depends on a balance between the rate of degradation and the rate of host remodeling. Naturally occurring extracellular matrix scaffolds such as SIS show rapid degradation with associated and subsequent remodeling to a tissue with strength that exceeds that of the native tissue when used as a body wall repair device.     

Development of a three-dimensional unit cell to model the micromechanical response of a collagen-based extracellular matrix

The three-dimensional microstructure and mechanical properties of the collagen fibrils within the extracellular matrix (ECM) is now being recognized as a primary factor in regulating cell proliferation and differentiation. Therefore, an appreciation of the mechanical aspects by which a cell interacts with its ECM is required for the development of engineered tissues. Ultimately, using these interactions to design tissue equivalents requires mathematical models with three-dimensional architecture. In this study, a three-dimensional model of a collagen fibril matrix undergoing uniaxial tensile stress was developed by making use of cellular solids. A structure consisting of thin struts was chosen to represent the arrangement of collagen fibrils within an engineered ECM. To account for the large deformation of tissues, the collagen fibrils were modeled as hyperelastic neo-Hookean or Mooney–Rivlin materials. The use of cellular solids allowed the fibril properties to be related to the ECM properties in closed form, which, in turn, allowed the estimation of fibril properties using ECM experimental data. A set of previously obtained experimental data consisting of simultaneous measures of the fibril microstructure and mechanical tests was used to evaluate the model’s capability to estimate collagen fibril mechanical property when given tissue-scale data and to predict the tissue-scale mechanical properties when given estimated fibril stiffness. The fibril tangent modulus was found to be 1.26 ± 0.70 and 1.62 ± 0.88 MPa when the fibril was modeled as neo-Hookean and Mooney–Rivlin material, respectively. There was no statistical significance of the estimated fibril tangent modulus among the different groups. Sensitivity analysis showed that the fibril mechanical properties and volume fraction were the two input parameters which required accurate values. While the volume fraction was easily obtained from the initial image of the gel, the fibril mechanical properties were not readily available. Therefore the fibril mechanical properties were estimated in the leave-one-out cross-validation (LOOCV) analysis. The LOOCV analysis showed that the model was able to predict the ECM stress–stretch curve with an average mean squared error of 9.71 kPa². The three-dimensional architecture expands on previous continuum models and two-dimensional representations to provide a useful model for studying the hierarchical effects of ECM microstructure on cell function. This model can be used as a design tool to engineer the optimum microstructure for cells to function.     

Elastic modulus of prepared canine jejunum,a new vascular graft material

The submucosal connective tissue of the jejunum has been shown to be suitable for use as a vascular graft in preliminary dog studies. To partially characterize the mechanical properties of this new graft material, longitudinal stress (σ)-strain (ε)-data were obtained on 13 specimens of canine jejunum, stripped of its mucosal and external smooth-muscle layers. The ratio of stress to strain is the modulus of elasticity (E). It was found that the stress σ-strain ε-data fitted the expressionγ=K∈ ^α very well. For a typical specimenγ=2.69×10⁶∈^2.33. The modulus of elasticity (E=γ ^1-1/α K ^1/α) was found to increase with increasing stress, ranging from about 2,000 to 9,000 mmHg. For the average specimenE=573γ ^0.57, where σ is in mmHg, (1 mmHg=133.3 Pascals).     

Prediction of equibiaxial loading stress in collagen-based extracellular matrix using a three-dimensional unit cell model

Mechanical signals are important factors in determining cell fate. Therefore, insights as to how mechanical signals are transferred between the cell and its surrounding three-dimensional collagen fibril network will provide a basis for designing the optimum extracellular matrix (ECM) microenvironment for tissue regeneration. Previously we described a cellular solid model to predict fibril microstructure–mechanical relationships of reconstituted collagen matrices due to unidirectional loads (Acta Biomater 2010;6:1471–86). The model consisted of representative volume elements made up of an interconnected network of flexible struts. The present study extends this work by adapting the model to account for microstructural anisotropy of the collagen fibrils and a biaxial loading environment. The model was calibrated based on uniaxial tensile data and used to predict the equibiaxial tensile stress–stretch relationship. Modifications to the model significantly improved its predictive capacity for equibiaxial loading data. With a comparable fibril length (model 5.9–8 μm, measured 7.5 μm) and appropriate fibril anisotropy the anisotropic model provides a better representation of the collagen fibril microstructure. Such models are important tools for tissue engineering because they facilitate prediction of microstructure–mechanical relationships for collagen matrices over a wide range of microstructures and provide a framework for predicting cell–ECM interactions.     

Morphologic study of small intestinal submucosa as a body wall repair device

BACKGROUND: The extracellular matrix (ECM) derived from porcine small intestinal submucosa (SIS) has been used as a constructive scaffold for tissue repair in both preclinical animal studies and human clinical trials. Quantitative characterization of the host tissue response to this xenogeneic scaffold material has been lacking. MATERIALS AND METHODS: The morphologic response to a multilaminate form of the SIS-ECM was evaluated in a chronic, 2-year study of body wall repair in two separate species: the dog and the rat. Morphologic response to the SIS-ECM was compared to that for three other commonly used bioscaffold materials including Marlex mesh, Dexon, and Perigard. Quantitative measurements were made of tissue consistency, polymorphonuclear cell response, mononuclear cell response, tissue organization, and vascularity at five time points after surgical implantation: 1 week, 1, 3, and 6 months, and 2 years. RESULTS: All bioscaffold materials functioned well as a repair device for large ventral abdominal wall defects created in these two animal models. The SIS-ECM bioscaffold showed a greater number of polymorphonuclear leukocytes at the 1-week time point and a greater degree of graft site tissue organization after 3 months compared to the other three scaffold materials. There was no evidence for local infection or other detrimental local pathology to any of the graft materials at any time point. CONCLUSIONS: Like Marlex, Dexon, and Perigard, the SIS-ECM is an effective bioscaffold for long-term repair of body wall defects. Unlike the other scaffold materials, the resorbable SIS-ECM scaffold was replaced by well-organized host tissues including differentiated skeletal muscle.