Three-Dimensional Scaffolds for Tissue Engineering: The Importance of Uniformity in Pore Size and Structure

Department of Biomedical Engineering, Washington University, St. Louis, Missouri 63130, United States.
Langmuir (Impact Factor: 4.46). 12/2010; 26(24):19001-6. DOI: 10.1021/la104206h
Source: PubMed


To validate the importance of uniformity in pore size and structure of a scaffold for tissue engineering, we fabricated two types of scaffolds with uniform (inverse opal scaffolds) and nonuniform pore sizes and structures, and then evaluated their properties in terms of diffusion of macromolecules, spatial distribution of fibroblasts, and differentiation of preosteoblasts. Our results confirmed the superior performance of the inverse opal scaffolds due to the uniform pore size, homogeneous environment, and high interconnectivity: a higher diffusion rate, a uniform distribution of cells, and a higher degree of differentiation. In addition, we found that both the differentiation of cells and secretion of extracellular matrix were dependent on the properties of the individual pore to which the cells were attached, rather than the bulk properties of a scaffold. Our results clearly indicate that inverse opal scaffolds could provide a better microenvironment for cells in comparison to a scaffold with nonuniform size and structure.

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    • "diffusion rates and a more uniform distribution of cells in comparison to a scaffold with non-uniform size and structure (Choi et al., 2010). The cultivation of dFbs for 7 days (our unpublished data) and of bovine chondrocytes for 14 days (Hacker et al., 2007) in uncoated PLGA scaffolds showed a homogeneous distribution of cells and GAG synthesis throughout the entire scaffold. "
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    ABSTRACT: Surface modification of materials designed for regenerative medicine may improve biocompatibility and functionality. The application of glycosaminoglycans (GAGs) and chemically sulphated GAG derivatives is a promising approach for designing functional biomaterials, since GAGs interact with cell-derived growth factors and have been shown to support fibroblast growth in two-dimensional (2D) cultures. Here, coatings with artificial extracellular matrix (aECM), consisting of the structural protein collagen I and the GAG hyaluronan (HA) or sulphated HA derivatives, were investigated for their applicability in a three-dimensional (3D) system. As a model, macroporous poly(lactic-co-glycolic acid) (PLGA) scaffolds were homogeneously coated with aECM. The resulting scaffolds were characterized by compressive moduli of 0.9-1.2 MPa and pore sizes of 40-420 µm. Human dermal fibroblasts (dFbs) colonized these aECM-coated PLGA scaffolds to a depth of 400 µm within 14 days. In aECM-coated scaffolds, collagen I(α1) and collagen III(α1) mRNA expression was reduced, while matrix metalloproteinase-1 (MMP-1) mRNA expression was increased within 7 days, suggesting matrix-degradation processes. Stimulation with TGFβ1 generally increased cell density and collagen synthesis, demonstrating the efficiency of bioactive molecules in this 3D model. Thus, aECM with sulphated HA may modulate the effectivity of TGFβ1-induced collagen I(α1) expression, as demonstrated previously in 2D systems. Overall, the tested aECM with modified HA is also a suitable material for fibroblast growth under 3D conditions. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    Journal of Tissue Engineering and Regenerative Medicine 05/2015; DOI:10.1002/term.2037 · 5.20 Impact Factor
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    • "There is also a need to model heterogeneously distributed properties and responses (cf. Ref. [51]), but fortunately this is simply an issue of numerics in solving more complex initial boundary value problems because the constitutive framework is defined point-wise and can easily address spatial and temporal heterogeneity. Failure, whether by stenosis, aneurysmal dilatation or frank rupture, is often local, hence this aspect must be considered carefully in design and quality control. "
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    ABSTRACT: Continued advances in the tissue engineering of vascular grafts have enabled a paradigm shift from the desire to design for adequate suture retention, burst pressure, and thrombo-resistance to the goal of achieving grafts having near native properties, including growth potential. Achieving this far more ambitious outcome will require the identification of optimal, not just adequate, scaffold structure and material properties. Given the myriad possible combinations of scaffold parameters, there is a need for a new strategy for reducing the experimental search space. Toward this end, we present a new modeling framework for in vivo neovessel development that allows one to begin to assess in silico the potential consequences of different combinations of scaffold structure and material properties. To restrict the number of parameters considered, we also utilize a non-dimensionalization to identify key properties of interest. Using illustrative constitutive relations for both the evolving fibrous scaffold and the neotissue that develops in response to inflammatory and mechanobiological cues, we show that this combined non-dimensionalization – computational approach predicts salient aspects of neotissue development that depend directly on two key scaffold parameters, porosity and fiber diameter. We suggest, therefore, that hypothesis-driven computational models should continue to be pursued given their potential to identify preferred combinations of scaffold parameters that have the promise of improving neovessel outcome. In this way, we can begin to move beyond a purely empirical trial-and-error search for optimal combinations of parameters and instead focus our experimental resources on those combinations that are predicted to have the most promise.
    Acta Biomaterialia 10/2014; 11(1). DOI:10.1016/j.actbio.2014.09.046 · 6.03 Impact Factor
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    • "Several studies have examined the degradation of porous poly(L-lactic acid) (PLLA) scaffolds in vitro [8] [9] [10] [11] [12] [13] and showed that thicker walls degrade faster than thinner ones due to the autocatalysis of lactic acid, and a higher surface per volume ratio decreases the degradation rate [11] [13]. Although previous studies examined the relationship between scaffold architecture and degradation behavior, most of the porous scaffolds were sponge-like or nanofibrous scaffolds whose internal architectures, such as pore interconnectivity, location, and strut size, could not be rigorously controlled and did not have adequate mechanical properties for bone tissue engineering applications [14] [15] [16] [17] [18] [19]. Significant architectural variations often lead to conflicting and confusing conclusions. "
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    ABSTRACT: Current developments in computer-aided design (CAD) and solid free-form fabrication (SFF) techniques enable fabrication of scaffolds with precisely designed architectures and mechanical properties. The present study demonstrates the effect of precisely designed three-dimensional scaffold architectures on in vivo degradation. Specifically, three types of porous poly(L-lactic acid) (PLLA) scaffolds with variable pore sizes, strut sizes, porosities, and surface areas fabricated by indirect SFF. In addition, one experimental group of PLLA solid cylinders was fabricated. The scaffolds and cylinders were subcutaneously implanted into mice for 6, 12 and 21 weeks. The solid cylinders exhibited a faster percentage mass loss than all porous scaffolds. Among the porous scaffolds the group with the largest strut size lost percentage mass faster than the other two groups. Strong correlations between surface area and percentage mass loss were found at 12 (R(2)=0.681) and 21 (R(2)=0.671) weeks. Scaffold porosity, however, was not significantly correlated with degradation rate. Changes in molecular weight and crystallinity also resulted in changes in the chemical structures due to degradation, and the solid cylinders had faster crystallization due to more advanced degradation than the porous scaffolds. Scaffold compressive moduli decreased with degradation, but the resulting modulus was still within the lower range of human trabecular bone even after 21 weeks. The loss in compressive moduli, however, was a complex function of both degradation and the initial scaffold architecture. This study suggests that CAD and fabrication, within a given material, can significantly influence scaffold degradation profiles.
    Acta biomaterialia 03/2012; 8(7):2568-77. DOI:10.1016/j.actbio.2012.03.028 · 6.03 Impact Factor
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